Nonsymbolic Numerosity Maps at the Occipitotemporal Cortex Respond to Symbolic Numbers.

Numerosity, the set size of a group of items, helps guide human and animals' behavior and decisions. Numerosity perception is thought to be a precursor of symbolic numerical cognition. Previously, we uncovered neural populations selectively tuned to numerosities organized in a network of topographic maps in human association cortex. Here we investigate whether these numerosity maps are also involved in the processing of symbolic numbers, using 7T fMRI and a number-detection task. We recruited 7 participants (3 females) and found that the numerosity map at the temporal-occipital cortex (NTO) also responds to symbolic numbers. Furthermore, we found that numerosity-tuned neuronal populations at the NTO map in the left hemisphere are tuned to symbolic numbers. These results reveal different functions of the numerosity maps and support a link between numerosity representation and symbolic number processing in the ventral temporal-occipital cortex.SIGNIFICANCE STATEMENT Humans and other animals share an intuitive "number sense" to approximately represent numerosity. However, humans possess a unique ability to process number symbols (e.g., Arabic numbers). It has been argued that the human understanding of symbolic numbers is rooted in our ability to numerosity perception. Here we investigate whether numerosity-tuned neuronal populations organized at a network of topographic maps also respond to symbolic numbers. We find one of the maps at the temporal-occipital cortex is involved in symbolic numerical cognition and the neuronal populations are tuned to numbers. These results provide evidence for a link between nonsymbolic numerosity and symbolic number processing.

Comparing BOLD and VASO-CBV population receptive field estimates in human visual cortex.

Vascular Space Occupancy (VASO) is an alternative fMRI approach based on changes in Cerebral Blood Volume (CBV). VASO-CBV fMRI can provide higher spatial specificity than the blood oxygenation level-dependent (BOLD) method because the CBV response is thought to be limited to smaller vessels. To investigate how this technique compares to BOLD fMRI for cognitive neuroscience applications, we compared population receptive field (pRF) mapping estimates between BOLD and VASO-CBV. We hypothesized that VASO-CBV would elicit distinct pRF properties compared to BOLD. Specifically, since pRF size estimates also depend on vascular sources, we hypothesized that reduced vascular blurring might yield narrower pRFs for VASO-CBV measurements. We used a VASO sequence with a double readout 3D EPI sequence at 7T to simultaneously measure VASO-CBV and BOLD responses in the visual cortex while participants viewed conventional pRF mapping stimuli. Both VASO-CBV and BOLD images show similar eccentricity and polar angle maps across all participants. Compared to BOLD-based measurements, VASO-CBV yielded lower tSNR and variance explained. The pRF size changed with eccentricity similarly for VASO-CBV and BOLD, and the pRF size estimates were similar for VASO-CBV and BOLD, even when we equate variance explained between VASO-CBV and BOLD. This result suggests that the vascular component of the pRF size is not dominating in either VASO-CBV or BOLD.

Individualized cognitive neuroscience needs 7T: Comparing numerosity maps at 3T and 7T MRI.

The field of cognitive neuroscience is weighing evidence about whether to move from the current standard field strength of 3 Tesla (3T) to ultra-high field (UHF) of 7T and above. The present study contributes to the evidence by comparing a computational cognitive neuroscience paradigm at 3T and 7T. The goal was to evaluate the practical effects, i.e. model predictive power, of field strength on a numerosity task using accessible pre-processing and analysis tools. Previously, using 7T functional magnetic resonance imaging and biologically-inspired analyses, i.e. population receptive field modelling, we discovered topographical organization of numerosity-selective neural populations in human parietal cortex. Here we show that these topographic maps are also detectable at 3T. However, averaging of many more functional runs was required at 3T to reliably reconstruct numerosity maps. On average, one 7T run had about four times the model predictive power of one 3T run. We believe that this amount of scanning would have made the initial discovery of the numerosity maps on 3T highly infeasible in practice. Therefore, we suggest that the higher signal-to-noise ratio and signal sensitivity of UHF MRI is necessary to build mechanistic models of the organization and function of our cognitive abilities in individual participants.

Adaptation to visual numerosity changes neural numerosity selectivity.

