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Introduction Transcranial motor-evoked potentials (TceMEPs) is conventionally performed without neuromuscular blockade (NMB) because of its potential interference with neuromuscular junction and signal interpretation. Sugammadex is the first highly selective antagonist that binds to rocuronium and can rapidly and effectively reverse NMB. This study aims to evaluate the success rate of intraoperative muscle relax reversal by sugammadex on intraoperative TceMEP recording.Methods and analysis We will conduct a single-centre randomised controlled study. In total, 162 patients undergoing thoracic or lumbar spinal surgery will be randomly divided into the sugammadex group or control group at a ratio of 1:1. Total intravenous anaesthesia by propofol and remifentanil will be performed in both groups. In the sugammadex group, patients will receive continuous infusion of rocuronium to produce a blockade maintained for at least two twitches in train-of-four, rocuronium infusion will be discontinued and 2 mg/kg sugammadex will be given while performing TceMEPs monitoring. In the control group, rocuronium infusion will be discontinued and the same volume of saline will be infused while performing TceMEPs monitoring. The primary aim of this study is to evaluate the success rate of TceMEPs recording between two groups.Ethics and dissemination The approval for the study was certificated by the Ethical Committee of Beijing Tiantan Hospital, Capital Medical University on, 16 July 2021 (KY2021-082-02). The study was registered on clincaltrials.gov on 25 October 2020. Our study might guide neuromuscular blockade plans in TceMEPs monitoring undergoing spinal surgery. The findings of the study will be published in peer-reviewed journals and will be presented at national or international conference.Trial registration number NCT04608682.

The aerosol−cloud impacts of the Tongan volcanic eruptions on the nearby tropical cyclone (TC) Cody on January 14∼15, 2022 are investigated by the MODIS satellite and ERA5 reanalysis data. Both the precipitation and intensity of Cody were obviously enhanced after the main blast of the Tongan volcanic eruption on January 15, although the sea surface temperature and vertical wind shear of the environmental wind did not change much according to ERA5 data. The vision that a large amount of volcanic aerosol flowed from the Tongan eruption into the inflow of Cody was captured by the MODIS observations on January 15. The cloud top temperature dropped, and the cloud particle effective radius decreased in Cody from then on, which indicated the occurrence of deep convection. The analyzed results of ERA5 show that convection was strengthened in the periphery of Cody at the beginning of the volcanic eruption at 03:00 UTC on January 15 and later in Cody’s inner core after the main blast at 06:00 UTC on January 15. This could be because of the microphysical process of aerosol−cloud interactions, which inhibited stratiform precipitation, increased vertical velocity and enhanced convective precipitation further. Since the deep convection in the inner core was conducive to the development of Cody, both the total precipitation and intensity of Cody increased after the main blast of the volcanic eruption. The result also suggests that major volcanic eruptions could increase the convective intensity and induce heavy precipitation in a nearby organized convective system (e.g., TC or mesoscale convective systems).

Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) first-line therapy, has shown good clinical outcomes in non-small cell lung cancer (NSCLC), but some serious adverse events such as cardiotoxicity have also been reported. Here, we present the first NSCLC case with osimertinib-induced cardiac failure. The case is successfully being treated by switching to another third-generation TKI, aumolertinib. A 62-year-old non-smoking woman was initially diagnosed with stage cT2aN2M1c IVB NSCLC with synchronous brain and bone metastasis in April 2020. Further genetic screening of the patient identified Leu858Arg (L858R) mutation in EGFR; thus, the patient was administered third-generation TKI osimertinib (80 mg/day) for 6 months. This treatment with osimertinib led to serious cardiac failure but no significant reduction in NSCLC tumor size. To cope with these conditions, another third-generation TKI, aumolertinib (110 mg/day), along with a supplement treatment plan was prescribed to the patient. Interestingly, this new treatment plan of aumolertinib significantly inhibited tumor growth in 8 months. Therefore, we conclude that the administration of second-line aumolertinib 110 mg/day has fewer adverse reactions and high efficacy against NSCLC as compared to osimertinib therapy.

Abstract Fusobacterium nucleatum is a critical microbe that contributes to colorectal cancer progression and chemoresistance. However, whether and how F. nucleatum regulates colorectal cancer stem‐like cells (CCSCs) remains unknown. Here, the authors show that F. nucleatum promotes CCSC self‐renewal, and non‐CCSCs to acquire CCSC features by manipulating cellular lipid accumulation. F. nucleatum infection decreases lipid accumulation in CCSCs by enhancing fatty acid oxidation, thus promoting CCSC self‐renewal. In contrast, F. nucleatum increases lipid accumulation in non‐CCSCs by promoting fatty acid formation. Lipids are deposited as lipid droplets, which recruits Numb, a key cell fate regulator, through the AP2A/ACSL3 complex, and MDM2, an E3 ubiquitin ligase, though VCP and UBXD8. On lipid droplets, Numb is degraded by MDM2, activating Notch signaling, thus promoting gain of stem‐like cell features. Their findings demonstrate that F. nucleatum directly manipulates colorectal cancer cell fate and reveal the mechanism of lipid droplet‐mediated Numb degradation for activating Notch signaling.

