Effects of Maternal SARS-CoV-2 Infection During Pregnancy on Fetal Development.

BACKGROUND: The severe acute respiratory syndrome coronavirus (SARS-CoV-2) outbreak in 2019 has necessitated investigating its potential adverse effects on pregnancy outcomes and fetal development. OBJECTIVE: This study aimed to review the evidence on the impact of SARS-CoV-2 infection during pregnancy on fetal outcomes. METHOD OF STUDY: Literatures since the outbreak of COVID-19 from PubMed and Web of Science were summarized in this narrative review, to show the effects of maternal SARS-CoV-2 infection during pregnancy on fetal development. RESULTS: SARS-CoV-2 infection during pregnancy can be transmitted vertically through the placenta, both in utero and perinatally, affecting the maternal-fetal immune interface and placental function. Viral infections during pregnancy have been linked to central nervous system development impairments and disorders such as autism. Changes in the structure and function of the respiratory, immune, and visceral systems have also been reported. SARS-CoV-2 infection during pregnancy has been linked with increased risks of stillbirth and preterm birth. However, the mechanisms involved remain unclear and may include cytokine storms, macrophage mediation, genetic mutations, methylation, and other epigenetic changes. Exploring the protective effects of antiviral treatment and other interventions in animal and clinical studies may help improve outcomes. CONCLUSION: SARS-CoV-2 infection during pregnancy activates the maternal-fetal immune interface through vertical transmission, and has short- and long-term effects on fetal development, including the central nervous system. Future long-term studies may help provide evidence that can inform interventions to reduce the risk of adverse outcomes.

Hepcidin depending on astrocytic NEO1 ameliorates blood-brain barrier dysfunction after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) significantly compromises the blood-brain barrier (BBB) and impairs patient recovery. This study elucidates the critical role of astrocytic Neogenin-1 (NEO1) in BBB integrity post-SAH and examines the regulatory effects of hepcidin on endothelial cell (EC) function amid NEO1-mediated disruptions in iron homeostasis. Proteomic analyses of cerebrospinal fluid (CSF) from SAH patients revealed a substantial decrease in NEO1 expression, identifying it as a key factor in BBB integrity. 111 CSF proteins were significantly reduced in early SAH stages (days 1-3), with NEO1 among the most significantly altered. This dysregulation was linked to poorer patient outcomes, as indicated by a negative correlation between NEO1 levels and Modified Rankin Scale scores six months post-SAH (R = -0.4743, P < 0.0001). Experimental models further highlighted the importance of NEO1: SAH model and NEO1GFAP-Cre mice exhibited exacerbated EC dysfunction and increased BBB permeability, evidenced by significant Evans Blue retention and dextran leakage in the parietal cortex, effects that were mitigated by hepcidin administration. Our findings highlight the complex interplay between astrocytic signaling and endothelial function in SAH pathophysiology. The loss of astrocytic NEO1 led to increased EC proliferation and altered BBB structure, as confirmed by transmission electron microscopy and immunostaining for PECAM-1, indicating heightened blood vessel density in the affected cortex. Hepcidin treatment effectively reversed the EC dysfunction and BBB disruption in both NEO1-cKO mice and the SAH model, highlighting its potential as a therapeutic agent to enhance recovery and improve prognosis following SAH.

Massive Chylous Leakage After Endoscopic Thyroidectomy with Central Lymph Node Dissection: A Case Report.