Perceiving numerosity, i.e. the set size of a group of items, is an evolutionarily preserved ability found in humans and animals. A useful method to infer the neural underpinnings of a given perceptual property is sensory adaptation. Like other primary perceptual attributes, numerosity is susceptible to adaptation. Recently, we have shown numerosity-selective neural populations with a topographic organization in the human brain. Here, we investigated whether numerosity adaptation can affect the numerosity selectivity of these populations using ultra-high field (7 Tesla) functional magnetic resonance imaging (fMRI). Participants viewed stimuli of changing numerosity (1 to 7 dots), which allowed the mapping of numerosity selectivity. We interleaved a low or high numerosity adapter stimulus with these mapping stimuli, repeatedly presenting 1 or 20 dots respectively to adapt the numerosity-selective neural populations. We analyzed the responses using custom-build population receptive field neural models of numerosity encoding and compared estimated numerosity preferences between adaptation conditions. We replicated our previous studies where we found several topographic maps of numerosity-selective responses. We found that overall, numerosity adaptation altered the preferred numerosities within the numerosity maps, resulting in predominantly attractive biases towards the numerosity of the adapter. The differential biases could be explained by the difference between the unadapted preferred numerosity and the numerosity of the adapter, with attractive biases being observed with higher difference. The results could link perceptual numerosity adaptation effects to changes in neural numerosity selectivity.

A New Strategy for the Treatment of Old Corrugated Container Pulping Wastewater by the Ozone-Catalyzed Polyurethane Sponge Biodegradation Process.

Old Corrugated Container (OCC) pulping wastewater has a complex organic composition and high levels of biotoxicity. The presence of dissolved and colloidal substances (DCSs) is a major limiting factor for pulp and paper companies to achieve closed-water recycling. In order to solve this problem, the coupled ozone-catalyzed oxidation and biodegradation (OCB) method was used to treat OCC pulping wastewater in this study. A polyurethane sponge was used as the basic skeleton, loaded with nano TiO2 and microorganisms, respectively, and then put into a reactor. After an 8-min ozone-catalyzed oxidation reaction, a 10-h biological reaction was carried out. The process was effective in removing organic pollutants such as COD and BOD5 from OCC paper whitewater. The removal rates of COD and BOD5 were 81.5% and 85.1%, respectively. By using the polyurethane sponge to construct a microenvironment suitable for microbial growth and metabolism, this study successfully applied and optimized engineered bacteria-white rut fungi (WRF)-in the system to achieve practical degradation of OCC pulping wastewater. Meanwhile, the biocompatibility of different microbial communities on the polyurethane sponge was analyzed by examining the degradation performance of OCC pulping wastewater. The structure of microbial communities loaded on the polyurethane sponge was analyzed to understand the degradation mechanism and microbial reaction behavior. White-rot fungi (Phanerochaete) contributed more to the degradation of OCC wastewater, and new strains adapted to OCC wastewater degradation were generated.

Familial Resilience in Crisis: Navigating the Mediating Landscape of Depressive Symptoms Between Uncertainty Stress and Suicide Behavior Among Chinese University Students.

Background: Previous findings indicate that stress has a profound influence on suicide behavior, but the potential mediating and moderating mechanisms are unknown between uncertainty stress and suicide behavior. The present study, therefore, examined the relationship between uncertainty stress and suicide behavior, the mediating effect of depressive symptoms, and the moderating effect of family relationship in a sample of university students in China. Methods: 1828 university students were assessed anonymously by using the Uncertainty Stress Scale, Center for Epidemiologic Studies Depression Scale, Brief Suicidal Scale, and Family Relationship Scale between May to June in 2021. SPSS 26.0 was used for descriptive statistics and Spearman correlation analysis. PROCESS 3.5 was used to calculate the significance of the mediating and moderating effects of the variables. Results: Moderated mediation model analyses showed that: (a) depressive symptoms partially mediated the link between uncertainty stress and suicide behavior (indirect effect = 0.14, 95%bootstrap CI = 0.10, 0.19). The indirect effect of the depressive symptoms accounted for 67.12% of the total variance in suicide behavior. (b) The indirect association between uncertainty stress and suicide behavior was moderated by family relationship. Specifically, the paths from uncertainty stress to depressive symptoms (interact effect = -0.06, P<0.001) and depressive symptoms to suicide behavior (interact effect = -0.08, P<0.01) were weakened in the context of higher family relationship. Conclusion: Depressive symptoms play a crucial role in bridging uncertainty stress and suicide behavior, while the family relationship can buffer the mediation impact of depressive symptoms. These findings significantly contribute to the prevention and intervention of suicide in Chinese university students.

