Search

Currently, the feature richness of text encoding vectors in the bug report classification model based on deep learning is limited by the size of the domain dataset and the quality of the text. However, it is difficult to further enrich the features of text encoding vectors. At the same time, most existing bug report classification methods ignore the submitter's personal information. To solve these problems, we construct nine personal information characteristics of bug report submitters in GitHub by survey. Then, we propose a GitHub bug report classification method named personal information fine‐tuning network (PIFTNet) based on transfer learning and the submitter's personal information. PIFTNet transfers the general text feature vectors in bidirectional encoder representation from transformers (BERT) to the domain of bug report classification by fine‐tuning the pre‐training parameters in BERT. It also combines the text characteristics and the characteristics of the submitter's personal information to construct the classification model. In addition, we propose a two‐stage training method to alleviate the catastrophic changes in the pre‐training parameters and loss of the initially learned knowledge caused by direct training of PIFTNet. We verify the proposed PIFTNet on the dataset extracted from GitHub and empirical results prove the effectiveness of PIFTNet. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to explore the prognostic factors of head and neck rhabdomyosarcoma (HNRMS) in children and adolescents and construct a simple but reliable nomogram model for estimating overall survival (OS) of patients. Methods: Data of all HNRMS patients during 2004-2018 were identified from the Surveillance, Epidemiology, and End Result database. Kaplan-Meier method was performed to calculate OS stratified by subgroups and comparison between subgroups was completed by log-rank test. Univariate and multivariate Cox regressions analysis were employed for identifying independent predictors, which subsequently were used for a predictive model by R software, and the efficacy of the model was evaluated by applying receiver operating curve (ROC), calibration and decision curve analysis (DCA). Results: A total of 446 patients were included in the study. The 1-, 3-, and 5-year OS rate of the whole cohort was 90.6%, 80.0%, and 75.5%, respectively. The results of univariate and multivariate Cox regression analysis indicated that the primary site in parameningeal region, alveolar RMS histology, M1 stage, IRS stage 4, surgery, and chemotherapy were significant prognostic factors (all P<0.05). The performance of nomogram model was validated by discrimination and calibration, with AUC values of 1, 3, and 5 years OS of 0.843, 0.851, and 0.890, respectively. Conclusion: We constructed a prognostic nomogram model for predicting the OS in HNRMS patients in children and adolescents and this model presented practical and applicable clinical value to predict survival when choosing treatment strategies. [ABSTRACT FROM AUTHOR]

Skin Cutaneous Melanoma (SKCM) is a form of cancer that originates in the pigment‐producing cells, known as melanocytes, of the skin. Delay wound healing is often correlated with the occurrence of and progression of SKCM. In this comprehensive study, we investigated the intricate roles of two important wound healing genes in SKCM, including Matrix Metalloproteinase‐2 (MMP2) and Matrix Metalloproteinase‐9 (MMP9). Through a multi‐faceted approach, we collected clinical samples, conducted molecular experiments, including RT‐qPCR, bisulphite sequencing, cell culture, cell Counting Kit‐8, colony formation, and wound healing assays. Beside this, we also used various other databases/tools/approaches for additional analysis including, UALCAN, GEPIA, HPA, MEXPRESS, cBioPortal, KM plotter, DrugBank, and molecular docking. Our results revealed a significant up‐regulation of MMP2 and MMP9 in SKCM tissues compared to normal counterparts. Moreover, promoter methylation analysis suggested an epigenetic regulatory mechanism. Validations using TCGA datasets and immunohistochemistry emphasized the clinical relevance of MMP2 and MMP9 dysregulation. Functional assays demonstrated their synergistic impact on proliferation and migration in SKCM cells. Furthermore, we identified potential therapeutic candidates, Estradiol and Calcitriol, through drug prediction and molecular docking analyses. These compounds exhibited binding affinities, suggesting their potential as MMP2/MMP9 inhibitors. Overall, our study elucidates the diagnostic, prognostic, and therapeutic implications of MMP2 and MMP9 in SKCM, shedding light on their complex interplay in SKCM occurrence and progression. [ABSTRACT FROM AUTHOR]

To improve the mechanical properties of casting aluminum-copper alloy, the mixed rare earth (RE) was added to ZL206 and its properties and the enhanced mechanism of alloy were researched. The results showed that the strength and hardness of the composite were improved by 10.2% and 6.2%, respectively. After adding mixed RE, which was led by the heterogeneous enrichment area blocking the growth of the α-Al phase and making grain refinement during the solidification process. The simulation results of RE surface adsorption models by first principles also showed that the elastic constant calculation improved the bulk modulus, shear modulus, and Young's modulus of the material. The addition of mixed RE enhances the strength and hardness, although it adversely affects toughness and reduces the machining index. Also, the work function decreased, and the Fermi level increased, reflecting that the electron locality on each band was strong and the bonding state of the alloy system was covalent, which showed that the corrosion resistance was enhanced after adding mixed RE. It provides a new method for the mechanism of RE-modified aluminum-copper alloys and expands the direction of cast aluminum-copper alloy modification. [ABSTRACT FROM AUTHOR]

