Insufficient Expression Research Articles

Semaphorin 3A Increases in the Plasma of Women with Diminished Ovarian Reserve Who Respond Better to Controlled Ovarian Stimulation.

Semaphorin 3A (SEMA3A) plays a crucial role in the development, differentiation, and plasticity of specific types of neurons that secrete Gonadotropin-Releasing Hormone (GnRH) and regulates the acquisition and maintenance of reproductive competence in humans and mice. Its insufficient expression has been linked to reproductive disorders in humans, which are characterized by reduced or failed sexual competence. Various mutations, polymorphisms, and alternatively spliced variants of SEMA3A have been associated with infertility. One of the common causes of infertility in women of reproductive age is diminished ovarian reserve (DOR), characterized by a reduced ovarian follicular pool. Despite its clinical significance, there are no universally accepted diagnostic criteria or therapeutic interventions for DOR. In this study, we analyzed the SEMA3A plasma levels in 77 women and investigated their potential role in influencing fertility in patients with DOR. The results revealed that the SEMA3A levels were significantly higher in patients with DOR than in healthy volunteers. Furthermore, the SEMA3A levels were increased in patients who underwent fertility treatment and had positive Beta-Human Chorionic Gonadotropin (βHCG) values (β+) after controlled ovarian stimulation (COS) compared to those who had negative βHCG values (β-). These findings may serve as the basis for future investigations into the diagnosis of infertility and emphasize new possibilities for the SEMA3A-related treatment of sexual hormonal dysfunction that leads to infertility.

CCR10-mediated Enhancement of T Cell Trafficking for Improved Tumor Immunotherapy.

The effectiveness of adoptive T cell therapy for solid tumors remains suboptimal, partly attributed to insufficient T cell infiltration into the tumor site. A promising strategy involves directing T cells towards the tumor utilizing tumor-specific chemokine receptors. We analyzed chemokine receptor expression in activated T cells and chemokine expression in breast and lung cancer using The Cancer Genome Atlas (TCGA) data. Subsequently, we generated 1G4 T cell receptor-engineered T (TCR-T) cells with CCR10 and performed in vitro and in vivo efficacy tests. CCR10 exhibited insufficient expression in various human T cells. Analysis of TCGA RNA sequencing data revealed elevated expression of the chemokine CCL28, the corresponding chemokine for CCR10, in breast and lung cancer. Consequently, we generated CCR10-1G4 TCR-T cells. CCR10-1G4 dual expressing TCR-T cells exhibited comparable cellular cytotoxicity but increased mobility compared to 1G4 TCR-T cells in vitro. Furthermore, injecting CCR10-1G4 dual expressing TCR-T cells into a xenograft tumor model demonstrated enhanced in vivo trafficking and a greater reduction of tumor burden. This study highlights the potential of CCR10 for developing efficient adoptive T-cell treatments targeting solid tumors.

Multimodal Sentiment Analysis Based on Composite Hierarchical Fusion

Abstract In the field of multimodal sentiment analysis, it is an important research task to fully extract modal features and perform efficient fusion. In response to the problems of insufficient semantic information and poor cross-modal fusion effect of traditional sentiment classification models, this paper proposes a composite hierarchical feature fusion method combined with prior knowledge. Firstly, the ALBERT (A Lite BERT) model and the improved ResNet model are constructed for feature extraction of text and image, respectively, and high-dimensional feature vectors are obtained. Secondly, to solve the problem of insufficient semantic information expression in cross-scene, a prior knowledge enhancement model is proposed to enrich the data characteristics of each modality. Finally, to solve the problem of poor cross-modal fusion effect, a composite hierarchical fusion model is proposed, which combines the temporal convolutional network and the attention mechanism to fuse the sequence features of each modality information and realizes the information interaction between different modalities. Experiments on MVSA-Single and MVSA-Multi datasets show that the proposed model is superior to a series of comparison models and has good adaptability in new scenarios.