ObjectivePrefrailty and frailty are two common conditions among older individuals. Recent studies have reported the association between frailty and depressive symptoms, but whether those conditions could predict depressive symptoms is still inconsistent in a few longitudinal studies. In our study, we aimed to estimate the cross-sectional and longitudinal associations between frailty and incident depressive symptoms in a nationally representative sample of community-dwelling middle-aged and older Chinese adults.MethodData were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which included 17,284 adults aged ≥ 45 years. Participants were followed every two years using a face-to-face, computer-aided personal interview (CAPI) and structured questionnaire. We excluded participants with no follow-up data. The numbers of individuals who completed the baseline surveys were 2,579 and follow-up surveys were 839 for the short-term (2 years from 2011 to 2013) and 788 for the long-term (4 years from 2011 to 2015). In addition, Frailty was measured by the Fried criteria and depressive symptoms were estimated by the Chinese version of the Center for Epidemiologic Studies-Depression scale (CES-D). Logistic regression was used to analyze the odds ratio (OR), and 95% confidence interval (CI) for the cross-sectional associations of frailty and its components with depressive symptoms in the participants at baseline. Cox proportional hazards analysis was conducted using the hazard ratio (HR), and 95% confidence interval (CI) for the prospective associations of baseline frailty and pre-frailty and its component in the participants without depressive symptoms at baseline.ResultsAt baseline, 57.93% of participants had depressive symptoms and 55.84% had pre-frail and 11.63% had frailty. In the cross-sectional analysis, both pre-frailty (OR = 5.293, 95%CI 4.363–6.422) and frailty (OR = 16.025, 95%CI 10.948–23.457) were associated with depressive symptoms. In the longitudinal analysis, frailty [HR = 1.395 (0.966–2.013)] and pre-frailty [HR = 2.458 (0.933, 6.479)] were not significantly associated with incident depressive symptoms in a full-adjusted model among participants free of baseline depressive symptoms during the short-term. However, frailty [HR = 1.397 (1.017, 1.920)] and pre-frailty [HR = 2.992 (1.210, 7.397)] were significantly associated with incident depressive symptoms during the short term. In the components of frailty, slowness [HR = 1.597 (1.078, 2.366)] was associated with an increased risk of depressive symptoms onset during the short-term. Weakness [HR = 2.08 (1.055, 4.104)] and exhaustion [HR = 1.928 (1.297, 2.867)] were associated with increased risk of depressive symptoms onset during the short-term.ConclusionAmong the middle-aged and older adults, frailty, pre-frailty did not predict depressive symptoms during 2 years of follow-up, when accounting for the potential confounders, slowness considered alone predicted depressive symptoms. Additionally, frailty, pre-frailty predicted depressive symptoms during 4 years of follow-up, when accounting for the potential confounders, weakness and exhaustion considered alone predicted depressive symptoms.

Paris L. section Axiparis H. Li (Melanthiaceae) is a taxonomically perplexing taxon with considerable confusion regarding species delimitation. Based on the analyses of morphology and geographic distribution of each species currently recognized in the taxon, we propose a revision scheme that reduces the number of species in P. sect. Axiparis from nine to two. To verify this taxonomic proposal, we employed a genome skimming approach to recover the plastid genomes (plastomes) and nuclear ribosomal DNA (nrDNA) regions of 51 individual plants across the nine described species of P. sect. Axiparis by sampling multiple accessions per species. The species boundaries within P. sect. Axiparis were explored using phylogenetic inference and three different sequence-based species delimitation methods (ABGD, mPTP, and SDP). The mutually reinforcing results indicate that there are two species-level taxonomic units in P. sect. Axiparis (Paris forrestii s.l. and P. vaniotii s.l.) that exhibit morphological uniqueness, non-overlapping distribution, genetic distinctiveness, and potential reproductive isolation, providing strong support to the proposed species delimitation scheme. This study confirms that previous morphology-based taxonomy overemphasized intraspecific and minor morphological differences to delineate species boundaries, therefore resulting in an overestimation of the true species diversity of P. sect. Axiparis. The findings clarify species limits and will facilitate robust taxonomic revision in P. sect. Axiparis.

Objectives: The aim of this study was to explore the genomic content of a blaKPC-2- and mcr-1-harbouring Escherichia coli strain and to clarify the molecular mechanism for the transmission of multidrug resistance. Methods: Antimicrobial susceptibility testing was conducted by the broth microdilution method to determine the resistance profile. Filter-mating conjugation assays were performed to confirm the plasmid transfer ability. Whole-genome sequence data were acquired by a combination of Illumina paired-end reads and Nanopore long-read sequencing. Results: Escherichia coli strain QE11−421 was an mcr-1-positive colistin-resistant isolate that co-harboured the blaKPC-2 gene conferring carbapenem resistance. Genome sequence data confirmed QE11−421 as a sequence type 48 (ST48) E. coli that harboured five large conjugative plasmids encoding several multidrug resistance genes. The blaKPC-2 gene was located on a Tn3–Tn4401 composite transposon, which is part of a 65-kb multidrug-resistant IncN plasmid. The mcr-1 gene was harboured on another 33-kb IncX4 plasmid that was more conserved and presented few antimicrobial resistance determinants. No copies of insertion sequence ISApl1 were found flanking the mcr-1 gene, decreasing the mobility of mcr-1 based on its original Tn6330 transposon. Conclusions: Horizontal transfer of multidrug resistance plasmids or resistance-related transposon units was responsible for the emergence of this notorious superbug. The coexistence of blaKPC-2–IncN and mcr-1–IncX4 plasmids in a ST48 E. coli strain in humans poses a great threat.

