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Facial expression recognition (FER) plays a crucial role in affective computing, enhancing human-computer interaction by enabling machines to understand and respond to human emotions. Despite advancements in deep learning, current FER systems often struggle with challenges such as occlusions, head pose variations, and motion blur in natural environments. These challenges highlight the need for more robust FER solutions. To address these issues, we propose the Attention-Enhanced Multi-Layer Transformer (AEMT) model, which integrates a dual-branch Convolutional Neural Network (CNN), an Attentional Selective Fusion (ASF) module, and a Multi-Layer Transformer Encoder (MTE) with transfer learning. The dual-branch CNN captures detailed texture and color information by processing RGB and Local Binary Pattern (LBP) features separately. The ASF module selectively enhances relevant features by applying global and local attention mechanisms to the extracted features. The MTE captures long-range dependencies and models the complex relationships between features, collectively improving feature representation and classification accuracy. Our model was evaluated on the RAF-DB and AffectNet datasets. Experimental results demonstrate that the AEMT model achieved an accuracy of 81.45% on RAF-DB and 71.23% on AffectNet, significantly outperforming existing state-of-the-art methods. These results indicate that our model effectively addresses the challenges of FER in natural environments, providing a more robust and accurate solution. The AEMT model significantly advances the field of FER by improving the robustness and accuracy of emotion recognition in complex real-world scenarios. This work not only enhances the capabilities of affective computing systems but also opens new avenues for future research in improving model efficiency and expanding multimodal data integration. [ABSTRACT FROM AUTHOR]

Borderline ovarian tumors (BOTs) have low malignant potential and favorable prognoses. The group of patients most affected by BOTs are women of childbearing age; therefore, fertility-sparing surgery is considered the first choice of treatment for young patients. Several studies have reported that conservation treatment was associated with a higher recurrence rate; however, data on the treatment and clinical management of patients after relapse are scarce. A 19-year-old woman was admitted to our hospital for two weeks due to unexplained abdominal distension. Palpation of the uterus showed no significant abnormality, but an ultrasound examination revealed abdominal effusion and a solid cystic mass in front of the uterus. Since the patient wanted to preserve fertility, she underwent fertility-sparing procedures, including abdominal right adnexectomy and excision of the left ovarian mass. Histological examination confirmed stage III serous BOTs (desmoplastic non-invasive implants associated with ovarian serous borderline tumor). After the surgery, the patient had normal menstruation. After 20 months, the patient experienced a recurrence of serous type BOTs (stage IIIC; serous carcinoma, non-invasive, low grade, ICD-O: 8460/2), and a second fertility-sparing surgery was performed. Presently, although no disease recurrence was detected at the last follow-up, the patient had no menses for six months and had not yet completed childbirth. In young women diagnosed with BOTs, fertility preservation surgery might be associated with a high risk of recurrence, especially for those with advanced staged disease. Clinically, pregnancy should be recommended as early as possible after surgery, and long-term follow-up is required. [ABSTRACT FROM AUTHOR]

The negative impact of lipid peroxidation on health is intimately tied to its oxidation products. In this study, methyl oleate was oxidized at 180℃ for 0, 2, 4, 8 and 12 h respectively. The free radicals and volatile components generated during the oxidation process were determined using electron spin resonance and headspace solid-phase microextraction (HS-SPME)-GC-MS. The pro-inflammatory effects of oxidized methyl oleate were evaluated in RAW264.7 cells. Then partial least-squares regression (PLSR) models were established for predicting the 3 pro-inflammatory genes expression based on the volatile components. The results revealed that the alkoxy radical content increased rapidly during oxidation from 4 h to 8 h, and the rate of oxidation of methyl oleate dropped after 8 h. A total of 27 volatile oxidation compounds were detected by HS-SPME-GC-MS. The content of most compounds, including aldehydes, esters, and acids, exhibited a pattern of initial increase and then decrease as the oxidation time increased. Similarly, the proinflammatory effects of oxidized methyl oleate peaked after 8 h of oxidation. The PLSR quantitative prediction models showed that the coefficient of determination (R² P) between the predicted and measured values of the 3 inflammatory gene expressions were 0.915, 0.946 and 0.951 respectively. The established PLSR model predicts the pro-inflammatory effects of oxidized methyl oleate well and provides a theoretical foundation for quick evaluation of the pro-inflammatory effects of oxidized lipids. [ABSTRACT FROM AUTHOR]

Background: Growing evidence indicated that to develop of atherosclerosis observed more often by people with Alzheimer's disease (AD), but the underlying mechanism is not fully clarified. Considering that amyloid-β (Aβ) deposition in the brain is the key pathophysiology of AD and plasma Aβ is closely relate to Aβ deposition in the brain, in the present study, we investigated the relationships between atherosclerosis and plasma Aβ levels. Methods: This was a population based cross-sectional study. Patients with high risk of atherosclerosis from Qubao Village, Xi'an were underwent carotid ultrasound for assessment of atherosclerosis. Venous blood was collected on empty stomach in the morning and plasma Aβ1−40 and Aβ1−42 levels were measured using ELISA. Multivariate logistic regression analysis was performed to investigate the relationships between carotid atherosclerosis (CAS) and plasma Aβ levels. Results: Among 344 patients with high risk of atherosclerosis, 251(73.0%) had CAS. In the univariate analysis, the plasma Aβ levels had no significant differences between CAS group and non-CAS group (Aβ1−40: 53.07 ± 9.24 pg/ml vs. 51.67 ± 9.11pg/ml, p = 0.211; Aβ1−42: 40.10 ± 5.57 pg/ml vs. 40.70 pg/ml ± 6.37pg/ml, p = 0.285). Multivariate logistic analysis showed that plasma Aβ levels were not associated with CAS (Aβ1−40: OR = 1.019, 95%CI: 0.985–1.054, p = 0.270;Aβ1−42: OR = 1.028, 95%CI: 0.980–1.079, p = 0.256) in the total study population. After stratified by hypertension, CAS was associated with plasma Aβ1−40 positively (OR = 1.063, 95%CI: 1.007–1.122, p = 0.028) in the non-hypertension group, but not in hypertensive group. When the plasma Aβ concentrations were classified into four groups according to its quartile, the highest level of plasma Aβ1−40 group was associated with CAS significantly (OR = 4.465, 95%CI: 1.024–19.474, p = 0.046). Conclusion: Among patients with high risk of atherosclerosis, CAS was associated with higher plasma Aβ1−40 level in non-hypertension group, but not in hypertension group. These indicated that atherosclerosis is associated with plasma Aβ level, but the relationship may be confounded by hypertension. [ABSTRACT FROM AUTHOR]