The Middle Permian Qixia Formation in the Shuangyushi area, northwestern Sichuan Basin, develops shoal-facies dolomite reservoirs. To pinpoint promising reservoirs in the Qixia Formation, deep thin shoal-facies dolomite reservoirs were predicted using the techniques of pre-stack Kirchhoff-Q compensation for absorption, inverse Q filtering, low-to high-frequency compensation, forward modeling, and facies-controlled seismic meme inversion. The results are obtained in six aspects. First, the dolomite reservoirs mainly exist in the middle and lower parts of the second member of Qixia Formation (Qi2 Member), which coincide with the zones shoal cores are developed. Second, the forward modeling shows that the trough energy at the top and bottom of shoal core increases with increasing shoal-core thickness, and weak peak reflections are associated in the middle of shoal core. Third, five types of seismic waveform are identified through waveform analysis of seismic facies. Type-I and Type-II waveforms correspond to promising facies (shoal core microfacies). Fourth, vertically, two packages of thin dolomite reservoirs turn up in the sedimentary cycle of intraplatform shoal in the Qi2 Member, and the lower package is superior to the upper package in dolomite thickness, scale and lateral connectivity. Fifth, in plane, significantly controlled by sedimentary facies, dolomite reservoirs laterally distribute with consistent thickness in shoal cores at topographical highs and extend toward the break. Sixth, the promising prospects are the zones with thick dolomite reservoirs and superimposition of horstegraben structural traps. [ABSTRACT FROM AUTHOR]

High quality is an important goal of wheat breeding. Several superstrong gluten wheat varieties, e.g. 'Xinmai 26' and 'Xinmai 45', have been bred to meet the needs of the consumer market. However, the genetic composition, transmission frequency, and genetic contribution of these varieties and their progeny are not clear. To analyse the genetic composition of the high-quality strong gluten wheat varieties 'Xinmai 26' and 'Xinmai 45', the genetic contribution rates of parents to the varieties were determined using 6056 single nucleotide polymorphism (SNP) markers detected by a widely used high-throughput wheat array (15 K chip). Additionally, the chromosome polymorphisms of five related wheat varieties were determined by fluorescence in situ hybridization (FISH) using four oligonucleotide probe sets. The results showed that the genetic contribution rate of 'Jinan 17' to 'Xinmai 26' was 55.97%, much higher than that (15.81%) of 'Xinmai 18'. 'Jimai 20' showed a genetic contribution rate of 57.53% to 'Xinmai 45', slightly higher than that of 'Xinmai 26' (40.21%). The specific fragment differences between male and female parents were identified in both breeding varieties, and 'Xinmai 26' had more specific fragments that differed from those of the male and female parents than 'Xinmai 45'. The chromosomes of group A and group B of the five varieties were significantly polymorphic, but no chromosomal translocations or inversions were found. These promising results will allow exploration of the genetic pattern of high-quality varieties, promote breeding efficiency, and facilitate the utilisation of the superior traits of backbone parents for wheat quality improvement. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a motor disorder resulting from dopaminergic neuron degeneration in the substantia nigra caused by age, genetics, and environment. The disease severely impacts a patient’s quality of life and can even be life-threatening. The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel is a member of the HCN1-4 gene family and is widely expressed in basal ganglia nuclei. The hyperpolarization-activated current mediated by the HCN channel has a distinct impact on neuronal excitability and rhythmic activity associated with PD pathogenesis, as it affects the firing activity, including both firing rate and firing pattern, of neurons in the basal ganglia nuclei. This review aims to comprehensively understand the characteristics of HCN channels by summarizing their regulatory role in neuronal firing activity of the basal ganglia nuclei. Furthermore, the distribution and characteristics of HCN channels in each nucleus of the basal ganglia group and their effect on PD symptoms through modulating neuronal electrical activity are discussed. Since the roles of the substantia nigra pars compacta and reticulata, as well as globus pallidus externus and internus, are distinct in the basal ganglia circuit, they are individually described. Lastly, this investigation briefly highlights that the HCN channel expressed on microglia plays a role in the pathological process of PD by affecting the neuroinflammatory response. [ABSTRACT FROM AUTHOR]