Application of Nanomedicine in Tumor Targeting Inflammatory Pathway.

Given the threat of ever-growing cancer morbidity, it is a cutting-edge frontier for multiple disciplines to apply nanotechnology in cancer therapy. Nanomedicine is now perpetually influencing the diagnosis and treatment of cancer. Meanwhile, tumorigenesis and cancer progression are intimately associated with inflammation. Inflammation can implicate in various tumor progression via the same or different pathways. Therefore, current nanomedicines exhibit tumor-suppressing function through inflammatory pathways. At present, the comprehensive understanding and research on the mechanism of various nanoparticles in cancer treatment are still in progress. In this review, we summarized the applications of nanomedicine in tumor-targeting inflammatory pathways, suggesting that nanoparticles could be a budding star for cancer therapy.

Fumarate Hydratase Enhances the Therapeutic Effect of PD-1 Antibody in Colorectal Cancer by Regulating PCSK9.

Despite the notable achievements of programmed death 1 (PD-1) antibodies in treating various cancers, the overall efficacy remains limited in the majority of colorectal cancer (CRC) cases. Metabolism reprogramming of tumors inhibits the tricarboxylic acid (TCA) cycle, leading to down-regulation of fumarate hydratase (FH), which is related to poor prognosis in CRC patients. By establishing a tumor-bearing mouse model of CRC with Fh1 expression deficiency, we confirmed that the therapeutic effect of PD-1 antibodies alone was suboptimal in mice with low Fh1 expression, which was improved by combination with a protein invertase subtilisin/kexin 9 (PCSK9) inhibitor. Mechanistically, FH binds to Ras-related nucleoprotein (RAN), which inhibits the nuclear import of the PCSK9 transcription factor SREBF1/2, thus reducing the expression of PCSK9. This leads to increased clonal expansion of CD8+ T cells while the number of Tregs remains unchanged, and the expression of PD-L1 does not change significantly, thus enhancing the immunotherapy response. On the contrary, the expression of PCSK9 increased in CRC cells with low FH expression, which antagonized the effects of immunotherapy. Overall, CRC patients with low FH expression may benefit from combinatorial therapy with PD-1 antibodies and PCSK9 inhibitors to enhance the curative effect.

Attention drives human numerosity-selective responses.

Numerosity, the set size of a group of items, helps guide behavior and decisions. Previous studies have shown that neural populations respond selectively to numerosities. How numerosity is extracted from the visual scene is a longstanding debate, often contrasting low-level visual with high-level cognitive processes. Here, we investigate how attention influences numerosity-selective responses. The stimuli consisted of black and white dots within the same display. Participants' attention was focused on either black or white dots, while we systematically changed the numerosity of black, white, and total dots. Using 7 T fMRI, we show that the numerosity-tuned neural populations respond only when attention is focused on their preferred numerosity, irrespective of the unattended or total numerosities. Without attention, responses to preferred numerosity are suppressed. Unlike traditional effects of attention in the visual cortex, where attention enhances already existing responses, these results suggest that attention is required to drive numerosity-selective responses.

High positively charged Fe3O4 nanocomposites for efficient and recyclable demulsification of hexadecane-water micro-emulsion.

Oily wastewater not only causes major environmental issues, but also threatens human health. Magnetic nanoparticles (MNPs) are an attractively alternative commercial demulsifiers for their recyclability and high surface area. The wettability and surface charge of magnetic materials are significant factors in oily wastewater treatment. However, the specific influence of surface charge on the demulsification performance has not been rigorously investigated. Herein, a series of MNPs coated by dimethyl-diallyl-ammonium chloride (PDDA) and fulvic acid (FA) (Fe3O4/FA/PDDA) with different surface positive charges were synthesized by adjusting the PDDA concentrations and applied in demulsification of hexadecane-water micro-emulsion. The oil-water separation efficiency (Es) was enhanced gradually with increasing the surface positive charge of demulsifiers. Derjaguin-Landau-Verwey-Overbeek (DLVO) theory confirmed that with increasing surface positive potential, the electrostatic attraction between demulsifiers and oil droplets increased, and thus, Es increased. In addition, the superior Es of Fe3O4/FA MNPs for hexadecyl trimethyl ammonium bromide (CTAB)-stabilized micro-emulsions and Fe3O4/FA/PDDA MNPs for sodium dodecyl sulfate (SDS)-stabilized micro-emulsions further confirmed that electrostatic force was critical in demulsification. The high positively charged Fe3O4/FA/PDDA MNPs can be used as an efficient and recyclable demulsifier for hexadecane-water micro-emulsion. This study provides a theoretical basis for designing demulsifiers.

