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Abstract Sirenians of the superorder Afrotheria were the first mammals to transition from land to water and are the only herbivorous marine mammals. Here, we generated a chromosome-level dugong (Dugong dugon) genome. A comparison of our assembly with other afrotherian genomes reveals possible molecular adaptations to aquatic life by sirenians, including a shift in daily activity patterns (circadian clock) and tolerance to a high-iodine plant diet mediated through changes in the iodide transporter NIS (SLC5A5) and its co-transporters. Functional in vitro assays confirm that sirenian amino acid substitutions alter the properties of the circadian clock protein PER2 and NIS. Sirenians show evidence of convergent regression of integumentary system (skin and its appendages) genes with cetaceans. Our analysis also uncovers gene losses that may be maladaptive in a modern environment, including a candidate gene (KCNK18) for sirenian cold stress syndrome likely lost during their evolutionary shift in daily activity patterns. Genomes from nine Australian locations and the functionally extinct Okinawan population confirm and date a genetic break ~10.7 thousand years ago on the Australian east coast and provide evidence of an associated ecotype, and highlight the need for whole-genome resequencing data from dugong populations worldwide for conservation and genetic management.

Osteosarcoma stands as the most prevalent bone tumor, characterized by a heightened tendency for local recurrence and distant metastasis, resulting in a bleak prognosis. Presently, there exists a shortage of novel markers to effectively determine the prognosis of osteosarcoma patients. Recent research indicates that hematological markers partially mirror an individual’s microenvironment, offering potential insights into predicting patient prognosis. However, prior studies predominantly focused on the prognostic significance of singular hematological indices, failing to comprehensively represent the tumor microenvironment of patients. In our investigation, we meticulously gathered data on 22 hematological and electrolyte markers, utilizing LASSO Cox regression analysis to devise an Electrolyte Prognostic Scoring System (EPSS). The EPSS encompasses various indicators, including immunity, inflammation, coagulation, and electrolyte levels. Our findings indicate that the EPSS stands as an independent prognostic factor for overall survival among osteosarcoma patients. It serves as a valuable addition to clinical characteristics, adept at discerning high-risk patients from those deemed clinically low-risk. Furthermore, EPSS-based nomograms demonstrate commendable predictive capabilities.

BackgroundManaging complicated acetabular fractures involving the quadrilateral plate (QLP) can be challenging for surgeons, especially when complicated by comminution and osteoporosis. Traditional implants do not provide sufficient fixed strength or a proper match. The new-type pre-contoured infrapectineal buttress plates may have drawbacks, such as inaccurate fitting on the medial surface of QLP and an inability to apply reversed compression force to resist medial displacement of femoral head. Therefore, the primary purpose of this study is to introduce a novel technique that utilizes a special contoured pelvic brim reconstruction titanium plate combined with quadrilateral screws to reduce and stabilize acetabular fractures involving the QLP through the ilioinguinal approach. Additionally, the secondary purpose is to evaluate both clinical effectiveness and radiological outcomes of this technique for QLP fractures.MethodsWe conducted a retrospective analysis of prospectively collected data from 48 patients (31 males and 17 females) who suffered from acute displaced fractures of the QLP and were treated between January 2012 and December 2019 using a special contoured plate combined with quadrilateral screws. The patients' mean age was 47.56 ± 11.31 years (range: 19–73 years). Fracture patterns included 20 both-column fractures, 12 anterior column and posterior hemitransverse fractures, eight T-type fractures, five transverse fractures and three anterior column fractures with the QLP affected, all of which had femoral head protrusion. Immediate postoperative reduction quality was evaluated according to Matta's criteria. Final clinical functions were assessed during follow-up using the modified Merle d’Aubigné and Harris Hip scores (HHS).ResultsThe patients were followed up for an average of 48.36 ± 12.94 months (ranging from 24 to 84 months). The mean operative time was 246.08 ± 54.30 min (ranging from 178 to 397 min), and the average blood loss was 715.16 ± 263.84 ml (ranging from 400 to 2000ml). The radiological grading at postoperative stage showed anatomical reduction in 30 patients (62.50%), satisfactory reduction in 14 patients (29.17%), and poor reduction in four patients (8.33%). At the final follow-up, no re-protrusion of the femoral head was observed. In terms of functional outcome, the mean modified Merle d’Aubigné-Postel score was excellent in 26 patients (54.17%), good in 17 patients (35.42%), fair in four patients (8.33%), and poor in one patient (2.08%). The HHS was excellent in 23 patients (47.92%), good in 20 patients (41.67%), fair in four patients (8.33%), and poor in one patient (2.08%). The average HHS was 87.38 ± 7.86 (ranging from 52 to 98). Postoperative complications included lateral femoral cutaneous nerve injury in two patients, delayed wound healing and subsequent development of an inguinal hernia in one patient. Late complications were observed in two patients, with one case of heterotopic ossification and another case of post-traumatic osteoarthritis underwent hip arthroplasty within two years after surgery.ConclusionOur results indicate that employing the contoured plate specifically designed for QLP injuries, in conjunction with quadrilateral screws through the ilioinguinal approach, can lead to positive outcomes in the treatment of displaced acetabular fractures involving the QLP. This straightforward and efficient technique offers a viable option for surgeons who are managing complex acetabular fractures.

Water resource asset (WRA) accounting holds great importance in ecological civilization construction. Existing WRA accounting methods heavily rely on statistical data, resulting in issues such as missing and inaccessible data. Moreover, they only consider the value brought by the physical resources, such as water quantity and quality, while neglecting the value brought by the ecological functions. Therefore, by fully exploiting the rapid, objective, and efficient advantages of remote sensing (RS) in monitoring surface objects, this article develops a surface WRA (SWRA) accounting method based on multi-source RS data. First, a representation model is innovatively proposed, with full consideration of the ecological service functions offered by water resources. Specifically, the SWRAs are represented by two parts: tangible and intangible assets. The tangible asset refers to the quantifiable stock of water resources. Surface water volume is adopted as the indicator for tangible assets in this article. The intangible asset, which primarily embodies the ecological service functions provided by water resources, encompasses five major categories: flood regulation, carbon fixation, oxygen release, water purification, and water conservation. Furthermore, due to different units, the total amounts cannot be summed or compared directly. Therefore, this article utilizes price tools to convert SWRAs into price value, ultimately achieving SWRA accounting. The established method was tested in Miyun, Beijing, China, from 2013 to 2023. The findings demonstrate that the SWRA value reached its peak in 2023, amounting to 56,9368.6×104 yuan, while it had its lowest point in 2014, standing at 14,7402.7×104 yuan. The experimental results indicate that the proposed method can quickly provide the SWRA values for many years, offering a methodological foundation for SWRA asset auditing and enhancing the timeliness of the auditing work.

BackgroundNitrogen dioxide (NO2), a crucial component of traffic pollutants, has been shown in studies to exert toxic effects on the nervous system. However, there is a limited body of research examining the relationship between NO2 exposure and neurological disorders in children. ObjectiveTo explore the impact of short-term NO2 exposure on the outpatient visits due to pediatric neurological diseases in Shijiazhuang. MethodsFrom 2013 to 2021, we collected outpatient data related to neurological diseases at the Children's Hospital in Shijiazhuang, Hebei Province. We also collected air pollution data and meteorological data of the same city. The air pollution data included daily average concentrations of inhalable particles (PM10), fine particulate matter (PM2.5), sulfur dioxide (SO2), NO2, carbon monoxide (CO), and daily maximum 8-hour average concentration of ozone (O3). The meteorological data comprised daily average atmospheric pressure, temperature, relative humidity, wind speed, and sunshine duration. Employing a time-stratified case-crossover design, we used conditional logistic regression models to analyze the association between NO2 and pediatric outpatient visits for neurological diseases. Stratification analyses were conducted based on gender (male, female) and age groups (0-6 years, 7-14 years). ResultsThe study included a total of 154348 valid pediatric outpatient visits for neurological diseases. The daily average concentration of NO2 was 49.3 μg·m−3 for the study period. The results from the single-pollutant model indicated that NO2 increased the risk of pediatric neurological outpatient visits, with the highest association observed at lag0. Specifically, for every 10 μg·m⁻³ increase in atmospheric NO2 exposure, there was a 1.40% increase (95%CI: 1.05%, 1.74%) in pediatric neurological outpatient visits. The stratification analyses revealed that increased atmospheric NO2 exposure was associated with an elevated risk of neurological outpatient visits for girls (ER=1.54, 95%CI: 1.01, 2.08) and children aged 7-14 years (ER=2.35, 95%CI: 1.68, 3.02). Even after introducing PM2.5 (ER=1.96, 95%CI: 1.49, 2.43), SO2 (ER=2.09, 95%CI: 1.62, 2.55), and O3 (ER=1.40, 95%CI: 1.06, 1.74) to the models, the impact of NO2 exposure on pediatric neurological outpatient visits remained statistically significant. The results of the multi-pollutant model also indicated a significant association (ER=2.53, 95%CI: 1.97, 3.08). ConclusionThe effect of short-term exposure to atmospheric NO2 on the outpatient visits of children with neurological diseases in Shijiazhuang is acute and independent, especially for children aged 7-14.