Background: A recent Mendelian randomization (MR) did not support an effect of the lead interleukin-6 receptor (IL-6 R) variant on risk of pulmonary arterial hypertension (PAH). Thus, we used two sets of genetic instrumental variants (IVs) and publicly available PAH genome-wide association studies (GWAS) to reassess the genetic causal link between IL-6 signaling and PAH. Methods: Six independent IL-6 signaling and 34 independent soluble IL-6 receptor (sIL-6 R) genetic IVs from recent MR reports and PAH GWAS including 162,962 European individuals were used to perform this two-sample MR study. Results: We found that as IL-6 signaling genetically increased, the risk of PAH reduced using IVW (odds ratio [OR] = 0.023, 95% confidence interval [CI]: 0.0013-0.393; p = .0093) and weighted median (OR = 0.033, 95% CI: 0.0024-0.467; p = .0116). Otherwise, as sIL-6 R genetically increased, the risk of PAH increased using IVW (OR = 1.34, 95% CI: 1.16-1.56; p = .0001), weighted median (OR = 1.36, 95% CI: 1.10-1.68; p = .005), MR-Egger (OR = 1.43, 95% CI: 1.05-1.94; p = .03), and weighted mode (OR = 1.35, 95% CI for OR: 1.12-1.63; p = .0035). Conclusion: Our analysis suggested the causal link between genetically increased sIL-6 R and increased risk of PAH and between genetically increased IL-6 signaling and reduced risk of PAH. Thus, higher sIL-6 R levels may be a risk factor for patients with PAH, whereas higher IL-6 signaling may be a protective factor for patients with PAH. [ABSTRACT FROM AUTHOR]

In this paper, we study gradient estimates for eigenfunctions associated to the operator £ on self-shrinkers. As applications, we obtain a Harnack type inequality concerning those eigenfunctions. Besides, we obtain a gradient estimate of the higher eigenfunctions of the operator £ on self-shrinkers. [ABSTRACT FROM AUTHOR]

NUS1 is responsible for encoding of the Nogo-B receptor (NgBR), which is a subunit of cis-prenyltransferase. Over 25 variants in NUS1 have been reported, and these variants have been found to be associated with various phenotypes, such as congenital disorders of glycosylation (CDG) and developmental and epileptic encephalopathy (DEE). We report on the case of a patient who presented with language and motor retardation, epilepsy, and electroencephalogram abnormalities. Upon conducting whole-exome sequencing, we discovered a novel pathogenic variant (chr6:118024873, NM_ 138459.5: c.791 + 6T>G) in NUS1, which was shown to cause Exon 4 to be skipped, resulting in a loss of 56 amino acids. Our findings strongly suggest that this novel variant of NUS1 is responsible for the development of neurological disorders, including epilepsy. It is believed that the truncation of Nogo-B receptor results in the loss of cis-prenyltransferase activity, which may be the underlying cause of the disease. [ABSTRACT FROM AUTHOR]

To further improve the mechanical properties of carbon nanotubes (CNTs) modified aluminum alloy (ZL105), the first principle was used to build the atomic structure of the alloy system and the alloy system was simulated by the VASP. After that, the heat treatment process of the cast aluminium alloy material with CNTs to enhance the alloy performance by the orthogonal experiment. The results of the research show that: (1) The energy status of the alloy system could be changed by adding the C atoms, but it did not affect the formation and structural stability of the alloy system, and the strong bond compounds formed by C atoms with other elements inside the solid solution structure can significantly affect the material properties. (2) The time of solid solution has the greatest influence on the performance of material that was modified by CNTs. The solution temperature and aging temperature were lower strength affection, and the aging time is the lowest affection. This paper provides a new research method of combining the atomic simulation with the casting experiment, which can provide the theoretical calculations to reduce the experiment times for the casting materials’ performance improvement. [ABSTRACT FROM AUTHOR]

Background and Purpose: Parvalbumin (PV)‐positive neurons are a type of neuron in the lateral globus pallidus (LGP) which plays an important role in motor control. The present study investigated the effect of histamine on LGPPV neurons and motor behaviour. Experimental Approach: Histamine levels in LGP as well as its histaminergic innervation were determined through brain stimulation, microdialysis, anterograde tracing and immunostaining. Mechanisms of histamine action were detected by immunostaining, single‐cell qPCR, whole‐cell patch‐clamp recording, optogenetic stimulation and CRISPR/Cas9 gene‐editing techniques. The effect of histamine on motor behaviour was detected by animal behavioural tests. Key Results: A direct histaminergic innervation in LGP from the tuberomammillary nucleus (TMN) and a histamine‐induced increase in the intrinsic excitability of LGPPV neurons were determined by pharmacological blockade or by genetic knockout of the histamine H1 receptor (H1R)‐coupled TWIK‐related potassium channel‐1 (TREK‐1) and the small‐conductance calcium‐activated potassium channel (SK3), as well as by activation or overexpression of the histamine H2 receptor (H2R)‐coupled hyperpolarization‐activated cyclic nucleotide‐gated channel (HCN2). Histamine negatively regulated the STN → LGPGlu transmission in LGPPV neurons via the histamine H3 receptor (H3R), whereas blockage or knockout of H3R increased the intrinsic excitability of LGPPV neurons. Conclusions and Implications: Our results indicated that the endogenous histaminergic innervation in the LGP can bidirectionally promote motor control by increasing the intrinsic excitability of LGPPV neurons through postsynaptic H1R and H2R, albeit its action was negatively regulated by the presynaptic H3R, thereby suggesting possible role of histamine in motor deficits manifested in Parkinson's disease (PD). [ABSTRACT FROM AUTHOR]