Abstract Background Interstitial fibrosis/tubular atrophy (T) score is a known determinant of the progression of immunoglobulin A nephropathy (IgAN). Strong evidence indicates that the components of the coagulation system closely linked with fibrotic events have been highlighted in the kidney. However, whether the coagulation system can affect the renal outcome of IgAN remains unclear. Herein, we investigated the association of coagulation parameters and pathological phenotype of IgAN and their combined effects on the deterioration of renal function. Methods This retrospective study included N = 291 patients with biopsy-proven IgAN from May 2009 to April 2013 in the Second Xiangya Hospital. Clinical data, pathological features were collected, and the associations of coagulation parameters at biopsy, T score, and renal outcome were evaluated. T score indicated the degree of tubular atrophy or interstitial fibrosis. The renal outcome was defined as an end-stage renal disease (ESRD) or an irreversible 50% estimated glomerular filtration rate (eGFR) reduction. Results Shorter prothrombin time (PT) and the activated partial thromboplastin time (APTT) were significantly associated with T (both p

Abstract Background The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a looming threat to human health. Although there are numerous studies regarding porin alteration in association with the production of ESBLs and/or AmpC β-lactamase, a systematic study on the treatment-emergence of porins alteration in antibiotic resistance does not yet exist. The aim of this study was to investigate the underlying mechanism of resistance of K. pneumoniae during carbapenem treatment. Results Here, we report three strains (FK-2624, FK-2723 and FK-2820) isolated from one patient before and after imipenem treatment during hospitalization. Antibiotic susceptibility testing indicated that that the first isolate, FK-2624, was susceptible to almost all tested antimicrobials, being resistant only to fosfomycin. The subsequent isolates FK-2723 and FK-2820 were multidrug resistant (MDR). After imipenem therapy, FK-2820 was found to be carbapenem-resistant. PCR and Genome Sequencing analysis indicated that oqxA, and fosA5, were identified in all three strains. In addition, FK-2624 also harbored bla SHV - 187 and bla TEM-116. The bla SHV - 187 and bla TEM-116 genes were not detected in FK-2723 and FK-2820. bla DHA -1, qnrB4, aac (6′)-IIc, and bla SHV - 12, EreA2, CatA2, SulI, and tetD, were identified in both FK-2723 and FK-2820. Moreover, the genes bla DHA-1, qnrB4, aac (6′)-IIc were co-harbored on a plasmid. Of the virulence factors found in this study, ybtA, ICEKp6, mrkD, entB, iroN, rmpA2–6, wzi16 and capsular serotype K57 were found in the three isolates. The results of pairwise comparisons, multi-locus sequencing typing (MLST) and pulsed-field gel electrophoresis (PFGE) revealed high homology among the isolates. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) results showed that isolate FK-2820 lacked OmpK36, with genome sequence data validating that there was a premature stop codon in the ompK36 gene and real-time RT-PCR suggesting high turnover of the ompK36 non-sense transcript in FK-2820, with the steady-state mRNA level 0.007 relative to the initial isolate. Conclusion This study in China highlight that the alteration of outer membrane porins due to the 14-day use of imipenem play a potential role in leading to clinical presentation of carbapenem-resistance. This is the first description of increased resistance developing from a carbapenem-susceptible K. pneumoniae with imipenem treatment driven by outer membrane remodeling.

Biosensing is a rising analytical field for detection of biological indicators using transducing systems. Smart materials can response to external stimuli, and translate the stimuli from biological domains into signals that are readable and quantifiable. Smart materials, such as nanomaterials, photonic crystals and hydrogels have been widely used for biosensing purpose. In this review, we illustrate the incorporation of smart materials in biosensing systems, including the design of responsive materials, their responsive mechanism of biosensing, and their applications in detection of four types of common biomolecules (including glucose, nucleic acids, proteins, and enzymes). In the end, we also illustrate the current challenges and prospective of using smart materials in biosensing research fields.

IntroductionBrucellosis is a systemic disease that exists prevalently in clinical manifestations. The symptoms present in organs such as the eyes (in ocular brucellosis) can lead to misdiagnosis or even failure to diagnose. Metagenomic Next-Generation Sequencing (mNGS), a high-throughput sequencing approach, could be applied for the detection of microorganisms.Case PresentationA 57-year-old female with acute right-eye vision loss, treated with clindamycin and dexamethasone sodium phosphate for 1.5 months, was difficult to diagnose using regular methods. mNGS was utilized for the aqueous fluid from the patient, and Brucella melitensis was identified. The inflammation was treated with 3 months of antibiotherapy. However, even with specific medicine and surgery, the vision remained poor because severe ocular conditions last for a long time.ConclusionIt suggests that brucella should still be a probable pathogen in endophthalmitis despite its low incidence in non-epidemic areas. Moreover, mNGS can achieve early diagnosis and timely treatment for difficult-to-diagnose ocular infections.