Abstract To address the problem of pillar instability in residual mining areas under repeated mining disturbances, the prediction of pillar instability time and mining technology is studied by using numerical simulations, theoretical examinations, and practical experimentation techniques utilizing the remaining facade of the Shenghua Coal Industry 3103. On the basis of the findings, employing a fully mechanized mining technique exerts greater pressure on the coal pillar, increasing the likelihood of plastic failure. However, adopting the segmental filling mining approach can effectively disperse this pressure, consequently mitigating potential damage to the coal pillar. Initially, the coal pillar undergoes a progressive yielding or collapsing process at its periphery, leading to instability once the area of the projectile core of the coal pillar decreases beyond a specific threshold. The dimensions of both the affected roadway and the coal pillar play a pivotal role in determining the coal pillar's load‐bearing capacity. A prediction model for pillar instability is established. If the area of the projectile core is less than 34% during remining, the mining method should be changed or pillar reinforcement should be implemented. The accurate prediction and adaptation of the model's mining approach ensure the secure extraction of coal pillars within the remaining mining region, with successful validation of the model's performance.

Abstract With the increasing depth of engineering in rock masses, the issue of significant rheological deformation becomes notably prominent. To accurately characterize the deformation and failure behavior of the surrounding rock near the goaf in deep small coal pillars, we have developed a viscoelastic–plastic constitutive model that takes into account the initial stress associated with creep. This model builds upon an existing viscoelastic–plastic constitutive framework and is implemented numerically using C++ in the FLAC3D. The Oedometer test method is used to check the creep components and the calculated parameter (η/G) ensure convergence of numerical operations. We conducted both pre‐improvement and post‐improvement tests of the constitutive model in a simple numerical analysis of roadways. The enhanced model demonstrates improved accuracy in deviational stress calculations and proves suitable for modeling deep, soft roadways. Furthermore, we applied the improved model to simulate actual working conditions at Zhaozhuang Mine, where mining operations near the working face induce a fracture zone of approximately 3 m in the small coal pillar located at the goaf's edge. The new model closely aligns with the observed results, further validating its suitability for tunneling along the goaf. Tunneling and mining activities result in significant deformation at various locations, including the shoulder socket of the working face, the top angle of the coal pillar, and the bottom angle of the floor. The crushing zone at the working face extends up to 4 m. Rheological effects transform the triangular elastic core, from its original high‐pressure elastic state to a fracture and plastic zone in the deep coal. Stress in deep coal is transmitted along the triangular elastic core. Numerical simulation results closely match the excavation profile of the tunneling, providing valuable insights into the impact of mining activities. This study can provide reference for deformation of similar geological conditions and engineering situation.

Cetaceans play a crucial role in marine ecosystems; however, research on their gastrointestinal microbiota remains limited due to sampling constraints. In this study, we collected hindgut samples from 12 stranded cetaceans and performed 16S rRNA gene amplicon sequencing to investigate microbial composition and functional potentials. Analysis of ZOTUs profiles revealed that the phyla Firmicutes, Proteobacteria, and Bacteroidetes dominated all hindgut samples. However, unique microbial profiles were observed among different cetacean species, with significant separation of gut microbiota communities according to biological evolutionary lineages. Different genera that contain pathogens were observed distinguishing delphinids from physeteroids/ziphiids. Delphinid samples exhibited higher abundances of Vibrio, Escherichia, and Paeniclostridium, whereas physeteroid and ziphiid samples showed higher abundances of Pseudomonas, Enterococcus, and Intestinimonas. Functional analysis indicated convergence in the gut microbiota among all cetaceans, with shared bacterial infection pathways across hindgut samples. In addition, a comparison of the gastrointestinal microbial composition between a stranded short-finned pilot whale (Globicephala macrorhynchus) and a stranded rough-toothed dolphin (Steno bredanensis) using 16S rRNA gene sequencing revealed distinct microbial community structures and functional capacities. To the best of our knowledge, this study represents the first report on the gastrointestinal microbiota of the pantropical spotted dolphin (Stenella attenuata), Blainville’s beaked whale (Mesoplodon densirostris), and rough-toothed dolphin, with various comparisons conducted among different cetacean species. Our findings enhance the understanding of microbial composition and diversity in cetacean gastrointestinal microbiota, providing new insights into co-evolution and complex interactions between cetacean microbes and hosts.

Abstract Enabling materials to undergo reversible dynamic transformations akin to the behaviors of living organisms represents a critical challenge in the field of material assembly. The pursuit of such capabilities using conventional materials has largely been met with limited success. Herein, the discovery of reversible constrained dissociation and reconfiguration in MXene films, offering an effective solution to overcome this obstacle is reported. Specifically, MXene films permit rapid intercalation of water molecules between their distinctive layers, resulting in a significant expansion and exhibiting confined dissociation within constrained spaces. Meanwhile, the process of capillary compression driven by water evaporation reinstates the dissociated MXene film to its original compact state. Further, the adhesive properties emerging from the confined disassociation of MXene films can spontaneously induce fusion between separate films. Utilizing this attribute, complex structures of MXene films can be effortlessly foamed and interlayer porosity precisely controlled, using only water as the inducer. Additionally, a parallel phenomenon has been identified in graphene oxide films. This work not only provides fresh insights into the microscopic mechanisms of 2D materials such as MXene but also paves a transformative path for their macroscopic assembly applications in the future.

Abstract This study aims to investigate the feasibility and efficacy of anterior atlantoaxial motion preservation fixation (AMPF) in treating axis complex fractures involving the odontoid process fracture and Hangman’s fractures with C2/3 instability. A retrospective study was conducted on eight patients who underwent AMPF for axis complex fractures at the General Hospital of Central Theater Command from February 2004 to October 2021. The types of axis injuries, reasons for injuries, surgery time, intraoperative blood loss, spinal cord injury classification (American Spinal Injury Association, ASIA), as well as complications and technical notes, were documented. This study included eight cases of type II Hangman’s fracture, five cases of type II and three cases of type III odontoid process fracture. Five patients experienced traffic accidents, while three patients experienced falling injuries. All patients underwent AMPF surgery with an average intraoperative blood loss of 288.75 mL and a duration of 174.5 min. Two patients experienced dysphagia 1 month after surgery. The patients were followed up for an average of 15.63 months. One case improved from C to E in terms of neurological condition, three cases improved from D to E, and four cases remained at E. Bony fusion and Atlantoaxial Motion Preservation were successfully achieved for all eight patients. AMPF is a feasible and effective way for simultaneous odontoid process fracture and Hangman’s fractures with C2/3 instability, while preserving atlantoaxial movement.

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignancies with a high lethality rate. ZMIZ2 is a transcriptional co-activator implicated in various human diseases. However, the role and molecular mechanism of ZMIZ2 in HCC remains to be elucidated. Methods The expression and prognostic value of ZMIZ2 in HCC was excavated from public databases and explored by bioinformatic analysis. Then the expression of ZMIZ2 and related genes was further validated by quantitative RT-PCR, western blotting, and immunohistochemistry. Loss and gain-of-function experiments were performed in vitro and in vivo to investigate the function of ZMIZ2 in HCC. In addition, transcriptome sequencing and immunoprecipitation was conducted to explore the potential molecular mechanisms of ZMIZ2. Results ZMIZ2 was highly expressed in HCC and associated with poor prognosis. Silencing ZMIZ2 significantly inhibited HCC cell proliferation, cell cycle process, migration, and invasion in vitro, and also inhibited the progression of HCC in vivo. Additionally, ZMIZ2 expression was correlated with immune cell infiltration in HCC samples. Somatic mutation analysis showed that ZMIZ2 and TP53 mutations jointly affected the progression of HCC. Mechanistically, ZMIZ2 interacted with LEF1 to regulate malignant progression of HCC by activating the Wnt/β-catenin pathway. Conclusion ZMIZ2 was overexpressed in HCC and associated with poor prognosis. The overexpression of ZMIZ2 was corelated with malignant phenotype, and it facilitated HCC progression via LEF1-mediated activation of the Wnt/β-catenin pathway. Furthermore, ZMIZ2 could be served as a prognostic biomarker and a new therapeutic target for HCC.

