Miracle-dz/UniFAR-FTUs huggingface dataset:
Backup transcription factor binding sites protect human genes from mutations in the promoter

This study was designed to test the idea that human gene promoters have evolved to be resistant to the effects of mutations in their primary function, the control of gene expression. It is proposed that the transcription factor/transcription factor binding site (TF/TFBS) pair having the greatest effect on control of a gene is the one with the highest abundance in the promoter. Other pairs would have the same effect on gene expression and would predominate in the event of a mutation in the most abundant pair. It is expected that the overall promoter architecture proposed here will be highly resistant to mutagenic change that would otherwise affect expression of the gene. The idea was tested beginning with a database of 42 human genes highly specific for expression in brain. For each gene, information was accumulated about its expression level and about the TFBS occupancy of the five most abundant TF/TFBS pairs. Expression level was then plotted against TFBS occupancy separately for each of the five pairs, and the plots were compared with each other. The plots were found to be similar, and the results were interpreted to indicate that the TFBS occupancy ranks evolved to yield the same effect on gene expression level with multiple ranks able to function in the event of mutation in another. A similar analysis was conducted with a database of 31 human liver specific genes, and the overall result was found to be the same. Backup TFBS occupancy ranks were interpreted to be present in both brain and liver specific genes. Finally, the TFBSs in the brain specific and liver specific gene populations were compared with each other with the goal of identifying any brain selective or liver selective TFBSs. Of the 89 TFBSs in the pooled population, 58 were found only in brain specific but not liver specific genes, 8 only in liver specific but not brain specific genes and 23 were found in both brain and liver specific genes. The results were interpreted to emphasize the large number of TFBS in brain specific but not liver specific genes.
Biflavonoid quercetin protects against cyclophosphamide–induced organ toxicities via modulation of inflammatory cytokines, brain neurotransmitters, and astrocyte immunoreactivity

Background Quercetin’s antioxidative properties make it of potential benefit in many clinical conditions where oxidative stress is implicated in the pathological processes. Objectives To investigate the possible protective effects of quercetin on neurobehaviour, brain oxidative status, markers of inflammation, neurotransmitter balance and astrocyte immunoreactivity in healthy rats administered cyclophosphamide. Methods Sixty rats were randomly assigned into six groups (n=10). Groups A and D served as normal and cyclophosphamide control respectively and were fed standard rat chow, groups B and E were fed quercetin supplemented diet (100 mg/kg of feed), while those in groups C and F were fed quercetin supplemented diet at 200 mg/kg of feed. Animals in group A-C also received intraperitoneal normal saline on days 1 and 2, while those in groups D-F got intraperitoneal cyclophosphamide (150 mg/kg/day on days 1 and 2). Standard diet and quercetin supplemented diet were administered daily for 21 days. At the end of the experimental period, behavioural tests were carried out, following which animals were sacrificed and blood taken for the assessment of biochemical parameters. Organs were either homogenised or processed for histological study. Results Quercetin mitigated CYP-induced weight loss and reduction in food consumption. It also improved total antioxidant capacity while reducing CYP-induced lipid peroxidation and biochemical markers of impaired liver function. A reduction in CYP-induced increase in urea and creatinine was also observed. Interleukin-10 increased, while the CYP-induced increase in interleukin-1 beta and TNF-α were also mitigated following quercetin administration. Open field exploratory activities and grooming increased with CYP and the lowest dose of quercetin. The anxiolytic effects of quercetin was demonstrable in the elevated plus maze; while its memory-enhancing effects were seen in the Y-maze and radial-arm maze. Finally, quercetin improved acetylcholine/dopamine levels and brain-derived neurotropic factor, while reducing serotonin levels and astrocyte immunoreactivity. Conclusion The results show quercetin’s ability to protect against CYP-induced changes in rats. They also highlight the possible use of quercetin as a possible adjunct in cancer chemotherapy-induced tissue damage. However, further research will be needed to delineate its exact role in cancer chemotherapy.
Hyperspectral imaging for detection of cholesterol in human skin