ПРОБЛЕМА ЭМОЦИОНАЛЬНОСТИ В ВОСПИТАНИИ ИСПОЛНИТЕЛЕЙ-ВОКАЛИСТОВ: В ПОИСКАХ БАЛАНСА И ГАРМОНИИ

Along with many technical tasks, the student and his or her teacher usually face the problem of understanding and adequately reflecting the content of a musical work, which requires a special emotional approach. Emotional lability and self-regulation are extremely important for the performer also because of the need for free and natural behavior on stage. In the matter of emotionality, any performer and especially a vocalist needs to find a balance, since both insufficient and excessive expression of emotions are unacceptable in professional art. Exploring the underlying causes of this phenomenon, the author of the article gives practical recommendations for overcoming both inexpressive and deliberately emotional performance. One of the author’s key ideas is to understand the need to develop a singer-vocalist as a multifaceted personality, interested in studying not only different types of art, but also various spheres of life. Some of the author’s important tips include practicing acting, setting several “super-tasks” while working on a piece, watching, and participating in master classes of outstanding teachers and artists, comparing different vocal interpretations, analysing one’s own recordings, etc. Most of the success depends on how the teacher builds contact with the student, and how much the mentor can support and inspire his or her mentee. The materials in the article can be useful to both vocal teachers and students at music colleges and universities.

RAAS-deficient organoids indicate delayed angiogenesis as a possible cause for autosomal recessive renal tubular dysgenesis

Autosomal Recessive Renal Tubular Dysgenesis (AR-RTD) is a fatal genetic disorder characterized by complete absence or severe depletion of proximal tubules (PT) in patients harboring pathogenic variants in genes involved in the Renin–Angiotensin–Aldosterone System. To uncover the pathomechanism of AR-RTD, differentiation of ACE-/- and AGTR1-/- induced pluripotent stem cells (iPSCs) and AR-RTD patient-derived iPSCs into kidney organoids is leveraged. Comprehensive marker analyses show that both mutant and control organoids generate indistinguishable PT in vitro under normoxic (21% O2) or hypoxic (2% O2) conditions. Fully differentiated (d24) AGTR1-/- and control organoids transplanted under the kidney capsule of immunodeficient mice engraft and mature well, as do renal vesicle stage (d14) control organoids. By contrast, d14 AGTR1-/- organoids fail to engraft due to insufficient pro-angiogenic VEGF-A expression. Notably, growth under hypoxic conditions induces VEGF-A expression and rescues engraftment of AGTR1-/- organoids at d14, as does ectopic expression of VEGF-A. We propose that PT dysgenesis in AR-RTD is primarily a non-autonomous consequence of delayed angiogenesis, starving PT at a critical time in their development.

Prediction, analysis and suggestions of shale gas production in China based on a new grey model with four parameters

Accurate prediction of shale gas production is important for the government to formulate energy policies. China’s shale gas production is characterized by limited data and unclear influencing factors. Grey prediction models hold advantages in solving problems with inadequate data and insufficient information. However, existing grey models for shale gas production prediction have drawbacks of insufficient characteristic expression and parameter optimization. Therefore, a new grey model with four parameters is proposed in this work. Firstly, the power index, accumulative order, and background value coefficient in the new model are optimized using the PSO algorithm. Then, based on an in-depth analysis of the model structure and tests using random samples, the new model’s compatibility and adaptability are demonstrated to be better than other similar grey models. Thirdly, the new model is applied to simulate China’s shale gas production. The results show that the comprehensive error of the new model is only 1.3626%, lower than that of the SGGM(1,1) and UGM(1,1) models, which are 1.6211% and 1.6575% respectively. Lastly, using the new model, China's shale gas production is predicted, which is expected to reach 752 hundred million cubic meters by 2030. After analyzing the rationality of the result, relevant suggestions are put forward.

Additional Cover

The cover image is based on the Original Article Insufficient GDF15 expression predisposes women to unexplained recurrent pregnancy loss by impairing extravillous trophoblast invasion by Chunzi Lyu et al., https://doi.org/10.1111/cpr.13514. image

Automatic food recognition based on efficientnet and ResNet

Automatic Food recognitionbased image is an emerging topic, which aims to extract the feature of given food image and then predict its category. Compared with the ordinary image recognition task, the food recognition is more challenging due to the high similarity between subcategories and the high inter-class variability of specific category. Early food image recognition methods are mainly based on manual features such as color, shape, texture and other information, which cannot meet actual application requirements limited by insufficient feature expression capabilities. Thanks to the rapid development of convolutional neural network, the methods based on deep learning boost the recognition accuracy and speed significantly. In this paper, we construct the food recognition models based on the EfficientNet and ResNet, respectively. Extensive experiments have been conducted on Food-101 dataset. All the results show the effectiveness of our models, which can recognize various foods accurately.