Abstract Background To compare the clinical and radiological outcomes of monoplanar screws (MSs) versus hybrid fixed axial and polyaxial screws (HSs) in percutaneous short-segment intermediate screw fixation (PSISF) for traumatic thoracolumbar burst fractures (TTBFs) in patients without neurologic impairment. Methods A consecutive series of 100 patients with single-segment TTBFs and no neurologic impairment who underwent PSISF with 6 monoplanar screws (MS group) or correct were retrospectively enrolled. The demographic data, radiologic evaluation indicators, perioperative indicators and clinical assessment indicators were analysed between the MS group and HS group. Results The demographic data and perioperative indicators were not significantly different in the two groups (P > 0.05). The postoperative anterior vertebral height ratio (AVHR), kyphosis Cobb angle (KCA), vertebral wedge angle (VWA) and spinal canal encroachment rate (SCER) were significantly improved in both groups (*P 0.05). In the MS group, no internal fixation failure was observed during the follow-up period, but, in the HS group, two cases of internal fixation failure were observed at the last follow-up (one case of rod loosening and one case of screw breakage). Conclusions Both MSs and HSs fixation are effective treatments for TTBFs and have comparable clinical outcomes. In contrast, MSs fixation can improve the correction effect, better improve the SCER, and further reduce correction loss as well as reduce the incidence of instrumentation failure. Therefore, MSs fixation might be a better option for treating TTBFs in patients without neurological deficits.

Abstract Background Mutations in TP53 gene is considered a main driver of hepatocellular carcinoma (HCC). While TP53 mutations are the leading cause of p53 dysfunction, their occurrence rates may drop to approximately 10% in cohorts without hepatitis B virus and aflatoxin exposure. This observation suggests that the deactivation of wild-type p53 (p53wt) may be a critical factor in the majority of HCC cases. However, the mechanism undermining p53wt activity in the liver remains unclear. Methods Microarray analysis and luciferase assay were utilized to confirm target associations. Gain- and/or loss-of-function methods were employed to assess alterations in signaling pathways. Protein interactions were analyzed by molecular immunological methods and further visualized by confocal microscopy. Bioinformatic analysis was performed to analyze clinical significance. Tumor xenograft nude mice were used to validate the findings in vivo. Results Our study highlights the oncogenic role of Rictor, a key component of the mammalian target of rapamycin complex 2 (mTORC2), in hepatocytes. Rictor exerts its oncogenic function by binding to p53wt and subsequently blocking p53wt activity based on p53 status, requiring the involvement of mTOR. Moreover, we observed a dynamic nucleocytoplasmic distribution pattern of Rictor, characterized by its translocation from the nucleus (in precancerous lesions) to the cytoplasm (in HCCs) during malignant transformation. Notably, Rictor is directly targeted by the liver-enriched microRNA miR-192, and the disruption of the miR-192-Rictor-p53-miR-192 signaling axis was consistently observed in both human and rat HCC models. Clinical analysis associated lower miR-192/higher Rictor with shorter overall survival and more advanced clinical stages (P

Alopecia intellectual disability syndromes 4 (APMR4) caused by Lanosterol synthase (LSS) gene variants is a very rare autosomal recessive neuroectodermal syndrome. It is characterized by congenital alopecia and variable degrees of intellectual disability (ID), frequently associated with developmental delay (DD) and epilepsy. Currently, only three studies regarding LSS-related APMR4 have been reported, the pathogenesis of APMR4 is poorly understood. We studied one patient with LSS-related APMR4 who presented with severe intellectual disability, alopecia, early-onset epilepsy and developmental delay. She is absence of hair on the eyebrows, eyelashes, and scalp. Two novel LSS variants (c.401 T > G and c.369C > G) were detected with whole-exome sequencing (WES). Analysis via WB experiment indicated that c.369 > G reduced the protein expression level of LSS. Analysis of protein stability prediction showed a destabilizing for LSS caused by the variant c.401 T > G. This study is the first study in Asia to date. These findings expanded the variantal spectrum of LSS-related APMR4 and revealed the potential pathogenic mechanism of LSS gene variants.

The control region (CR) regulates the replication and transcription of the mitochondrial genome (mitogenome). Some avian mitogenomes possess two CRs, and the second control region (CR2) may enhance replication and transcription; however, the CR2 in lark mitogenome appears to be undergoing loss and is accompanied by tandem repeats. Here, we characterized six lark mitogenomes from Alaudala cheleensis, Eremophila alpestris, Alauda razae, and Calandrella cinerea and reconstructed the phylogeny of Passerida. Through further comparative analysis among larks, we traced the evolutionary process of CR2. The mitochondrial gene orders were conserved in all published lark mitogenomes, with Cytb-trnT-CR1-trnP-ND6-trnE-remnant CR2 with tandem repeat-trnF-rrnS. Phylogenetic analysis revealed Alaudidae and Panuridae are sister groups at the base of Sylvioidea, and sporadic losses of CR2 may occur in their common ancestor. CR sequence and phylogeny analysis indicated CR2 tandem repeats were generated within CR2, originating in the ancestor of all larks, rather than inherited from CR1. The secondary structure comparison of tandem repeat units within and between species suggested slipped-strand mispairing and DNA turnover as suitable models for explaining the origin and evolution of these repeats. This study reveals the evolutionary process of the CR2 containing tandem repeat in Alaudidae, providing reference for understanding the evolutionary characteristics and dynamics of tandem repeats.

IntroductionThe cases of MOG-AD (MOG antibody-associated disorder) and anti-NMDAR encephalitis overlapping syndrome (MNOS) are rare, especially among pediatric patients, and their clinical understanding is limited. This study aimed to investigate the clinical manifestations, imaging findings, treatments, and prognosis of Chinese pediatric patients who tested positive for anti-NMDAR and MOG antibodies.MethodsThis retrospective study enrolled 10 MNOS pediatric patients, 50 MOG-AD (anti-NMDAR antibody-negative), and 81 anti-NMDAR encephalitis (MOG antibody-negative) pediatric patients who were admitted from July 2016 to June 2022 and used their clinical data for comparison.ResultsThe MNOS patients had a significantly lower incidence of psycho-behavioral abnormalities and involuntary movements than anti-NMDAR antibody (+)/MOG antibody (−) patients and had a significantly higher incidence of sleep disorders, seizures, and psycho-behavioral abnormalities than MOG antibody (+)/anti-NMDAR antibody (−) patients. The MNOS patients had a significantly higher incidence of MRI abnormalities than the anti-NMDAR antibody (+)/MOG antibody (−) patients, while there was no significant difference in the incidence between the MNOS patients and the MOG antibody (+)/anti-NMDAR antibody (−) patients. No significant difference was seen in the initial mRS score between the three groups of patients. The anti-NMDAR antibody (+)/MOG antibody (−) patients had a higher rate of admission to the ICU, a longer length of in-hospital stay, and a higher rate of introduction to second-line treatment than the other two groups of patients. No significant difference was seen in the mRS score at the last follow-up and in the disease recurrence rate between the three groups. All these patients respond well to immunosuppressive therapy.DiscussionIn the presence of psycho-behavioral abnormalities, sleep disorders, and frequent seizures in MOG-AD patients or demyelinating symptoms of the central nervous system or demyelinating lesions on head MRI in anti-NMDAR encephalitis patients, the coexistence of MOG and anti-NMDAR antibodies should be considered and would suggest a diagnosis of MNOS for these patients. Immunotherapy is effective among these patients and should be given possibly earlier.

IntroductionCandida auris, a fungal pathogen first reported in 2009, has shown strong resistance to azole antifungal drugs and has caused severe nosocomial outbreaks. It can also form biofilms, which can colonize patients’ skin and transmit to others. Despite numerous reports of C. auris isolation in various countries, many studies have reported contradictory results.MethodA bibliometric analysis was conducted using VOSviewer to summarize research trends and provide guidance for future research on controlling C. auris infection. The analysis revealed that the United States and the US CDC were the most influential countries and research institutions, respectively. For the researchers, Jacques F. Meis published the highest amount of related articles, and Anastasia P. Litvintseva’s articles with the highest average citation rate. The most cited publications focused on clade classification, accurate identification technologies, nosocomial outbreaks, drug resistance, and biofilm formation. Keyword co-occurrence analysis revealed that the top five highest frequencies were for ‘drug resistance,’ ‘antifungal susceptibility test,’ ‘infection,’ ‘Candida auris,’ and ‘identification.’ The high-frequency keywords clustered into four groups: rapid and precise identification, drug resistance research, pathogenicity, and nosocomial transmission epidemiology studies. These clusters represent different study fields and current research hotspots of C. auris.ConclusionThe bibliometric analysis identified the most influential country, research institution, and researcher, indicating current research trends and hotspots for controlling C. auris.