Hypercholesterolemia is characterized by high levels of cholesterol in the blood and is associated with an increased risk of atherosclerosis and coronary heart disease. Early detection of hypercholesterolemia is necessary to prevent onset and progress of cardiovascular disease. Optical imaging techniques might have a potential for early diagnosis and monitoring of hypercholesterolemia. In this study, hyperspectral imaging was investigated for this application. The main aim of the study was to identify spectral and spatial characteristics that can aid identification of hypercholesterolemia in facial skin. The first part of the study involved a numerical simulation of human skin affected by hypercholesterolemia. A literature survey was performed to identify characteristic morphological and physiological parameters. Realistic models were prepared and Monte Carlo simulations were performed to obtain hyperspectral images. Based on the simulations optimal wavelength regions for differentiation between normal and cholesterol rich skin were identified. Minimum Noise Fraction transformation (MNF) was used for analysis. In the second part of the study, the simulations were verified by a clinical study involving volunteers with elevated and normal levels of cholesterol. The faces of the volunteers were scanned by a hyperspectral camera covering the spectral range between 400 nm and 720 nm, and characteristic spectral features of the affected skin were identified. Processing of the images was done after conversion to reflectance and masking of the images. The identified features were compared to the known cholesterol levels of the subjects. The results of this study demonstrate that hyperspectral imaging of facial skin can be a promising, rapid modality for detection of hypercholesterolemia.
Anteromedial Thalamus Gates the Selection & Stabilization of Long-Term Memories

Memories initially formed in hippocampus gradually stabilize to cortex, over weeks-to-months, for long-term storage. The mechanistic details of this brain re-organization process remain poorly understood. In this study, we developed a virtual-reality based behavioral task and observed neural activity patterns associated with memory reorganization and stabilization over weeks-long timescales. Initial photometry recordings in circuits that link hippocampus and cortex revealed a unique and prominent neural correlate of memory in anterior thalamus that emerged in training and persisted for several weeks. Inhibition of the anteromedial thalamus-to-anterior cingulate cortex projections during training resulted in substantial memory consolidation deficits, and gain amplification more strikingly, was sufficient to enhance consolidation of otherwise unconsolidated memories. To provide mechanistic insights, we developed a new behavioral task where mice form two memories, of which only the more salient memory is consolidated, and also a technology for simultaneous and longitudinal cellular resolution imaging of hippocampus, thalamus, and cortex throughout the consolidation window. We found that whereas hippocampus equally encodes multiple memories, the anteromedial thalamus forms preferential tuning to salient memories, and establishes inter-regional correlations with cortex, that are critical for synchronizing and stabilizing cortical representations at remote time. Indeed, inhibition of this thalamo-cortical circuit while imaging in cortex reveals loss of contextual tuning and ensemble synchrony in anterior cingulate, together with behavioral deficits in remote memory retrieval. We thus identify a thalamo-cortical circuit that gates memory consolidation and propose a mechanism suitable for the selection and stabilization of hippocampal memories into longer term cortical storage.
Clinical usefulness of NGS multi-gene panel testing in hereditary cancer analysis

Introduction: A considerable number of families with pedigrees suggestive of a Mendelian form of Breast Cancer (BC), Ovarian Cancer (OC), or Pancreatic Cancer (PC) do not show detectable BRCA1/2 mutations after genetic testing. The use of multi-gene hereditary cancer panels increases the possibility to identify individuals with cancer predisposing gene variants. Our study was aimed to evaluate the increase in the detection rate of pathogenic mutations in BC, OC, and PC patients when using a multi-gene panel. Methods: 546 patients affected by BC (423), PC (64), or OC (59) entered the study from January 2020 to December 2021. For BC patients, inclusion criteria were i) positive cancer family background, ii) early onset, and iii) triple negative BC. PC patients were enrolled when affected by metastatic cancer, while OC patients were all submitted to genetic testing without selection. The patients were tested using a Next-Generation Sequencing (NGS) panel containing 25 genes in addition to BRCA1/2. Results: Forty-four out of 546 patients (8%) carried germline pathogenic/likely pathogenic variants (PV/LPV) on BRCA1/2 genes, and 46 (8%) presented PV or LPV in other susceptibility genes. Discussion: Our findings demonstrate the utility of expanded panel testing in patients with suspected hereditary cancer syndromes, since this approach increased the mutation detection rate of 15% in PC, 8% in BC and 5% in OC cases. In absence of multi-gene panel analysis, a considerable percentage of mutations would have been lost.
Testing New Materials to Deliver Medicine to Sick Bones