Water conservation is one of the most critical ecosystem service functions of river basins and is an important indicator of regional eco-environmental conditions. Beijiang River Basin (BRB) is an important water source and ecological barrier for the Guangdong-Hong Kong-Macau Greater Bay Area (GBA), and its water conservation function is of widespread concern. In this study, based on the hydrological model WEP-L (Water and Energy transfer Processes in Large River basin), and the water balance principle, we analysed the multiple time-scale characteristics of water conservation in the BRB during 1960–2018 and revealed the response of water conservation to climate change based on scenario setting and hydrological simulation. The results showed that annual water conservation exhibited an insignificant reducing trend of −4.69 mm/10a. Water conservation reduced insignificantly in spring, summer, and autumn, while it showed a nonsignificant increasing trend of 4.69 mm/10a in winter. The spatial distribution of water conservation in the BRB was low in the south and high in the north, mainly due to the spatial distribution of land use. Precipitation was the main factor affecting water conservation. The results can provide a reference for water resource planning and management, and provide a theoretical foundation for ecosystem restoration and reconstruction.

We report a vitreous amyloidosis patient with white vitreous opacities (footplates) adhering to the posterior lens capsule. A positive Congo-red stain and transthyretin (TTR) Lys55Asn mutation confirmed the diagnosis of vitreous amyloidosis. Optical coherence tomography (OCT) revealed fern-like material adhering to the the posterior pole retinal surface in both eyes. Visual acuity significantly improved after the first vitrectomy, but vitreous opacities recurred 4 years later. The patient appeared to have aggravated sensorimotor neuropathy and severe autonomic dysfunction at the same time. He developed intraoperative suprachoroidal hemorrhage during the second vitrectomy.

Purpose. To investigate the aqueous levels of angiogenic factors in nonproliferative diabetic retinopathy (NPDR) patients with diabetic macular edema (DME) and to ascertain their association with optical coherence tomography angiography (OCTA) metrics. Methods. This study enrolled 21 NPDR eyes with DME (NPDR/DME+), 17 NPDR eyes without DME (NPDR/DME-), and 16 diabetic eyes without retinopathy (DWR). Luminex bead-based multiplex array was used to measure the levels of 25 cytokines. OCTA system with a scan area of 3×3 mm was used to measure retinal thickness (RT), retinal volume (RV), superficial vessel density (SVD), deep vessel density (DVD), foveal avascular zone (FAZ) area, perimeter and acircularity index. Results. The levels of ANGPTL4 were significantly different among the three groups (P

The cyp19a1 gene codes aromatase that converts androgen to estrogen, which plays a central role in early female differentiation and ovarian development in teleosts. For the blotched snakehead (Channa maculata), an important aquaculture fish that is susceptible to hormone-induced sex reversal, two aromatase genes were characterized in the present study, cyp19a1a and cyp19a1b. We analyzed gene expression and the epigenetic state of cyp19a1a and cyp19a1b in different adult tissues: the gonad and brain from normal XX females (XX-F), normal XY males (XY-M), sex-reversal females (XY-F) induced by estrogen, and YY super-males (YY-M), and gonads at different development stages. Cyp19a1a exhibited strong female-biased expression patterns in the ovary, and cyp19a1b dominantly expressed in the brain with no sex bias. Cyp19a1a’s expression pattern in the XY-F ovary was similar to that in the XX-F ovary, with a relatively high expression level, which was far higher than that in XY-M and YY-M testis. Meanwhile, CpG methylation levels of cyp19a1a promoter were lower in XX-F and XY-F ovaries compared with XY-M and YY-M testis. A significantly negative correlation between the CpG methylation levels and cyp19a1a expression was elucidated in XX-F, XY-M, XY-F, and YY-M gonads. Furthermore, the strong female-biased cyp19a1a expression was closely related to ovarian differentiation and maturation, and the overall methylation levels of cyp19a1a promoter were inversely correlated with cyp19a1a expression. There were no detectable sexually dimorphic differences in cyp19a1b expression and CpG methylation levels of cyp19a1b promoter in the brain and gonad between sexes in C. maculata, thus the function of cyp19a1b in C. maculata needs further research. Our research illustrates that cyp19a1a is closely related to estrogen production, ovary differentiation/maintenance, and sex reversal, and epigenetic modification plays a crucial part in maintaining the sexual dimorphic expression of cyp19a1a, ovarian differentiation and oogenesis in C. maculata.