BACKGROUND Massive chylous leakage represents a rare yet potentially life-threatening complication following neck dissection, and its occurrence is even less common in the context of endoscopic thyroid surgery. Chylous leakage poses significant clinical management challenges, encompassing prolonged hospitalization, nutritional deficiencies, electrolyte imbalances, and the potential for infection. It is imperative for surgeons to remain vigilant and proactive in recognizing and managing chylous leakage to mitigate its potential impact on patient outcomes. CASE REPORT A 37-year-old woman presented with a thyroid nodule, and subsequent fine-needle aspiration biopsy confirmed the diagnosis of papillary thyroid carcinoma. She then underwent endoscopic thyroidectomy with central lymph node dissection via a bilateral areola approach and experienced significant postoperative chylous leakage. Various conservative management strategies were used to treat the leak, including fasting, parenteral nutrition, maintenance of electrolyte balance, and continuous infusion of somatostatin. After failure of a series of conservative treatments, the patient underwent a reoperation to address the leak via the initial approach. After identification of the leak site, the residual end of the lymphatic vessel was clamped with a biological clamp, and no further chylous leakage was observed. The drainage was removed 4 days after the second operation, and the patient was discharged on the fifth day. During follow-up, no abnormalities were observed. CONCLUSIONS Managing significant chylous leakage poses a challenge for surgeons. This complication is rare following endoscopic thyroidectomy with central lymph node dissection, and there remains a lack of experience in effective prevention and treatment. We aim to raise awareness through our case report.

Programming tumor evolution with selection gene drives to proactively combat drug resistance.

Most targeted anticancer therapies fail due to drug resistance evolution. Here we show that tumor evolution can be reproducibly redirected to engineer therapeutic opportunity, regardless of the exact ensemble of pre-existing genetic heterogeneity. We develop a selection gene drive system that is stably introduced into cancer cells and is composed of two genes, or switches, that couple an inducible fitness advantage with a shared fitness cost. Using stochastic models of evolutionary dynamics, we identify the design criteria for selection gene drives. We then build prototypes that harness the selective pressure of multiple approved tyrosine kinase inhibitors and employ therapeutic mechanisms as diverse as prodrug catalysis and immune activity induction. We show that selection gene drives can eradicate diverse forms of genetic resistance in vitro. Finally, we demonstrate that model-informed switch engagement effectively targets pre-existing resistance in mouse models of solid tumors. These results establish selection gene drives as a powerful framework for evolution-guided anticancer therapy.

Adaptive Temporal-Spatial Pyramid Variational Autoencoder Model for Multirate Dynamic Chemical Process Soft Sensing Application.

Data-driven soft sensors play an important role in practical processes and have been widely applied. They provide real-time prediction of quality variables and then guide production and improve product quality. In practical chemical production processes, nonlinear dynamic multirate data is widespread and challenging to model. This paper innovatively proposes a temporal-spatial pyramid variational autoencoder (TS-PVAE) model for the nonlinear temporal-spatial feature pyramid extraction from multirate data. This structure not only selectively utilizes multirate data but also handles complex nonlinear time-series data. Based on this, integrated with just-in-time (JIT) learning, an adaptive TS-PVAE (ATS-PVAE) model is developed. In this model, historical data are used for real-time fine-tuning of the model, leading to the development of an adaptive model. Finally, the proposed models are validated by an industrial case of a methanation furnace, demonstrating a superior estimation performance.

Effects of high-dose glucose-insulin-potassium on acute coronary syndrome patients receiving reperfusion therapy: a meta-analysis.