Background: Nonsuicidal self-injury (NSSI) is a common mental health threat in adolescents, peaking in adolescence with a lifetime prevalence of ~17%-60%, making it a high-risk risk factor for suicide. In this study, we compared changes in microstate parameters in depressed adolescents with NSSI, depressed adolescents, and healthy adolescents during exposure to negative emotional stimuli, and further explored the improvement of clinical symptoms and the effect of microstate parameters of repetitive transcranial magnetic stimulation (rTMS) in depressed adolescents with NSSI, and more evidence was provided for potential mechanisms and treatment optimization for the occurrence of NSSI behaviors in adolescents. Methods: Sixty-six patients with major depressive disorder (MDD) exhibiting NSSI behavior (MDD + NSSI group), 52 patients with MDD (MDD group), and 20 healthy subjects (HC group) were recruited to perform neutral and negative emotional stimulation task. The age range of all subjects was 12-17 years. All participants completed the Hamilton Depression Scale, the Patient Health Questionnaire-9, the Ottawa Self-Injury Scale and a self-administered questionnaire to collect demographic information. We provided two different treatments to 66 MDD adolescents with NSSI; 31 patients received medication and completed posttreatment scale assessments and EEG acquisitions, and 21 patients received medication combined with rTMS and completed post-treatment scale assessments and EEG acquisitions. Multichannel EEG was recorded continuously from 64 scalp electrodes using the Curry 8 system. EEG signal preprocessing and analysis was performed offline, using the EEGLAB toolbox in MATLAB. Use the Microstate Analysis Toolbox in EEGLAB for segmentation and computation of microstates, and calculate a topographic map of the microstate segmentation of the EEG signal for a single subject in each dataset, and four parameters were obtained for each microstate classification: global explained variance (GEV), mean duration (Duration), average number of occurrences per second (Occurrence), and average percentage of total analysis time occupied (Coverage), which were then statistically analyzed. Results: Our results indicate that MDD adolescents with NSSI exhibit abnormalities in MS 3, MS 4, and MS 6 parameters when exposed to negative emotional stimuli compared to MDD adolescents and healthy adolescents. The results also showed that medication combined with rTMS treatment improved depressive symptoms and NSSI performance more significantly in MDD adolescents with NSSI compared to medication treatment, and affected MS 1, MS 2, and MS 4 parameters in MDD adolescents with NSSI, providing microstate evidence for the moderating effect of rTMS. Conclusion: MDD adolescents with NSSI showed abnormal changes in several microstate parameters when receiving negative emotional stimuli, and compared to those not receiving rTMS treatment, MDD adolescents with NSSI treated with rTMS showed more significant improvements in depressive symptoms and NSSI performance, as well as improvements in EEG microstate abnormalities. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) has now spread to most countries and regions of the world. Risk factors associated with multi-drug resistant organism (MDRO) infections in patients with COVID-19 have not been well studied yet. In the present study, we aimed to identify the risk factors associated with the MDRO infections and their impact on in-hospital mortality of COVID-19 patients. Methods: This retrospective cohort study was conducted between December 2019 and April 2020 at two tertiary hospitals in Wuhan, China. Data of cases were collected through electronic medical records system. This study was focused on cases with bacterial culture records. Risk factors and outcomes associated with MDRO infections were analyzed using logistic regression model. Results: Of the 2891 patients, 370 patients have bacterial culture results, and MDROs were isolated in 38 patients. Respiratory tract infections (67.3%) were the most common hospital acquired infections. Variables independently associated with MDRO infections were dyspnea at admission (odds ratio (OR) 4.74; 95% confidence interval (CI) 2.06-10.88; P < 0.001), intensive care unit (ICU) admission (OR 5.02; 95% CI 1.99-12.63; P < 0.01), and invasive mechanical ventilation (OR 5.13; 95% CI 2.15-12.27; P < 0.001), adjusted for age and gender. MDROs infection was also a significant risk factor of death for the patients, adjusted for age, gender, severity of illness, ICU admission and mechanical ventilation (OR 1.12, 95% CI: 0.43-2.96, P = 0.817). Conclusion: In our study, dyspnea at admission, ICU admission and invasive mechanical ventilation were associated with the presence of MDRO infections, and clinicians should be alert in MDRO infections in COVID-19 hospitalized patients. [ABSTRACT FROM AUTHOR]

To prepare a high-quality asymmetrical bending pipe of aluminum alloy by casting, the parting surfaces of the asymmetrical parts were determined based on the characteristics of the parts. Also, the forming process was designed and calculated. After that, the different types of gating systems were designed and the casting process was calculated by ProCAST, and then the influence of different casting gating systems on asymmetrical bending pipes was analyzed. The simulation results show that in the solidification process, although the filling speed of the single runner was slow, but the filling was stable. The gating system with a single runner-round flange filling system would lead to being more uniform for filling flow field and be sequential solidification of temperature field distribution, and stronger of the feeding ability. During the solidification process, the solid phase ratio of the single runner-round flange casting system is larger, and the shrinkage volume is smaller, which made the quality of castings better. Finally, a metal mold and core were made to cast a perfect asymmetric bending pipe of aluminum alloy product in a die casting machine. So the single runner-round flange filling system is suitable for asymmetrical bending pipe casting. [ABSTRACT FROM AUTHOR]

