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Introduction: Precise fault diagnosis is crucial for enhancing the reliability and lifespan of the flexible converter valve equipment. To address this issue, depthwise separable convolution, bidirectional gate recurrent unit, and multi-head attention module (DSC-BiGRU-MAM) based fault diagnosis approach is proposed.Methods: By DSC and BiGRU operation, the model can capture the correlation between local features and temporal information when processing sequence data, thereby enhancing the representation ability and predictive performance of the model for complex sequential data. In addition, by incorporating a multi-head attention module, the proposed method dynamically learns important information from different time intervals and channels. The proposed MAM continuously stimulates fault features in both time and channel dimensions during training, while suppressing fault independent expressions. As a result, it has made an important contribution to improving the performance of the fault diagnosis model.Results and Discussion: Experimental results demonstrate that the proposed method achieves higher accuracy compared to existing methods, with an average accuracy of 95.45%, average precision of 88.67%, and average recall of 89.03%. Additionally, the proposed method has a moderate number of model parameters (17,626) and training time (935 s). Results indicate that the proposed method accurately diagnoses faults in flexible converter valve equipment, especially in real-world situations with noise overlapping signals.

Soil nitrogen (N) availability is one of the limiting factors of crop productivity, and it is strongly influenced by global change and agricultural management practices. However, very few studies have assessed how the winter drought affected soil N availability during the subsequent growing season under chemical fertilization. We conducted a field investigation involving snow removal to simulate winter drought conditions in a Mollisol cropland in Northeast China as part of a 6-year fertilization experiment, and we examined soil physicochemical properties, microbial characteristics, and N availability. Our results demonstrated that chemical fertilization significantly increased soil ammonium and total N availability by 42.9 and 90.3%, respectively; a combined winter drought and fertilization treatment exhibited the highest soil N availability at the end of the growing season. As the growing season continued, the variation in soil N availability was explained more by fertilization than by winter drought. The Mantel test further indicated that soil Olsen-P content and microbial carbon use efficiency (CUE) were significantly related to soil ammonium availability. A microbial community structure explained the largest fraction of the variation in soil nitrate availability. Microbial CUE showed the strongest correlation with soil N availability, followed by soil available C:P and bacteria:fungi ratios under winter drought and chemical fertilization conditions. Overall, we clarified that, despite the weak effect of the winter drought on soil N availability, it cannot be ignored. Our study also identified the important role of soil microorganisms in soil N transformations, even in seasonally snow-covered northern croplands.

Exosomes, vesicular structures originating from cells, participate in the conveyance of proteins and nucleic acids. Presently, the centrality of epigenetic modifications in neurological disorders is widely acknowledged. Exosomes exert influence over various epigenetic phenomena, thereby modulating post-transcriptional regulatory processes contingent upon their constituent makeup. Consequently, the heightened attention directed toward exosomes as instigators of epigenetic alterations has burgeoned in recent years. Notably, exosomes serve as vehicles for delivering methyltransferases to recipient cells. More significantly, non-coding RNAs, particularly microRNAs (miRNAs), represent pivotal contents within exosomes, wielding the capacity to influence the expression of diverse factors within the cerebral milieu. The transfer of these exosomal contents amidst brain cells, encompassing neuronal cells and microglia, assumes a critical role in the genesis and progression of neurological disorders, also, this role is not limited to neurological disorders, it may deal with any human disease, such as cancer, and cardiovascular diseases. This review will concentrate on elucidating the regulation of exosome-induced epigenetic events and its subsequent ramifications for neurological diseases. A more profound comprehension of the involvement of exosome-mediated epigenetic regulation in neurological disorders contributes to a heightened awareness of the etiology and advancement of cerebral afflictions.

IntroductionWe have demonstrated that transposons derived from ctDNA can be transferred between cancer cells. The present research aimed to investigate the cellular uptake and intracellular trafficking of Multiple Myeloma-zip code (MM-ZC), a cell-specific zip code, in myeloma cell lines. We demonstrated that MM-ZC uptake by myeloma cells was concentration-, time- and cell-type-dependent.MethodsFlow cytometry and confocal microscopy methods were used to identify the level of internalization of the zip codes in MM cells. To screen for the mechanism of internalization, we used multiple inhibitors of endocytosis. These experiments were followed by biotin pulldown and confocal microscopy for validation. Single interference RNA (siRNA) targeting some of the proteins involved in endocytosis was used to validate the role of this pathway in ZC cell internalization.ResultsEndocytosis inhibitors identified that Monensin and Chlorpromazine hydrochloride significantly reduced MM-ZC internalization. These findings suggested that Clathrin-mediated endocytosis and endosomal maturation play a crucial role in the cellular uptake of MM-ZC. Biotin pulldown and confocal microscopic studies revealed the involvement of proteins such as Clathrin, Rab5a, Syntaxin-6, and RCAS1 in facilitating the internalization of MM-ZC. Knockdown of Rab5a and Clathrin proteins reduced cellular uptake of MM-ZC and conclusively demonstrated the involvement of Clathrin-Rab5a pathways in MM-ZC endocytosis. Furthermore, both Rab5a and Clathrin reciprocally affected their association with MM-ZC when we depleted their proteins by siRNAs. Additionally, the loss of Rab5a decreased the Syntaxin-6 association with MMZC but not vice versa. Conversely, MM-ZC treatment enhanced the association between Clathrin and Rab5a.ConclusionOverall, the current study provides valuable insights into the cellular uptake and intracellular trafficking of MM-ZC in myeloma cells. Identifying these mechanisms and molecular players involved in MM-ZC uptake contributes to a better understanding of the delivery and potential applications of cell-specific Zip-Codes in gene delivery and drug targeting in cancer research.

We investigated the effect of melatonin on bisphenol A (BPA)-induced oxidative stress damage in testicular tissue and Leydig cells. Mice were gavaged with 50 mg/kg BPA for 30 days, and concurrently, were injected with melatonin (10 mg/kg and 20 mg/kg). Leydig cells were treated with 10 μmol/L of BPA and melatonin. The morphology and organ index of the testis and epididymis were observed and calculated. The sperm viability and density were determined. The expressions of melatonin receptor 1A and luteinizing hormone receptor, and the levels of malonaldehyde, antioxidant enzymes, glutathione, steroid hormone synthases, aromatase, luteinizing hormone, testosterone, and estradiol were measured. TUNEL assay was utilized to detect testicular cell apoptosis. The administration of melatonin at 20 mg/kg significantly improved the testicular index and epididymis index in mice treated with BPA. Additionally, melatonin promoted the development of seminiferous tubules in the testes. Furthermore, the treatment with 20 mg/kg melatonin significantly increased sperm viability and sperm density in mice, while also promoting the expressions of melatonin receptor 1A and luteinizing hormone receptor in Leydig cells of BPA-treated mice. Significantly, melatonin reduced the level of malonaldehyde in testicular tissue and increased the expression of antioxidant enzymes (superoxide dismutase 1, superoxide dismutase 2, and catalase) as well as the content of glutathione. Moreover, melatonin also reduced the number of apoptotic Leydig cells and spermatogonia, aromatase expression, and estradiol level, while increasing the expression of steroid hormone synthases (steroidogenic acute regulatory protein, cytochrome P450 family 17a1, cytochrome P450 17α-hydroxylase/20-lyase, and, 17β-hydroxysteroid dehydrogenase) and the level of testosterone. Melatonin exhibited significant potential in alleviating testicular oxidative stress damage caused by BPA. These beneficial effects may be attributed to melatonin’s ability to enhance the antioxidant capacity of testicular tissue, promote testosterone synthesis, and reduce testicular cell apoptosis.

Background: Type 2 diabetes mellitus (T2DM) and inflammatory bowel disease (IBD) have been associated, according to various epidemiological research. This study uses Mendelian randomization (MR) to investigate the causal link between T2DM and IBD.Methods: To investigate the causal relationship between IBD and T2DM risk using European population data from the genome-wide association study (GWAS) summary datasets, we constructed a two-sample MR study to evaluate the genetically predicted impacts of liability towards IBD outcomes on T2DM risk. As instrumental variables (IVs), we chose 26 single nucleotide polymorphisms (SNPs) associated with IBD exposure data. The European T2DM GWAS data was obtained from the IEU OpenGWAS Project database, which contains 298,957 cases as the outcome data. The causal relationship between T2DM and IBD using a reverse MR analysis was also performed.Results: The two-sample MR analysis, with the Bonferroni adjustment for multiple testing, revealed that T2DM risk in Europeans is unaffected by their IBD liability (odds ratio (OR): 0.950–1.066, 95% confidence interval (CI): 0.885–1.019, p = 0.152–0.926). The effects of liability to T2DM on IBD were not supported by the reverse MR analysis either (OR: 0.739–1.131, 95% confidence interval (CI): 0.651–1.100, p = 0.058–0.832). MR analysis of IBS on T2DM also have no significant causal relationship (OR: 0.003–1.007, 95% confidence interval (CI): 1.013–5.791, p = 0.069–0.790). FUMA precisely mapped 22 protein-coding genes utilizing significant SNPs of T2DM acquired from GWAS.Conclusion: The MR study showed that the existing evidence did not support the significant causal effect of IBD on T2DM, nor did it support the causal impact of T2DM on IBD.