ABSTRACTIntroduction An effective salvage regimen for the reinduction of remission is lacking for refractory or relapsed primary central nervous system lymphoma (r/r PCNSL). This study aimed to evaluate the efficacy and safety of cytarabine plus temozolomide in treating r/r PCNSL and to explore the associated prognostic factors.Methods A single-center retrospective cohort study was conducted to assess the efficacy and safety of cytarabine and temozolomide (AT) in r/r PCNSL patients. KIR and HLA genotyping was performed on peripheral blood samples.Results Thirty PCNSL patients receiving an AT regimen (cytarabine 3 g/m2 for 2 days combined with temozolomide 150 mg/m2 for 5 days) in our institution were analyzed. The median age was 65 years (range 25–79 years). A total of 43.4% of patients (13/30) achieved an overall response within a median follow-up of 16 months (95% confidence interval [CI]: 11–23 months). The median PFS and OS of the cohort were 1.5 months (95% CI: 1–4 months) and 19.5 months (95% CI: 11 months to not calculable), respectively. Patients harboring KIR3DL1/HLA-B genotypes predicting low affinity had a higher response rate (p = 0.042) and longer median PFS (3 months) than those with KIR3DL1/HLA-B genotypes predicting high affinity (1 month) (p = 0.0047). Cox regression analysis indicated that KIR/HLA-B genotypes were independently associated with PFS (p = 0.043). However, KIR/HLA-B genotypes had no impact on the OS of the cohort. The toxicity of AT treatment was mild and manageable.Conclusion The AT regimen was well tolerated, and patients with specific KIR-HLA genotypes may benefit from this regimen.

Abstract To improve the performance of named entity recognition in the lack of well-annotated entity data, a transfer learning-based Chinese named entity recognition model is proposed in this paper. The specific tasks are as follows: (1) first/, a data transfer method based on entity features is proposed. By calculating the similarity of feature distribution between low resource data and high resource data, the most representative entity features are selected for feature transfer mapping, and the distance of entity distribution between the two domains is calculated to make up the gap between the data of the two domains then model is trained by high resource data. (2) Then, an entity boundary detection method is proposed. This method utilizes the BiLSTM+CRF as the main structure and integrates character boundary information to assist the attention network to improve the model’s ability to recognize entity boundaries. (3) Finally, multiple named entity recognition methods are selected as baseline methods for comparison, and experiments are conducted on several datasets. The results show that the model proposed in this paper improves the accuracy of named entity recognition by 1%, the recall rate by 2%, and the F1 value by 2% on average in the field with low-resource.

Abstract Background Cell death and inflammation are the two important triggers of wear particle-induced osteolysis. Particles, including cobalt-chromium-molybdenum and tricalcium phosphate, have been reported to induce pyroptosis in macrophages and osteocytes. Although macrophage pyroptosis facilitates osteoclastic bone resorption and osteolysis, whether osteocyte pyroptosis is involved in osteoclastic osteolysis still needs further investigation. Desferrioxamine (DFO), an FDA-approved medication and a powerful iron chelator, has been proven to reduce ultrahigh-molecular-weight polyethylene (UHMWPE) particle-induced osteolysis. However, whether DFO can ameliorate UHMWPE particle-induced osteolysis by decreasing pyroptosis in osteocytes is unknown. Results A mouse calvarial osteolysis model and the mouse osteocyte cell line MLO-Y4 was used, and we found that pyroptosis in osteocytes was significantly induced by UHMWPE particles. Furthermore, our findings uncovered a role of caspase-1-dependent pyroptosis in osteocytes in facilitating osteoclastic osteolysis induced by UHMWPE particles. In addition, we found that DFO could alleviate UHMWPE particle-induced pyroptosis in osteocytes in vivo and in vitro. Conclusions We uncovered a role of caspase-1-dependent pyroptosis in osteocytes in facilitating osteoclastic osteolysis induced by UHMWPE particles. Furthermore, we found that DFO alleviated UHMWPE particle-induced osteoclastic osteolysis partly by inhibiting pyroptosis in osteocytes. Graphical Abstract Schematic of DFO reducing UHMWPE particle-induced osteolysis by inhibiting osteocytic pyroptosis. Wear particles, such as polymers, generated from prosthetic implant materials activate canonical inflammasomes and promote the cleavage and activation of caspase-1. This is followed by caspase-1-dependent IL-β maturation and GSDMD cleavage. The N-terminal fragment of GSDMD binds to phospholipids on the cell membrane and forms holes in the membrane, resulting in the release of mature IL-β and inflammatory intracellular contents. This further facilitates osteoclastic differentiation of BMMs, resulting in excessive bone resorption and ultimately leading to prosthetic osteolysis. DFO reduces UHMWPE particle-induced osteolysis by inhibiting osteocytic pyroptosis.

BackgroundPrimary central nervous system lymphoma (PCNSL) is an aggressive extranodal non-Hodgkin lymphoma with a poor prognosis. We aimed to evaluate the prognostic impact of circulating NK cells in PCNSL.Materials and methodsPatients diagnosed with PCNSL who were treated at our institution between December 2018 and December 2019 were retrospectively screened. Patient variables including age, sex, Karnofsky performance status, diagnostic methods, location of lesions, lactate dehydrogenase, cerebrospinal fluids (CSF), and vitreous fluids involvement or not were documented. NK cell count and NK cell proportion (NK cell count/lymphocyte count) in the peripheral blood were evaluated by flow cytometry. Some patients underwent two consecutive NK cell tests before and three weeks after chemotherapy (before the next chemotherapy). The fold change in NK cell proportion and NK cell counts were calculated. CD56-positive NK cells in tumor tissue were assessed by immunohistochemistry. NK cell cytotoxicity assay was performed using flow cytometry.ResultsA total of 161 patients with PCNSL were included in this study. The median NK cell count of all NK cell tests was 197.73/μL (range 13.11–1889.90 cells/μL). The median proportion of NK cells was 14.11% (range 1.68–45.15%) for all. Responders had a higher median NK cell count (p165 cells/μL) appeared to have a longer median overall survival than those with a low NK cell count (p=0.0054). A high fold change in the proportion of NK cells (>0.1957; p=0.0367) or NK cell count (>0.1045; p=0.0356) was associated with longer progression-free survival. Circulating NK cells from newly-diagnosed PCNSL demonstrated an impaired cytotoxicity capacity compared to those from patients with PCNSL in complete remission or healthy donors.ConclusionOur study indicated that circulating NK cells had some impact on the outcome of PCNSL.

Melatonin’s role in regulating the biosynthesis of phenolic compounds, particularly stilbenes, remains unknown in grape seeds. In this study, widely targeted metabolomics analysis revealed that 82 phenolic compounds were differentially accumulated in grape seeds from the berries treated with melatonin. The accumulation of resveratrol and its 11 derivatives was largely increased in melatonin-treated berry seeds. Additionally, melatonin treatment of preveraison grape berries increased the resveratrol content in seeds during berry ripening. The results of RNA-Seq showed that a total of 399 genes were differentially expressed, which were mainly involved in the plant hormone signal transduction, metabolic, and biosynthesis of secondary metabolites pathways, in melatonin-treated berry seeds compared to control seeds. Additionally, five PALs, four 4CLs, one C4H, and four STSs were elucidated to be induced by melatonin in seeds at different time points after treatment. Therefore, melatonin promotes resveratrol accumulation and its derivatives, probably by upregulating the genes in the phenylpropanoid pathway, which provides precursors for resveratrol biosynthesis, and the STS genes in grape seeds.

BackgroundIndividual lead or cadmium exposure can cause abnormal blood glucose level and changes in telomere length, and the role of telomere length in the relationship between heavy metal joint exposure and blood glucose level is still unclear. ObjectiveTo explore the role of telomere length in the relationship between lead and cadmium coexposure and blood glucose. MethodsA cross-sectional study was conducted. By convenient sampling method, 600 residents living in two communities in a city in North China were selected as participants from April to June 2016. Face-to-face interviews were performed to collect general demographics and lifestyles of the participants. The peripheral blood samples of the participants were collected for blood glucose and telomere length detection, the urine samples were collected for urinary cadmium, urinary lead, and urinary creatinine measurement, and both urinary cadmium and urinary lead were corrected by urinary creatinine. The included participants were divided into a control group, a high-cadmium and low-lead group, a high-lead and low-cadmium group, and a high-lead and high-cadmium group, according to the median levels of urinary cadmium and urinary lead. A restricted cubic spline model was constructed to analyze the relationship between urinary lead/cadmium levels and blood glucose concentrations in the four groups and the relationship between cadmium exposure and telomere length in the high-lead and high-cadmium group. Intermediary model test was conducted to analyze the effect of telomere length on the relationship between exposures to lead and cadmium and blood glucose. ResultsThe included participants were divided into the control group (n=99), the high-cadmium and low-lead group (n=91), the high-lead and low-cadmium group (n=145), and the high-lead and high-cadmium group (n=265). The differences in age, education level, per capita monthly household income, smoking, blood glucose, and telomere length were statistically significant among the four groups (P＜0.05). The high-lead and high-cadmium group had the highest blood glucose concentration, (5.63±1.68) mmol·L−1, and the shortest telomere length, (2.63±1.05) Kb. The restricted cubic spline results showed that urinary cadmium level was correlated with blood glucose concentration in the high-lead and high-cadmium group (F=3.45, P=0.037), and there was a non-linear association (F=6.91, P=0.002); the association between urinary cadmium level and telomere length was also non-linear (F=5.93, P=0.043). The intermediary model test results showed that telomere length was a mediating variable between urinary cadmium level and blood glucose concentration, and the mediating effect size was 0.0192 (95%CI: 0.0007-0.0563), with a mediation ratio of 15.57%. ConclusionCorrelations between urinary cadmium and blood glucose and between urinary cadmium and telomere length were observed in the high-lead and high-cadmium coexposure group, and telomere length may play a mediating role in the relationship between them.