The dorsolateral striatum (DLS) is the critical neural substrate that plays a role in motor control and motor learning. Our past study revealed a direct histaminergic projection from the tuberomammillary nucleus (TMN) of the hypothalamus to the rat striatum. However, the afferent of histaminergic fibers in the mouse DLS, the effect of histamine on DLS neurons, and the underlying receptor and ionic mechanisms remain unclear. Here, we demonstrated a direct histaminergic innervation from the TMN in the mouse DLS, and histamine excited both the direct-pathway spiny projection neurons (d-SPNs) and the indirect-pathway spiny projection neurons (i-SPNs) of DLS via activation of postsynaptic H1R and H2R, albeit activation of presynaptic H3R suppressed neuronal activity by inhibiting glutamatergic synaptic transmission on d-SPNs and i-SPNs in DLS. Moreover, sodium-calcium exchanger 3 (NCX3), potassium-leak channels linked to H1R, and hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) coupled to H2R co-mediated the excitatory effect induced by histamine on d-SPNs and i-SPNs in DLS. These results demonstrated the pre- and postsynaptic receptors and their downstream multiple ionic mechanisms underlying the inhibitory and excitatory effects of histamine on d-SPNs and i-SPNs in DLS, suggesting a potential modulatory effect of the central histaminergic system on the DLS as well as its related motor control and motor learning. [ABSTRACT FROM AUTHOR]

Major advances have been made over the past few decades in identifying and managing disorders of consciousness (DOC) in patients with acquired brain injury (ABI), bringing the transformation from a conceptualized definition to a complex clinical scenario worthy of scientific exploration. Given the continuously-evolving framework of precision medicine that integrates valuable behavioral assessment tools, sophisticated neuroimaging, and electrophysiological techniques, a considerably higher diagnostic accuracy rate of DOC may now be reached. During the treatment of patients with DOC, a variety of intervention methods are available, including amantadine and transcranial direct current stimulation, which have both provided class II evidence, zolpidem, which is also of high quality, and non-invasive stimulation, which appears to be more encouraging than pharmacological therapy. However, heterogeneity is profoundly ingrained in study designs, and only rare schemes have been recommended by authoritative institutions. There is still a lack of an effective clinical protocol for managing patients with DOC following ABI. To advance future clinical studies on DOC, we present a comprehensive review of the progress in clinical identification and management as well as some challenges in the pathophysiology of DOC. We propose a preliminary clinical decision protocol, which could serve as an ideal reference tool for many medical institutions. [ABSTRACT FROM AUTHOR]

Virus-related diseases are seriously threatening human health, but there are currently only 10 viruses with clinically approved antiviral drugs available. As non-cellular organisms, viruses parasitize in living cells and rely on the protein synthesis mechanism of the host cells. In this study, we found that the antipsychotic drug trifluoperazine (TFP), a dual dopamine receptor D2 (DRD2)/calmodulin (CALM) antagonist, increases the phosphorylation of eukaryotic initiation factor 2α (eIF2α), a key factor in the regulation of protein synthesis and significantly inhibits vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1) replication. CALM but not DRD2 is involved in the antiviral activity of TFP. By knockdown of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) we found that the antiviral function of TFP is dependent on PERK, a stress response kinase that mediates eIF2α phosphorylation. Furthermore, the results of animal experiments showed that TFP protects mice from lethal VSV attacks, improving the survival rate and reducing lung injury. Taken together, these data suggests that TFP inhibits virus replication through PERK-eIF2α axis, and this broad-spectrum of mechanisms are worth further evaluation in clinical trials in the future. [ABSTRACT FROM AUTHOR]

Xanthomonas campestris pv. campestris (Xcc) is a vascular bacteria pathogen causing black rot in cabbage. Here, the resistance mechanisms of cabbage against Xcc infection were explored by integrated metabolome and transcriptome analysis. Pathogen perception, hormone metabolisms, sugar metabolisms, and phenylpropanoid metabolisms in cabbage were systemically re-programmed at both transcriptional and metabolic levels after Xcc infection. Notably, the salicylic acid (SA) metabolism pathway was highly enriched in resistant lines following Xcc infection, indicating that the SA metabolism pathway may positively regulate the resistance of Xcc. Moreover, we also validated our hypothesis by showing that the flavonoid pathway metabolites chlorogenic acid and caffeic acid could effectively inhibit the growth of Xcc. These findings provide valuable insights and resource datasets for further exploring Xcc–cabbage interactions and help uncover molecular breeding targets for black rot-resistant varieties in cabbage. [ABSTRACT FROM AUTHOR]