BackgroundObstructive sleep apnea-hypopnea syndrome (OSAHS) is a common sleep disorder. The lower atmospheric pressure and decreased oxygen levels of high-altitude areas can exacerbate the severity of OSAHS, but research into OSAHS in high-altitude areas remains limited. This study, from June 2015 to January 2020, involved 4,667 patients with suspected OSAHS and 38 healthy volunteers. The non-OSAHS group (AHI

Background: Metastatic colorectal cancer (mCRC) is a heterogeneous disease, often associated with poor outcomes and resistance to therapies. The racial variations in the molecular and microbiological profiles of mCRC patients, however, remain under-explored.Methods: Using RNA-SEQ data, we extracted and analyzed actively transcribing microbiota within the tumor milieu, ensuring that the identified bacteria were not merely transient inhabitants but engaged in the tumor ecosystem. Also, we independently acquired samples from 12 mCRC patients, specifically, 6 White individuals and 6 of Black or African American descent. These samples underwent 16S rRNA sequencing.Results: Our study revealed notable racial disparities in the molecular signatures and microbiota profiles of mCRC patients. The intersection of these data showcased the potential modulating effects of specific bacteria on gene expression. Particularly, the bacteria Helicobacter cinaedi and Sphingobium herbicidovorans emerged as significant influencers, with strong correlations to the genes SELENBP1 and SNORA38, respectively.Discussion: These findings underscore the intricate interplay between host genomics and actively transcribing tumor microbiota in mCRC’s pathogenesis. The identified correlations between specific bacteria and genes highlight potential avenues for targeted therapies and a more personalized therapeutic approach.

Melatonin (Mel) is an endogenous active molecule whose metabolism progress significantly influences its bioactivity. However, the detailed metabolic pathway of Mel in the pathological state has not yet been fully illustrated. In this study, 16 metabolites of Mel in cancer cells and human liver microsomes were identified, of which seven novel metabolites were newly discovered. Among them, 2-hydroxymelatonin (2-O-Mel), as the major metabolite in cancer cells, was revealed for the first time, which was different from the metabolite found in the human liver. Furthermore, CYP1A1/1A2- and reactive oxygen species (ROS)-mediated 2-hydroxylation reactions of Mel were verified to be the two metabolic pathways in the liver and cancer cells, respectively. ROS-dependent formation of 2-O-Mel was the major pathway in cancer cells. Furthermore, the underlying catalytic mechanism of Mel to 2-O-Mel in the presence of ROS was fully elucidated using computational chemistry analysis. Therefore, the generation of 2-O-Mel from Mel could serve as another index for the endogenous reactive oxygen level. Finally, based on the ROS-dependent production of 2-O-Mel, Mel was successfully used for detecting the oxygen-carrying capacity of hemoglobin in human blood. Our investigation further enriched the metabolic pathway of Mel, especially for the ROS-dependent formation of 2-O-Mel that serves as a diagnostic and therapeutic target for the rational use of Mel in clinics.

This paper addresses the critical need to determine the stable operating limit of modular multilevel converter-based high voltage direct current (MMC-HVDC) systems, particularly concerning the integration of extensive renewable energy sources. To achieve this, the steady-state mathematical model and state-space model of bundled hydropower and photovoltaic integration through MMC-HVDC systems are established. A novel methodology considering steady-state and small-signal stability constraints is proposed to compute the stable operating region of the system. The quantitative assessment reveals that diminishing AC system short-circuit capacities amplify restrictions from small-signal stability constraints, thereby reducing the system's stable operating region. Eigenvalue and participation factor analyses shed light on the pivotal factors affecting small-signal stability in weak AC systems. To expand the system's stable operating region, a supplementary frequency damping control strategy is proposed. The theoretical analysis and calculation results are validated by building a simulation model for the bundled hydropower and photovoltaic integration through MMC-HVDC systems in PSCAD/EMTDC.

Bergenin is a typical carbon glycoside and the primary active ingredient in antitussive drugs widely prescribed for central cough inhibition in China. The bergenin extraction industry relies on the medicinal plant species Bergenia purpurascens and Ardisia japonica as their resources. However, the bergenin biosynthetic pathway in plants remains elusive. In this study, we functionally characterized a shikimate dehydrogenase (SDH), two O-methyltransferases (OMTs), and a C-glycosyltransferase (CGT) involved in bergenin synthesis through bioinformatics analysis, heterologous expression, and enzymatic characterization. We found that BpSDH2 catalyzes the two-step dehydrogenation process of shikimic acid to form gallic acid (GA). BpOMT1 and AjOMT1 facilitate the methylation reaction at the 4-OH position of GA, resulting in the formation of 4-O-methyl gallic acid (4-O-Me-GA). AjCGT1 transfers a glucose moiety to C-2 to generate 2-Glucosyl-4-O-methyl gallic acid (2-Glucosyl-4-O-Me-GA). Bergenin production ultimately occurs in acidic conditions or via dehydration catalyzed by plant dehydratases following a ring-closure reaction. This study for the first time uncovered the biosynthetic pathway of bergenin, paving the way to rational production of bergenin in cell factories via synthetic biology strategies.

Umbilical incision implant cancer after LC is rare. Elective cholecystectomy was planned for a 49 years-old female patient with symptomatic gallstones. The patient underwent transumbilical single-port LC after admission to our hospital. Gallbladder specimens were obtained directly through the umbilical puncture hole, and histopathology suggested chronic cholecystitis. Three months after surgery, the patient experienced painful induration in the umbilicus. We initially considered incision scar hyperplasia complicated with pain, and used drugs to treat it conservatively without taking special treatment measures. Six months after LC, the umbilical induration pain affected her quality of life, and the patient requested surgical resection. Preoperative ultrasonography and abdominal computerized tomography (CT) revealed nodular changes around the umbilicus and no abdominal mass. Local resection of the periumbilical mass was performed, and the pathological confirmation was invasive adenocarcinoma. Subsequently, the patient underwent repeat periumbilical mass enlargement resection. Postoperative pathology showed no cancer at the enlarged resection margin, yet the umbilical center pathology showed invasive adenocarcinoma. The excised pathology was sent to the Sun Yat-sen University Cancer Center for consultation because of the rare nature of the findings associated with the case. After consultation, a diagnosis of umbilical urachus adenocarcinoma was confirmed based on pathological morphology, immunohistochemistry, and the specific anatomical location of the tumor. This case report shown that when there is a persistent mass induration in the navel after LC surgery, the possibility of incision tumor should be considered, rather than simply excluding the possibility of a cancer based on a non-cancer medical history.

Yolk sac–derived microglia and peripheral monocyte–derived macrophages play a key role during Parkinson’s disease (PD) progression. However, the regulatory mechanism of microglia/macrophage activation and function in PD pathogenesis remains unclear. Recombination signal–binding protein Jκ (RBP-J)–mediated Notch signaling regulates macrophage development and activation. In this study, with an 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) hydrochloride-induced acute murine PD model, we found that Notch signaling was activated in amoeboid microglia accompanied by a decrease in tyrosine hydroxylase (TH)–positive neurons. Furthermore, using myeloid-specific RBP-J knockout (RBP-JcKO) mice combined with a PD model, our results showed that myeloid-specific disruption of RBP-J alleviated dopaminergic neurodegeneration and improved locomotor activity. Fluorescence-activated cell sorting (FACS) analysis showed that the number of infiltrated inflammatory macrophages and activated major histocompatibility complex (MHC) II+ microglia decreased in RBP-JcKO mice compared with control mice. Moreover, to block monocyte recruitment by using chemokine (C-C motif) receptor 2 (CCR2) knockout mice, the effect of RBP-J deficiency on dopaminergic neurodegeneration was not affected, indicating that Notch signaling might regulate neuroinflammation independent of CCR2+ monocyte infiltration. Notably, when microglia were depleted with the PLX5622 formulated diet, we found that myeloid-specific RBP-J knockout resulted in more TH+ neurons and fewer activated microglia. Ex vitro experiments demonstrated that RBP-J deficiency in microglia might reduce inflammatory factor secretion, TH+ neuron apoptosis, and p65 nuclear translocation. Collectively, our study first revealed that RBP-J–mediated Notch signaling might participate in PD progression by mainly regulating microglia activation through nuclear factor kappa-B (NF-κB) signaling.