Additional glial cell line-derived neurotrophic factor in vitro promotes the proliferation of undifferentiated spermatogonia from sterile cattleyak

Cattleyak is a typically male sterile species. The meiosis process is blocked and the scarcity of spermatogenic stems cells are both contributing factors to the inability of male cattleyak to produce sperm. While Glial cell line-derived neurotrophic factor (GDNF) is the first discovered growth factor known to promote the proliferation and self-renewal of spermatogenic stem cells, its relationship to the spermatogenesis arrest of cattleyak remains unclear. In this report, we studied the differential expression of GDNF in the testis of yak and cattleyak, and discussed the optimal concentration of GDNF in the culture medium of undifferentiated spermatogonia (UDSPG) of cattleyak in vitro and the effect of GDNF on the proliferation of cattleyak UDSPG. The results indicated that GDNF expression in the testicular tissue of cattleyak was inferior to that of yak. Moreover, the optimum value for the UDSPG in vitro culture was determined to be 20–30 ng/mL for cattleyak. In vitro, the proliferation activity of UDSPG was observed to increase with additional GDNF due to the up-regulation of proliferation-related genes and the down-regulation of differentiation-related genes. We hereby report that the scarcity of cattleyak UDSPG is due to insufficient expression of GDNF, and that the addition of GDNF in vitro can promote the proliferation of cattleyak UDSPG by regulating the expression of genes related to proliferation and differentiation. This work provides a new insight to solve the issue of spermatogenic arrest in cattleyak.

Preconditioning with Substance P Restores Therapeutic Efficacy of Aged ADSC by Elevating TNFR2 and Paracrine Potential.

Aging leads to a decline in stem cell activity by reducing the repopulation rate and paracrine potential, ultimately diminishing efficacy in vivo. TNF-α can exert inflammatory and cell death actions via Erk by binding to TNFR-1, and survival and tissue repair actions via Akt by binding to TNFR-2. Aged cells are reported to have insufficient expression of TNFR-2, indicating that aged adipose-derived stem cells (ADSCs-E) lack the ability for cell survival and immune control compared to young ADSCs (ADSCs-Y). This study aims to assess the preconditioning effect of SP on the response of ADSCs-E to inflammation. ADSCs-E were treated with SP and then exposed to a high dose of TNF-α for 24 h. Consequently, ADSC-E exhibited weaker viability and lower TNFR2 levels compared to ADSC-Y. In response to TNF-α, the difference in TNFR2 expression became more pronounced in ADSC-E and ADSC-Y. Moreover, ADSC-E showed a severe deficiency in proliferation and paracrine activity. However, preconditioning with SP significantly enhanced the viability of ADSCs-E and also restored TNFR2 expression and paracrine potential, similar to ADSC-Y under inflammatory conditions. Our findings support the idea that preconditioning with SP has the potential to restore the cellular function of senescent stem cells before transplantation.

SAR-ATR with knowledge hierarchy division and information dissemination networks

Synthetic aperture radar (SAR) images possess diverse domain characteristics that describe targets from multiple perspectives, including scattering center, intensity, phase, azimuth angle, and shadow. The imaging mechanism of SAR images significantly differs from optical images due to its use of radio waves instead of visible light for imaging purposes. However, current deep learning (DL)-based automatic target recognition (ATR) approaches for SAR primarily focus on the intensity information while neglecting the comprehensive consideration of SAR domain characteristics. This limitation results in insufficient expression of target features and hampers further improvement in SAR target recognition performance. To address these issues, this paper proposes a novel SAR target recognition method called KDNets based on information dissemination networks (IDNets) and knowledge hierarchy division (KnHD). KDNets effectively enhances the feature representation ability of SAR targets by exploiting multiple domain characteristics at sample, feature, and decision levels. Specifically, IDNets incorporates scattering center and azimuth angle at sample and feature levels to extract rich multi-scale semantic features for representing SAR targets. At the decision stage, KnHD utilizes azimuth information to rapidly search and fuse prior knowledge about targets from a knowledge base to achieve interpretable and high-precision SAR target recognition. Experimental results on the MSTAR dataset and MA-SAR dataset demonstrate that our proposed KDNets can achieve state-of-the-art performance in SAR target recognition tasks, with the accuracy of 99.75 % in the MSTAR dataset and 98.61 % in the MA-SAR dataset, validating its effectiveness and superiority. Furthermore, this study highlights the significant potential and application prospects of leveraging domain characteristics in SAR-ATR tasks.