Mitochondria harbor the oxidative phosphorylation (OXPHOS) system to sustain cellular respiration. However, the transcriptional regulation of OXPHOS remains largely unexplored. Through the cancer genome atlas (TCGA) transcriptome analysis, transcription factor THAP domain-containing 3 (THAP3) was found to be strongly associated with OXPHOS gene expression. Mechanistically, THAP3 recruited the histone methyltransferase SET and MYND domain-containing protein 3 (SMYD3) to upregulate H3K4me3 and promote OXPHOS gene expression. The levels of THAP3 and SMYD3 were altered by metabolic cues. They collaboratively supported liver cancer cell proliferation and colony formation. In clinical human liver cancer, both of them were overexpressed. THAP3 positively correlated with OXPHOS gene expression. Together, THAP3 cooperates with SMYD3 to epigenetically upregulate cellular respiration and liver cancer cell proliferation. [ABSTRACT FROM AUTHOR]

For over 170 years, general anesthesia has played a crucial role in clinical practice, yet a comprehensive understanding of the neural mechanisms underlying the induction of unconsciousness by general anesthetics remains elusive. Ongoing research into these mechanisms primarily centers around the brain nuclei and neural circuits associated with sleep-wake. In this context, two sophisticated methodologies, optogenetics and chemogenetics, have emerged as vital tools for recording and modulating the activity of specific neuronal populations or circuits within distinct brain regions. Recent advancements have successfully employed these techniques to investigate the impact of general anesthesia on various brain nuclei and neural pathways. This paper provides an in-depth examination of the use of optogenetic and chemogenetic methodologies in studying the effects of general anesthesia on specific brain nuclei and pathways. Additionally, it discusses in depth the advantages and limitations of these two methodologies, as well as the issues that must be considered for scientific research applications. By shedding light on these facets, this paper serves as a valuable reference for furthering the accurate exploration of the neural mechanisms underlying general anesthesia. It aids researchers and clinicians in effectively evaluating the applicability of these techniques in advancing scientific research and clinical practice. [ABSTRACT FROM AUTHOR]

Jujube (Ziziphus jujuba var. jujuba Mill.) and sour jujube (Z. jujuba var. spinosa (Bunge) Hu ex H.F.Chow.) are economically, nutritionally, and ecologically significant members of the Rhamnaceae family. Despite their importance, insufficient research on their genetics and habitats has impeded effective conservation and utilization. To address this knowledge gap, we conducted plastome sequencing, integrated distribution data from China, and assessed genetic diversity and suitable habitat. The plastomes of both species exhibited high conservation and low genetic diversity. A new-found 23 bp species-specific Indel in the petL-petG enabled us to develop a rapid Indel-based identification marker for species discrimination. Phylogenetic analysis and dating illuminated their genetic relationship, showing speciation occurred 6.9 million years ago, in a period of dramatic global temperature fluctuations. Substantial variations in suitable climatic conditions were observed, with the mean temperature of the coldest quarter as the primary factor influencing distributions (-3.16°C-12.73°C for jujube and -5.79°C to 4.11°C for sour jujube, suitability exceeding 0.6). Consequently, distinct conservation strategies are warranted due to differences in suitable habitats, with jujube having a broader distribution and sour jujube concentrated in Northern China. In conclusion, disparate habitats and climatic factors necessitate tailored conservation approaches. Comparing genetic diversity and developing rapid species-specific primers will further enhance the sustainable utilization of these valuable species. [ABSTRACT FROM AUTHOR]

Background: Small extracellular vesicles (sEVs) mediate intercellular communication in the tumor microenvironment (TME) and contribute to the malignant transformation of tumors, including unrestricted growth, metastasis, or therapeutic resistance. However, there is a lack of agents targeting sEVs to overcome or reverse tumor chemotherapy resistance through sEVs-mediated TME reprogramming. Methods: The paclitaxel (PTX)-resistant A549T cell line was used to explore the inhibitory effect of alpha-hederin on impeding the transmission of chemoresistance in non-small cell lung cancer (NSCLC) through the small extracellular vesicles (sEVs) pathway. This investigation utilized the CCK-8 assay and flow cytometry. Transcriptomics, Western blot, oil red O staining, and targeted metabolomics were utilized to evaluate the impact of alpha-hederin on the expression of signaling pathways associated with chemoresistance transmission in NSCLC cells before and after treatment. In vivo molecular imaging and immunohistochemistry were conducted to assess how alphahederin influences the transmission of chemoresistance through the sEVs pathway. RT-PCR was employed to examine the expression of miRNA and lncRNA in response to alpha-hederin treatment. Results: The resistance to PTX chemotherapy in A549T cells was overcome by alpha-hederin through its dependence on sEV secretion. However, the effectiveness of alpha-hederin was compromised when vesicle secretion was blocked by the GW4869 inhibitor. Transcriptomic analysis for 463 upregulated genes in recipient cells exposed to A549T-derived sEVs revealed that these sEVs enhanced TGFß signaling and unsaturated fatty acid synthesis pathways. Alphahederin inhibited 15 types of unsaturated fatty acid synthesis by reducing the signaling activity of the sEVs-mediated TGFß/SMAD2 pathway. Further, we observed that alpha-hederin promoted the production of three microRNAs (miRNAs, including miR-21-5p, miR-23a-3p, and miR-125b-5p) and the sorting to sEVs in A549T cells. These miRNAs targeted the TGFß/SMADs signaling activity in sEVs-recipient cells and sensitized them to the PTX therapy. Conclusion: Our finding demonstrated that alpha-hederin could sensitize PTXresistant NSCLC cells by sEV-mediated multiple miRNAs accumulation, and inhibiting TGFß/SMAD2 pathways in recipient cells. [ABSTRACT FROM AUTHOR]