Carbapenem-resistant Acinetobacter baumannii (CRAB) isolates of global clone 1 (GC1) and global clone 2 (GC2) have been widely reported. Nevertheless, non-GC1 and non-GC2 CRAB strains have been studied less. In particular, no reports concerning sequence type 46 (ST46Pas) CRAB strains have been described thus far. In this work, the genomic features and possible evolution mechanism of ST46Pas OXA-23-producing CRAB isolates from clinical specimens are reported for the first time. Antimicrobial susceptibility testing of three ST46Pas strains revealed identical resistance profiles (resistance to imipenem, meropenem, ciprofloxacin and the combination of cefoperazone/sulbactam at a 2:1 ratio). They were found to belong to ST46Pas and ST462Oxf with capsular polysaccharide 28 (KL28) and lipooligosaccharide 1 (OCL1), respectively. Whole-genome sequencing (WGS) revealed that all contained one copy of chromosomal blaOXA-23, which was located in a novel ISAba1-based Tn7534 composite transposon. In particular, another copy of the Tn7534 composite transposon was identified in an Hgz_103-type plasmid with 9 bp target site duplications (TSDs, ACAACATGC) in the A. baumannii ZHOU strain. As the strains originated from two neighboring intensive care units (ICUs), ST46Pas OXA-23-producing CRAB strains may have evolved via transposition events or a pdif module. Based on the GenBank database, ST46Pas strains were collected from various sources; however, most were collected in Hangzhou (China) from 2014 to 2021. Pan-genome analysis revealed 3276 core genes, 0 soft-core genes, 768 shell genes and 443 cloud genes shared among all ST46Pas strains. In conclusion, the emergence of ST46Pas CRAB strains might present a new threat to healthcare settings; therefore, effective surveillance is required to prevent further dissemination.

Since the invention of rockets, mankind has been constantly trying to explore the universe. It was not until the beginning of the last century that electric propulsion technology was introduced. With the same weight of fuel consumed as chemical propulsion, electric propulsion technology can transport a spacecraft to a more distant universe. With its excellent performance in terms of specific impulse and thrust, the MPDT (MagnetoPlasmaDynamic Thruster) is garnering significant attention in the field of electric propulsion. Recent research has focused on improving its propulsion performance and service life. Due to the complexity of its working mechanism, there is no perfect explanation for it. Further analysis of its working mechanism may lead to a solution to the improvement of certain significant performance aspects such as thrust. An ideal magnetic fluid model of the MPDT is established based on the MHD method, and the working mechanism is analyzed and summarized according to simulations and experiments. The results of the analysis indicate that reducing the size of the cathode could significantly improve the thruster’s performance.

Electrocardiogram (ECG) signals are among the significant physiological signals that indicate the essential properties of the human body. In recent years, the measurement of ECG signals has become more portable thanks to the increasing usage of wearable health testing technology. However, the enormous amount of signal data gathered over a long period of time does impose a heavy load on medical professionals. In addition, false alarms might occur due to the potential for the detected signal to become jumbled with noise and motion perturbations. Therefore, analyzing the quality of the measured raw ECG signal automatically is a valuable task. In this paper, we propose a new single-channel ECG signal quality assessment method that combines the Resnet network structure and the principle of self-attention to extract ECG signal features using the principle of similarity between individual QRS heartbeats within a time slice of ten seconds. In addition, an improved self-attention module is introduced into the deep neural network to learn the similarity between features. Finally, the network distinguishes between acceptable and unacceptable ECG segments. The model test results indicate that the F1-score can approach 0.954, which leads to a more accurate assessment of the ECG signal quality.

As wheels are important components of train operation, diagnosing and predicting wheel faults are essential to ensure the reliability of rail transit. Currently, the existing studies always separately deal with two main types of wheel faults, namely wheel radius difference and wheel flat, even though they are both reflected by wheel radius changes. Moreover, traditional diagnostic methods, such as mechanical methods or a combination of data analysis methods, have limited abilities to efficiently extract data features. Deep learning models have become useful tools to automatically learn features from raw vibration signals. However, research on improving the feature-learning capabilities of models under noise interference to yield higher wheel diagnostic accuracies has not yet been conducted. In this paper, a unified training framework with the same model architecture and loss function is established for two homologous wheel faults. After selecting deep residual networks (ResNets) as the backbone network to build the model, we add the squeeze and excitation (SE) module based on a multichannel attention mechanism to the backbone network to learn the global relationships among feature channels. Then the influence of noise interference features is reduced while the extraction of useful information features is enhanced, leading to the improved feature-learning ability of ResNet. To further obtain effective feature representation using the model, we introduce supervised contrastive loss (SCL) on the basis of ResNet + SE to enlarge the feature distances of different fault classes through a comparison between positive and negative examples under label supervision to obtain a better class differentiation and higher diagnostic accuracy. We also complete a regression task to predict the fault degrees of wheel radius difference and wheel flat without changing the network architecture. The extensive experimental results show that the proposed model has a high accuracy in diagnosing and predicting two types of wheel faults.