ObjectivesThe aim of the present study was to describe the experience at a single institution in the management of hepatic epithelioid hemangioendothelioma (HEHE).MethodsWe included 51 patients with histologically confirmed HEHE. We performed log-rank (Cox–Mantel) survival analyses using Kaplan–Meier methods to test differences in survival between patients in different groups. Univariate Cox regression analyses and multivariate proportional hazards regression model were carried out to identify independent prognostic factors.ResultsDifferent imaging modalities were used to diagnose HEHE with various presentations. Liver resection (LR), liver transplantation (LT), systemic treatment (ST), and surveillance had been used in our study. A significant difference was noted between the LR group and the surveillance group with respect to mean survival (p = 0.006), as was in the LR group and the ST group (p = 0.036), and in surgical approach (LR and LT) and nonsurgical approach (ST and surveillance) (p = 0.008). The mean survival between the ST group and the surveillance group was not significantly different (p = 0.851). LR (p = 0.010) and surgical approach (p = 0.014) were favorable predictors of outcome, while macrovascular invasion (MaVI) (p = 0.037), lung metastasis (p = 0.040), and surveillance (p = 0.033) were poor prognostic factors in univariate analysis. Multivariate analysis showed that LR (p = 0.010) and surgical approach (p = 0.014) were independently associated with good OS, while surveillance (p = 0.033) was independently associated with poor OS. After adjusting for confounding factors, patients in the LR group have much better OS than those in the surveillance group (p = 0.013). However, there was no significant difference in OS between the LR group and ST group (p = 0.254), as was in the ST group and the surveillance group (p = 0.857).ConclusionsThe definitive diagnosis of HEHE was dependent on histopathology, and it was not possible to make a specific diagnosis without biopsy because the radiological findings were similar to those in some hepatic malignancies. ST was not recommended for patients who were not candidates for surgical approaches, and surgical approaches should be warranted regardless of disease stage. The retrospective nature and the small size of the data limited the generalizability of the study, designing a worldwide database that contains all data about patients with HEHE independent of their therapy, which was highly recommended.

BackgroundIn-stent restenosis (ISR) is an adverse and notable event in the treatment of intracranial atherosclerotic stenosis (ICAS) with percutaneous transluminal angioplasty and stenting (PTAS). The incidence and contributing factors have not been fully defined. This study was performed to evaluate factors associated with ISR after PTAS.Data sourceWe identified studies on ISR after PTAS from an electronic search of articles in PubMed, Ovid MEDLINE, and the Cochrane Central Database (dated up to July 2022).ResultsA total of 19 studies, including 452 cases of ISR after 2,047 PTAS, were included in the meta-analysis. The pooled incidence rate of in-stent restenosis was 22.08%. ISR was more likely to occur in patients with coronary artery disease (OR = 1.686; 95% CI: 1.242–2.288; p = 0.0008), dissection (OR = 6.293; 95% CI: 3.883–10.197; p < 0.0001), and higher residual stenosis (WMD = 3.227; 95% CI: 0.142–6.311; p = 0.0404). Patients treated with Wingspan stents had a significantly higher ISR rate than those treated with Enterprise stents (29.78% vs. 14.83%; p < 0.0001).ConclusionsThe present study provides the current estimates of the robust effects of some risk factors for in-stent restenosis in intracranial atherosclerotic stenosis. The Enterprise stent had advantages compared with the Wingspan stent for ISR. The significant risk factors for ISR were coronary artery disease, dissection, and high residual stenosis. Local anesthesia was a suspected factor associated with ISR.

BackgroundSocial interaction is a fundamental human need. Social isolation (SI) can have negative effects on both emotional and cognitive function. However, it is currently unclear how age and the duration of SI affect emotion and recognition function. In addition, there is no specific treatment for the effects of SI.MethodsThe adolescence or adult mice were individually housed in cages for 1, 6 or 12 months and for 2 months to estabolish SI mouse model. We investigated the effects of SI on behavior in mice at different ages and under distinct durations of SI, and we explored the possible underlying mechanisms. Then we performed deep brain stimulation (DBS) to evaluate its influences on SI induced behavioral abnormalities.ResultsWe found that social recognition was affected in the short term, while social preference was damaged by extremely long periods of SI. In addition to affecting social memory, SI also affects emotion, short-term spatial ability and learning willingness in mice. Myelin was decreased significantly in the medial prefrontal cortex (mPFC) and dorsal hippocampus of socially isolated mice. Cellular activity in response to social stimulation in both areas was impaired by social isolation. By stimulating the mPFC using DBS, we found that DBS alleviated cellular activation disorders in the mPFC after long-term SI and improved social preference in mice.ConclusionOur results suggest that the therapeutic potential of stimulating the mPFC with DBS in individuals with social preference deficits caused by long-term social isolation, as well as the effects of DBS on the cellular activity and density of OPCs.

Gastrointestinal (GI) bleeding is a common clinical condition that can be caused by a variety of reasons. Bleeding can occur anywhere in the GI tract, and it usually presents as vomiting of blood, melena or black stools. We herein present a case of a 48-year-old man who was ultimately diagnosed with perforation of the lower ileum, pseudoaneurysm of the right common iliac artery, lower ileum-right common iliac artery fistula, and pelvic abscess caused by accidental ingestion of a toothpick. This case suggests that accidental ingestion of a toothpick may also be the cause of GI bleeding in some patients. For patients with unexplained GI bleeding, especially those with small bowel bleeding, a rational and combined use of gastroduodenoscopy, colonoscopy, unenhanced and contrast-enhanced abdominal CT can help detect the causes of GI bleeding and improve diagnostic accuracy.

IntroductionAs a biomarker of depression, speech signal has attracted the interest of many researchers due to its characteristics of easy collection and non-invasive. However, subjects’ speech variation under different scenes and emotional stimuli, the insufficient amount of depression speech data for deep learning, and the variable length of speech frame-level features have an impact on the recognition performance.MethodsThe above problems, this study proposes a multi-task ensemble learning method based on speaker embeddings for depression classification. First, we extract the Mel Frequency Cepstral Coefficients (MFCC), the Perceptual Linear Predictive Coefficients (PLP), and the Filter Bank (FBANK) from the out-domain dataset (CN-Celeb) and train the Resnet x-vector extractor, Time delay neural network (TDNN) x-vector extractor, and i-vector extractor. Then, we extract the corresponding speaker embeddings of fixed length from the depression speech database of the Gansu Provincial Key Laboratory of Wearable Computing. Support Vector Machine (SVM) and Random Forest (RF) are used to obtain the classification results of speaker embeddings in nine speech tasks. To make full use of the information of speech tasks with different scenes and emotions, we aggregate the classification results of nine tasks into new features and then obtain the final classification results by using Multilayer Perceptron (MLP). In order to take advantage of the complementary effects of different features, Resnet x-vectors based on different acoustic features are fused in the ensemble learning method.ResultsExperimental results demonstrate that (1) MFCC-based Resnet x-vectors perform best among the nine speaker embeddings for depression detection; (2) interview speech is better than picture descriptions speech, and neutral stimulus is the best among the three emotional valences in the depression recognition task; (3) our multi-task ensemble learning method with MFCC-based Resnet x-vectors can effectively identify depressed patients; (4) in all cases, the combination of MFCC-based Resnet x-vectors and PLP-based Resnet x-vectors in our ensemble learning method achieves the best results, outperforming other literature studies using the depression speech database.DiscussionOur multi-task ensemble learning method with MFCC-based Resnet x-vectors can fuse the depression related information of different stimuli effectively, which provides a new approach for depression detection. The limitation of this method is that speaker embeddings extractors were pre-trained on the out-domain dataset. We will consider using the augmented in-domain dataset for pre-training to improve the depression recognition performance further.

Verticillium wilt (VW) is often referred to as the cancer of cotton and it has a detrimental effect on cotton yield and quality. Since the root system is the first to be infested, it is feasible to detect VW by root analysis in the early stages of the disease. In recent years, with the update of computing equipment and the emergence of large-scale high-quality data sets, deep learning has achieved remarkable results in computer vision tasks. However, in some specific areas, such as cotton root MRI image task processing, it will bring some challenges. For example, the data imbalance problem (there is a serious imbalance between the cotton root and the background in the segmentation task) makes it difficult for existing algorithms to segment the target. In this paper, we proposed two new methods to solve these problems. The effectiveness of the algorithms was verified by experimental results. The results showed that the new segmentation model improved the Dice and mIoU by 46% and 44% compared with the original model. And this model could segment MRI images of rapeseed root cross-sections well with good robustness and scalability. The new classification model improved the accuracy by 34.9% over the original model. The recall score and F1 score increased by 59% and 42%, respectively. The results of this paper indicate that MRI and deep learning have the potential for non-destructive early detection of VW diseases in cotton.