The article provides an overview of first-line immunotherapy for advanced non-small cell lung cancer (NSCLC). It explains the mechanism of action of immune checkpoint inhibitors (ICIs) and their role in enhancing the immune system's ability to recognize and kill tumor cells. The article discusses the current status of immunotherapy for NSCLC, including the use of ICIs as monotherapy or in combination with chemotherapy. It emphasizes the clinical benefits of ICI monotherapy for patients with high PD-L1 expression, but suggests that combination therapy is important for expanding the population that will benefit from immunotherapy. The article also discusses the development of novel ICIs and the importance of biomarkers, such as PD-L1 expression, in guiding treatment decisions. It highlights the need for further research and collaboration to improve cancer diagnosis and treatment. [Extracted from the article]

With the expansion and implementation of rural revitalization strategies, there is a constant need for new energy sources for the construction of new townships. Consequently, integrated energy systems with the interconnection and interaction of multiple energy sources are developing rapidly. Biomass energy, a renewable green energy source with low pollution and wide distribution, has significant application potential in integrated energy systems. Considering the application of biomass energy in townships, this study established an integrated biomass energy system and proposed a model to optimize its operation. Lowest economic cost and highest clean energy utilization rate were considered as the objective functions. In addition, a plan was suggested to adjust the heat-electricity ratio based on the characteristics of the combined heat and power of the biomass. Finally, a simulation analysis conducted for a town in China was discussed, demonstrating that the construction of a township integrated-energy system and the use of biomass can significantly reduce operating costs and improve the energy utilization rate. Moreover, by adjusting the heat-electricity ratio, the economic cost was further reduced by 6.70%, whereas the clean energy utilization rate was increased by 5.14%. [ABSTRACT FROM AUTHOR]

Context: Several observational studies have found that hypothyroidism is associated with diabetes and its microvascular complications. However, the cause and effect have not been clarified. Objective: The aim of the study was to examine the causality of such associations by a Mendelian randomization study. Methods: Two-sample Mendelian randomization analysis was conducted to investigate the associations. Summary statistics for hypothyroidism were from the UK Biobank, and diabetes and its microvascular complications were from the largest available genome-wide association studies. MR-Egger, weighted median, inverse variance weighted, simple mode and weighted mode were used to examine the causal associations, and several sensitivity analyses were used to assess pleiotropy. Results: Inverse variance weighted estimates suggested that hypothyroidism was associated with type 1 diabetes and type 1 diabetes with renal complications (b= 9.059926, se= 1.762903, P = 2.76E-07 and b= 10.18375, se= 2.021879, P = 4.73E-07, respectively) but not type 2 diabetes and type 2 diabetes with renal complications. In addition, hypothyroidism was positively associated with severe nonproliferative diabetic retinopathy and proliferative diabetic retinopathy (b= 8.427943, se= 2.142493, P = 8.36E-05 and b= 3.100939, se= 0.74956, P=3.52E-05, respectively). Conclusions: The study identified the causal roles of hypothyroidism in diabetes and its microvascular complications. Hypothyroidism can lead to type 1 diabetes, type 1 diabetes with renal complications, severe nonproliferative diabetic retinopathy and proliferative diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Objectives To assess whole-joint histogram analysis of mono-exponential and bi-exponential diffusion weighted and diffusion kurtosis imaging in evaluating disease activity of axial spondyloarthritis (axSpA). Methods A total of 82 patients with axSpA who underwent both DKI and multi b diffusion weighted imaging of the sacroiliac joints were divided into active and inactive disease groups based on clinical activity indices. Another 17 patients with nonspecific low back pain were included as a control group. The SPARCC scoring system was used to assess the level of sacroiliac joint bone marrow edema. Histogram parameters of apparent diffusion coefficient (ADC), true diffusion coefficient (D), perfusion fraction (f), pseudodiffusion coefficient (D*), mean kurtosis (MK), and mean diffusivity (MD) were calculated. Regions of interest were placed covering the entire sacroiliac joint. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of imaging parameters in distinguishing different groups. Regression analysis was applied to determine the correlation between imaging parameters and clinical activity indices. Results All of the histogram parameters distinguished the active from inactive groups with a low area under the curve (AUC) (max AUCs≤0.71), while the SPARCC score failed to differentiate the two groups (p = 0.08). MD, MK, D, D*, and ADC showed good performance in differentiating active and inactive from control groups (max AUC = 0. 81 ~ 0.98). f50 differentiated the active from control groups with an AUC of 0.72, significantly lower than the maximum AUC for MD, MK, D, ADC, and SPARCC score (all p < 0.05). The max AUC of MD in differentiating inactive from control groups was significantly higher than that of D* and the SPARCC score. MD, D, D*, f, and ADC were positively correlated with BASDAI, while MK was negatively correlated with BASDAI. Only MD was positively correlated with hsCRP. Conclusions Whole-joint histogram analysis of monoexponential, bi-exponential diffusion weighted, and diffusion kurtosis imaging showed good diagnostic performance in differentiating active and inactive axSpA from patients with non-specific back pain. All the imaging parameters were correlated with BASDAI except for SPARCC score. Only DKI-derived MD was correlated with an increase in hsCRP, suggesting its potential use as an imaging biomarker for disease activity in axSpA. Advances in knowledge 1. No significant difference was found between the three models of diffusion weighted imaging in evaluating disease activity of axial spondyloarthritis. 2. Only DKI-derived MD was correlated with an increase in hsCRP, suggesting its potential use as an imaging biomarker for disease activity in axSpA. [ABSTRACT FROM AUTHOR]