Effectively evaluating therapeutic efficacy, detecting minimal residual disease (MRD) after therapy completion, and predicting early occurrence of malignancy in cancer patients remain as unmet imperative clinical demands. This article presents a case of a laryngeal carcinoma patient who had a surgical resection and complete post-operative chemoradiotherapy in combination with the targeted therapy, then rapidly developed pancreatic adenocarcinoma. Detected by SE-iFISH, the patient had a substantial amount of 107 nonhematological aneuploid circulating rare cells including 14 circulating tumor cells (CTCs, CD31-/CD45-) and 93 circulating tumor endothelial cells (CTECs, CD31+/CD45-) with a high ratio of CTECs/CTCs > 5 upon finishing postsurgical combination regimens. Positive detection of those aneuploid nonhematological circulating rare cells was five months prior to subsequent plasma CA19-9 increasing and ten months before the de novo pancreatic cancer was diagnosed by medical imaging modalities. Besides previously reported clinical utilities of co-detection of aneuploid CD31-CTCs and CD31+ CTECs in real-time evaluation of therapeutic efficacy, longitudinal monitoring of emerging treatment resistance and adequate detection of MRD, a large cohort study is necessary to further investigate whether, and how, a high ratio of MRD CTECs to CTCs may function as an appropriate index forecasting either occurrence or metastatic distant recurrence of malignancy in post-therapeutic cancer patients. [ABSTRACT FROM AUTHOR]

Introduction: Nonspecific low back pain (LBP) is an idiopathic musculoskeletal condition that affects four of five individuals in their lifetime and is the leading cause of job-related disability in the United States. The interest in interactive and dynamic telehealth treatments for LBP continues to grow, and it is important for the medical community to remain up-to-date on the state of the science. Literature survey: Relevant studies published from March 2016 until March 2021 were identified through a systematic search of EMBASE, MedLine, and Web of Science. The search strategy combined the concepts of back pain, telehealth, and mobile applications. Methodology: Titles and abstracts were screened to select full-text randomized controlled trials or protocols, and methodological quality and risk of bias was assessed using the Cochrane risk-of-bias tool. Data were synthesized narratively. Synthesis: We included seven concluded randomized-controlled trials and two study protocols reporting mobile health (mHealth) solutions for LBP. Six of the seven concluded trials found a significant improvement in self-reported numerical pain rating scale compared to the control group. A single trial compared a mHealth solution to physical therapy, with the majority of studies comparing interventions to "usual care." Substantial heterogeneity in reporting of sample characteristics was found, indicating a lack of standardization through the field. Conclusions: mHealth solutions may positively impact people with LBP. Larger trials should be encouraged and the field should coalesce around a set of baseline variables for collection and reporting. Because many interventions involve patient engagement, future trials should aim to further quantify adherence levels and begin to define telehealth "doses" associated with better outcomes. [ABSTRACT FROM AUTHOR]

Damage-associated molecular patterns secreted from activated kidney cells initiate the inflammatory response, a critical step in the development of sepsis-induced acute kidney injury (AKI). However, the underlying mechanism remains to be clarified. Here, we established a mouse model of sepsis-induced AKI through intraperitoneal injection of lipopolysaccharide (LPS) and demonstrated that LPS induced dramatical upregulation of C-C motif chemokine ligand 2 (CCL2) at both the mRNA and protein levels in the kidney, which was mainly expressed by tubular epithelial cells (TECs), especially by proximal TECs. Proximal tubule-specific ablation of CCL2 reduced LPS-induced macrophage infiltration, proinflammatory cytokine expression, and attenuated AKI. In vitro, using a Transwell migration assay, we found that deficiency of CCL2 in TECs decreased macrophage migration ability. However, myeloid-specific depletion of CCL2 could not protect the kidneys from the aforementioned effects. Mechanistically, LPS activated Toll-like receptor (TLR)2 signaling in TECs, which induced activation of its downstream effector NF-κB. Blockade of TLR2 signaling or inhibition of NF-κB activation in TECs significantly suppressed LPS-induced CCL2 expression. Furthermore, chromatin immunoprecipitation analyses confirmed a direct binding of NF-κB p65 in the CCL2 promoter region, and LPS increased the binding of NF-κB p65 to the CCL2 promoter, suggesting that TLR2/NF-κB p65 regulates CCL2 expression in TECs. Together, these results demonstrate that endogenous CCL2 released from proximal TECs, not from myeloid cells, was responsible for sepsis-induced kidney inflammation and AKI. Specifically targeting tubular TLR2/NF-κB/CCL2 signaling may be a potential therapeutic strategy for the prevention or attenuation of septic AKI. [ABSTRACT FROM AUTHOR]