Pulmonary hypertension (PH) is a refractory and fatal disease characterized by excessive pulmonary arterial cell remodeling. Uncontrolled proliferation and hypertrophy of pulmonary arterial smooth muscle cells (PASMCs), dysfunction of pulmonary arterial endothelial cells (PAECs), and abnormal perivascular infiltration of immune cells result in pulmonary arterial remodeling, followed by increased pulmonary vascular resistance and pulmonary pressure. Although various drugs targeting nitric oxide, endothelin-1 and prostacyclin pathways have been used in clinical settings, the mortality of pulmonary hypertension remains high. Multiple molecular abnormalities have been implicated in pulmonary hypertension, changes in numerous transcription factors have been identified as key regulators in pulmonary hypertension, and a role for pulmonary vascular remodeling has been highlighted. This review consolidates evidence linking transcription factors and their molecular mechanisms, from pulmonary vascular intima PAECs, vascular media PASMCs, and pulmonary arterial adventitia fibroblasts to pulmonary inflammatory cells. These findings will improve the understanding of particularly interactions between transcription factor-mediated cellular signaling pathways and identify novel therapies for pulmonary hypertension.

IntroductionSalt stress is a major environmental factor limiting plant growth and development. Previous studies have indicated that the steroidal hormones—brassinosteroids (BRs) are important regulators of plant responses to salt stress. However, the underlying molecular mechanisms have not been fully understood.Methods(1) Phenotypic analysis of bes1-D, BES1-RNAi and their wild-type (Col-0) under salt treatments with different concentrations of NaCl. (2) Transcriptomic and proteomic profiling of BES1-regulated genes and proteins under salt treatment; (3) qRT-PCR validation of selected BES1-regulated genes under salt stress; (4) Transient transcriptional assay of BES1 regulation on its putative target genes in Arabidopsis protoplasts; (5) Electrophoresis Mobility Shift Assay (EMSA) of BES1 binding with its potential target genes.Results and DiscussionPhenotypic analysis indicated that bes1-D, a gain-of-function mutant of the BR-regulated transcription factor BES1 in Arabidopsis showed better salt tolerance than the wild-type plant, while a BES1 RNA interference (BES1-RNAi) line was more sensitive to salt stress. Global gene expression profiling and time series clustering analyses identified a total of 1,170 genes whose expression was boosted in bes1-D under salt stress. Further GO enrichment and gene functional network analyses identified several key modules that are regulated by BES1 and most sensitive to salt stress perturbations, including stress response, response to ABA and ROS, flavonoid biosynthesis and transmembrane transport. A comparative proteomic analysis performed under the same stress conditions supported the results from the transcriptome analysis. In addition, transient gene transcription assays in Arabidopsis protoplasts and in vitro DNA binding assays verified that BES1 regulates the expression of some ion transporter genes directly and indirectly. Taken together, our results support a positive role of BES1 in plant salt tolerance.

IntroductionDepression is an affective disorder that contributes to a significant global burden of disease. Measurement-Based Care (MBC) is advocated during the full course management, with symptom assessment being an important component. Rating scales are widely used as convenient and powerful assessment tool, but they are influenced by the subjectivity and consistency of the raters. The assessment of depressive symptoms is usually conducted with a clear purpose and restricted content, such as clinical interviews based on the Hamilton Depression Rating Scale (HAMD), so that the results are easy to obtain and quantify. Artificial Intelligence (AI) techniques are used due to their objective, stable and consistent performance, and are suitable for assessing depressive symptoms. Therefore, this study applied Deep Learning (DL)-based Natural Language Processing (NLP) techniques to assess depressive symptoms during clinical interviews; thus, we proposed an algorithm model, explored the feasibility of the techniques, and evaluated their performance.MethodsThe study included 329 patients with Major Depressive Episode. Clinical interviews based on the HAMD-17 were conducted by trained psychiatrists, whose speech was simultaneously recorded. A total of 387 audio recordings were included in the final analysis. A deeply time-series semantics model for the assessment of depressive symptoms based on multi-granularity and multi-task joint training (MGMT) is proposed.ResultsThe performance of MGMT is acceptable for assessing depressive symptoms with an F1 score (a metric of model performance, the harmonic mean of precision and recall) of 0.719 in classifying the four-level severity of depression and an F1 score of 0.890 in identifying the presence of depressive symptoms.DisscussionThis study demonstrates the feasibility of the DL and the NLP techniques applied to the clinical interview and the assessment of depressive symptoms. However, there are limitations to this study, including the lack of adequate samples, and the fact that using speech content alone to assess depressive symptoms loses the information gained through observation. A multi-dimensional model combing semantics with speech voice, facial expression, and other valuable information, as well as taking into account personalized information, is a possible direction in the future.

Maintaining and monitoring low-voltage overhead power lines are of great importance because such lines are the key link between the power system and low-voltage power users. At present, few networks can be detected accurately on intelligent edge identification devices because of the complex backgrounds and limited characteristics in unmanned aerial vehicle images as well as the low computing abilities of hardware. In order to give consideration to accuracy and speed, a novel power line detection method was proposed, denoted by Gabor-YOLONet, used for intelligent edge identification devices available to UAV. Unlike existing methods, the proposed method uses the Gabor algorithm to extract foreground of power lines from cluttered backgrounds automatically and predict power lines and their auxiliary targets such as insulators in the foreground scene. In addition, a new inference method was introduced, which can summarize the average location and orientation of auxiliary targets by clustering to verify the rationality of the predicted results for power lines. The experiment results showed that the proposed method had the higher accuracy and consumed less computing resources; compared with other methods, the mAP of identification for power lines was 86.6% and the running time was only 25 ms, with excellent performance on intelligent edge devices.

Leaf nitrogen concentration (LNC) is a critical indicator of crop nutrient status. In this study, the feasibility of using visible and near-infrared spectroscopy combined with deep learning to estimate LNC in cotton leaves was explored. The samples were collected from cotton’s whole growth cycle, and the spectra were from different measurement environments. The random frog (RF), weighted partial least squares regression (WPLS), and saliency map were used for characteristic wavelength selection. Qualitative models (partial least squares discriminant analysis (PLS-DA), support vector machine for classification (SVC), convolutional neural network classification (CNNC) and quantitative models (partial least squares regression (PLSR), support vector machine for regression (SVR), convolutional neural network regression (CNNR)) were established based on the full spectra and characteristic wavelengths. Satisfactory results were obtained by models based on CNN. The classification accuracy of leaves in three different LNC ranges was up to 83.34%, and the root mean square error of prediction (RMSEP) of quantitative prediction models of cotton leaves was as low as 3.36. In addition, the identification of cotton leaves based on the predicted LNC also achieved good results. These results indicated that the nitrogen content of cotton leaves could be effectively detected by deep learning and visible and near-infrared spectroscopy, which has great potential for real-world application.

BackgroundWe aimed to evaluate the predictive power of systemic inflammation response index (SIRI), a novel biomarker, to predict all-cause mortality in patients with traumatic brain injury (TBI) in the intensive care unit (ICU).MethodsClinical data were retrieved from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. Kaplan-Meier (KM) methods and cox proportional hazard models were performed to examine the association between SIRI and all-cause mortality. The predictive power of SIRI was evaluated compared to other leukocyte-related indexes including neutrophils, lymphocytes, monocytes and white blood cells (WBC) by the Receiver Operating Characteristic (ROC)curve for 30-day mortality. In addition, propensity score matching (PSM) was conducted to reduce confounding.ResultsA total of 350 TBI patients were enrolled overall in our study. The optimal cutoff point of SIRI was determined at 11.24 × 109/L. After 1:1 PSM, 66 matched pairs (132 patients) were generated. During the 30-day, in-hospital and 365-day follow-up periods, patients with low SIRI level were associated with improved survival (p < 0.05) compared with patients with high SIRI level. Cox regression analysis identified that higher SIRI values was an independent risk factor for all-cause mortality and results were stable on multiple subgroup analyses. Furthermore, ROC analysis indicated that the area under the curve of SIRI [0.6658 (95% Confidence Interval, 0.5630–0.7687)] was greater than that of neutrophils, monocytes, lymphocytes and WBC. The above results were also observed in the matched cohort.ConclusionIt was suggested that TBI patients with high SIRI level would suffer from a high risk of 30-day, in-hospital and 365-day mortality. SIRI is a promising inflammatory biomarker for predicting TBI patients' prognosis with relatively better predictive power than other single indicators related to peripheral differential leukocyte counts.

ObjectiveTo identify factors associated with visual acuity regression following successful treatment of anisometropic amblyopia.Design and methodThis was a retrospective cohort study. Database records for 100 and 61 children with anisometropic amblyopia who met at least one criterion for successful treatment proposed by the Pediatric Eye Disease Investigator Group (PEDIG) and had at least 1 year of follow-up data available after the criterion was met were analyzed. The study sample was split into two groups, those who regressed within 1 year of successful treatment (no longer met any of the PEDIG criteria for successful treatment) and those who did not. A two-step analysis involving a least absolute shrinkage and selection operator (LASSO) regression and a logistic regression were used to identify predictor variables for increased risk of regression. A broad range of clinical, perceptual, and demographic variables were included in the analyses.ResultsSixty-eight (42.5%) children regressed within 1 year of successful treatment. Among the 27 predictor variables considered within the statistical modeling process, the three most important for predicting treatment regression were the extent of amblyopic eye visual acuity improvement, age at first hospital visit and sex. Specifically, lower risk of regression was associated with larger amblyopic eye visual acuity improvement with treatment, younger age at initiation of treatment and female sex.ConclusionPatients who received treatment at a younger age and responded well to treatment had a lower risk of treatment regression. This pattern of results suggests that early detection of amblyopia and strategies that enhance treatment adherence may reduce the risk of treatment regression. The higher risk of regression in boys than girls that we observed may reflect known sex differences in brain development and /or sex differences in environment within our sample of children from South China.