BACKGROUND: Emergency patients with sepsis or septic shock are at high risk of death. Despite increasing attention to microhemodynamics, the clinical use of advanced microcirculatory assessment is limited due to its shortcomings. Since blood gas analysis is a widely used technique reflecting global oxygen supply and consumption, it may serve as a surrogate for microcirculation monitoring in septic treatment. METHODS: We performed a search using PubMed, Web of Science, and Google scholar. The studies and reviews that were most relevant to septic microcirculatory dysfunctions and blood gas parameters were identified and included. RESULTS: Based on the pathophysiology of oxygen metabolism, the included articles provided a general overview of employing blood gas analysis and its derived set of indicators for microhemodynamic monitoring in septic care. Notwithstanding flaws, several parameters are linked to changes in the microcirculation. A comprehensive interpretation of blood gas parameters can be used in order to achieve hemodynamic optimization in septic patients. CONCLUSION: Blood gas analysis in combination with clinical performance is a reliable alternative for microcirculatory assessments. A deep understanding of oxygen metabolism in septic settings may help emergency physicians to better use blood gas analysis in the evaluation and treatment of sepsis and septic shock. [ABSTRACT FROM AUTHOR]

Discrimination has been shown in many machine learning applications, which calls for sufficient fairness testing before their deployment in ethic-relevant domains. One widely concerning type of discrimination, testing against group discrimination, mostly hidden, is much less studied, compared with identifying individual discrimination. In this work, we propose TestSGD, an interpretable testing approach that systematically identifies and measures hidden (which we call “subtle”) group discrimination of a neural network characterized by conditions over combinations of the sensitive attributes. Specifically, given a neural network, TestSGD first automatically generates an interpretable rule set that categorizes the input space into two groups. Alongside, TestSGD also provides an estimated group discrimination score based on sampling the input space to measure the degree of the identified subtle group discrimination, which is guaranteed to be accurate up to an error bound. We evaluate TestSGD on multiple neural network models trained on popular datasets including both structured data and text data. The experiment results show that TestSGD is effective and efficient in identifying and measuring such subtle group discrimination that has never been revealed before. Furthermore, we show that the testing results of TestSGD can be used to mitigate such discrimination through retraining with negligible accuracy drop. [ABSTRACT FROM AUTHOR]

Recently, there has been significant growth of interest in applying software engineering techniques for the quality assurance of deep learning (DL) systems. One popular direction is DL testing-that is, given a property of test, defects of DL systems are found either by fuzzing or guided search with the help of certain testing metrics. However, recent studies have revealed that the neuron coverage metrics, which are commonly used by most existing DL testing approaches, are not necessarily correlated with model quality (e.g., robustness, the most studied model property), and are also not an effective measurement on the confidence of the model quality after testing. In this work, we address this gap by proposing a novel testing framework calledQuoTe (i.e., Quality-oriented Testing). A key part of QuoTe is a quantitative measurement on (1) the value of each test case in enhancing the model property of interest (often via retraining) and (2) the convergence quality of the model property improvement. QuoTe utilizes the proposed metric to automatically select or generate valuable test cases for improving model quality. The proposedmetric is also a lightweight yet strong indicator of how well the improvement converged. Extensive experiments on both image and tabular datasets with a variety of model architectures confirm the effectiveness and efficiency of QuoTe in improving DL model quality-that is, robustness and fairness. As a generic quality-oriented testing framework, future adaptations can be made to other domains (e.g., text) as well as other model properties. [ABSTRACT FROM AUTHOR]

Background: The role of the microbiota-gut-brain axis in Parkinson's disease (PD) has received increasing attention. Although gender differences are known to an essential role in the epidemiology and clinical course of PD, there are no studies on the sex specificity of the microbiota-gut-brain axis in the development and progression of PD. Methods: Fresh fecal samples from 24 PD patients (13 males, 11 females) were collected for metagenomic sequencing. The composition and function of the gut microbiota were analyzed by resting-state functional magnetic resonance imaging (fMRI). Gender-dependent differences in brain ALFF values and their correlation with microbiota were further analyzed. Results: The relative abundance of Propionivibrio, Thermosediminibacter, and Flavobacteriaceae_noname was increased in male PD patients. LEfse analysis showed that Verrucomicrobial, Akkermansiaceae, and Akkermansia were dominant in the males. In female patients, the relative abundance of Propionicicella was decreased and Escherichia, Escherichia_coli, and Lachnospiraceae were predominant. The expression of the sesquiterpenoid and triterpenoid biosynthesis pathways was increased in male PD patients and was statistically different from females. Compared to the Male PD patients, female patients showed decreased ALFF values in the left inferior parietal regions, and the relative abundance of Propionivibrio was positively correlated with the regional ALFF values. Conclusion: Our study provides novel clinical evidence of the gender-specific relationship between gut microbiota alterations and brain function in PD patients, highlighting the critical role of the microbiota-gut-brain axis in gender differences in PD. [ABSTRACT FROM AUTHOR]

Radiation and chemicals were the major clinical toxicants known to cause cellular damage during prognostic interventions in vivo. Cellular and molecular damages in the liver were the major causes for the hepatocellular injury due to various toxicities. Though many antioxidants alleviate various types of hepatotoxicities, protection exerted by the combination of N-acetyl cysteine (NA) and Thymoquinone (TQ) in the combined toxicities of radiation and carbon tetrachloride (CCLR) in Sprague-Dawley (SD) rats were unknown. Current research was focused on the protective efficacy of combination of NA with optimized dose of TQ (NATQ) in radiation/CCl4 (CCLR)-induced hepatotoxicities. At the end of the experimental period (6 weeks), body weight, liver weight, serum and liver tissues were analyzed for marker enzymes (AST, ALT, LDH), oxidative stress level (MDA, GSSG), antioxidant status (GSH, Vitamin E, Vitamin C), activities of enzymatic antioxidants (SOD, GPx, CAT, GST), liver histopathology and studies for the hepatic levels of NfkB, IL-6, TNF-a, MMP-3, MMP-12, Nrf2 and HO-1 were done. Significant (p=0.05) toxicological alterations in the above parameters were recovered to normal in the treatment of NATQ combinations in SD rats. In conclusion, we provide evidence of protective efficacy of NATQ combination in alleviating the hepatotoxicities produced by CCLR in SD rats. [ABSTRACT FROM AUTHOR]