BACKGROUND: This meta-analysis aimed to assess the efficacy of high-dose glucose-insulin-potassium (GIK) therapy on clinical outcomes in acute coronary syndrome (ACS) patients receiving reperfusion therapy. METHODS: We searched the PubMed, Web of Science, MEDLINE, Embase, and Cochrane Library databases from inception to April 26, 2022, for randomized controlled trials (RCTs) that compared high-dose GIK and placebos in ACS patients receiving reperfusion therapy. The primary endpoint was major adverse cardiovascular events (MACEs). RESULTS: Eleven RCTs with 884 patients were ultimately included. Compared with placebos, high-dose GIK markedly reduced MACEs (risk ratio [RR] 0.57, 95% confidence interval [95% CI]: 0.35 to 0.94, P=0.03) and the risk of heart failure (RR 0.48, 95% CI: 0.25 to 0.95, P=0.04) and improved the left ventricular ejection fraction (LVEF) (mean difference [MD] 2.12, 95% CI: 0.40 to 3.92, P=0.02) at 6 months. However, no difference was observed in all-cause mortality at 30 d or 1 year. Additionally, high-dose GIK was significantly associated with increased incidences of phlebitis (RR 4.78, 95% CI: 1.36 to 16.76, P=0.01), hyperglycemia (RR 9.06, 95% CI: 1.74 to 47.29, P=0.009) and hypoglycemia (RR 6.50, 95% CI: 1.28 to 33.01, P=0.02) but not reinfarction, hyperkalemia or secondary reperfusion. In terms of oxidative stress-lowering function, high-dose GIK markedly reduced superoxide dismutase (SOD) activity but not glutathione peroxidase (GSH-Px) or catalase (CAT) activity. CONCLUSION: Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering efficacy in response to high-dose GIK. Moreover, with a higher incidence of complications such as phlebitis, hyperglycemia, and hypoglycemia. Furthermore, there were no observed survival benefits associated with high-dose GIK. More trials with long-term follow-up are still needed.

A cocktail nanovaccine targeting key entry glycoproteins elicits high neutralizing antibody levels against EBV infection.

Epstein-Barr virus (EBV) infects more than 95% of adults worldwide and is closely associated with various malignancies. Considering the complex life cycle of EBV, developing vaccines targeting key entry glycoproteins to elicit robust and durable adaptive immune responses may provide better protection. EBV gHgL-, gB- and gp42-specific antibodies in healthy EBV carriers contributed to sera neutralizing abilities in vitro, indicating that they are potential antigen candidates. To enhance the immunogenicity of these antigens, we formulate three nanovaccines by co-delivering molecular adjuvants (CpG and MPLA) and antigens (gHgL, gB or gp42). These nanovaccines induce robust humoral and cellular responses through efficient activation of dendritic cells and germinal center response. Importantly, these nanovaccines generate high levels of neutralizing antibodies recognizing vulnerable sites of all three antigens. IgGs induced by a cocktail vaccine containing three nanovaccines confer superior protection from lethal EBV challenge in female humanized mice compared to IgG elicited by individual NP-gHgL, NP-gB and NP-gp42. Importantly, serum antibodies elicited by cocktail nanovaccine immunization confer durable protection against EBV-associated lymphoma. Overall, the cocktail nanovaccine shows robust immunogenicity and is a promising candidate for further clinical trials.

Deep learning-based computer-aided diagnosis system for the automatic detection and classification of lateral cervical lymph nodes on original ultrasound images of papillary thyroid carcinoma: a prospective diagnostic study.

PURPOSE: This study aims to develop a deep learning-based computer-aided diagnosis (CAD) system for the automatic detection and classification of lateral cervical lymph nodes (LNs) on original ultrasound images of papillary thyroid carcinoma (PTC) patients. METHODS: A retrospective data set of 1801 cervical LN ultrasound images from 1675 patients with PTC and a prospective test set including 185 images from 160 patients were collected. Four different deep leaning models were trained and validated in the retrospective data set. The best model was selected for CAD system development and compared with three sonographers in the retrospective and prospective test sets. RESULTS: The Deformable Detection Transformer (DETR) model showed the highest diagnostic efficacy, with a mean average precision score of 86.3% in the retrospective test set, and was therefore used in constructing the CAD system. The detection performance of the CAD system was superior to the junior sonographer and intermediate sonographer with accuracies of 86.3% and 92.4% in the retrospective and prospective test sets, respectively. The classification performance of the CAD system was better than all sonographers with the areas under the curve (AUCs) of 94.4% and 95.2% in the retrospective and prospective test sets, respectively. CONCLUSIONS: This study developed a Deformable DETR model-based CAD system for automatically detecting and classifying lateral cervical LNs on original ultrasound images, which showed excellent diagnostic efficacy and clinical utility. It can be an important tool for assisting sonographers in the diagnosis process.