DUXAP8: A Promising lncRNA with Carcinogenic Potential in Cancer.

BACKGROUND: Long non-coding RNAs (lncRNA) have influenced numerous biology processes, which has provoked great interest. Not only that, LncRNA DUXAP8 mediates tumorigenesis by affecting the activity of miRNAs, signaling pathways, and oncogene. METHODS: The functions of DUXAP8 have been summarized by reading relevant articles on PubMed. RESULTS: lncRNA DUXAP8 acts as an oncogene in most tumors. The abnormal overexpression is associated with the proliferation, invasion, migration, and anti-autophagy of tumors. DUXAP8 exerts promotion on Akt / mTOR signaling pathway, facilitating the occurrence of tumors. Furthermore, DUXAP8 affects the activity of miRNAs and proteins, showing its significant potential as a therapeutic target in human cancers. CONCLUSION: LncRNA DUXAP8 has been identified as an indispensable therapeutic target of the tumors, providing clinical treatment plans.

The Regulatory Role of Both MBNL1 and MBNL1-AS1 in Several Common Cancers.

BACKGROUND: Muscle blind-like-proteins (MBNL) are a class of tissue-specific RNA metabolism regulators that control pre-messenger RNA-splicing. Inactivation of MBNL can lead to myotonic dystrophy in adults. MBNL is mainly expressed in skeletal muscle, neuron tissue, thymus, liver, and kidney and plays an important role in the ultimate differentiation of muscle cells and neurons. MBNL1 is a member of the MBNL protein family. The inactivation of MBNL1 protein is particularly important in the development of myotonic dystrophy and can lead to cataract formation, abnormal muscle relaxation, cardiac and neurological dysfunction, etc. The induction of MBNL1 in tumors is known to significantly inhibit tumor progression and thus significantly prolong survival. MBNL1 antisense protein MBNL1-AS1 also plays an important role in tumor migration and development. OBJECTIVE: This review reveals the role of MBNL1 and MBNL1-AS1 in the complex pathogenesis of many tumors, which provide a new target for the treatment of tumors. METHODS: Correlated research are systematically retrieved via PubMed. In this review, the role of MBNL1 and MBNL1- AS1 were analyzed. RESULTS: MBNL1 is down-regulated in breast cancer, leukemia, stomach cancer, esophageal cancer, glioma, and Huntington's disease. The function of inhibiting tumor cell metastasis decreased. It is up-regulated in cervical cancer and colorectal cancer, which can promote the development of tumor cells. Antisense protein MBNL1- AS1 can inhibit tumor cell proliferation and metastasis in colorectal cancer, non-small cell lung cancer, and gastric cancer. CONCLUSION: MBNL1 is an important regulator of tumor metastasis and growth, which exhibits a promising therapeutic target and can be further explored.

Alkaloids Exhibit a Meaningful Function as Anticancer Agents by Restraining Cellular Signaling Pathways.

Alkaloids are nitrogen-containing organic compounds widely found in natural products, which play an essential role in clinical treatment. Cellular signaling pathways in tumors are a series of enzymatic reaction pathways that convert extracellular signals into intracellular signals to produce biological effects. The ordered function of cell signaling pathways is essential for tumor cell proliferation, differentiation, and programmed death. This review describes the antitumor progression mediated by various alkaloids after inhibiting classical signaling pathways; related studies are systematically retrieved and collected through PubMed. We selected the four currently most popular pathways for discussion and introduced the molecular mechanisms mediated by alkaloids in different signaling pathways, including the NF-kB signaling pathway, PI3K/AKT signaling pathway, MAPK signaling pathway, and P53 signaling pathway. The research progress of alkaloids related to tumor signal transduction pathways and the realization of alkaloids as cancer prevention drugs by targeting signal pathways remains.