RNA-based translation activators for targeted gene upregulation

Technologies capable of programmable translation activation offer strategies to develop therapeutics for diseases caused by insufficient gene expression. Here, we present “translation-activating RNAs” (taRNAs), a bifunctional RNA-based molecular technology that binds to a specific mRNA of interest and directly upregulates its translation. taRNAs are constructed from a variety of viral or mammalian RNA internal ribosome entry sites (IRESs) and upregulate translation for a suite of target mRNAs. We minimize the taRNA scaffold to 94 nucleotides, identify two translation initiation factor proteins responsible for taRNA activity, and validate the technology by amplifying SYNGAP1 expression, a haploinsufficiency disease target, in patient-derived cells. Finally, taRNAs are suitable for delivery as RNA molecules by lipid nanoparticles (LNPs) to cell lines, primary neurons, and mouse liver in vivo. taRNAs provide a general and compact nucleic acid-based technology to upregulate protein production from endogenous mRNAs, and may open up possibilities for therapeutic RNA research.

Research on the Identification of a Winter Olympic Multi-Intent Chinese Problem Based on Multi-Model Fusion

Aiming at addressing the inability of traditional web technologies to effectively respond to Winter-Olympics-related user questions containing multiple intentions, this paper explores a multi-model fusion-based multi-intention recognition model BCNBLMATT to solve this problem. The model is proposed to address the characteristics of complex semantics, strong contextual relevance, and a large number of informative features of the Chinese problem text related to the Winter Olympics, as well as the limitations of the traditional word vector model, such as insufficient expression in the textual representation and the relative concern mechanism of feature expression. The BCNBLMATT model first obtains a comprehensive feature vector representation of the problem text through BERT. Then, a multi-scale text convolutional neural network model and a BiLSTM-Multi-heads attention model (a joint model combining a bidirectional long- and short-term attention network with a multi-head attention mechanism) are used to capture local features at more scales and contextually critical information features at more levels. Finally, the two obtained kinds of features are concatenated and fused to obtain richer and more comprehensive information about the problem text features, which improves the model’s performance in the multi-attention recognition task. Comparative experiments on the Winter Olympics Chinese question dataset and the MixATIS question dataset show that the BCNBLMATT model significantly improves the three metrics of macro-averaged precision, macro-averaged recall, and macro-averaged F1 value and exhibits better generalization. This study provides an effective solution to the multi-intent recognition task for Winter Olympic problems, overcomes the limitations of traditional models, and provides new ideas for improving the performance of multi-intent recognition.

PKAMNet: A Transmission Line Insulator Parallel- Gap Fault Detection Network Based on Prior Knowledge Transfer and Attention Mechanism

Insulator parallel gaps in a transmission line protect the insulator from arc burn and provide protection from lightning. Detection of insulator parallel-gap faults based on aerial inspection images of transmission lines may be hindered by various factors, such as complex background, scale distortion, and occlusion. In this study, we propose a prior knowledge transfer and attention mechanism network (PKAMNet) to detect faulty insulator parallel gaps. First, the capability of PKAMNet to learn the features of different types of parallel-gap faults is improved by constructing a prior knowledge transfer model based on visual saliency. Owing to the difficulty of effectively expressing the features of the fault target due to the deviation of the shooting angle and complex background of the inspection image, we enhance the feature expression ability of the fault area by embedding the coordinate attention block. Additionally, the parameters of the detection network are simplified, and the modules are optimized to improve detection efficiency. Comparison results on 3-year aerial inspection videos of 500 kV high-voltage transmission lines show that PKAMNet has a high detection accuracy and can ameliorate the phenomenon of missed and erroneous detection caused by insufficient expression of parallel-gap faults.