An optimization algorithm for nonsmooth nonconvex constrained optimization problems with upper-C² objective functions is proposed and analyzed. Upper-C² is a weakly concave property that exists in difference of convex (DC) functions and arises naturally in many applications, particularly certain classes of solutions to parametric optimization problems e.g., recourse of stochastic programming and projection onto closed sets. The algorithm can be viewed as an extension of sequential quadratic programming (SQP) to nonsmooth problems with upper-² objectives or a simplified bundle method. It is globally convergent with bounded algorithm parameters that are updated with a trust-region criterion. The algorithm handles general smooth constraints through linearization and uses a line search to ensure progress. The potential inconsistencies from the linearization of the constraints are addressed through a penalty method. The capabilities of the algorithm are demonstrated by solving both simple upper-² problems and a real-world optimal power flow problem used in current power grid industry practices. [ABSTRACT FROM AUTHOR]

The amygdala, hippocampus, and subgenual cortex area 25 (A25) are engaged in complex cognitive-emotional processes. Yet pathway interactions from hippocampus and A25 with postsynaptic sites in amygdala remain largely unknown. In rhesus monkeys of both sexes, we studied with neural tracers how pathways from A25 and hippocampus interface with excitatory and inhibitory microcircuits in amygdala at multiple scales. We found that both hippocampus and A25 innervate distinct as well as overlapping sites of the basolateral (BL) amygdalar nucleus. Unique hippocampal pathways heavily innervated the intrinsic paralaminar basolateral nucleus, which is associated with plasticity. In contrast, orbital A25 preferentially innervated another intrinsic network, the intercalated masses, an inhibitory reticulum that gates amygdalar autonomic output and inhibits fear-related behaviors. Finally, using high-resolution confocal and electron microscopy (EM), we found that among inhibitory postsynaptic targets in BL, both hippocampal and A25 pathways preferentially formed synapses with calretinin (CR) neurons, which are known for disinhibition and may enhance excitatory drive in the amygdala. Among other inhibitory postsynaptic sites, A25 pathways innervated the powerful parvalbumin (PV) neurons which may flexibly regulate the gain of neuronal assemblies in the BL that affect the internal state. In contrast, hippocampal pathways innervated calbindin (CB) inhibitory neurons, which modulate specific excitatory inputs for processing context and learning correct associations. Common and unique patterns of innervation in amygdala by hippocampus and A25 have implications for how complex cognitive and emotional processes may be selectively disrupted in psychiatric disorders. [ABSTRACT FROM AUTHOR]

Microtubules are essential for regulating cell morphogenesis, plant growth, and the response of plants to abiotic stresses. TPX2 proteins are the main players determining the spatiotemporally dynamic nature of the MTs. However, how TPX2 members respond to abiotic stresses in poplar remains largely unknown. Herein, 19 TPX2 family members were identified from the poplar genome and analyzed the structural characteristics as well as gene expression patterns. All TPX2 members had the conserved structural characteristics, but exhibited different expression profiles in different tissues, indicating their varying roles during plant growth. Additionally, several light, hormone, and abiotic stress responsive cis-acting regulatory elements were detected on the promoters of PtTPX2 genes. Furthermore, expression analysis in various tissues of Populus trichocarpa showed that the PtTPX2 genes responded differently to heat, drought and salt stress. In summary, these results provide a comprehensive analysis for the TPX2 gene family in poplar and an effective contribution to revealing the mechanisms of PtTPX2 in the regulatory network of abiotic stress. [ABSTRACT FROM AUTHOR]

Aim. Due to the changes of bowel physiological structure and functional disorders after rectal cancer surgery, patients will face many bowel dysfunction for a long time, which will greatly affect their quality of life. The purpose of this review is to integrate the qualitative research on the experience of bowel dysfunction and coping strategies in postoperative patients with rectal cancer. Methods. Systematic retrieval of PubMed, EMbase, Cochrane Library, CINAHL, Web of Sciences, PsycINFO, Willey and other databases was carried out by using the method of subject words and keywords. The Critical Appraisal Skill Programme (CASP) Qualitative Studies Checklist was used for Qualitative assessment. The findings were extracted from the included study and synthesized into the final themes, which was evaluated strictly in accordance with the ConQual process. Results. Nine studies involving 345 participants were included and two main themes were extracted: ``Experience a series of changes caused by bowel dysfunction" and ``nmet needs and coping strategies facing bowel dysfunction". The changes of rectal cancer patients who experience bowel dysfunction after operation mainly include three parts: bowel dysfunction is more than just a bowel reaction, which covers the bowel symptoms themselves and the subsequent body-related symptoms. The interruption of a normal life, mainly reflected in personal, family, and social life. Complex psychological reactions to bowel dysfunction, psychological changes have a dual nature, showing a positive and negative intertwined. There are two main aspects of unmet needs and coping strategies: the demand is mainly manifested in the need for information and support from medical professionals, while the coping strategy mainly includes diet, activity and drug management. Conclusion. Rectal cancer patient often experience persistent bowel dysfunction after operation, which has a certain physical and mental effects. A series of new needs of postoperative patients are often not fully met, and patients often rely on their own empirical attempts to seek balance, less can get professional support. Future studies need to focus on how to provide continuous information support for postoperative rectal cancer patients, especially professional care from health care staff. [ABSTRACT FROM AUTHOR]