Acupressure: a possible therapeutic strategy for anxiety related to COVID-19: a meta-analysis of randomized controlled trials.

Background: From the end of 2019 to December 2023, the world grappled with the COVID-19 pandemic. The scope and ultimate repercussions of the pandemic on global health and well-being remained uncertain, ushering in a wave of fear, anxiety, and worry. This resulted in many individuals succumbing to fear and despair. Acupoint massage emerged as a safe and effective alternative therapy for anxiety relief. However, its efficacy was yet to be extensively backed by evidence-based medicine. This study aimed to enhance the clinical effectiveness of acupoint massage and extend its benefits to a wider population. It undertakes a systematic review of the existing randomized controlled trials (RCTs) assessing the impact of acupoint massage on anxiety treatment, discussing its potential benefits and implications. This research aims to furnish robust evidence supporting anxiety treatment strategies for patients afflicted with COVID-19 disease and spark new approaches to anxiety management. Objectives: This study evaluates the evidence derived from randomised controlled trials (RCTs), quantifies the impact of acupressure on anxiety manifestations within the general population, and proposes viable supplementary intervention strategies for managing COVID-19 related anxiety. Materials and methods: This review included RCTs published between February 2014 and July 2023, that compared the effects of acupressure with sham control in alleviating anxiety symptomatology as the outcome measure. The studies were sourced from the multiple databases, including CINAHL, EBM Reviews, Embase, Medline, PsycINFO, Scopus and Web of Science. A meta-analysis was performed on the eligible studies, and an overall effect size was computed specifically for the anxiety outcome. The Cochrane Collaboration Bias Risk Assessment Tool (RevMan V5.4) was employed to assess bias risk, data integration, meta-analysis, and subgroup analysis. The mean difference, standard mean deviation, and binary data were used to represent continuous outcomes. Results: Of 1,110 studies of potential relevance, 39 met the criteria for inclusion in the meta-analysis. The majority of the studies reported a positive effect of acupressure in assuaging anticipatory anxiety about treatment. Eighteen studies were evaluated using the STAI scale. The acupressure procedures were thoroughly documented, and studies exhibited a low risk of bias. The cumulative results of the 18 trials showcased a more substantial reduction in anxiety in the acupressure group compared to controls (SMD = -5.39, 95% CI -5.61 to -5.17, p < 0.01). A subsequent subgroup analysis, based on different interventions in the control group, demonstrated improvement in anxiety levels with sham acupressure in improving changes in anxiety levels (SMD -1.61, 95% CI: -2.34 to -0.87, p < 0.0001), and blank controls (SMD -0.92, 95% CI: -2.37 to 0.53, p = 0.22). Conclusion: In the clinical research of traditional Chinese medicine treatment of anxiety, acupressure demonstrated effectiveness in providing instant relief from anxiety related to multiple diseases with a medium effect size. Considering the increasing incidence of anxiety caused by long COVID, the widespread application of acupressure appears feasible. However, the results were inconsistent regarding improvements on physiological indicators, calling for more stringent reporting procedures, including allocation concealment, to solidify the findings.

[Effect of Intensive Insulin Therapy on Prognosis in Patients With Acute Myocardial Infarction].