ATM-AMPKα mediated LAG-3 expression suppresses T cell function in prostate cancer

Immunotherapy for prostate cancer (PCa) faces serious challenges. Therefore, the co-inhibitory receptors that regulate T cell function of PCa must be elucidated. Here we identified that the inhibitory receptor LAG3 was significantly induced in T cells from PCa patients. Gene array analysis revealed that insufficient ataxia telangiectasia mutated (ATM) gene expression in PCa T cells was responsible for the elevated LAG3 expression. Mechanistically, insufficient ATM expression impaired its ability to activate AMPKα signaling and CD4+ T cell functions, which further enhances the binding of the transcription factors XBP1 and EGR2 to LAG3 promoter. Reconstitution of ATM and inhibition of XBP1 or EGR2 in PCa T cells suppressed LAG3 expression and restored the effector function of CD4+ T cells from PCa. Our study revealed the mechanism of LAG3 upregulation in CD4+ T lymphocytes of PCa patients and may provide insights for the development of immunotherapeutic strategies for PCa treatment.

How to improve the integrity and sustainability of historic architectural complexes and their environments in modern urban planning--an example from the "Wenming Street" historic district renovation project in Kunming

Historic buildings are the bearers of human civilization. Kunming, a famous historical and cultural city in China, has numerous historical and cultural heritages and a diverse and prosperous historical and cultural background. This study takes the renovation project of the historic district of Wenming Street in Kunming as the research object and proposes a holistic, multi-dimensional, and multi-factor planning and renovation method that should focus on the district in the conservation and renovation of historic buildings through the hierarchical analysis method. Through expert scoring and weighting analysis, questionnaires, and index scores, it is found that there is a lack of "spirit of place" and insufficient expression of non-material elements in the renovation of the historic district. This study aims to realize the integration of the historic environment with the needs of modern life using a monistic logic and to provide theoretical reference and practical guidance for the conservation, renovation, and sustainable development of historic buildings and the historic environment.

Left-Right Reversal Recurrently Evolved Regardless of Diaphanous-Related Formin Gene Duplication or Loss in Snails.

Bilateria exhibit whole-body handedness in internal structure. This left-right polarity is evolutionarily conserved with virtually no reversed extant lineage, except in molluscan Gastropoda. Phylogenetically independent snail groups contain both clockwise-coiled (dextral) and counterclockwise-coiled (sinistral) taxa that are reversed from each other in bilateral handedness as well as in coiling direction. Within freshwater Hygrophila, Lymnaea with derived dextrality have diaphanous related formin (diaph) gene duplicates, while basal sinistral groups possess one diaph gene. In terrestrial Stylommatophora, dextral Bradybaena also have diaph duplicates. Defective maternal expression of one of those duplicates gives rise to sinistral hatchlings in Lymnaea and handedness-mixed broods in Bradybaena, through polarity change in spiral cleavage of embryos. These findings led to the hypothesis that diaph duplication was crucial for the evolution of dextrality by reversal. The present study discovered that diaph duplication independently occurred four times and its duplicate became lost twice in gastropods. The dextrality of Bradybaena represents the ancestral handedness conserved across gastropods, unlike the derived dextrality of Lymnaea. Sinistral lineages recurrently evolved by reversal regardless of whether diaph had been duplicated. Amongst the seven formin gene subfamilies, diaph has most thoroughly been conserved across eukaryotes of the 14 metazoan phyla and choanoflagellate. Severe embryonic mortalities resulting from insufficient expression of the duplicate in both of Bradybaena and Lymnaea also support that diaph duplicates bare general roles for cytoskeletal dynamics other than controlling spiralian handedness. Our study rules out the possibility that diaph duplication or loss played a primary role for reversal evolution.

Decreased level of TREM like Transcript 1 (TLT-1) is associated with prematurity and promotes the in-utero inflammatory response to maternal lipopolysaccharide (LPS) exposure.