Background: Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease and poses a global major public health burden. The preparation of Tripterygium wilfordii Hook F (TwHF) is widely applied for treating patients with Immunoglobulin A nephropathy in China, while the molecular mechanisms remain unclear. This study aimed to verify the therapeutic mechanism of TwHF on IgAN by undertaking a holistic network pharmacology strategy in combination with in vitro and in vivo experiments.Methods: TwHF active ingredients and their targets were obtained via the Traditional Chinese Medicine Systems Pharmacology Database. The collection of IgAN-related target genes was collected from GeneCards and OMIM. TwHF-IgAN common targets were integrated and visualized by Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to determine the predominant molecular mechanisms and pathways of TwHF on the treatment of IgAN. The protein-protein interaction network was constructed by the STRING online search tool, and hub genes were identified using R software. The expression of hub gene and related signaling were evaluated in TwHF-treated mice through immunohistochemistry and western blot and further validated in human mesangial cells (HMCs). In addition, Cell counting kit 8 (CCK8) and flow cytometry were used to detect the effects of TwHF on cell proliferation and cell cycle of mesangial cells.Results: A total of 51 active ingredients were screened from TwHF and 61 overlapping targets related to IgAN were considered potential therapeutic targets, GO functions and KEGG analyses demonstrated that these genes were primarily associated with DNA-binding transcription factor binding, lipid and atherosclerosis pathway. Genes with higher degrees including AKT1, CXCL8, MMP9, PTGS2, CASP3, JUN are hub genes of TwHF against IgAN. Verification of hub gene JUN both in vitro and in vivo showed that TwHF significantly attenuated JUN phosphorylation in the kidneys of IgAN mice and aIgA1-activated HMCs, meanwhile suppressing HMCs proliferation and arresting G1-S cell cycle progression.Conclusion: Our research strengthened the mechanisms of TwHF in treating IgAN, inhibition of JUN activation may play a pivotal role in TwHF in alleviating IgAN renal injury.

This paper investigates the transmission performance of a novel dual-drive hydrostatic lead screw micro-nano feed system (DDHLS) that can obtain extremely low speed. Firstly, the oil film liquid friction of hydrostatic transmission is modelled, and the calculation model of oil film dynamic friction is proposed based on the variable viscosity theory. Secondly, on this basis, combined with the LuGre friction model, a novel all-components refinement friction identification method (ACRFIM) for DDHLS was developed. The friction parameters of the feed drive components such as LM guide and hydrostatic lead screw can be identified independently using the proposed method, ensuring precise friction force modelling in all components. Then, an all-component adaptive friction compensation control algorithm (AACA) was designed by introducing the temperature and disturbance influence factors into the friction model and considering the influence of the dynamic friction of liquid. The experiments illustrate that the calculation accuracy of the oil film friction model based on the variable viscosity theory is substantially improved. DDHLS can effectively suppress the adverse effects of nonlinear friction, and the proposed AACA has an obvious compensation effect for the friction of the time-varying system.

Cyprinidae is one of the largest family in freshwater fishes, and it is most intensively cultured fish taxon of the world. However, studies about sex determination in this large family is still rear, and one of the reasons is lack of high quality and complete genome. Here, we used nanopore to sequence the genome of a male bighead carp, obtaining contig N50 = 24.25 Mb, which is one of the best assemblies in Cyprinidae. Five males and five females were re-sequenced, and a male-specific region on LG19 was confirmed. We find this region holds many male-specific markers in other Cyprinidae fishes, such as grass carp and silver carp. Transcriptome analyses of hypothalamus and pituitary tissues showed that several sex-specific differentially expressed genes were associated with steroid biosynthesis. The UCH64E gene, located in the male-specific region on LG19, showed higher expression levels in male than female tissues of bighead carp. The methyl-RAD of hypothalamus tissues between males and females indicated that the sexual methylation differences are significant in bighead carp. We also compared the methylation sites recognized using methyl-RAD and nanopore raw reads and found that approximately 73% of the methylation sites identified using methyl-RAD were within nanopore CpG sites.

Overweight employees are viewed as lazy, slow, inactive, and even incapable. Even if such attributes are false, this perspective can seriously undermine others' evaluation of their work performance. The current study explores a broader phenomenon of weight bias that has an effect on weight change. In a longitudinal study with a time lag of 6 months, we surveyed 226 supervisor-employee dyads. We found supervisor perceptions of employee weight change notably altered their evaluation of the employee performance from Time 1, especially following low vs. high Time-1 performance evaluation. Meanwhile, the moderating effects among different levels of supervisor anti-fat bias functioned as boundary conditions for such performance evaluation alteration. In particular, the interaction between the Time-1 performance evaluation and the impact of supervisor perception of employee weight change on the Time-2 performance evaluation was significant only if supervisors held a stronger anti-fat bias.

The extant literature has revealed that leader narcissism has paradoxical impacts on follower outcomes. In this research, we argue that its paradoxical effects can be disentangled by the presence of two distinct types of leader narcissism--narcissistic admiration and narcissistic rivalry--which can shape leaders' initial relationship-building with new followers (i.e., newcomers) differently. Integrating a dual-type view of narcissism with leader-member exchange (LMX) theory and conducting a multi-wave, multi-source field study with 151 leader-newcomer dyads, we found that leader narcissistic admiration is negatively related to leader perceived threat of a newcomer whereas leader narcissistic rivalry is positively related to it. Leader perceived threat of a newcomer, in turn, reduces the newcomer's LMX perceptions and ultimately hinders the newcomer's job satisfaction and task performance. Moreover, leader perceived similarity with a newcomer was found to strengthen the negative (positive) effect of leader narcissistic admiration (rivalry) on leader perceived threat of a newcomer. We did not find support for the moderation effect of newcomer acceptance seeking from the leader. This research sheds light on the value of adopting a content-specific and multidimensional approach in studying leader narcissism. [ABSTRACT FROM AUTHOR]