PurposeCompare peripheral contrast sensitivity functions (CSF) between myopes and emmetropes to reveal potential myogenic risks during emmetropization.Materials and methodsThis observational, cross-sectional, non-consecutive case study included data from 19 myopes (23.42 ± 4.03 years old) and 12 emmetropes (22.93 ± 2.91 years old) who underwent central and peripheral quick CSF (qCSF) measurements. Summary CSF metrics including the cut-off spatial frequency (cut-off SF), area under log CSF (AULCSF), low-, intermediate-, and high-spatial-frequency AULCSFs (l-, i-, and h-SF AULCSFs), and log CS at 19 SFs in the fovea and 15 peripheral locations (superior, inferior, temporal, and nasal quadrants at 6, 12, 18, and 24° eccentricities, excluding the physiological scotoma at 18°) were analyzed with 3-way and 4-way between-subjects analysis of variance (ANOVA) (α = 0.05).ResultsThree-way ANOVA showed that myopes had significantly increased AULCSF at 6° (mean difference, 0.08; 95% CI, 0.02–0.13; P = 0.007) and 12° (mean difference, 0.09; 95% CI, 0.03–0.14; P = 0.003). Log CS at all 19 SFs were higher in the myopia group compared to the normal group (mean differencesuperior, 0.02; 95% CI, 0.01–0.20; P = 0.02 and mean differenceinferior, 0.11; 95% CI, 0.02–0.21; P = 0.01) at 12°. The h-SF AULCSF at 6° (mean differenceinferior, 1.27; 95% CI, 0.32–2.22; P = 0.009) and i-SF AULCSF at 12° (mean differencesuperior, 5.31; 95% CI, 4.35–6.27; P < 0.001; mean differenceinferior, 1.14; 95% CI, 0.19–2.10; P = 0.02) were higher in myopia vs. normal group.ConclusionWe found myopia increased contrast sensitivity in superior and inferior visual field locations at 6° parafoveal and 12° perifoveal regions of the retina. The observation of increased contrast sensitivities within the macula visual field in myopia might provide important insights for myopia control during emmetropization.

PurposeThe need to elucidate risk factors for adolescent suicide is urgent, as suicide consistently ranks among the top causes of death globally. Understanding suicide risk factors could inform more effective interventions. Previous studies have identified certain risk factors associated with suicide, but there is a paucity of research among adolescent and multi-ethnic Asian populations.Materials and methodsThis case-control study sampled 13-to-19-year-old Asian adolescents who had attempted suicide (N = 60) and controls (N = 58) matched by age, ethnicity and gender at group-level (73.7% female). Life stressors, temperament, parenting style, mental health conditions and help-seeking behavior were examined.ResultsAll domains of life stress apart from emerging adult responsibility were higher among cases than controls, especially home life, peer pressure and romantic relationships. Suicide attempters tended to avoid new situations, be less adaptable to changes, have a negative outlook and irregular sleep-wake cycle. Additionally, they perceived their parents to be significantly more aggressive, neglecting, rejecting and cold, while parents’ perceptions of their own parenting were only significantly different in the domain of parental neglect. Cases were more likely to exhibit disorders of disruptive behavior, eating, mood, anxiety, symptoms of schizophrenia and experience of disturbing events. Significant differences were also found for 10 out of 12 Axis II disorders, particularly borderline, depressive, and avoidant personality disorder traits. No significant case-control differences were found regarding overall rates of help-seeking.ConclusionFindings from this study may help in suicide prevention efforts through more tailored interventions.

PurposeSchool-age children in China have more advanced motor development than their North American counterparts. This is likely due to cultural differences in children’s regular motor activities. It is unknown whether the motor function impairments associated with binocular visual disorders (BVDs) such as amblyopia in children raised in North America exist for children raised in China.DesignProspective case-control study.MethodsA major tertiary eye hospital in China tested children aged 3 to

China has become the world’s largest market for the production and sales of new energy vehicles. In the Internet era, online review data is becoming more and more important, and it is a great challenge for new energy vehicle manufacturers and consumers to quickly obtain and find out the effective information in the review data. In view of the above understanding, this study uses the Bert-wwm-ext model structure, data mining, and deep learning to study the new energy vehicle selection, and also analyzes the positioning of domestic and foreign new energy vehicle brands and their brand development from the perspective of complex networks. The research results found that: 1) Consumers pay more and more attention to the quality of new energy vehicles. 2) The comparative analysis of BEV and PHEV reveals that consumers’ evaluation of both types of vehicles is roughly comparable, but the difference in satisfaction with the endurance of both types of vehicles is very obvious. 3) Most of the brands of new energy vehicles are concentrated in the price range of RMB80,000 to RMB350,000, and within this range, consumers’ evaluation is positively correlated with the price of the vehicle. Among the new energy vehicle brands over RMB350,000, consumer evaluation does not rise with the price of the vehicle. 4) The head effect of Chinese brands is significant, Foreign brands have formed strong brands with high brand premiums.

BackgroundWhere applicable, regional anesthesia has been shown to be superior to opioid or non-opioid analgesic modalities alone. However, some studies have shown ethnic-based disparities in the use of regional anesthesia in patients undergoing surgical procedures. In this study of patients who had undergone major oncologic surgery, our main objective was to compare the use of regional anesthesia between patients of different ethnicities.MethodsA retrospective review of adults who had undergone major open abdominal surgical procedures between 2016 and 2021 was performed. Logistic regression models were used to assess the association between baseline patient characteristics and the use of regional anesthesia.ResultsA total of 4,791 patients were included in the analysis. The median age was 60.5 years [interquartile range, 49, 69], the majority were female (65%), and of American Society of Anesthesiologists Physical Status Class (ASA) 3 (94.7%). Regional anesthesia was used in 2,652 patients (55.4%) and was not associated with race or ethnicity (p = 0.287). Compared to White patients, the odds of regional anesthesia use in other racial/ethnic groups were: Asian {odds ratio (OR) 0.851 [95% confidence interval (CI), 0.660–1.097]; p = 0.2125}, Black/African American [OR 0.807 (95% CI, 0.651–1.001); p = 0.0508], Hispanic/Latino [OR 0.957 (95% CI, 0.824–1.154); p = 0.7676], Other race [OR 0.957 (95% CI, 0.627–1.461); p = 0.8376]. In the multivariable analysis, age [OR 0.995 (95% CI, 0.991–1.000); p = 0.0309] and female gender [OR 1.231 (95% CI, 1.090–1.390); p = 0.0008] were associated with the use of regional anesthesia.ConclusionIn this single-institution retrospective study of adults who had undergone major open abdominal surgery, the use of regional anesthesia was not associated with race or ethnicity. In the multivariable analysis, age and female gender were associated with the use of regional anesthesia.

In order to solve the different pains caused by traditional cancer treatment methods such as surgical treatment, the nano-drug delivery system provides new ideas for cancer treatment. In this paper, a novel anti-tumor therapy nanoparticle, P(AAm-co-AN)-AuNRs@CeO2-Ce6(PA/Ce6), is prepared, which provides a novel idea for liver cancer treatment. The CeO2-coated gold nanorods were grafted onto the surface of the temperature-sensitive polymer P(AAm-co-AN)-CTPD. The photosensitizer Ce6 is loaded on the surface of the nanoparticles and the polymer layer. CeO2 can effectively alleviate the tumor anaerobic microenvironment, and under 808 nm near-infrared (NIR) excitation, the gold nanorods achieve photothermal conversion to induce local heating, which leads to the phase transition of the polymer layer and realizes a controllable release mechanism. In addition, 660 nm NIR light can effectively induce Ce6 to produce singlet oxygen, thereby effectively killing cancer cells. Under the 808 nm laser irradiation within 600 s, the PA/Ce6 solution can heat up to about 60°C, which was enough to ablate both cancer cells and tumor tissues. When the temperature was 50°C, the cumulative release rate of Ce6 was 95.31%. Under the 808 nm laser irradiation, oxygen production capacity of PA/Ce6 was higher and can effectively reduce the content of hydrogen peroxide in cancer cells. Compared to free Ce6, the reactive oxygen species-mediated fluorescence of PA/Ce6 nanoparticles was greater. The cell viability and migration of HepG2 cells were decreased after the 660 and 880 nm lasers were irradiated at the same time. The cancer cells were further inhibited, showing a good in vitro anti-tumor effect. PA-DOX showed the best tumor growth inhibitory effect under NIR laser irradiation and had no acute toxicity in vivo. Due to the existence of AuNRs, nanoparticles had high-efficiency photothermal conversion ability to achieve photothermal therapy. Ce6 can generate singlet oxygen under the excitation of 660 nm laser to realize photodynamic therapy. The experimental results also showed that PA/Ce6 can effectively decompose hydrogen peroxide under laser irradiation, aiming to effectively alleviate the anaerobic microenvironment of tumors. These indicate that PA/Ce6 plays a promising role for hepatocellular carcinoma treatment.