Objective To evaluate the clinical efficacy and safety of intensive insulin therapy in the patients with acute myocardial infarction and provide guidance for improving the prognosis. Methods The articles involving the randomized controlled trials(RCT)focusing on the effects of intensive versus conventional insulin therapy on the clinical outcomes of the patients with acute myocardial infarction were retrieved from Cochrane,Embase,PubMed,CNKI,Wanfang Data,VIP,and CBM with the time interval from inception to October 2022.The data of each RCT were extracted and used for meta-analysis in RevMan5.4. Results A total of 8 articles were included in this study,involving 726 patients(372 in the intensive insulin group and 354 in the normal insulin group).The meta-analysis results showed that the intensive insulin group had lower incidence of major cardiovascular adverse events (RR=0.53, 95%CI=0.44-0.64, P<0.001), lower all-cause mortality (RR=0.51, 95%CI=0.33-0.78, P=0.002),lower high-sensitivity C-reactive protein level on day 7(WMD=-2.00,95%CI=-2.17- -1.83,P<0.001),higher left ventricular ejection fraction on day 30 (WMD=3.94, 95%CI=2.45-5.43,P<0.001), and higher incidence of hypoglycemia events (RR=2.96, 95%CI=1.12-7.83,P=0.030) than the normal insulin group.There was no significant difference between the two groups in terms of no-reflow event after percutaneous coronary intervention(RR=0.39,95%CI=0.14-1.13,P=0.080). Conclusion Intensive insulin therapy might be associated with more clinical benefits in the patients with acute myocardial infarction,while the conclusion remains to be confirmed by more studies.

PGR-KITLG signaling drives a tumor-mast cell regulatory feedback to modulate apoptosis of breast cancer cells.

The immune microenvironment constructed by tumor-infiltrating immune cells and the molecular phenotype defined by hormone receptors (HRs) have been implicated as decisive factors in the regulation of breast cancer (BC) progression. Here, we found that the infiltration of mast cells (MCs) informed impaired prognoses in HR(+) BC but predicted improved prognoses in HR(-) BC. However, molecular features of MCs in different BC remain unclear. We next discovered that HR(-) BC cells were prone to apoptosis under the stimulation of MCs, whereas HR(+) BC cells exerted anti-apoptotic effects. Mechanistically, in HR(+) BC, the KIT ligand (KITLG), a major mast cell growth factor in recruiting and activating MCs, could be transcriptionally upregulated by the progesterone receptor (PGR), and elevate the production of MC-derived granulin (GRN). GRN attenuates TNFα-induced apoptosis in BC cells by competitively binding to TNFR1. Furthermore, disruption of PGR-KITLG signaling by knocking down PGR or using the specific KITLG-cKIT inhibitor iSCK03 potently enhanced the sensitivity of HR(+) BC cells to MC-induced apoptosis and exerted anti-tumor activity. Collectively, these results demonstrate that PGR-KITLG signaling in BC cells preferentially induces GRN expression in MCs to exert anti-apoptotic effects, with potential value in developing precision medicine approaches for diagnosis and treatment.

Mitochondrial ferritin alleviates ferroptosis in a kainic acid-induced mouse epilepsy model by regulating iron homeostasis: Involvement of nuclear factor erythroid 2-related factor 2.

BACKGROUND: Epilepsy is a widespread and chronic disease of the central nervous system caused by a variety of factors. Mitochondrial ferritin (FtMt) refers to ferritin located within the mitochondria that may protect neurons against oxidative stress by binding excess free iron ions in the cytoplasm. However, the potential role of FtMt in epilepsy remains unclear. We aimed to investigate whether FtMt and its related mechanisms can regulate epilepsy by modulating ferroptosis. METHODS: Three weeks after injection of adeno-associated virus (AAV) in the skull of adult male C57BL/6 mice, kainic acid (KA) was injected into the hippocampus to induce seizures. Primary hippocampal neurons were transfected with siRNA using a glutamate-mediated epilepsy model. After specific treatments, Western blot analysis, immunofluorescence, EEG recording, transmission electron microscopy, iron staining, silver staining, and Nissl staining were performed. RESULTS: At different time points after KA injection, the expression of FtMt protein in the hippocampus of mice showed varying degrees of increase. Knockdown of the FtMt gene by AAV resulted in an increase in intracellular free iron levels and a decrease in the function of iron transport-related proteins, promoting neuronal ferroptosis and exacerbating epileptic brain activity in the hippocampus of seizure mice. Additionally, increasing the expression level of FtMt protein was achieved by AAV-mediated upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) gene in the hippocampus of seizure mice. CONCLUSIONS: In epilepsy, Nrf2 modulates ferroptosis by involving the expression of FtMt and may be a potential therapeutic mechanism of neuronal injury after epilepsy. Targeting this relevant process for treatment may be a therapeutic strategy to prevent epilepsy.