Abstract Background Robust phylogenies for species with giant genomes and closely related taxa can build evolutionary frameworks for investigating the origin and evolution of these genomic gigantisms. Paris japonica (Melanthiaceae) has the largest genome that has been confirmed in eukaryotes to date; however, its phylogenetic position remains unresolved. As a result, the evolutionary history of the genomic gigantisms in P. japonica remains poorly understood. Results We used next-generation sequencing to generate complete plastomes of P. japonica, P. verticillata, Trillium govanianum, Ypsilandra thibetica and Y. yunnanensis. Together with published plastomes, the infra-familial relationships in Melanthiaceae and infra-generic phylogeny in Paris were investigated, and their divergence times were calculated. The results indicated that the expansion of the ancestral genome of extant Paris and Trillium occurred approximately from 59.16 Mya to 38.21 Mya. The sister relationship between P. japonica and the section Euthyra was recovered, and they diverged around the transition of the Oligocene/Miocene (20 Mya), when the Japan Islands were separated from the continent of Asia. Conclusions The genome size expansion in the most recent common ancestor for Paris and Trillium was most possibly a gradual process that lasted for approximately 20 million years. The divergence of P. japonica (section Kinugasa) and other taxa with thick rhizome may have been triggered by the isolation of the Japan Islands from the continent of Asia. This long-term separation, since the Oligocene/Miocene boundary, would have played an important role in the formation and evolution of the genomic gigantism in P. japonica. Moreover, our results support the taxonomic treatment of Paris as a genus rather than dividing it into three genera, but do not support the recognition of T. govanianum as the separate genus Trillidium.

Abstract Background Heading date is crucial for rice reproduction and geographic expansion. Many heading date genes are sensitive to photoperiod and jointly regulate flowering time in rice. However, it is not clear how these genes coordinate rice heading. Results Here, we performed a genetic interaction analysis among four major rice heading date genes Ghd7, Ghd8, OsPRR37/Ghd7.1 (hereafter PRR37) and Hd1 in the near-isogenic background under both natural long-day (NLD) and natural short-day (NSD) conditions. The 4-gene segregating population exhibited a large heading date variation with more than 95 days under NLD and 42 days under NSD conditions. Tetragenic, trigenic and digenic interactions among these four genes were observed under both conditions but more significant under NLD conditions. In the functional Hd1 backgrounds, the strongest digenic interaction was Ghd7 by Ghd8 under NLD but was Ghd7 by PRR37 under NSD conditions. Interestingly, PRR37 acted as a flowering suppressor under NLD conditions, while it functioned alternatively as an activator or a suppressor under NSD conditions depending on the status of the other three genes. Based on the performances of 16 homozygous four-gene combinations, a positive correlation between heading date and spikelets per panicle (SPP) was found under NSD conditions, but changed to a negative correlation when heading date was over 90 days under NLD conditions. Conclusions These results demonstrate the importance of genetic interactions in the rice flowering regulatory network and will help breeders to select favorable combinations to maximize rice yield potential for different ecological areas.

ABSTRACT Objective: To evaluate the influence of sub-minimum inhibitory concentrations (MICs) of ciprofloxacin (CIP) on biofilm formation and virulence factors of Escherichia coli clinical isolates. Methods: Sub-MICs of CIP were determined using growth curve experiments. The biofilm-forming capacity of E. coli clinical isolates and E. coli ATCC 25922 treated or untreated with sub-MICs of CIP was assessed using a crystal violet staining assay. The biofilm structure of E. coli isolate was assessed with scanning electron microscopy (SEM). The expression levels of the virulence genes fim, usp, and iron and the biofilm formation genes of the pgaABCD locus were measured using quantification RT-PCR (qRT-PCR) in E. coli isolates and E. coli ATCC 25922. Results: Based on our results, the sub-MICs of CIP were 1/4 MICs. Sub-MICs of CIP significantly inhibited biofilm formation of E. coli clinical isolates and E. coli ATCC 25922 (p < 0.01). SEM analyses indicated that the biofilm structure of the E. coli changed significantly after treatment with sub-MICs of CIP. Expression levels of the virulence genes fim, usp, and iron and the biofilm formation genes of the pgaABCD locus were also suppressed. Conclusions: The results revealed that treatment with sub-MICs of CIP for 24 h inhibited biofilm formation and reduced the expression of virulence genes and biofilm formation genes in E. coli.