The green peach aphid, Myzus persicae, is the most serious agricultural pest worldwide, and its control relies mainly on insecticides such as neonicotinoids, due to their broad spectrum. Nicotinic acetylcholine receptors (nAChRs) are the target genes of neonicotinoids, and better knowledge of their toxicological mechanisms is crucial for developing new specific neonicotinoids, especially for non-model insects. In this study, we successfully cloned four nAChR a subunits in M. persicae and coexpressed them with Rattus norvegicus ß2 in the Xenopus oocyte system. Screening results showed that Mpa1 and Mpa8 were narrowly tuned to sulfoxaflor and thiamethoxam, with EC50 values of 1.117 × 10-4 M and 9.681 × 10-5 M, respectively. Molecular modeling and docking results showed that a combination of positive (Lys) and aromatic (Trp) residues or positive (Lys) and polar (Ser) residues located at the interface of the corresponding a and ß subunits of nAChR in Mpa1/ratß2 or Mpa8/ratß2 was the main contributor to ligand binding. Therefore, three residues (W143A, K144A and F260A) of Mpa1 and four residues (K63A, K134A, S146A and V290A) of Mpa8 were mutated to validate their contributions to the binding affinity of the corresponding ligand. In Mpa1, W143A resulted in a significantly lower sensitivity to sulfoxaflor than the other three mutations, and in Mpa8, S146A significantly reduced the response to thiamethoxam, suggesting crucial roles of these predicted hydrogen bonding sites in channel activation. These results provide evidence of the neonicotinoid toxicological mechanism in M. persicae and reveal new gene targets and binding sites for future pesticide design. [ABSTRACT FROM AUTHOR]

Traditional international tax rules empower a source state to tax non-residents who have a strong physical connection to that state. Digitalized business models reduce, or even eliminate, the need for a physical presence to conduct economic activities in the state where customers are located. This change has created significant challenges for tax administrations, and many jurisdictions have adopted unilateral digital services taxes to increase collection from digitalized businesses. The OECD/G20 Inclusive Framework aims to reform the 'outdated' international tax rules by promoting the Pillar One project on the tax challenges of digitalization in order to enable greater taxing rights by market jurisdiction. However, Pillar One seems to foster uncertainty rather than reassurance. This article considers the possibility of coordinating digital services taxes among individual jurisdictions: instead of focusing on the uncertainty and complexity of Pillar One, the OECD could use the Inclusive Framework to provide guidance on the collection of digital services taxes to protect taxing rights of market states and prevent double taxation of multinational enterprises. [ABSTRACT FROM AUTHOR]

Cold hazard is one of the major meteorological disasters in winter. However, the meteorological conditions for the cold hazard events vary significantly with both the feature of the event and the region of occurrence. This study divides winter cold hazard events in China into three categories based on the daily gridded dataset of cold hazards from November 1980 to March 2020: events without wintry precipitation (hazardous low temperature, abrupt temperature drop, and/or freezing), with wintry precipitation only (hazardous sleet and/or snowstorm), and with both. The region-dependent multivariate meteorological conditions for each category of cold hazards are investigated using ERA5 reanalysis data. Results show that the surface air temperature (T2m) and its anomaly (T2m_anom) are lower than climatology during cold hazards. But the difference in T2m among provinces exceeds 30 °C, and even for the same province, the difference among different categories of cold hazards exceeds 10 °C. The region- and category-dependent differences of T2m_anom and daily temperature drop (∆T24) are also large, about 5 °C and 2 °C d−1, respectively. The Multivariate Empirical Orthogonal Function analysis has further been applied to not only the abovementioned temperature-related variables but also the precipitation-related variables (i.e., daily accumulated total precipitation, daily accumulated snowfall, and daily mean snow depth) in the middle and lower Yangtze River region, which reveals the event-mean state and spatial–temporal coupling evolution during the progression of the event for the selected key meteorological variables. The meteorological conditions for cold hazards put forward by this study could provide region-dependent and category-dependent reference for the prediction and warning of cold hazards. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is a chronic autoimmune-related disease that causes inflammation of the intestine. Ankylosing spondylitis (AS) is a common extraintestinal complication of UC involving the sacroiliac joint. However, the pathogenesis of AS secondary to UC has not been studied. This study aimed to investigate the shared pathways and potential common biomarkers of UC and AS. Methods: Microarray data downloaded from the Gene Expression Omnibus (GEO) database were used to screen differentially expressed genes (DEGs) in the UC and AS datasets. Weighted gene co-expression network analysis (WGCNA) was performed to identify co-expression modules related to UC and AS. Shared genes were then further analyzed for functional pathway enrichment. Next, the optimal common biomarker was selected using SVM-RFF and further validated using two independent GEO datasets. Finally, immune infiltration analysis was used to investigate the correlation of immune cell infiltration with common biomarkers in UC and AS. Results: A total of 4428 and 2438 DEGs in UC and AS, respectively, were screened. Four modules were identified as significant for UC and AS using WGCNA. A total of 25 genes overlapped with the strongest positive and negative modules of UC and AS. KEGG analysis showed these genes may be involved in the mitogen-activated protein kinase (MAPK) signaling pathway. GO analysis indicated that these genes were significantly enriched for RNA localization. PAN3 was selected as the optimal common biomarker for UC and AS. Immune infiltration analysis showed that the expression of PAN3 was correlated with changes in immune cells. Conclusion: This study first explored the common pathways and genetic diagnostic markers involved in UC and AS using bioinformatic analysis. Results suggest that the MAPK signaling pathway may be associated with both pathogeneses and that PAN3 may be a potential diagnostic marker for patients with UC complicated by AS. [ABSTRACT FROM AUTHOR]

Warburg effect is characterized by excessive consumption of glucose by the tumor cells under both aerobic and hypoxic conditions. This metabolic reprogramming allows the tumor cells to adapt to the unique microenvironment and proliferate rapidly, and also promotes tumor metastasis and therapy resistance. Metabolic reprogramming of tumor cells is driven by the aberrant expression and activity of metabolic enzymes, which results in the accumulation of oncometabolites, and the hyperactivation of intracellular growth signals. Recent studies suggest that tumor-associated metabolic remodeling also depends on intercellular communication within the tumor microenvironment (TME). Small extracellular vesicles (sEVs), also known as exosomes, are smaller than 200 nmin diameter and are formed by the fusion of multivesicular bodies with the plasma membrane. The sEVs are instrumental in transporting cargoes such as proteins, nucleic acids or metabolites between the tumor, stromal and immune cells of the TME, and are thus involved in reprogramming the glucose metabolism of recipient cells. In this review, we have summarized the biogenesis and functions of sEVs and metabolic cargos, and the mechanisms through they drive the Warburg effect. Furthermore, the potential applications of targeting sEV-mediated metabolic pathways in tumor liquid biopsy, imaging diagnosis and drug development have also been discussed. [ABSTRACT FROM AUTHOR]