The occurrence of preterm birth is associated with multiple factors including bleeding, infection and inflammation. Platelets are mediators of hemostasis and can modulate inflammation through interactions with leukocytes. TREM like Transcript 1 (TLT-1) is a type 1 single Ig domain receptor on activated platelets. In adults, it plays a protective role by dampening the inflammatory response and facilitating platelet aggregation at sites of vascular injury. TLT-1 is expressed in human placenta and found in cord blood. We thus hypothesized that TLT-1 deficiency is associated with prematurity and fetal inflammation. To test this hypothesis, we examined cord blood levels of soluble TLT-1 (sTLT) in premature and term infants and compared the inflammatory response in C57BL/6 (WT) and TLT-1-/- (treml1-/- , KO) mice given intraperitoneal LPS mid-gestation RESULTS: The preterm infant cord blood level of sTLT was significantly lower than that found at term. On exposure to LPS, histology of KO (as compared to WT) placenta and decidua showed increased hemorrhage, and KO decidual RNA expression of IL-10 was significantly lower. KO fetal interface tissues (placenta, membranes, amniotic fluid) over time showed increased expression of inflammatory cytokines such as IL-6, IFN-γ,and TNF, but not MCP-1. However, fetal organs showed similar levels. There is a potential association between insufficient TLT-1 expression and increased fetal inflammatory responses in the setting of prematurity. The data support further study of TLT-1 in the mechanistic link between bleeding, inflammation and preterm birth, and perhaps as a biomarker in human pregnancy.

Both intratumoral regulatory T cell depletion and CTLA-4 antagonism are required for maximum efficacy of anti-CTLA-4 antibodies

Anti-CTLA-4 antibodies have successfully elicited durable tumor regression in the clinic; however, long-term benefit is limited to a subset of patients for select cancer indications. The incomplete understanding of their mechanism of action has hindered efforts at improvement, with conflicting hypotheses proposing either antagonism of the CTLA-4:B7 axis or Fc effector-mediated regulatory T cell (Treg) depletion governing efficacy. Here, we report the engineering of a nonantagonistic CTLA-4 binding domain (b1s1e2) that depletes intratumoral Tregs as an Fc fusion. Comparison of b1s1e2-Fc to 9d9, an antagonistic anti-CTLA-4 antibody, allowed for interrogation of the separate contributions of CTLA-4 antagonism and Treg depletion to efficacy. Despite equivalent levels of intratumoral Treg depletion, 9d9 achieved more long-term cures than b1s1e2-Fc in MC38 tumors, demonstrating that CTLA-4 antagonism provided additional survival benefit. Consistent with prior reports that CTLA-4 antagonism enhances priming, treatment with 9d9, but not b1s1e2-Fc, increased the percentage of activated T cells in the tumor-draining lymph node (tdLN). Treg depletion with either construct was restricted to the tumor due to insufficient surface CTLA-4 expression on Tregs in other compartments. Through intratumoral administration of diphtheria toxin in Foxp3-DTR mice, we show that depletion of both intratumoral and nodal Tregs provided even greater survival benefit than 9d9, consistent with Treg-driven restraint of priming in the tdLN. Our data demonstrate that anti-CTLA-4 therapies require both CTLA-4 antagonism and intratumoral Treg depletion for maximum efficacy-but that potential future therapies also capable of depleting nodal Tregs could show efficacy in the absence of CTLA-4 antagonism.

Haploinsufficiency of A20 caused by a novel pathogenic missense variant of TNFAIP3 and successfully treated with anti-TNF and immunosuppressive therapies

Loss-of-function of protein A20, encoded by TNFAIP3, leads to an early-onset haploinsufficiency of A20 (HA20). This study reports one Chinese child with HA20 and explores the genetic etiology of TNFAIP3 variant. The patient exhibited transient recurrent episodes of fever, intermittent signs of arthritis, gastrointestinal symptoms and multiple colonic ulcers. Laboratory tests revealed elevated inflammatory indicators and mild to moderate anemia. Genetic analysis identified a heterozygous de novo variant in his TNFAIP3 gene (c.740C＞T, p. P247L), which had never been reported before. The novel missense variation was validated to be pathogenic through causing insufficient expression of A20, over-activation of NF-κB signaling pathway and elevated levels of proinflammatory cytokines in response to stimulation by lipopolysaccharide. A combination of oral corticosteroids, TNF-α inhibitors and thalidomide freed him from symptoms and abnormal inflammatory indicators. Furthermore, continual improvement of the patient's condition was observed during a follow-up period of five months. We demonstrate a case with a de novo missense variant resulting in a loss-of-function of TNFAIP3, which expands the clinical spectrum of HA20. Cytokine antagonists and immunosuppressants may be effective drugs.