Functional brain network controllability dysfunction in Alzheimer's disease and its relationship with cognition and gene expression profiling.

Objective. In recent studies, network control theory has been applied to clarify transitions between brain states, emphasizing the significance of assessing the controllability of brain networks in facilitating transitions from one state to another. Despite these advancements, the potential alterations in functional network controllability associated with Alzheimer's disease (AD), along with the underlying genetic mechanisms responsible for these alterations, remain unclear.Approach. We conducted a comparative analysis of functional network controllability measures between patients with AD (n= 64) and matched normal controls (NCs,n= 64). We investigated the association between altered controllability measures and cognitive function in AD. Additionally, we conducted correlation analyses in conjunction with the Allen Human Brain Atlas to identify genes whose expression was correlated with changes in functional network controllability in AD, followed by a set of analyses on the functional features of the identified genes.Main results. In comparison to NCs, patients with AD exhibited a reduction in average controllability, predominantly within the default mode network (DMN) (63% of parcellations), and an increase in average controllability within the limbic (LIM) network (33% of parcellations). Conversely, AD patients displayed a decrease in modal controllability within the LIM network (27% of parcellations) and an increase in modal controllability within the DMN (80% of parcellations). In AD patients, a significant positive correlation was found between the average controllability of the salience network and the mini-mental state examination scores. The changes in controllability measures exhibited spatial correlation with transcriptome profiles. The significant genes identified exhibited enrichment in neurobiologically relevant pathways and demonstrated preferential expression in various tissues, cell types, and developmental periods.Significance. Our findings have the potential to offer new insights into the genetic mechanisms underlying alterations in the controllability of functional networks in AD. Additionally, these results offered perspectives for a deeper understanding of the pathogenesis and the development of therapeutic strategies for AD.

Recent Advances in Signaling Pathways and Kinase Inhibitors for Leukemia Chemotherapy.

Leukemia is a malignant clonal disease of hematopoietic stem cells, which accounts for about 3% of the total incidence of tumors and is particularly prevalent among children and adolescents. It mainly includes four types of leukemia, namely ALL, AML, CLL, and CML, which are often aggressive and challenging diseases to treat. Several signaling pathways are dysregulated in almost all types of leukemia, such as JAK, PI3K, and MAPK, and others are dysregulated in specific types of leukemia, like Wnt/ß-catenin, Hedgehog, FLT3, Bcr-Abl, and so on. Many efforts have been devoted to developing small molecule inhibitors targeting protein kinases involved in leukemia-related signaling pathways. In this review, we focus on the study of signaling pathways and protein kinases that developed as targets of anti-leukemia drug therapy and report the research progress of relevant small molecule kinase inhibitors over the last five years.

The Effect of Micronutrients on Obese Phenotype of Adult Mice Is Dependent on the Experimental Environment.

The environment of the test laboratory affects the reproducibility of treatment effects on physiological phenotypes of rodents and may be attributed to the plasticity of the epigenome due to nutrient-gene-environment interactions. Here, we explored the reproducibility of adding a multi-vitamin-mineral (MVM) mix to a nutrient-balanced high-fat (HF) diet on obesity, insulin resistance (IR), and gene expression in the tissues of adult male mice. Experiments of the same design were conducted in three independent animal facilities. Adult C57BL/6J male mice were fed an HF diet for 6 weeks (diet induced-obesity model) and then continued for 9-12 weeks on the HF diet with or without 5-fold additions of vitamins A, B1, B6, B12, Zn, and 2-fold Se. The addition of the MVM affected body weight, fat mass, gene expression, and markers of IR in all three locations (p < 0.05). However, the direction of the main effects was influenced by the interaction with the experimental location and its associated environmental conditions known to affect the epigenome. In conclusion, MVM supplementation influenced phenotypes and expression of genes related to adipose function in obese adult male mice, but the experimental location and its associated conditions were significant interacting factors. Preclinical studies investigating the relationship between diet and metabolic outcomes should acknowledge the plasticity of the epigenome and implement measures to reproduce studies in different locations.