BackgroundPrimary central nervous system lymphoma (PCNSL) is an uncommon variant of non-Hodgkin lymphoma (NHL) with high aggressiveness and poor prognosis. Although complete remission (CR) could be achieved with therapy, some patients remain refractory or recurrently with a worse response to salvage treatment and poor prognosis. No consensus on rescue therapy has been established currently. This study is aimed to evaluate the efficacy of radiotherapy or chemotherapy in first-time relapsed or refractory progressed PCNSL (R/R PCNSL) and analysis the prognostic factors, to explore differences between relapsed and refractory PCNSL.MethodsTotally 105 R/R PCNSL patients from Huashan Hospital between 1 January 2016 and 31 December 2020 were enrolled, underwent salvage radiotherapy or chemotherapy and received response assessments after each course. PFS1 was defined as the time from diagnosis to the first time of recurrence or refractory progression. Statistical analysis was performed with SPSS version 26.0.ResultsResponse and survival were analyzed over a 17.5months (median) follow-up. Compared to relapsed PCNSL (n = 42), refractory PCNSL (n = 63) had a shorter median PFS1 related to deep lesions. 82.4% of cases were discovered as the second relapse or progression. ORR and PFS were both higher in relapsed PCNSL than those in refractory PCNSL. ORR of radiotherapy in both relapsed and refractory PCNSL was higher than that of chemotherapy. Elevated CSF protein and ocular involvement were related to PFS and OS after recurrence respectively in relapsed PCNSL. Age ≥ 60y was unfavorable to OS-R (OS after recurrence or progression) in refractory PCNSL.ConclusionsOur results indicate that relapsed PCNSL responds well to inducing and salvage therapy and has a better prognosis compared to refractory PCNSL. Radiotherapy is effective for PCNSL after the first relapse or progression. Age, CSF protein level, and ocular involvement could be potential factors to predict prognosis.

Abstract Background The newly developed monoplanar pedicle screws (MPPSs) can mobile in axial plane but fixed in the sagittal plane, which holds potential to combine ease of rod placement with sagittal plane strength theoretically. So far, few clinical studies focused on the outcomes of MPPSs for treatment of thoracolumbar fractures (TLFs). The aim of this study was to compare the efficacy of MPPSs to polyaxial pedicle screws (PAPSs) in percutaneous intermediate fixation of TLFs. Methods Seventy-eight patients who sustained TLFs without neurological deficits and underwent percutaneous intermediate fixation using MPPSs (40 patients) or PAPSs (38 patients) with a minimum 1-year follow-up were included in this study. The operation time, blood loss, local Cobb angle (LCA), vertebral wedge angle (VWA), anterior body height ratio (ABHR), visual analogue scale (VAS) and Oswestry Disability Index (ODI) were collected. Results No significant differences were observed in baseline demographics, clinical characteristics, operation time or blood loss between the two groups (P > 0.05). The postoperative LCA, VWA and ABHR were significantly corrected compared to these parameters preoperatively in both groups (# P

Abstract Background Rotator cuff tear is one of the most common complaint with shoulder pain, disability, or dysfunction. So far, different arthroscopic techniques including single row (SR), double row (DR), modified Mason–Allen (MMA), suture bridge (SB) and transosseous (TO) have been identified to repair rotator cuff. However, no study has reported the comparative efficacy of these 5 suture configurations. The overall aim of this network meta-analysis was to analyze the clinical outcomes and healing rate with arthroscopy among SR, DR, MMA, SB and TO. Methods A systematic literature was searched from PubMed, EBSCO-MEDLINE, Web of Science, google scholar and www.dayi100.com , and checked for the inclusion and exclusion standards. The network meta-analysis was conducted using Review Manager 5.3 and SATA 15.0 software. Results Thirty-four studies were eligible for inclusion, including 15 randomized controlled trials, 17 retrospective and 2 prospective cohort studies, with total 3250 shoulders. Two individual reviewers evaluated the quality of the 34 studies, the score form 5 and 9 of 10 were attained according to the Newcastle–Ottawa Scale for the 17 retrospective and 2 prospective studies. There was no significant distinction for the Constant score among 5 groups in the 16 studies with 1381 shoulders. The treatment strategies were ranked as MMA, DR, SB, SR and TO. In ASES score, 14 studies included 1464 shoulders showed that no significant differences was showed among all 5 groups after surgery. Whereas the efficacy probability was TO, MMA, DR, SB and SR according to the cumulative ranking curve. The healing rate in 25 studies include 2023 shoulders was significant in both SR versus DR [risk ratio 0.45 with 95% credible interval (0.31, 0.65)], and SR versus SB [risk ratio 0.45 (95% credible interval 0.29, 0.69)], and no significant in the other comparison, the ranking probability was MMA, SB, DR, TO and SR. Conclusion Based on the clinical results, this network meta-analysis revealed that these 5 suture configurations shows no significant difference. Meanwhile, suture bridge may be the optimum treatment strategy which may improve the healing rate postoperatively, whereas the DR is a suboptimal option for arthroscopic rotator cuff repairs.

Abstract Our article aims to provide a comprehensive portrayal of how seven Asian jurisdictions have sought to address the challenge of genetic discrimination (GD) by presenting an analysis of the relevant legislation, policies, and practices. Based on our findings, policy discussion and action on preventing or mitigating GD have been narrowly framed in terms of employment, insurance, disability, marriage, and family planning. Except for South Korea, none of the jurisdictions we examined has adopted specific legislation to prevent GD. However, for Asia to truly benefit from its recent scientific and technological progress in genomics, we highlight the need for these jurisdictions to engage more proactively with the challenges of GD through a coordinated regulatory and governance mechanism.

Abstract Introduction Dexmedetomidine (Dex) is suggested to be neuroprotective. However, influence of Dex on postoperative cognitive dysfunction (POCD) in the elderly remains unknown. Methods We performed a meta‐analysis of randomized controlled trials (RCTs) to evaluate the effect of Dex on POCD. Relevant studies were obtained by search of PubMed, Embase, and Cochrane's Library databases. A random‐effect model was used to pool the results. Results Fourteen RCTs including 1626 adults of 60 years or older who received surgery with general anesthesia were included. Because methodologically diverse scales were used for POCD, eight RCTs with POCD diagnosed with Mini‐Mental State Examination (MMSE) were included in the meta‐analysis, while the remaining six RCTs with POCD diagnosed with other scales were qualitative synthesized. Pooled results of RCTs with MMSE showed that Dex significantly reduced the incidence of POCD (risk ratio: 0.47, 95% confidence interval: 0.37–0.60, p

The prognosis of relapsed/refractory (R/R) primary central nervous system lymphoma (PCNSL) is dismal, and there are limited treatment options for these patients. This was a prospective single-arm phase II study of combined pemetrexed and lenalidomide for salvage treatment of R/R PCNSL. Patients with R/R PCNSL (n = 38) who had undergone two or more different therapeutic regimens and experienced disease progression or recurrence were enrolled. The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Patients were followed up for a median of 18 (range, 1–36) months. ORR was 68.4%, with median PFS and OS of 6 and 18 months, respectively. Adverse events (AEs) included myelosuppression, fatigue, nausea, fever, infection, cardiac disease, and thrombogenesis. Commonly observed grade ≥ 3 AEs included neutropenia (5.3%), leukopenia (2.6%), thrombocytopenia (7.9%), and infection (2.6%). Elevated lactate dehydrogenase (LDH) levels (χ2 = 13.25; P = 0.0003) and bulky disease (P = 0.032; χ2 = 4.580) were associated with short PFS. Elevated serum LDH level (P = 0.011; χ2 = 6.560), abnormal lymphoma cells in the cerebrospinal fluid (CSF) [P = 0.011; χ2 = 6.445], and multiple lesions (P = 0.036; χ2 = 4.404) were significantly associated with poorer OS. Abnormal lymphoma cells in the CSF were an independent predictor of poor prognosis on multivariate analysis (P = 0.034; hazard ratio (HR) = 2.836; 95% confidence interval, 1.082–7.434). Our results indicate that pemetrexed plus lenalidomide is effective for heavily treated R/R PCNSL, with moderate toxicity. Trial registration: #ChiCTR1900028070.