Cross-site scripting (XSS) attacks are currently one of the most threatening network attack methods. Effectively detecting and intercepting XSS attacks is an important research topic in the network security field. This manuscript proposes a convolutional neural network based on a modified ResNet block and NiN model (MRBN-CNN) to address this problem. The main innovations of this model are to preprocess the URL according to the syntax and semantic characteristics of XSS attack script encoding, improve the ResNet residual module, extract features from three different angles, and replace the full connection layer in combination with the 1*1 convolution characteristics. Compared with the traditional machine learning and deep learning detection models, it is found that this model has better performance and convergence time. In addition, the proposed method has a detection rate compared to a baseline of approximately 75% of up to 99.23% accuracy, 99.94 precision, and a 98.53% recall value.

Fuel additives are considered to be a cost-effective and simple approach to improve combustion and reduce the harmful emissions of internal combustion engines. In addition to the use of conventional fuel additives, some unconventional fuel additives also have potential to improve fuel properties. Exploring the effects of different unconventional additives can provide a valuable reference to improve vehicle performance by fuel optimization. In this study, five unconventional gasoline additives (i.e., isopropyl ether, aniline, diethylamine, dimethyl malonate and p-tert-butylphenol) were blended with the baseline gasoline (G92). The five blended fuels are referred to as G92-1, G92-2, G92-3, G92-4, and G92-5, respectively. Fuels with different additives were tested on a compact passenger vehicle with a 1.4-L gasoline direct injection engine to assess the effects of these additives on performance and emission characteristics, and G92 gasoline was compared as a baseline. The new European drive cycle (NEDC), which is representative for passenger car and light duty vehicles, was chosen in the tests. The experimental results show little or slight improvement in fuel consumption for fuels blended with additives. With respect to gaseous emissions, the vehicle obtains the lowest and highest NOx emissions by fueling G92-5 (blended with p-tert-butylphenol) and G92-3 (blended with diethylamine), respectively; the lowest and highest CO emission is acquired using G92-2 (blended with aniline) and G92-4 (blended with dimethyl malonate), respectively; the vehicle reaches the lowest and highest THC emissions when fueling G92-3 (blended with diethylamine) and G92-4 (blended with dimethyl malonate), respectively; and the lowest and highest CO2 emission using G92-3 (blended with diethylamine) and G92-2 (blended with aniline), respectively. Compared with the baseline gasoline fuel, all of the fuels with additives show improved engine-out PM emissions. Furthermore, all five additives can improve the acceleration performance slightly. In brief, diethylamine is potential gasoline additive to reduce carbon emissions, improve fuel consumption, and enhance performance.

The effect of heat stress on ruminants is an important issue. In recent years, the growth of the Chinese dairy industry has rapidly increased, generating RMB 468,738 million revenue in 2021. A decreased milk yield is the most recognized impact of heat stress on dairy cows and results in significant economic loss to dairy producers. Heat stress also lowers immunity and antioxidant capacity and changes the bacterial composition and metabolites of the rumen. The purpose of this study was to investigate the effect of addition Saccharomyces cerevisiae culture on heat-stressed cows. The impact of S. cerevisiae culture on microbiota composition, functional profiles, and metabolomics was assessed in heat-stressed cows. A total of 45 Holstein cows in mid-lactation were selected and randomly divided into three groups (15 cows per group). Groups D-C, D-A, and D-B were fed with the basal diet, the basal diet + first S. cerevisiae culture 100 g/day, and the basal diet + second S. cerevisiae culture 30 g/day, respectively. The trial lasted 60 days. There was an increased abundance of the Phylum Firmicutes in the rumen of heat-stressed dairy cows fed with S. cerevisiae, of which four genera had significantly higher abundance, Ruminococcus_gauvreauii_group, Butyrivibrio_2, Moryella, and Ruminiclostridium_6. At the functional level, ten pathways differed significantly between the three groups (P < 0.05), with an increase in fatty acid biosynthesis, fatty acid metabolism, PPAR signaling pathway, ferroptosis, and biotin metabolism in the treatment groups. More differential metabolites were found in the D-C and D-A groups than in the D-C and D-B groups. These results indicate that S. cerevisiae cultures can influence the health status of heat-stressed cows by modulating rumen microbial composition, function, and metabolites, thereby improving rumen cellulolytic capacity. This study can provide or offer suggestions or recommendations for the development and utilization of feed additives.

Background: Dementia is a global challenge with 10 million individuals being diagnosed every year. Currently, there are no established disease-modifying treatments for dementia. Impaired nutrient sensing has been implicated in the pathogenesis of dementia. Compounds that inhibit the glycogen synthase kinase-3 (GSK3) pathway have been investigated as a possible treatment to attenuate the progression of the disease, particularly the suppression of the hyper-phosphorylation process of the tau protein.Aims: Systematically summarizing compounds which have been tested to inhibit the GSK3 pathway to treat cognitive impairment and dementia.Methods: PubMed, Embase and Web of Science databases were searched from inception until 28 July 2021 for articles published in English. Interventional animal studies inhibiting the GSK3 pathway in Alzheimer’s disease (AD), Parkinson’s dementia, Lewy body dementia, vascular dementia, mild cognitive impairment (MCI) and normal cognitive ageing investigating the change in cognition as the outcome were included. The Systematic Review Centre for Laboratory animal Experimentation’s risk of bias tool for animal studies was applied.Results: Out of 4,154 articles, 29 described compounds inhibiting the GSK3 pathway. All studies were based on animal models of MCI, AD or normal cognitive ageing. Thirteen out of 21 natural compounds and five out of nine synthetic compounds tested in MCI and dementia animal models showed an overall positive effect on cognition. No articles reported human studies. The risk of bias was largely unclear.Conclusion: Novel therapeutics involved in the modulation of the GSK3 nutrient sensing pathway have the potential to improve cognitive function. Overall, there is a clear lack of translation from animal models to humans.

The diamides, chlorantraniliprole (CHL) and cyantraniliprole (CYA), have been used as seed treatment agents against the fall armyworm (FAW), Spodoptera frugiperda in China. However, large-scale application of these two insecticides is prohibited because of their high cost. The neonicotinoid insecticides, clothianidin (CLO) and thiamethoxam (THI), are cheaper and widely used. In this study, we tested the efficacy of CHL + CLO and CYA + THI as seed treatment agents against FAW larvae both in laboratory and field conditions. Laboratory experiments showed that the two binary mixtures (both 240 g.a.i.100 kg−1 corn seeds) caused FAW mortality exceeded 84.00% at 14 days after seedling emergence (DAE). The mortality of the binary mixtures were similar to either CHL (300 g.a.i.100 kg−1corn seeds) or CYA (144 g a.i.100 kg−1corn seeds), but higher than CLO (120 g.a.i.100 Kg−1corn seeds) or THI (180 g a.i.100 kg−1corn seeds). Two independent field experiments showed that both binary mixtures resulted in above 68.00% control efficacy at 14 DAE, suggesting that these insecticidal combinations could effectively control FAW over a relative long period. In addition, both binary mixtures showed no negative effects on the growth and development of corn seedlings. The residues of binary mixtures in corn leave were also lower at 28 DAE as compared to residues in CHL or CYA alone. Most importantly, the costs of CHL + CLO were reduced up to 50% and CYA + THI up to 20% when compared to singly used chemical. Totally, our results indicated that CHL + CLO and CYA + THI had the same control efficacy as CHL or CYA alone, but with much lower cost.