Application of deep-learning to the automatic segmentation and classification of lateral lymph nodes on ultrasound images of papillary thyroid carcinoma.

PURPOSE: It is crucial to preoperatively diagnose lateral cervical lymph node (LN) metastases (LNMs) in papillary thyroid carcinoma (PTC) patients. This study aims to develop deep-learning models for the automatic segmentation and classification of LNM on original ultrasound images. METHODS: This study included 1000 lateral cervical LN ultrasound images (consisting of 512 benign and 558 metastatic LNs) collected from 728 patients at the Chongqing General Hospital between March 2022 and July 2023. Three instance segmentation models (MaskRCNN, SOLO and Mask2Former) were constructed to segment and classify ultrasound images of lateral cervical LNs by recognizing each object individually and in a pixel-by-pixel manner. The segmentation and classification results of the three models were compared with an experienced sonographer in the test set. RESULTS: Upon completion of a 200-epoch learning cycle, the loss among the three unique models became negligible. To evaluate the performance of the deep-learning models, the intersection over union threshold was set at 0.75. The mean average precision scores for MaskRCNN, SOLO and Mask2Former were 88.8%, 86.7% and 89.5%, respectively. The segmentation accuracies of the MaskRCNN, SOLO, Mask2Former models and sonographer were 85.6%, 88.0%, 89.5% and 82.3%, respectively. The classification AUCs of the MaskRCNN, SOLO, Mask2Former models and sonographer were 0.886, 0.869, 0.90.2 and 0.852 in the test set, respectively. CONCLUSIONS: The deep learning models could automatically segment and classify lateral cervical LNs with an AUC of 0.92. This approach may serve as a promising tool to assist sonographers in diagnosing lateral cervical LNMs among patients with PTC.

Variations in species diversity patterns and community assembly rules among vegetation types in the karst landscape.

The various vegetation types in the karst landscape have been considered the results of heterogeneous habitats. However, the lack of a comprehensive understanding of regional biodiversity patterns and the underlying ecological processes limits further research on ecological management. This study established forest dynamic plots (FDPs) of the dominant vegetation types (shrubland, SL; mixed tree and shrub forest, MTSF; coniferous forest, CF; coniferous broadleaf mixed forest, CBMF; and broadleaf forest, BF) in the karst landscape and quantified the species diversity patterns and potential ecological processes. The results showed that in terms of diversity patterns, the evenness and species richness of the CF community were significantly lower than other vegetation types, while the BF community had the highest species richness. The other three vegetation types showed no significant variation in species richness and evenness. However, when controlling the number of individuals of FDPs, the rarefied species richness showed significant differences and ranked as BF > SL > MTSF > CBMF > CF, highlighting the importance of considering the impacts of abundance. Additionally, the community assembly of climax communities (CF or BF) was dominated by stochastic processes such as species dispersal or species formation, whereas deterministic processes (habitat filtering) dominated the secondary forests (SL, MTSF, and CBMF). These findings proved that community assembly differs mainly between the climax community and other communities. Hence, it is crucial to consider the biodiversity and of the potential underlying ecological processes together when studying regional ecology and management, particularly in heterogeneous ecosystems.

IInception-CBAM-IBiGRU based fault diagnosis method for asynchronous motors.