Prostate cancer, recognized as a “cold” tumor, has an immunosuppressive microenvironment in which regulatory T cells (Tregs) usually play a major role. Therefore, identifying a prognostic signature of Tregs has promising benefits of improving survival of prostate cancer patients. However, the traditional methods of Treg quantification usually suffer from bias and variability. Transcriptional characteristics have recently been found to have a predictive power for the infiltration of Tregs. Thus, a novel machine learning-based computational framework has been presented using Tregs and 19 other immune cell types using 42 purified immune cell datasets from GEO to identify Treg-specific mRNAs, and a prognostic signature of Tregs (named “TILTregSig”) consisting of five mRNAs (SOCS2, EGR1, RRM2, TPP1, and C11orf54) was developed and validated to monitor the prognosis of prostate cancer using the TCGA and ICGC datasets. The TILTregSig showed a stronger predictive power for tumor immunity compared with tumor mutation burden and glycolytic activity, which have been reported as immune predictors. Further analyses indicate that the TILTregSig might influence tumor immunity mainly by mediating tumor-infiltrating Tregs and could be a powerful predictor for Tregs in prostate cancer. Moreover, the TILTregSig showed a promising potential for predicting cancer immunotherapy (CIT) response in five CIT response datasets and therapeutic resistance in the GSCALite dataset in multiple cancers. Our TILTregSig derived from PBMCs makes it possible to achieve a straightforward, noninvasive, and inexpensive detection assay for prostate cancer compared with the current histopathological examination that requires invasive tissue puncture, which lays the foundation for the future development of a panel of different molecules in peripheral blood comprising a biomarker of prostate cancer.

Current aptamer discovery approaches are unable to probe the complete space of possible sequences. Here, the authors use machine learning to facilitate the development of DNA aptamers with improved binding affinities, and truncate them without significantly compromising binding affinity.

The process of ripening and softening in grape begins at veraison and is closely related to the depolymerization of pectin components. A variety of enzymes are involved in pectin metabolism and one class of enzyme, pectin lyases (PLs), have been reported to play an important role in softening in many fruits; however, little information is available on the VvPL gene family in grape. In this study, 16 VvPL genes were identified in the grape genome using bioinformatics methods. Among them, VvPL5, VvPL9, and VvPL15 had the highest expression levels during grape ripening, which suggests that these genes are involved in grape ripening and softening. Furthermore, overexpression of VvPL15 affects the contents of water-soluble pectin (WSP) and acid-soluble pectin (ASP) in the leaves of Arabidopsis and significantly changes the growth of Arabidopsis plants. The relationship between VvPL15 and pectin content was further determined by antisense expression of VvPL15. In addition, we also studied the effect of VvPL15 on fruit in transgenic tomato plants, which showed that VvPL15 accelerated fruit ripening and softening. Our results indicate that VvPL15 plays an important role in grape berry softening during ripening by depolymerizing pectin.

Abstract Background In plants, CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) is a key negative regulator in photoperiod response. However, the biological function of COP1-interacting protein 1 (CIP1) and the regulatory mechanism of the CIP1-COP1 interaction are not fully understood. Results Here, we identified the apple MdCIP1 gene based on the Arabidopsis AtCIP1 gene. Expression pattern analysis showed that MdCIP1 was constitutively expressed in various tissues of apple, and responded to stress and hormone signals at the transcriptional level. Ectopic expression of MdCIP1 complemented the phenotypes of the Arabidopsis cip1 mutant, and MdCIP1 inhibited anthocyanin biosynthesis in apple calli. In addition, the biochemical assay demonstrated that MdCIP1 could interact with MdCOP1 protein by their coiled-coil domain, and MdCIP1-OX/cop1–4 had a similar phenotype in photomorphogenesis with the cop1–4 mutant, suggesting that COP1 is epistatic to CIP1. Furthermore, the transient transformation assay indicated that MdCIP1 repressed anthocyanin biosynthesis in an MdCOP1-mediated pathway. Conclusion Take together, this study finds that MdCIP1 acts as a repressor in regulating hypocotyl elongation and anthocyanin biosynthesis through MdCOP1 in apple.

Abstract Background Lateral recess stenosis (LRS) is a common degenerative disease in the elderly. Since the rise of comorbidity is associated with increasing age, transforaminal endoscopic lateral recess decompression (TE-LRD) is advocated. The objective of this study was to compare the clinical outcomes of TE-LRD in patients with LRS via visualized drilled foraminoplasty (VDF) or visualized reamed foraminoplasty (VRF) technique. Methods A total of 45 and 42 consecutive patients with limp or unilateral radiculopathy symptoms underwent TE-LRD using the VDF and VRF technique, respectively. The radiation exposure and operation time, time to return to work, and complications were compared between two groups. Their clinical outcomes were evaluated with the visual analogue scale (VAS) leg pain score, VAS back pain score, Oswestry Disability Index (ODI) and modified MacNab’s criteria. Results The average values of radiation exposure and operative time in the VDF group were significantly higher than those in the VRF group (P

Maize is an important food crop and its fungal disease has become a limiting factor to improve the yield and quality of maize. In the control of plant pathogens, commercial fungicides have no obvious effect on corn diseases due to the emergence of drug resistance. Therefore, it is of great significance to develop new fungicides with novel structure, high efficiency, and low toxicity to control maize diseases. In this paper, a series of 1,3,4-oxadiazole derivatives were designed and synthesized from benzoyl hydrazine and aromatic aldehydes through condensation and oxidation cyclization reaction. The antifungal activity of oxadiazole derivatives against three maize disease pathogens, such as Rhizoctonia solani (R. solani), Gibberella zeae (G. zeae), and Exserohilum turcicum (E. turcicum), were evaluated by mycelium growth rate method in vitro. The results indicated that most of the synthesized derivatives exhibited positive antifungal activities. Especially against E. turcicum, several compounds demonstrated significant antifungal activities and their EC50 values were lower than positive control carbendazim. The EC50 values of compounds 4k, 5e, and 5k were 50.48, 47.56, 32.25 μg/ml, respectively, and the carbendazim was 102.83 μg/ml. The effects of active compounds on E. turcicum microstructure were observed by scanning electron microscopy (SEM). The results showed that compounds 4k, 5e, and 5k could induce the hyphae of E. turcicum to shrink and collapse obviously. In order to elucidate the preliminary mechanism of oxadiazole derivatives, the target compounds 5e and 5k were docked with the theoretical active site of succinate dehydrogenase (SDH). Compounds 5e and 5k could bind to amino acid residues through hydrophobic contact and hydrogen bonds, which explained the possible mechanism of binding between the inhibitor and target protein. In addition, the compounds with antifungal activities had almost no cytotoxicity to MCF-7. This study showed that 1,3,4-oxadiazole derivatives were worthy for further attention as potential antifungal agents for the control of maize diseases.

Abstract Background Short-segment internal fixation with intermediate straight-forward monoaxial screws (SSIF-SFM) and long-segment internal fixation (LSIF) are the two major surgical options for thoracolumbar (TL) fracture. However, SSIF-SFM might not provide adequate support to the spine, and LSIF is unnecessarily extensive. SSIF with intermediate inclined-angle polyxial screw (SSIF-IAP) might offer an alternative solution for the treatment of TL fracture. Methods A retrospective study was conducted. Sixty-nine patients (47 males and 22 females; average 34.5 years) with Denis type B TL fracture who met the criteria for inclusion were enrolled. Sagittal Cobb’s angle (SCA), anterior vertebral body height (AVBH), vertebral body index (VBI), and spinal canal encroachment (SCE) were measured and assessed. Visual analogue scale (VAS) and Oswestry disability index (ODI) were also evaluated. Results The average values of incision length, blood loss, duration of operation, and hospital stay in the SSIF-IAP group and SSIF-SFM group were significantly decreased compared with those in the LSIF group. The AVBH and VBI in the SSIF-IAP group and LSIF group were significantly improved than those in the SSIF-SFM group at 6-month and the latest follow-ups (P < 0.05). The correction losses of AVBH and VBI (calculated by the reduction of AVBH and VBI) in the SSIF-IAP group and LSIF group were also significantly decreased compared with those in the SSIF-SFM group at 6-month and the latest follow-ups (P < 0.05). There was no significant difference of SCE among the three groups postoperatively. The VAS and ODI in the SSIF-IAP group and SSIF-SFM group were significantly decreased compared with those in the LSIF group at 6-month and the latest follow-ups (P < 0.05). Conclusion Both SSIF-IAP and LSIF can improve the biomechanical stability as compared with SSIF-SFM. Moreover, SSIF-IAP was less extensive compared to LSIF. SSIF-IAP was an effective and reliable operative technique for patients with Denis type B TL fracture.