BackgroundThe prognostic effect of admission blood glucose (ABG) for patients with acute myocardial infarction (AMI) has not been well validated, especially in patients with diabetes. We performed this study to assess the predictive value of ABG for all-cause mortality in AMI patients with different glucose metabolism status.MethodsWe evaluated a total of 6,892 AMI patients from the prospective, nationwide, multicenter CAMI registry, of which 2,820 had diabetes, 2,011 had pre-diabetes, and 2,061 had normal glucose regulation (NGR). Patients were divided into high ABG and low ABG groups according to the optimal cutoff values of ABG to predict 2-year mortality for patients with diabetes, pre-diabetes and NGR, respectively. The primary endpoint was all-cause mortality.ResultsThe optimal cutoff values of ABG for predicting 2-year mortality was 9.0mmol/l, 7.2mmol/l and 6.2mmol/l for patients with diabetes, pre-diabetes and NGR, respectively. Overall, the risk of all-cause mortality in high ABG group was significantly increased compared with that in low ABG group among patients with diabetes (15.2% vs. 8.9%; hazard ratio [HR] 1.787, 95% confidence interval [CI] 1.413-2.260; P

β-Glucosidase (β-Glc) is an enzyme capable of the selective hydrolysis of the β-glycosidic bond of glycosides and glycans containing glucose. β-Glc expressed by intestinal microbiota has attracted increasing levels of interest, due to their important roles for the metabolism of exogenous substances in the gut. Using the 2-((6-hydroxy-2,3-dihydro-1H-xanthen-4-yl)methylene)malononitrile fluorophore (DXM-OH, λem 636 nm) and the recognition group β-Glucose, an enzymatic activatable turn-on fluorescent probe (DXM-Glc) was developed for the selective and sensitive sensing of β-Glc. In addition, DXM-Glc could be used to sense endogenous β-Glc in living fungal cells. Using DXM-Glc, Pichia terricola M2 was identified as a functional intestinal fungus with β-Glc expression. P. terricola M2 could transform the flavone glycoside Icariin to Icariside Ⅱ efficiently, which confirmed the metabolism of glycosides in the gut mediated by fungi. Furthermore, Icariside Ⅱ could inhibit the proliferation of human endometrial cancer cells (RL 95-2 and ishikawa) significantly, suggesting the metabolic activation of Icariin by intestinal fungi in vivo. Therefore, DXM-Glc as a probe for β-Glc provided a novel technique for the investigation of the metabolism of bioactive substances by intestinal microbiota.

ObjectiveTo explore the correlation between word frequency and 17 items of the Hamilton Depression Scale (HAMD-17) in assessing the severity of depression in clinical interviews.MethodsThis study included 70 patients with major depressive disorder (MDD) who were hospitalized in the Beijing Anding Hospital. Clinicians interviewed eligible patients, collected general information, disease symptoms, duration, and scored patients with HAMD-17. The words used by the patients during the interview were classified and extracted according to the HowNet sentiment dictionary, including positive evaluation words, positive emotional words, negative evaluation words, negative emotional words. Symptom severity was grouped according to the HAMD-17 score: mild depressive symptoms is 8–17 points, moderate depressive symptoms is 18–24 points and severe depressive symptoms is >24 points. Analysis of Variance (ANOVA) was used to analyze the four categories of words among the groups, and partial correlation analysis was used to analyze the correlation between the four categories of word frequencies based on HowNet sentiment dictionary and the HAMD-17 scale to evaluate the total score. Receiver operating characteristic (ROC) curves were used to determine meaningful cut-off values.ResultsThere was a significant difference in negative evaluation words between groups (p = 0.032). After controlling for gender, age and years of education, the HAMD-17 total score was correlated with negative evaluation words (p = 0.009, r = 0.319) and negative emotional words (p = 0.027, r = 0.272), as the severity of depressive symptoms increased, the number of negative evaluation and negative emotional words in clinical interviews increased. Negative evaluation words distinguished patients with mild and moderate-severe depression. The area under the curve is 0.693 (p = 0.006) when the cut-off value is 8.48, the Youden index was 0.41, the sensitivity was 55.2%, and the specificity was 85.4%.ConclusionIn the clinical interview with MDD patients, the number of word frequencies based on HowNet sentiment dictionary may be beneficial in evaluating the severity of depressive symptoms.

Radiotherapy resistance is an important cause of treatment failure in esophageal squamous cell carcinoma (ESCC). Circular RNAs have attracted a lot of attention in cancer research, but their role in ESCC radiosensitivity has not been elucidated yet. Here, we aimed to evaluated the functional impacts of circ-0007022 on ESCC radiosensitivity. In this study, a stable radiotherapy-resistant cell line was established and verified by a series of functional experiments. Subsequently, high-throughput sequencing revealed that circ-0007022 was significantly overexpressed in the radiotherapy-resistant cell line and this conclusion was verified in ESCC patients’ tumor tissues by real-time quantitative PCR. Moreover, loss-of-function and overexpression experiments in vitro and in vivo revealed that, after irradiation, the abilities of proliferation and migration in circ-0007022-overexpressing stable transgenic strain were significantly higher than that in circ-0007022-knockdown stable transgenic strain. Additionally, RNA Immunoprecipitation, RNA pull-down, luciferase reporter assays, and fluorescence in situ hybridization experiments demonstrated the mechanism of how circ-0007022 could sponge miR-338-3p and upregulate downstream target of miR-338-3p, neuropilin-1 (NRP1). Moreover, NRP1 led to poor prognosis for ESCC patients receiving radiotherapy, and NRP1 knock-down enhanced radiosensitivity of ESCC cells. Furthermore, circ-0007022 overexpression activated Epithelial-to-mesenchymal transition and PI3K/Akt pathway, and NRP1 knock-down could reversed this phenomenon. Finally, Akt Inhibitor reversed circ-0007022s role in radiotherapy in ESCC cells. Taken together, the circ-0007022/miR-338-3p/NRP1 axis enhances the radiation resistance of ESCC cells via regulating EMT and PI3K/Akt pathway. The new circRNA circ-0007022 is thus expected to be a therapeutic target for ESCC patients.

The dairy farming industry is facing massive economic losses as heat stress continues to rise. The purpose of this study was to see how feeding Saccharomyces cerevisiae culture (SC) influences productive performance, lactation performance, serum biochemical indexes, hormonal level, antioxidant capacity, and immune function in mid-lactating cows during heat stress. Forty-five healthy mid-lactation dairy cows with comparable milk yield, lactation days, and parity were randomly divided into 3 groups (15 cows in each group). The control group (CON) was fed the basal diet, while the treatment groups were fed the basal diet + first Saccharomyces cerevisiae culture 100 g/d (SC-1) and the basal diet + second Saccharomyces cerevisiae culture 30 g/d (SC-2), respectively. The SC-1 and SC-2 groups with SC added in the treatment groups reduced rectal temperature and respiratory rate in heat-stressed cows (P < 0.05). The milk yield of SC-1 and SC-2 treatment groups was significantly higher than that of CON (P < 0.05). Except for somatic cell count, which was significantly lower in SC-1 and SC-2 than in CON (P < 0.05), there were no significant differences in the milk components. The addition of SC: (i) increased serum urea levels (P < 0.05), but there was no significant difference in glucose, total cholesterol, alanine transaminase, aspartate aminotransferase, total protein, albumin and alkaline phosphatase levels (P > 0.05); (ii) increased serum levels of immunoglobulin-A, immunoglobulin-G, immunoglobulin M, interleukin-4, interleukin-10 and heat shock protein-70 (P < 0.05), while decreasing serum levels of interleukin-1β, interleukin-6, interleukin-2, interferon-γ and tumor necrosis factor-α (P < 0.05); (iii) increased total antioxidant capacity, glutathione peroxidase and superoxide dismutase in serum (P < 0.05), while decreasing malondialdehyde; (iv) increased serum levels of glucocorticoids, insulin, cortisol and prolactin (P < 0.05), while decreasing the serum levels of triiodothyronine and thyroxine (P < 0.05). In conclusion, under the current experimental conditions, the addition of SC can reduce rectal temperature and respiratory rate in heat-stressed mid-lactation cows, reduce the number of somatic cells in milk and improve the mid-lactation cow performance. In addition, SC addition to the diet can raise serum urea levels, regulate serum hormone levels, boost antioxidant capacity in mid-lactation cows, and boost overall immunity.

ObjectiveJailed balloon technique (JBT) is an active side branch (SB) protection strategy and is considered to be superior to the jailed wire technique (JWT) in reducing SB occlusion. However, no randomized trials have proved that. We aim to investigate whether JBT could decrease the SB occlusion rate.MethodsConventional versus Intentional straTegy in patients with high Risk prEdiction of Side branch OccLusion in coronary bifurcation interVEntion (CIT-RESOLVE) (NCT02644434, registered on December 31, 2015) (https://clinicaltrials.gov) is a randomized trial that assessed the effects of different strategies on SB occlusion rate in patients with a high risk of SB occlusion. The present subgroup analysis enrolled bifurcation lesions (2 mm ≤ reference vessel diameter of SB < 2.5 mm) with Visual estimation for Risk prEdiction of Side branch OccLusion in coronary bifurcation intervention (V-RESOLVE) score ≥ 12 points. The primary endpoint is SB occlusion. One-year clinical events were compared.ResultsA total of 284 subjects at 16 sites were randomly assigned to the JBT group (n = 143) or the JWT group (n = 141). The rate of SB occlusion (9.1 vs. 19.9%, p = 0.02) and periprocedural myocardial infarction (defined by WHO, 7 vs. 14.9%, p = 0.03) is significantly lower in the JBT group than in the JWT group. The JBT and JWT groups showed no significant differences in cardiac death (0.7 vs. 0.7%, p = 1), myocardial infarction (MI, 6.3 vs. 7.1%, p = 0.79), target lesion revascularization (TLR, 1.4 vs. 2.1%, p = 0.68), and major cardiac adverse events (MACE, a composite of all-cause death, MI, or TLR, 8.4 vs. 10.6%, p = 0.52) during a 1-year follow-up.ConclusionIn patients with a high risk of SB occlusion (V-RESOLVE score ≥ 12 points), JBT is superior to JWT in reducing SB occlusion. However, no significant differences were detected in 1-year MACE.