The role of neural tuning in quantity perception.

Perception of quantities, such as numerosity, timing, and size, is essential for behavior and cognition. Accumulating evidence demonstrates neurons processing quantities are tuned, that is, have a preferred quantity amount, not only for numerosity, but also other quantity dimensions and sensory modalities. We argue that quantity-tuned neurons are fundamental to understanding quantity perception. We illustrate how the properties of quantity-tuned neurons can underlie a range of perceptual phenomena. Furthermore, quantity-tuned neurons are organized in distinct but overlapping topographic maps. We suggest that this overlap in tuning provides the neural basis for perceptual interactions between different quantities, without the need for a common neural representational code.

Topographic maps representing haptic numerosity reveals distinct sensory representations in supramodal networks.

Dedicated maps for cognitive quantities such as timing, size and numerosity support the view that topography is a general principle of brain organization. To date, however, all of these maps were driven by the visual system. Here, we ask whether there are supramodal topographic maps representing cognitive dimensions irrespective of the stimulated sensory modality. We measured haptically and visually driven numerosity-selective neural responses using model-based analyses and ultra-high field (7T) fMRI. We found topographically organized neural populations tuned to haptic numerosity. The responses to visual or haptic numerosity shared a similar cortical network. However, the maps of the two modalities only partially overlap. Thus, although both visual and haptic numerosities are processed in a similar supramodal functional network, the underlying neural populations may be related, but distinct. Therefore, we hypothesize that overlap between modality-specific maps facilitates cross-modal interactions and supramodal representation of cognitive quantities.

The Functional Role of Oncogenic LncRNA BCAR4 for Cancer Outcome.

BACKGROUND: Long non-coding RNA (lncRNA) breast cancer anti-estrogen resistance 4 (BCAR4) is a characterized oncogenic lncRNA in different cancers. This review is dedicated to summarize various molecular mechanisms of BCAR4 and demonstrate that the biological functions exerted by BCAR4 are good entry points for therapy. METHODS: The molecular mechanism of BCAR4 acting on tumors is summarized by reviewing PubMed. RESULTS: The expression of lncRNA BCAR4 is abnormally increased in all kinds of tumors, including colorectal cancer, prostate cancer, bladder cancer, gastric cancer, chondrosarcoma, glioma, breast cancer, glioma, gastric cancer, liver cancer, cervical cancer, lung cancer, etc. Besides, BCAR4 mediates multiple processes involved in carcinogenesis, including proliferation, invasion, anti-apoptosis, migration. CONCLUSION: BCAR4 may show great clinical value in this direction as a therapeutic cancer target.

CASC15: A Tumor-Associated Long Non-Coding RNA.

BACKGROUND: CASC15, one of long non-coding RNA, is involved in the regulation of many tumor biological processes, and is expected to become a new biological therapeutic target. This paper aims to elucidate the pathophysiological function of CASC15 in various tumors. METHODS: The relationship between CASC15 and tumors was analyzed by searching references, and summarized the specific pathophysiological mechanism of CASC15. RESULTS: LncRNA CASC15 is closely related to tumor development, and has been shown to be abnormally high expressed in all kinds of tumors, including breast cancer, cervical cancer, lung cancer, hepatocellular carcinoma, gastric cancer, bladder cancer, colon cancer, colorectal cancer, cardiac hypertrophy, intrahepatic cholangiocarcinoma, leukemia, melanoma, tongue squamous cell carcinoma and nasopharyngeal carcinoma. However, CASC15 has been found to be down-expressed abnormally in ovarian cancer, glioma and neuroblastoma. Besides, it is identified that CASC15 can affect the proliferation, invasion and apoptosis of tumors. CONCLUSION: LncRNA CASC15 has the potential to become a new therapeutic target or marker for a variety of tumors.

Molecular Mechanism of the Canonical Oncogenic lncRNA MALAT1 in Gastric Cancer.