Abstract Background The fall webworm Hyphantria cunea is an invasive and polyphagous defoliator pest that feeds on nearly any type of deciduous tree worldwide. The silk web of H. cunea aids its aggregating behavior, provides thermal regulation and is regarded as one of causes for its rapid spread. In addition, both chemosensory and detoxification genes are vital for host adaptation in insects. Results Here, a high-quality genome of H. cunea was obtained. Silk-web-related genes were identified from the genome, and successful silencing of the silk protein gene HcunFib-H resulted in a significant decrease in silk web shelter production. The CAFE analysis showed that some chemosensory and detoxification gene families, such as CSPs, CCEs, GSTs and UGTs, were expanded. A transcriptome analysis using the newly sequenced H. cunea genome showed that most chemosensory genes were specifically expressed in the antennae, while most detoxification genes were highly expressed during the feeding peak. Moreover, we found that many nutrient-related genes and one detoxification gene, HcunP450 (CYP306A1), were under significant positive selection, suggesting a crucial role of these genes in host adaptation in H. cunea. At the metagenomic level, several microbial communities in H. cunea gut and their metabolic pathways might be beneficial to H. cunea for nutrient metabolism and detoxification, and might also contribute to its host adaptation. Conclusions These findings explain the host and environmental adaptations of H. cunea at the genetic level and provide partial evidence for the cause of its rapid invasion and potential gene targets for innovative pest management strategies.

In this paper, a test method of the forward collision warning (FCW) function is proposed and the forward collision risk factor is defined. Firstly, the concept of the minimum alarm distance is given according to the road scene and vehicle movement state, and then the calculation equation of the minimum alarm distance is derived by combining kinematics equation and driver's response time. We compare the actual vehicle distance and the minimum alarm distance to determine whether the FCW test is successful. The actual vehicle distance and the minimum alarm distance are used as the parameters to derive the calculation method of the vehicle's FCW risk factor. Finally, the test scenario is deployed in simulation software, and multiple test cases of FCW are established. By observing the simulation process and analyzing the experimental data, we found that the motion rule of the tested vehicle conforms to our theoretical analysis, and the experimental result is similar to the predicted result, so the conclusion is drawn: The FCW test method based on minimum alarm distance has confidence. At the same time, we conduct a comparative experiment on the hazard factor. The hazard factor we propose is applicable to more automatic driving conditions, and can be continuously output in the test process, which is more conducive to analysis.

Decentralization of grid systems plays an important role in improving their efficiency and fault tolerance. To enhance the performance and stability of grid and mitigate the problems of centralized grid, an agent-based decentralized gird model (ADGM) with universality and functional integrity is proposed. In this paper, we build an agent-based grid structure and propose an agent-based grid consensus algorithm (AGCA). A group membership protocol, a consistency protocol and a view change protocol in AGCA are also designed. Furthermore, based on Pi calculus, the information registration, resource sharing and error recovery of the grid model in the decentralized environment are formally specified. Finally, we analyze the performance of the AGCA algorithm and compare it with other consensus algorithms, the simulation results demonstrate that the AGCA algorithm achieves better comprehensive performance and more symmetrical time performance, space performance and fault tolerance than other consensus algorithms.

Feature selection is an effective method to eliminate irrelevant, redundant and noisy features, which improves the performance of classification and reduces the computational burden in machine learning. In this paper, an improved binary dragonfly algorithm (IBDA) which extends from the conventional dragonfly algorithm (DA) is proposed as a search strategy to design a wrapper-based feature selection method. First, a novel evolutionary population dynamics (EPD) strategy is introduced in IBDA to enhance the exploitation ability while ensuring population diversity of the algorithm. Second, IBDA proposes a novel crossover operator which establishes connections between the crossover rates and iterations so that making the algorithm can adjust the crossover rates of solutions dynamically, thereby balancing the exploitation and exploration of the algorithm. Finally, a binary mechanism is proposed to make the algorithm suitable for the binary feature selection problems. Simulations are conducted on 27 classical datasets from the UC Irvine Machine Learning Repository, and the results demonstrate that the proposed IBDA has better performance than some other comparison algorithms. Moreover, the effectiveness and performance of the proposed improved factors are evaluated by tests.

To improve the accuracy of user implicit rating prediction, we combine the traditional latent factor model (LFM) and bidirectional gated recurrent unit neural network (BiGRU) model to propose a hybrid model that deeply mines the latent semantics in the unstructured content of the text and generates a more accurate rating matrix. First, we utilize the user’s historical behavior (favorites records) to build a user rating matrix and decompose the matrix to obtain the latent factor vectors of users and literature. We also apply the BERT model for word embedding of the research papers to obtain the sequence of word vectors. Then, we apply the BiGRU with the user attention mechanism to mine the research paper textual content and to generate the new literature latent feature vectors that are used to replace the original literature latent factor vectors decomposed from the rating matrix. Finally, a new rating matrix is generated to obtain users’ ratings of noninteractive research papers and to generate the recommendation list according to the user latent factor vector. We design experiments on the real datasets and verify that the research paper recommendation model is superior to traditional recommendation models in terms of precision, recall, F1-value, coverage, popularity and diversity.

The rough-toothed dolphin (Steno bredanensis), the single extant species of the genus Steno, inhabits tropical and subtropical oceans. It is an attractive species for studying aquatic adaptation and evolution. The latest advances in high-throughput sequencing are transforming the study of marine mammals and contributing to understanding various phenomena at the species and population level by determining high-quality genomes. Here, to comprehensively understand the genetic features and explore the molecular basis of aquatic adaption, the chromosome-level genome assembly and comparative genomics analyses of S. bredanensis were performed. The 2.30 Gb final genome assembly of S. bredanensis (scaffold N50 length of 105.53 Mb) was obtained using single-tube long fragment read (stLFR) and Hi-C technologies. The genome assembly clearly revealed the preservation of large chromosomal fragments between S. bredanensis and the melon-headed whale (Peponocephala electra). The S. bredanensis genome contained 19,451 predicted protein-coding genes, of which about 92.33% have functional annotations. The genome assembly and gene sets showed high completeness, with a BUSCO score of 90.6% and 97.3%, respectively. We also identified several positively selected genes specific to S. bredanensis, which may be related to fat cell differentiation, tooth morphogenesis, and immunoregulatory activity. Finally, the demographic dynamics of S. bredanensis were estimated by the pairwise sequentially Markovian coalescent (PSMC) model and found that the population was affected by the climate at the time. We demonstrated that improved continuity and accuracy of the assembled sequence warranted the adoption of this chromosome-level genome as the reference genome and advanced the understanding of genetic features of the rough-toothed dolphin, which will be essential for future evolutionary studies and the protection of this species.

Hepatic fibrosis can develop into cirrhosis or even cancer without active therapy at an early stage. Long non-coding RNAs (lncRNAs) have been shown to be involved in the regulation of a wide variety of important biological processes. However, lncRNA mechanism(s) involved in cholestatic liver fibrosis remain unclear. RNA sequence data of hepatic stellate cells from bile duct ligation (BDL) mice or controls were analyzed by weighted gene co-expression network analysis (WGCNA). Based on WGCNA analysis, a competing endogenous RNA network was constructed. We identified LINC00663 and evaluated its function using a panel of assays, including a wound healing assay, a dual-luciferase reporter assay, RNA binding protein immunoprecipitation and chromatin immunoprecipitation. Functional research showed that LINC00663 promoted the activation, migration and epithelial–mesenchymal transition (EMT) of LX-2 cells and liver fibrosis in BDL mice. Mechanistically, LINC00663 regulated splicing factor 2 (SF2)-fibronectin (FN) alternative splicing through the sponging of hsa-miR-3916. Moreover, forkhead box A1 (FOXA1) specifically interacted with the promoter of LINC00663. In summary, we elaborated the fibrotic effects of LINC00663 in human hepatic stellate LX-2 cells and in bile duct-ligated cholestasis mice. We established a FOXA1/LINC00663/hsa-miR-3916/SF2-FN axis that provided a potential target for the diagnosis and targeted therapy of cholestatic liver fibrosis.