Glutamate excitotoxicity may contribute to retinal ganglion cell (RGC) degeneration in glaucoma and other optic neuropathies, leading to irreversible blindness. Growing evidence has linked impaired mitochondrial quality control with RGCs degeneration, while parkin, an E3 ubiquitin ligase, has proved to be protective and promotes mitophagy in RGCs against excitotoxicity. The purpose of this study was to explore whether a small molecule S3 could modulate parkin-mediated mitophagy and has therapeutic potential for RGCs. The results showed that as an inhibitor of deubiquitinase USP30, S3 protected cultured RGCs and improved mitochondrial health against NMDA-induced excitotoxicity. Administration of S3 promoted the parkin expression and its downstream mitophagy-related proteins in RGCs. An upregulated ubiquitination level of Mfn2 and protein level of OPA1 were also observed in S3-treated RGCs, while parkin knockdown resulted in a major loss of the protective effect of S3 on RGCs under excitotoxicity. These findings demonstrated that S3 promoted RGC survival mainly through enhancing parkin-mediated mitophagy against excitotoxicity. The neuroprotective value of S3 in glaucoma and other optic neuropathies deserves further investigation.

The two-stroke micro free piston swing engine (MFPSE) is a portable power device. Its seal performance plays an important role in the dynamic properties and efficiency of microengines. The present work established the leakage model of the two-stroke micro free piston swing engine by utilizing the compressible flow Reynolds Navier–Stokes equation. The obtained nondimensional mass leakage was related to the seal gap height, seal inlet pressure, size factor and compression ratio. Simulation investigated how the different seal gap heights and size factors affected the pressure, temperature and mass leakage of micro engines. The results showed that when the seal gap height of the combustion chamber increased, the maximum pressure and cycle power declined, obviously. However, the maximum temperature was scarcely affected. The mass leakage was not greatly impacted when the compression ratio was less than 5. However, the mass leakage dramatically increased when the seal gap was more than 10 μm or the size factor was less than 0.4. The investigation revealed these mass leakage effect factors and provided a guide for the seal and structure design of the two-stroke micro free piston swing engine.

As a key component of a drip irrigation system, the performance of the drip irrigation emitters is mainly determined by the flow channel structures and structural parameters. In this study, a novel type of circular water-retaining labyrinth channel (CWRLC) structure emitter was proposed, inspired by the effect of roundabouts that make vehicles slow down and turn. Using the single-factor experiment method, the influence of the hydraulic performance of CWRLC emitters was researched under different circular radii. The internal flow characteristics and energy dissipation mechanism were analyzed by a computational fluid dynamics (CFD) simulation. It can be seen from the analysis that the energy dissipation abilities of the flow channel depend on the proportion of low-speed vortex areas. The larger the proportion of low-speed vortex areas, the smaller the flow index of the CWRLC emitter. Quadrate water-retaining labyrinth channel (QWRLC) and stellate water-retaining labyrinth channel (SWRLC) structures were obtained by structural improvements for increasing the proportion of low-speed vortex areas. The simulation results showed that the flow indexes of two improved structural emitters were significantly decreased. CWRLC, QWRLC, SWRLC, and widely used tooth labyrinth channel (TLC) emitters were manufactured by using technologies of electrical discharge machining (EDM) and injection molding (IM). The physical test results showed that the SWRLC emitter achieved the best hydraulic performance compared with the other three emitters. Therefore, the SWRLC emitter has a broad prospect of application in water-saving irrigation.

The purpose of this study is to investigate the current state of post-traumatic growth (PTG) and identify its influencing factors in discharged COVID-19 patients. PTG refers to individual experiences of significant positive change arising from the struggle with a major life crisis. This descriptive cross-sectional study used the convenient sampling method to recruit 140 discharged COVID-19 patients in Hunan, China. The results show that the PTG of the discharged COVID-19 patients was positively correlated with self-esteem, post-traumatic stress disorder, coping style tendency, and social support, but negatively correlated with the time from onset to diagnosis. Our findings could provide guidance on improving the psychological state and well-being of discharged COVID-19 patients.

A rapid, highly sensitive, and robust diagnostic technique for point-of-care (PoC) testing can be developed using the combination of the nanoparticle-based lateral flow biosensors (LFB) and isothermal nucleic acid amplification technology. Here, we developed a polymerase spiral reaction (PSR) containing FITC-labeled DNA probes coupled with the nanoparticle-based LFB assay (PSR-LFB) to detect the amplified products to detect HBV visually. Under the optimized conditions, the PSR assay involved incubation of the reaction mixture for 20 min at 63°C, followed by visual detection of positive amplicons using LFB, which would generate a red test line based on the biotin/streptavidin interaction and immunoreactions, within 5 min. A cross-reactivity test revealed that the developed PSR-LFB assay showed good specificity for HBV and could distinguish HBV from other pathogenic microorganisms. For the analytical sensitivity, the limit of detection (LoD) of PSR-LFB assay was recorded as 5.4 copies/mL of HBV genomic DNA, which was ten-times more sensitive than qPCR and loop-mediated isothermal amplification (LAMP). Additionally, all the HBV-positive (29/82) samples, identified using ELISA, were also successfully detected by the PSR-LFB assay. We found that the true positive rate of the PSR-LFB assay was higher than that of qPCR (100 vs. 89.66%, respectively), as well as the LAMP assay (100 vs. 96.55%, respectively). Furthermore, the integrated procedure could be completed in 60 min, including the processing of the blood samples (30 min), an isothermal reaction (20 min), and result visualization (5 min). Thus, this PSR-LFB assay could be a potentially useful technique for PoC diagnosis of HBV in resource-limited countries.