Enterprise Network (EN) has increasingly gained popularity in academia. Over the past few decades, a substantial amount of EN studies have been published in China. Drawing upon a sample of 603 papers retrieved from the Chinese Social Sciences Citation Index database (CSSCI) between 1998 and 2020, this study aims to delve into the status quo, knowledge base, research focus, and evolutionary trends of EN research in China. A multifaceted bibliometric analysis was performed using CiteSpace. The findings mainly indicate that the research on EN in China has a clear development context, and the research content gradually changes from macro to micro. In addition to foreign Social Network theories, the research results of domestic scholars have become the basic knowledge in this field. The research includes these topics: the conceptualization of EN, EN as indicators of enterprise development, EN's impact on start-ups, mechanisms of EN's effect and governance of EN. The potential direction for future research has been identified as the integration between EN and other forms of networks, and the structure of EN. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is associated with high mortality and disability, with a substantial socioeconomic burden. With the standardization of the treatment process, there is increasing interest in the role that the secondary insult of TBI plays in outcome heterogeneity. The secondary insult is neither detrimental nor beneficial in an absolute sense, among which the inflammatory response was a complex cascade of events and can thus be regarded as a double-edged sword. Therefore, clinicians should take the generation and balance of neuroinflammation following TBI seriously. In this review, we summarize the current human and animal model studies of neuroinflammation and provide a better understanding of the inflammatory response in the different stages of TBI. In particular, advances in neuroinflammation using proteomic and transcriptomic techniques have enabled us to identify a functional specific delineation of the immune cell in TBI patients. Based on recent advances in our understanding of immune cell activation, we present the difference between diffuse axonal injury and focal brain injury. In addition, we give a figurative profiling of the general paradigm in the pre- and post-injury inflammatory settings employing a bow-tie framework. [ABSTRACT FROM AUTHOR]

Carbon nanotubes (CNTs) are a good reinforcement for metal matrix composite materials; they can significantly improve the mechanical, wear-resistant, and heat-resistant properties of the materials. Due to the differences in the atomic structure and surface energy between CNTs and aluminum-based materials, the bonding interface effect that occurs when nanoscale CNTs are added to the aluminum alloy system as a reinforcement becomes more pronounced, and the bonding interface is important for the material mechanical performance. Firstly, a comparative analysis of the interface connection methods of four CNT-reinforced aluminum matrix composites is provided, and the combination mechanisms of various interface connection methods are explained. Secondly, the influence of several factors, including the preparation method and process as well as the state of the material, on the material bonding interface during the composite preparation process is analyzed. Furthermore, it is explained how the state of the bonding interface can be optimized by adopting appropriate technical and technological means. Through the study of the interface of CNT-reinforced aluminum-based composite materials, the influence of the interface on the overall performance of the composite material is determined, which provides directions and ideas for the preparation of future high-performance CNT-reinforced aluminum-based composite materials. [ABSTRACT FROM AUTHOR]

Despite high charge capacity, iridium oxide (IrOx) coating is susceptible to delamination under prolonged stimulation, restricting its long-term application. Here, a flower-shaped platinum (Pt) nanocrystal with intensive high-surface area is developed as an intermediate layer for accumulating IrOx (<3 wt% Ir) with enhanced adhesion, showing a multiplier effect. The impedance of IrOx/Pt flower coated microelectrode at 1 kHz is down to ≈2 kΩ (reduction of 94.23%). The corresponding cathodic charge storage capacity (CSCc) and charge injection capacity (CIC) are increased up to 202.75 ± 2.18 and 6.53 ± 0.16 mC cm-2, respectively. IrOx layer adheres tightly to Pt nanocrystals, demonstrating robust chronic stability under continuous electrostimulation for 1 x 108 cycles. Besides, the as-prepared coatings show good biosafety, and exhibit promising electrocatalytic activity toward oxygen evolution reaction (OER) in 0.5 m sulfuric acid (H2SO4), requiring a low overpotential of ≈150 mV to reach 10 mA cm-2. IrOx helps in reducing the Tafel slope of Pt flower from 162.9 to 41.1 mV dec-1 drastically, also with excellent durability after chronoamperometry test. Excellent antibacterial properties toward Escherichia coli are also observed. This coating strategy provides a functionalized flexible electrode for neural interface, water oxidation, and anti-microbial contamination, which will moreover extend to numerous applications. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global pandemic of the Coronavirus disease in late 2019 (COVID-19). Vaccine development efforts have predominantly been aimed at 'Extra-viral' Spike (S) protein as vaccine vehicles, but there are concerns regarding ‘viral immune escape’ since multiple mutations may enable the mutated virus strains to escape from immunity against S protein. The ‘Intra-viral’ Nucleocapsid (N-protein) is relatively conserved among mutant strains of coronaviruses during spread and evolution. Herein, we demonstrate novel vaccine candidates against SARS-CoV-2 by using the whole conserved N-protein or its fragment/peptides. Using ELISA assay, we showed that high titers of specific anti-N antibodies (IgG, IgG1, IgG2a, IgM) were maintained for a reasonably long duration (> 5 months), suggesting that N-protein is an excellent immunogen to stimulate host immune system and robust B-cell activation. We synthesized three peptides located at the conserved regions of N-protein among CoVs. One peptide showed as a good immunogen for vaccination as well. Cytokine arrays on post-vaccination mouse sera showed progressive up-regulation of various cytokines such as IFN-γ and CCL5, suggesting that TH1 associated responses are also stimulated. Furthermore, vaccinated mice exhibited an elevated memory T cells population. Here, we propose an unconventional vaccine strategy targeting the conserved N-protein as an alternative vaccine target for coronaviruses. Moreover, we generated a mouse monoclonal antibody specifically against an epitope shared between SARS-CoV and SARS-CoV-2, and we are currently developing the First-in-Class humanized anti-N-protein antibody to potentially treat patients infected by various CoVs in the future. [ABSTRACT FROM AUTHOR]