BACKGROUND: Experimental evidence has shown that lncRNA MALAT1 is related to proliferation ability, invasion and migration ability, autophagy ability, and chemoresistance in gastric cancer. Moreover, MALAT1 is related to metastasis and patient prognosis in gastric cancer. This review aims to reveal the biological functions and specific mechanisms of MALAT1 in gastric cancer. METHODS: After a comprehensive and systematic search in PubMed, various molecular mechanisms of MALAT1 in mediating gastric carcinogenesis are collated and summarized. RESULTS: MALAT1-mediated gastric cancer is involved in a variety of molecular mechanisms. For example, MALAT1 can enhance the proliferation ability of gastric cancer cells by inhibiting the expressions of miR-122, miR-1297, miR-22-3p, miR-202, etc. MALAT1 enhances the metastasis and invasion of gastric cancer by participating in the EMT process, PI3-Akt and other pathways. MALAT1 enhances the proliferation and invasion of gastric cancer by inhibiting the function of the tumor suppressor gene PCDH10. MALAT1 can increase the autophagy ability of gastric cancer cells by inhibiting miR-183 and increasing the level of autophagy markers. MALAT1 enhances chemical resistance by inhibiting UPF1 and miR-30e levels. CONCLUSIONS: MALAT1 is tightly linked to gastric carcinogenesis through various molecular mechanisms. Moreover, MALAT1 is also closely associated with chemoresistance and poor prognosis in gastric cancer patients, suggesting the possibility of its use as a clinical therapeutic target and a promising independent risk factor for predicting patient prognosis.

ADAMTS9-AS2: A Functional Long Non-coding RNA in Tumorigenesis.

BACKGROUND: Long non-coding RNAs (lncRNA) have been identified as novel molecular regulators in cancers. LncRNA ADAMTS9-AS2 can mediate the occurrence and development of cancer through various ways, such as regulating miRNAs, activating the classical signaling pathways in cancer, and so on, which have been studied by many scholars. In this review, we summarize the molecular mechanisms of ADAMTS9-AS2 in different human cancers. METHODS: Through a systematic search of PubMed, lncRNA ADAMTS9-AS2 mediated molecular mechanisms in cancer are summarized inductively. RESULTS: ADAMTS9-AS2 aberrantly expression in different cancers is closely related to cancer proliferation, invasion, migration, and inhibition of apoptosis. The involvement of ADAMTS9-AS2 in DNA methylation, mediating PI3K / Akt / mTOR signaling pathways, and regulating miRNAs and proteins, shows its significant potential as a therapeutic cancer target. CONCLUSION: LncRNA ADAMTS9-AS2 can become a promising biomolecular marker and a therapeutic target for human cancer.

DLEU2: A Meaningful Long Noncoding RNA in Oncogenesis.

BACKGROUND: Long non-coding RNA (lncRNA) with little or no coding ability has shown a variety of biological functions in cancer, including epigenetic regulation, DNA damage, regulation of microRNAs, and participation in signal transduction pathways. LncRNA can be used as an oncogene and tumor suppressor gene through transcriptional regulation in cancer. For example, the over-expressed lncRNA DLEU2 promotes the occurrence of laryngeal cancer, lung cancer, hepatocellular carcinoma, etc., and inhibits the progression of chronic lymphocytic leukemia. Deleted in Lymphocytic Leukemia 2 (DLEU2), as one of the long non-coding RNAs, was first found in chronic lymphoblastic leukemia and drawn into the progress of innumerable cancers. The molecular mechanism of DLEU2 in multiple tumors will be revealed. METHODS: In this review, current studies on the biological functions and mechanisms of DLEU2 in tumors are summarized and analyzed; related researches are systematically retrieved and collected through PubMed. RESULTS: DLEU2, a novel cancer-related lncRNA, has been demonstrated to be abnormally expressed in various malignant tumors, including leukemia, esophageal cancer, lung cancer, glioma, hepatocellular carcinoma, malignant pleural mesothelioma, bladder cancer, pancreatic cancer, pharynx and throat cancer, renal clear cell carcinoma, breast cancer, osteosarcoma. Besides, lncRNA DLEU2 has been shown to be involved in the process of proliferation, migration, invasion and inhibition of apoptosis of cancer cells. CONCLUSION: Due to the biological functions and mechanisms involved in DLEU2, it may represent an available biomarker or potential therapeutic target in a variety of malignant tumors.