Gynostemma longipes contains an abundance of dammarane-type ginsenosides and gypenosides that exhibit extensive pharmacological activities. Increasing attention has been paid to the elucidation of cytochrome P450 monooxygenases (CYPs) and UDP-dependent glycosyltransferases (UGTs) that participate downstream of ginsenoside biosynthesis in the Panax genus. However, information on oxidosqualene cyclases (OSCs), the upstream genes responsible for the biosynthesis of different skeletons of ginsenoside and gypenosides, is rarely reported. Here, an integrative study of the metabolome and the transcriptome in the leaf, stolon, and rattan was conducted and the function of GlOSC1 was demonstrated. In total, 46 triterpenes were detected and found to be highly abundant in the stolon, whereas gene expression analysis indicated that the upstream OSC genes responsible for saponin skeleton biosynthesis were highly expressed in the leaf. These findings indicated that the saponin skeletons were mainly biosynthesized in the leaf by OSCs, and subsequently transferred to the stolon via CYPs and UGTs biosynthesis to form various ginsenoside and gypenosides. Additionally, a new dammarane-II synthase (DDS), GlOSC1, was identified by bioinformatics analysis, yeast expression assay, and enzyme assays. The results of the liquid chromatography–mass spectrometry (LC–MS) analysis proved that GlOSC1 could catalyze 2,3-oxidosqualene to form dammarenediol-II via cyclization. This work uncovered the biosynthetic mechanism of dammarenediol-II, an important starting substrate for ginsenoside and gypenosides biosynthesis, and may achieve the increased yield of valuable ginsenosides and gypenosides produced under excess substrate in a yeast cell factory through synthetic biology strategy.

The chiral puzzle of biological molecules is thought to be closely related to the origin of life and is still a mystery so far. Previously, we proposed a new model on the origin of life, Nebula-Relay hypothesis, which assumed that the life on Earth originated at the planetary system of the Sun’s predecessor star and then filled in the pre-solar nebula after its death. As primitive lives existed in the pre-solar nebula for a long time, did the chiral biomolecules form during this period? We explore such a possibility in this work and find that the ultra-low temperature environment of molecular clouds is beneficial to generating the chiral polymer chain of biological molecules.

BackgroundMacular edema is the most common cause of impaired vision due to uveitis. Although various medications are available, not all uveitis patients with macular edema are satisfied with the treatment results. Therefore, solving this gap becomes the utmost concern worldwide. This study attempted to use bibliometric analysis to compare the valuable information in the top 100 highly cited studies in the field of drug therapy for uveitic macular edema (UME) and then determine the research hot spots and trends in this field.MethodsIn this study, the Science Citation Index Expanded (SCIE) of Web of Science (WOS) was used to collect the top 100 most cited studies on UME and analyze the literature from different countries/regions, institutions, and journals. The visualization knowledge maps is generated by VOSviewer and Citespace software.ResultsThe top 100 highly cited studies are from 34 countries/regions. The United States has the largest number of publications, followed by the England, Spain and Germany. The top three institutions publishing highly cited literature are all from the England: University of London, University College London, and Moorfields Eye Hospital NHS Foundation Trust. Ophthalmology is the most widely published journal with 14 papers. The total number of citations is 1,371, meaning that Ophthalmology is the most authoritative journal in the field of UME drug therapy. The top two articles with the most cited times are from the United States, accounting for 36.5% of the total cited times of the top 10 articles. Keywords were divided into three clusters: the corticosteroid administration pathway, biological agents, and clinical trials. Uveitis, cystoid macular edema, efficacy, dexamethasone, and triamcinolone acetonide appeared more frequently in keywords. Researches on local and long-acting drug has gradually becoming the hot spots and trends.ConclusionThis study concludes that bibliometric analysis can intuitively and quickly obtain the frontiers and hot spots of research in the field of UME drug therapy. Corticosteroid administration, biological agents, and clinical trials are considered the potential focus of future research.

Litchi is an important Sapindaceae fruit tree. Flowering in litchi is triggered by low temperatures in autumn and winter. It can be divided into early-, medium-, and late-flowering phenotypes according to the time for floral induction. Early-flowering varieties need low chilling accumulation level for floral induction, whereas the late-flowering varieties require high chilling accumulation level. In the present study, RNA-Seq of 87 accessions was performed and transcriptome-based genome-wide association studies (GWAS) was used to identify candidate genes involved in chilling accumulation underlying the time for floral induction. A total of 98,155 high-quality single-nucleotide polymorphism (SNP) sites were obtained. A total of 1,411 significantly associated SNPs and 1,115 associated genes (AGs) were identified, of which 31 were flowering-related, 23 were hormone synthesis-related, and 27 were hormone signal transduction-related. Association analysis between the gene expression of the AGs and the flowering phenotypic data was carried out, and differentially expressed genes (DEGs) in a temperature-controlled experiment were obtained. As a result, 15 flowering-related candidate AGs (CAGs), 13 hormone synthesis-related CAGs, and 11 hormone signal transduction-related CAGs were further screened. The expression levels of the CAGs in the early-flowering accessions were different from those in the late-flowering ones, and also between the flowering trees and non-flowering trees. In a gradient chilling treatment, flowering rates of the trees and the CAGs expression were affected by the treatment. Our present work for the first time provided candidate genes for genetic regulation of flowering in litchi using transcriptome-based GWAS.

CYP3A4-mediated Phase I biotransformation is the rate-limiting step of elimination for many commonly used clinically agents. The modulatory effects of herbal medicines on CYP3A4 activity are one of the risk factors affecting the safe use of drug and herbal medicine. In the present study, the inhibitory effects of nearly hundred kinds of herbal medicines against CYP3A4 were evaluated based on a visual high-throughput screening method. Furthermore, biflavone components including bilobetin (7-demethylginkgetin, DGK), ginkgetin (GK), isoginkgetin (IGK), and amentoflavone (AMF) were identified as the main inhibitory components of Ginkgo biloba L. (GB) and Selaginella tamariscina (P. Beauv.) Spring (ST), which displayed very strong inhibitory effects toward CYP3A4. The inhibitory effects of these biflavones on clinical drugs that mainly undergo CYP3A4-dependent metabolism were evaluated. The IC50 of GK toward tamoxifen, gefitinib and ticagrelor were found to be of 0.478 ± 0.003, 0.869 ± 0.001, and 1.61 ± 0.039 μM, respectively. These results suggest the potential pharmacokinetic interactions between the identified biflavones and clinical drugs undergoing CYP3A4-mediated biotransformation. The obtained information is important for guiding the rational use of herbal medicine in combination with synthetic pharmaceuticals.

Background: The relative benefit of immediate complete revascularization, staged complete revascularization, and culprit-only percutaneous coronary intervention (PCI) remains unclear in hemodynamically stable patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. The aim of this study was to compare the clinical outcomes of the 3 PCI strategies in this population.Methods: We followed a pre-specified protocol (PROSPERO number: CRD42020183801). A comprehensive search of the electronic databases including PubMed, EMBASE and Cochrane Library from inception through February 21, 2020 was conducted. Randomized trials evaluating the comparative efficacy and safety of at least 2 of the 3 PCI strategies were identified. The primary endpoint was the composite of cardiovascular mortality or myocardial infarction (MI) during the longest follow-up. Pairwise and network meta-analyses were performed with random-effects model.Results: Eleven trials including 6,942 patients were analyzed. Pairwise meta-analysis noted that immediate complete revascularization and staged complete revascularization were respectively associated with a 52 and 27% reduction in the risk of cardiovascular death or MI (relative risk [RR] 0.48, 95% confidence interval [CI] 0.32–0.73, I2 = 0%; and RR 0.73, 95% CI 0.61–0.88, I2 = 0%, respectively), compared with culprit-only PCI. The risk of cardiovascular death or MI was not statistically different in staged and immediate complete revascularization groups (RR 0.88, 95% CI 0.45–1.72, I2 = 0%). Network meta-analysis obtained almost similar results compared with pairwise meta-analysis, and immediate complete revascularization had a 77% probability of being the best strategy for reducing cardiovascular death or MI among the 3 PCI strategies.Conclusion: The current evidence suggests that both immediate and staged complete revascularization were associated with a reduction of cardiovascular death or MI compared with culprit-only PCI. Further trials are warranted to directly compare immediate vs. staged complete revascularization in this population.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, PROSPERO [CRD42020183801].