Coptis huanjiangensis, a new species of Ranunculaceae distributed in the valleys of Jiuwanshan National Natural Reserve in Huanjiang county (Guangxi, China), is described and illustrated for the first time based on morphological and plastome sequences data. It differs from C. chinensis, C. deltoidei and C. omeiensis mainly by having notably longer petiole, scape, bigger leaf blade with lobes obviously remote and robust rhizomes without stolons. Phylogenetic analyses support that C. huanjiangensis is sister to C. omeiensis and C. deltoidei. [ABSTRACT FROM AUTHOR]

The genus Coptis belongs to the Ranunculaceae family, containing 15 recognized species highly diverse in morphology. It is a conspicuous taxon with special evolutionary position, distribution pattern and medicinal value, which makes it to be of great research and conservation significance. In order to better understand the evolutionary dynamics of Coptis and promote more practical conservation measures, we performed plastome sequencing and used the sequencing data in combination with worldwide occurrence data of Coptis to estimate genetic diversity and divergence times, rebuild biogeographic history and predict its potential suitable distribution area. The average nucleotide diversity of Coptis was 0.0067 and the hotspot regions with the highest hypermutation levels were located in the ycf1 gene. Coptis is most likely to have originated in North America and Japanese archipelago and has a typical Eastern Asian and North American disjunct distribution pattern, while the species diversity center is located in Mid-West China and Japan. The crown age of the genus is estimated at around 8.49 Mya. The most suitable climatic conditions for Coptis were as follows: precipitation of driest quarter > 25.5 mm, annual precipitation > 844.9 mm and annual mean temperature -3.1 to 19 °C. The global and China suitable area shows an upward trend in the future when emission of greenhouse gases is well controlled, but the area, especially in China, decreases significantly without greenhouse gas policy interventions. The results of this study provide a comprehensive insight into the Coptis evolutionary dynamics and will facilitate future conservation efforts. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a devastating central nervous system disease, caused by physical traumas. With the characteristic of high disability rate, catastrophic dysfunction, and enormous burden on the patient's family, SCI has become a tough neurological problem without efficient treatments. Contemporarily, the pathophysiology of SCI comprises complicated and underlying mechanisms, in which oxidative stress (OS) may play a critical role in contributing to a cascade of secondary injuries. OS substantively leads to ion imbalance, lipid peroxidation, inflammatory cell infiltration, mitochondrial disorder, and neuronal dysfunction. Hence, seeking the therapeutic intervention of alleviating OS and appropriate antioxidants is an essential clinical strategy. Previous studies have reported that traditional Chinese medicine (TCM) has antioxidant, anti-inflammatory, antiapoptotic and neuroprotective effects on alleviating SCI. Notably, the antioxidant effects of some metabolites and compounds of TCM have obtained numerous verifications, suggesting a potential therapeutic strategy for SCI. This review aims at investigating the mechanisms of OS in SCI and highlighting some TCM with antioxidant capacity used in the treatment of SCI. [ABSTRACT FROM AUTHOR]

Natural rubber (NR) is an essential industrial raw material widely used in our life. Hevea brasiliensis (Reyan7-33-97) is an economic plant producing natural rubber. Long non-coding RNAs (lncRNAs) are emerging as crucial regulators in numerous biological processes while the characterization and analysis of lncRNAs in Hevea brasiliensis are still largely unrevealed. We integrated the transcriptome datasets from multiple tissues to identify rubber lncRNAs. As a result, 12,029 lncRNAs were found and characterized with notably distinctive features such as longer exon, lower expression levels and GC content, and more tissue specificity in comparison with mRNAs. We discovered thousands of tissue-specific lncRNAs in rubber root, latex, bark, leaf, flower, and seed tissues. The functional enrichment result reveals that tissue-specific lncRNAs are potentially referred to particular functions of tissues, while the non-tissue specific is related to the translation and metabolic processes. In the present study, a comprehensive lncRNA dataset was identified and its functional profile in Hevea brasiliensis was explored, which provides an annotation resource and important clues to understand the biological functions of lncRNAs in Hevea brasiliensis. [ABSTRACT FROM AUTHOR]

Establishing a portable diagnostic method for identifying plant pathogens is essential to prevent the spread of plant disease, especially in field and customs inspections. Leptosphaeria maculans (L. maculans) is an aggressive fungus, which causes severe phoma stem canker of Brassica napus, responsible for major yield losses of oilseed rape worldwide. In this study, CRISPR/Cas12a-based detection system and recombinase polymerase amplification (RPA) technique were employed to develop a rapid and sensitive detection method for identifying L. maculans. The involved RPA pre-amplification and CRISPR/Cas12a cleavage confer considerable sensitivity and selectivity, which can be finished within 45min with a LOD of 4.7 genomic DNA copies. This detection system was further developed to two portable platforms, i.e., one-pot lateral flow detection and all-in-one chip lateral flow assay (AOCLFA), which integrates the lyophilized recombinase polymerase amplification (RPA) reagents and lyophilized Cas12a cleavage reagents in one tube or chip. The developed portable platforms have flexible portability and simple operation for the detection of L. maculans from plant tissues in the field. The proposed portable suitcase containing the minimum equipment, regents, and AOCLFA meets the practical needs of rapid on-site disease screening of plant fungi, port quarantine, or pathogen spreading control. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) is a severe public health concern, and Gastrointestinal (GI) symptoms are becoming more common among co-morbidities. The evidence has to be updated depending on differences in different parts of the world. This systematic review and meta-analysis aimed to better understand the existing epidemiological condition and help make health-related decisions. Methods: Searches in PubMed, Web of Science, Embase databases are limited to 14 March 2022. We reviewed the global prevalence of ASD and the prevalence of GI in people with ASD. Data were extracted by two independent researchers. Literature quality assessment using the National Institutes of Health Study Quality Assessment Tool. Results: We discovered that the global pooled prevalence of ASD was 98/10,000 (95% confidence interval, 95%CI: 81/10,000-118/10,000, I2 = 99.99%, p < 0.001), with 48.67% (95%CI: 43.50 -53.86, I2 = 99.51%) of individuals with ASD reporting GI symptoms. Based on the subgroup analyses, we found a higher prevalence of ASD in males (90/10,000, 95%CI: 71/10,000-112/10,000, I2 = 99.99%) than females (21/10,000, 95%CI: 15/10,000-27/10,000, I2 = 99.99%). Prevalence of pooling is higher in developing countries (155/10,000, 95% CI: 111/10,000-204/10,000, I2 = 99.87%) than in developed countries (85/10,000, 95%CI: 67/10,000-105/10,000, I2 = 99.99%). Conclusion: The global prevalence of ASD and the prevalence of GI symptoms in ASD are both significant. The prevalence of ASD is much higher in men than in women. Further attention to ASD and its related comorbidities will be required in the future to inform coping strategy adaptation. [ABSTRACT FROM AUTHOR]