Background and Aims: Grapevine shoot growth and light utilization are typically adjusted through the use of canopy management strategies that are adapted to the local climate. In this study, we analyze the effects of a pergola (PER) and single-curtain training system (SCT) on the microclimate, light interception, photosynthetic capacity, and assimilate distribution of ‘Miguang’ grape in a rainy region of China. Methods and Results: We measured light interception, spectral absorptance, leaf area, chlorophyll content, photosynthetic rate, soluble sugar and starch content per cane, assimilate distribution berry weight, soluble solids, and titratable acid content. SCT produced a higher photosynthetic photon flux density in the cluster region, a canopy light absorptance in the 450–800 nm wavelength range, higher chlorophyll content, and larger leaf area of the middle node leaves. It produced lower basal and top leaves leaf areas. At berry expansion (E-L-31) and veraison (E-L-35), the net photosynthetic capacity of the leaves from the base to the middle nodes was higher with SCT than with the PER, and the net photosynthetic capacity of leaves near the top was reduced with SCT. At the harvest period, the net photosynthetic rate of the middle and top node leaves and the shoot photosynthetic rate were higher with SCT than with the PER. The distribution of assimilates to the fruit was higher with SCT. In addition, SCT produced a higher shoot soluble sugar and lower internode length from the fourth to sixth nodes, and it produced a higher shoot starch content and internode diameter in the fourth internode. Conclusions: SCT significantly improved photosynthetic photon flux density in the cluster, promoted assimilate distribution to fruit, decreased vegetative growth, increased chlorophyll content, increased the leaf size of the middle node on the primary shoot, and increased shoot soluble sugar from the fourth to sixth nodes. Significance of this Study: The results of this study can provide a relevant theoretical basis and technical support for grape canopy management.

Ozone (O3) stress severely affects the normal growth of grape (Vitis vinifera L.) leaves. Melatonin (MT) plays a significant role in plant response to various abiotic stresses, but its role in O3 stress and related mechanisms are poorly understood. In order to understand the mechanism of MT in alleviate O3 stress in grape leaves, we perform a transcriptome analyses of grapes leaves under O3 stress with or without MT treatment. Transcriptome analysis showed that the processes of ethylene biosynthesis and signaling were clearly changed in “Cabernet Sauvignon” grapes under O3 and MT treatment. O3 stress induced the expression of genes related to ethylene biosynthesis and signal transduction, while MT treatment significantly inhibited the ethylene response mediated by O3 stress. Further experiments showed that both MT and aminoethoxyvinylglycine (AVG, an inhibitor of ethylene biosynthesis) enhanced the photosynthetic and antioxidant capacities of grape leaves under O3 stress, while ethephon inhibited those capacities. The combined treatment effect of MT and ethylene inhibitor was similar to that of MT alone. Exogenous MT reduced ethylene production in grape leaves under O3 stress, while ethephon and ethylene inhibitors had little effect on the MT content of grape leaves after O3 stress. However, overexpression of VvACO2 (1-aminocyclopropane-1-carboxylate oxidase2) in grape leaves endogenously induced ethylene accumulation and aggravated O3 stress. Overexpression of the MT synthesis gene VvASMT1 (acetylserotonin methyltransferase1) in tobacco (Nicotiana tabacum L.) alleviated O3 stress and reduced ethylene biosynthesis after O3 stress. In summary, MT can alleviate O3 stress in grape leaves by inhibiting ethylene biosynthesis.

Sugars are important energy source and signaling molecule in plant, and sugar transporters such as SWEET (sugars will eventually be exported transporters) play important roles in plant growth and development as well as biotic and abiotic stresses. In this study, a gene named MdSWEET17 was isolated from apple (Malus×domestic). Expression analysis suggested that MdSWEET17 expressed in all tested tissues (root, stem, leaf, flower and fruit) and the transcript levels were different. Furthermore, MdSWEET17 transgenic tomatoes and wild type were treated with drought. The results showed transgenic lines had higher drought tolerance and accumulated more fructose. Taken together, these findings indicated that MdSWEET17 take part in drought stress response and the regulation of fructose.

Abstract Background The autoverification system for coagulation consists of a series of rules that allow normal data to be released without manual verification. With new advances in medical informatics, the laboratory information system (LIS) has growing potential for the autoverification, allowing rapid and accurate verification of clinical laboratory tests. The purpose of the study is to develop and evaluate a LIS-based autoverification system for validation and efficiency. Methods Autoverification decision rules, including quality control, analytical error flag, critical value, limited range check, delta check and logical check, as well as patient’s historical information, were integrated into the LIS. Autoverification limited range was constructed based on 5 and 95% percentiles. The four most commonly used coagulation assays, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and fibrinogen (FBG), were followed by the autoverification protocols. The validation was assessed by the autoverification passing rate, the true-positive cases, the true-negative cases, the false-positive cases, the false-negative cases, the sensitivity and the specificity; the efficiency was evaluated in the turnaround time (TAT). Results A total of 157,079 historical test results of coagulation profiles from January 2016 to December 2016 were collected to determine the distribution intervals. The autoverification passing rate was 77.11% (29,165/37,821) based on historical patient data. In the initial test of the autoverification version in June 2017, the overall autoverification passing rate for the whole sample was 78.75% (11,257/14,295), with 892 true-positive cases, 11,257 true-negative cases, 2146 false-positive cases, no false-negative cases, sensitivity of 100% and specificity of 83.99%. After formal implementation of the autoverification system for 6 months, 83,699 samples were assessed. The average overall autoverification passing rate for the whole sample was 78.86% and the 95% confidence interval (CI) of the passing rate was [78.25, 79.59%]. TAT was reduced from 126 min to 101 min, which was statistically significant (P

Background: Diagnosis of rib fractures plays an important role in identifying trauma severity. However, quickly and precisely identifying the rib fractures in a large number of CT images with increasing number of patients is a tough task, which is also subject to the qualification of radiologist. We aim at a clinically applicable automatic system for rib fracture detection and segmentation from CT scans. Methods: A total of 7,473 annotated traumatic rib fractures from 900 patients in a single center were enrolled into our dataset, named RibFrac Dataset, which were annotated with a human-in-the-loop labeling procedure. We developed a deep learning model, named FracNet, to detect and segment rib fractures. 720, 60 and 120 patients were randomly split as training cohort, tuning cohort and test cohort, respectively. Free-Response ROC (FROC) analysis was used to evaluate the sensitivity and false positives of the detection performance, and Intersection-over-Union (IoU) and Dice Coefficient (Dice) were used to evaluate the segmentation performance of predicted rib fractures. Observer studies, including independent human-only study and human-collaboration study, were used to benchmark the FracNet with human performance and evaluate its clinical applicability. A annotated subset of RibFrac Dataset, including 420 for training, 60 for tuning and 120 for test, as well as our code for model training and evaluation, was open to research community to facilitate both clinical and engineering research. Findings: Our method achieved a detection sensitivity of 92.9% with 5.27 false positives per scan and a segmentation Dice of 71.5%on the test cohort. Human experts achieved much lower false positives per scan, while underperforming the deep neural networks in terms of detection sensitivities with longer time in diagnosis. With human-computer collobration, human experts achieved higher detection sensitivities than human-only or computer-only diagnosis. Interpretation: The proposed FracNet provided increasing detection sensitivity of rib fractures with significantly decreased clinical time consumed, which established a clinically applicable method to assist the radiologist in clinical practice. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section. The funding sources played no role in the study design; collection, analysis, and interpretation of data; writing of the report; or decision to submit the article for publication .

Tissue engineering with 3D scaffold is a simple and effective method for bone healing after large-scale bone loss. So far, bone marrow-derived mesenchymal stem cells (BMSCs) are mostly used in the treatment of bone healing in animal models due to their self-renewal capability and osteogenic potential. Due to the fact that the main functional cells in promoting osteoid mineralization and bone remodeling were osteocytes, we chose an osteoblast-to-osteocyte transition cell line, IDG-SW3, which are not proliferative under physiological conditions, and compared the healing capability of these cells to that of BMSCs in bone defect. In vitro, IDG-SW3 cells revealed a stronger mineralization capacity when grown in 3D collagen gel, compared to that of BMSCs. Although both BMSC and IDG-SW3 can generate stable calcium-phosphate crystal similar to hydroxyapatite (HA), the content was much more enriched in IDG-SW3-mixed collagen gel. Moreover, the osteoclasts co-cultured with IDG-SW3-mixed collagen gel were easier to be activated, indicating that the IDG-SW3 grafting could promote the bone remodeling more efficiently in vivo. Last, in order to reduce the self-healing capability, we assessed the healing capability between the IDG-SW3 cells and BMSCs in osteoporotic mice. We found that the collagen hydrogel mixed with IDG-SW3 cells has a better healing pattern than what was seen in hydrogel mixed with BMSCs. Therefore, these results demonstrated that by promoting osteoblast-to-osteocyte transition, the therapeutic effect of BMSCs in bone defect repair could be improved.