To deal with the invalidation of commonly employed series model and parallel model in capacitance–voltage (C–V) characterization of organic thin films when current injection is significant, a three-element equivalent circuit model is proposed. On this basis, the expression of real capacitance in consideration of current injection is theoretically derived by small-signal analysis method. The validity of the proposed equivalent circuit and theoretical expression are verified by a simulating circuit consisting of a capacitor, a diode, and a resistor. Moreover, the accurate C–V characteristic of an organic thin film device is obtained via theoretical correction of the experimental measuring result, and the real capacitance is 35.7% higher than the directly measured capacitance at 5-V bias in the parallel mode. This work strongly demonstrates the necessity to consider current injection in C–V measurement and provides a strategy for accurate C–V characterization experimentally. [ABSTRACT FROM AUTHOR]

Tumor-derived circulating tumor DNA (ctDNA) has demonstrated its excellent potential for cancer diagnosis by DNA methylome; therefore, this study aimed to identify the retinoblastoma (RB) specific methylated CpG loci as the RB diagnostic biomarkers and design a methylation specific assay to detect these biomarker from aqueous humor of RB patients. Through a genome-wide methylation profiling of tissue samples from patients with RB, normal retina and other retinal diseases, we shortlisted two CpG loci were only methylated in RB but not in normal retina or other retinal diseases. Both of these two CpG loci were located in the genome of TFAP2A. Through the screening, a primer and probe set for the twoCpGloci were tested in fully methylated standards and RB tissues with a significant differentiation of RB. Our results of this assay tested in aqueous humor from RB revealed an accuracy of 92.7% for RB diagnosis. These results suggested our assay targeting the TFAP2A ctDNA methylation can be utilized for RB diagnosis and cancer monitoring. [ABSTRACT FROM AUTHOR]

A new ocotillol-type ginsenoside, namely 12-one-pseudoginsenoside F11 (12-one-PF11), was isolated from stems and leaves of Panax quinquefolium, whose structure was elucidated 6-O-[α-L-rhamnopyranosyl-(1-2)-β-D-glucopyranosyl]-dammar-12-one-20S,24R-epoxy-3β,6α,25-triol. 12-one-PF11 significantly suppressed hydrogen peroxide induced oxidative stress in human lung carcinoma A549 cells. As compared with model group, 12-one-PF11 improved cell viability of A549 cells in a dose-dependent manner, and significantly decreased the generation of malondialdehyde (MDA) and increased production of superoxide dismutase (SOD) and glutathione (GSH) and protein expression levels of nuclear related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in A549 cells. [ABSTRACT FROM AUTHOR]

To solve the cooling problems of power battery with variable discharging conditions, a hybrid thermal management system combined with phase change materials (PCM) and cooling plate is designed. Moreover, the ANSYS FLUENT is adopted to simulate the three-dimensional model. As a result, the effects of water flow direction and variable discharging conditions are discussed on the maximum temperature and maximum temperature difference inside the battery as well as the liquid fraction of PCM. The numerical results indicate that the maximum temperature is governed by the physical parameters of PCM, whereas the water flow direction in the cooling plate plays a dominant role on the maximum temperature difference. Moreover, the flow direction scheme of case 5 is benefit to reduce the maximum temperature and temperature difference simultaneously. Although the cooling performance of hybrid thermal management system can be deteriorated by increasing the pulse duration and heat flux, the melting of PCM dramatically suppresses the increase in maximum temperature and temperature difference. Considering the limited quality of PCM, enhancing the thermal conductivity of PCM and employing cooling scheme with staggered flow direction are recommendable ways to extend the applicability of the hybrid thermal management system for power battery with complex discharging conditions. [ABSTRACT FROM AUTHOR]

In order to identify the influence of different Mn, Cd, V and Zr content on the properties of Al-Cu casting alloys in hydraulic valves, orthogonal test methods were used to prepare alloy test bars with different elements and contents. Tensile tests were performed on the test bars so obtained. The microstructure of alloys with different compositions is studied. The results show that adding approximately 0.4% of Mn can not only form a strengthening phase but also reduce the excessive segregation of the matrix along the grain boundary. A Cd content of 0.2% can promote the formation of micro Cd spheres in the softer aluminum matrix. Hard spots increase the wear resistance of the material; however, an excess of Cd will cause element segregation and deteriorate the mechanical properties of the valve body. Zr and V refine the grains in the alloy; however, an excess of these elements will lead to a large area of segregation. If proper heat treatment is lacking, the mechanical properties of the valve body deteriorate. [ABSTRACT FROM AUTHOR]