Leaf rolling is an important agronomic trait in wheat (Triticum aestivum L.). Moderate leaf rolling keeps leaves upright and maintains the relatively normal photosynthesis of plants under drought stress. However, the molecular mechanism of wheat leaf rolling remains unclear. Here, we identified a candidate gene TaMYB5-3A that regulates leaf rolling by using a genome-wide association study (GWAS) in a panel of 323 wheat accessions. Phenotype analysis indicated that the leaves of tamyb5 mutants were flatter than that of the wild type under drought condition. A nucleotide variation in the TaMYB5-3A coding region resulted in a substitution of Thr to Lys, which corresponds to two alleles SNP-3A-1 and SNP-3A-2. The leaf rolling index (LRI) of the SNP-3A-1 genotype was significantly lower than that of the SNP-3A-2 genotype. In addition, TaMYB5-3A alleles were associated with canopy temperature (CT) in multiple environments. The CT of the SNP-3A-1 genotype was lower than that of the SNP-3A-2 genotype. Gene expression analysis showed that TaMYB5-3A was mainly expressed in leaves and down-regulated by PEG and ABA treatment. TaMYB5 induces TaNRL1 gene expression through the direct binding to the AC cis-acting element of the promoter of the target gene, which was validated by EMSA (electrophoretic mobility shift assay). Our results revealed a crucial molecular mechanism in wheat leaf rolling and provided the theoretical basis and a gene resource for crop breeding. [ABSTRACT FROM AUTHOR]

Background: Biomarkers that predict the efficacy of first-line tyrosine kinase inhibitors (TKIs) are pivotal in epidermal growth factor receptor (EGFR) mutant advanced lung adenocarcinoma. Imaging-based biomarkers have attracted much attention in anticancer therapy. This study aims to use the machine learning method to distinguish EGFR mutation status and further explores the predictive role of EGFR mutation-related radiomics features in response to first-line TKIs. Methods: We retrospectively analyzed pretreatment CT images and clinical information from a cohort of lung adenocarcinomas. We entered the topranked features into a support vector machine (SVM) classifier to establish a radiomics signature that predicted EGFR mutation status. Furthermore, we identified the best response-related features based on EGFR mutant-related features in first-line TKI therapy patients. Then we test and validate the predictive effect of the best response-related features for progression-free survival (PFS). Results: Six hundred ninety-two patients were enrolled in building radiomics signatures. The 13 top-ranked features were input into an SVM classifier to establish the radiomics signature of the training cohort (n = 514), and the predictive score of the radiomics signature was assessed on an independent validation group with 178 patients and obtained an area under the curve (AUC) of 74.13%, an F1 score of 68.29%, a specificity of 79.55%, an accuracy of 70.79%, and a sensitivity of 62.22%. More importantly, the skewness-Low (=0.882) or 10th percentile-Low group (=21.132) had a superior partial response (PR) rate than the skewness-High or 10th percentile-High group (p < 0.01). Higher skewness (hazard ratio (HR) = 1.722, p = 0.001) was also found to be significantly associated with worse PFS. Conclusions: The radiomics signature can be used to predict EGFR mutation status. Skewness may contribute to the stratification of disease progression in lung cancer patients treated with first-line TKIs. [ABSTRACT FROM AUTHOR]

Background: Non-small cell lung cancer (NSCLC), caused by abnormal gene drive, may have primary drug resistance after treatment with tyrosine kinase inhibitors (EGFR-TKIs). Therefore, we explore whether the primary drug-resistant NSCLC treated with EGFR-TKI is related to the miR-21/Sonic Hedgehog (SHH)/PI3K/AKT pathway. Methods: The patients from our hospital who meet the AJCC TNM staging (7th edition) stage IIIB and stage IV NSCLC were selected in this case study. Thereafter, the treatment response of EGFR-TKIs was evaluated according to the solid tumor efficacy evaluation standard (version 1.1). The patients were divided into the EGFR-TKIs primary drug resistance group (EGFR-TKIs-Primary-R) and the EGFR-TKIs sensitive group (EGFR-TKIs-Primary-S). Apoptosis level and degree of fibrosis in patients' tumor tissues were detected by the TUNEL assay and Masson staining, respectively. The levels of miR-21 and GLI1 were measured by qRT-PCR technique. The contents of E-cadherin and Snail were detected by IF method, and the degree of PI3K/AKT phosphorylation was measured using IHC technique. Results: Compared with the EGFR-TKIs-Primary-S group, the EGFR-TKIs-Primary-R group showed lower levels of apoptosis and tumor tissue fibrosis. The levels of miR-21, GLI1, Snail, p-PI3K and p-AKT increased, while the level of E-cadherin decreased. However, the levels of total protein PI3K and AKT remained the same. Conclusion: NSCLC of primary EGFR-TKI resistance was found to be related to miR-21/SHH, the process of epithelial to mesenchymal transition (EMT), and PI3K/AKT phosphorylation. The present study provides a reference for future research in drug resistance, and paves the way to discover new therapeutic gene targets to alleviate lung cancer drug resistance. [ABSTRACT FROM AUTHOR]