Aiming at the problems of insufficient extraction of asynchronous motor fault features by traditional deep learning algorithms and poor diagnosis of asynchronous motor faults in robust noise environments, this paper proposes an end-to-end fault diagnosis method for asynchronous motors based on IInception-CBAM-IBiGRU. The method first uses a signal-to-grayscale image conversion method to convert one-dimensional vibration signals into two-dimensional images and initially extracts shallow features through two-dimensional convolution; then the Improved Inception (IInception) module is used as a residual block to learning features at different scales with a residual structure, and extracts its important feature information through the Convolutional Block Attention Module (CBAM) to extract important feature information and adjust the weight parameters; then the feature information is input to the Improved Bi-directional Gate Recurrent Unit (IBiGRU) to extract its timing features further; finally, the fault identification is achieved by the SoftMax function. The primary hyperparameters in the model are optimized by the Weighted Mean Of Vectors Algorithm (INFO). The experimental results show that the method is effective in fault diagnosis of asynchronous motors, with an accuracy rate close to 100%, and can still maintain a high accuracy rate under the condition of low noise ratio, with good robustness and generalization ability.

Atypical dynamic network reconfiguration and genetic mechanisms in patients with major depressive disorder.

BACKGROUND: Brain dynamics underlie complex forms of flexible cognition or the ability to shift between different mental modes. However, the precise dynamic reconfiguration based on multi-layer network analysis and the genetic mechanisms of major depressive disorder (MDD) remains unclear. METHODS: Resting-state functional magnetic resonance imaging (fMRI) data were acquired from the REST-meta-MDD consortium, including 555 patients with MDD and 536 healthy controls (HC). A time-varying multi-layer network was constructed, and dynamic modular characteristics were used to investigate the network reconfiguration. Additionally, partial least squares regression analysis was performed using transcriptional data provided by the Allen Human Brain Atlas (AHBA) to identify genes associated with atypical dynamic network reconfiguration in MDD. RESULTS: In comparison to HC, patients with MDD exhibited lower global and local recruitment coefficients. The local reduction was particularly evident in the salience and subcortical networks. Spatial transcriptome correlation analysis revealed an association between gene expression profiles and atypical dynamic network reconfiguration observed in MDD. Further functional enrichment analyses indicated that positively weighted reconfiguration-related genes were primarily associated with metabolic and biosynthetic pathways. Additionally, negatively enriched genes were predominantly related to programmed cell death-related terms. CONCLUSIONS: Our findings offer robust evidence of the atypical dynamic reconfiguration in patients with MDD from a novel perspective. These results offer valuable insights for further exploration into the mechanisms underlying MDD.

Transmembrane modification of tumor vascular targeting peptide A7R as molecular cargo delivery tool.

In recent years, targeting tumor angiogenesis has emerged as a prominent research focus in the treatment and prevention of tumor expansion. A7R (ATWLPPR) exhibits high affinity and specificity for VEGFR-2, which is overexpressed in various tumors. To enhance the tumor tissue and cell penetration capabilities of A7R, we substituted its non-critical amino acid with Arginine (R) and Glutamic acid (E), cyclized the mutant peptide, and linked it to the membrane permeation sequence using coordination principles. We designed and synthesized fifteen novel penetrating peptides that target tumor blood vessels and cells, followed by conducting various biological evaluations and cell imaging experiments. The results demonstrated that Cyclo-A7R-RRR and A7R-RLLRLLR exhibited excellent permeability towards tumor cells, with Cyclo-A7R-RRR showing superior serum stability compared to A7R. Furthermore, the modified peptides showed no toxicity towards HeLa cells, U251 cells, HuH-7 cells, and HEK293 cells under 10 µmol/L. Utilizing Cyclo-A7R-RRR or A7R-RLLRLLR for transmembrane delivery of drug molecules could significantly improve their efficacy. Our findings broaden the potential application scenarios of A7R in targeted tumor angiogenesis.