Bones are the building blocks of our skeletons—they give our bodies structure and allow us to walk, dance, and pick things up. Healthy bones are strong, lightweight, hard, and even able to fix themselves when they get worn out or damaged. But if bones get sick, they can no longer repair themselves and they start to break down. One disease that makes bones sick is called osteoporosis and it can be very painful. Currently, doctors cannot cure osteoporosis. While there are medications to slow bone loss, there are no safe treatments to repair bone that is already damaged. Therefore, doctors and scientists are working together to find ways to prevent and even cure diseases like osteoporosis. One important challenge that needs to be addressed is: how can medicine be delivered to sick bones? In this article, we discuss how tiny carbon nanoparticles could help doctors deliver medicine to sick bones to repair them.
A novel terpolymer nanocomposite (carboxymethyl β-cyclodextrin–nano chitosan–glutaraldehyde) for the potential removal of a textile dye acid red 37 from water

Carboxymethyl β-cyclodextrin–nanochitosan–glutaraldehyde (CM-βCD:nChi:Glu) terpolymer was prepared as a nano-adsorbent for the removal of the anionic textile dye, acid red 37. The terpolymer nanocomposite formation and characterization were clarified by FTIR, XRD, scanning electron microscopy, TEM, Brunauer–Emmett–Teller specific surface area (BET-SSA), and zeta potential. The removal of the textile dye was investigated by using the batch adsorption method, investigating the effect of pH, dye concentration, adsorbent dose, contact time, and temperature. The results revealed that the maximum removal efficiency of 102.2 mg/L of the dye is about 99.67% under pH 6.0, the optimal contact time is 5 min, and the adsorbent dosage is 0.5 g/L. At 29°C; the adsorption capacity increased from 81.29 to 332.60 mg/g when the initial concentration of the dye was increased from 40.97 to 212.20 mg/L. Adsorption kinetics fitted well with the pseudo–second-order model with a good correlation (R 2 = 0.9998). The Langmuir isotherm model can best describe the adsorption isotherm model. Based on the experimental results, the CM-βCD:nChi:Glu terpolymer has a promising potential as an efficient novel adsorbent for the removal of textile dye acid red 37 from contaminated water. This study’s preparation techniques and demonstrated mechanisms offer valuable insights into the adsorbent–adsorbate interactions mechanism, analysis, challenges, and future directions of beta-cyclodextrin/chitosan–based adsorbents in wastewater treatment.
A flexible speller based on time-space frequency conversion SSVEP stimulation paradigm under dry electrode

Introduction Speller is the best way to express the performance of the brain-computer interface (BCI) paradigm. Due to its advantages of short analysis time and high accuracy, the SSVEP paradigm has been widely used in the BCI speller system based on the wet electrode. It is widely known that the wet electrode operation is cumbersome and that the subjects have a poor experience. In addition, in the asynchronous SSVEP system based on threshold analysis, the system flickers continuously from the beginning to the end of the experiment, which leads to visual fatigue. The dry electrode has a simple operation and provides a comfortable experience for subjects. The EOG signal can avoid the stimulation of SSVEP for a long time, thus reducing fatigue. Methods This study first designed the brain-controlled switch based on continuous blinking EOG signal and SSVEP signal to improve the flexibility of the BCI speller. Second, in order to increase the number of speller instructions, we designed the time-space frequency conversion (TSFC) SSVEP stimulus paradigm by constantly changing the time and space frequency of SSVEP sub-stimulus blocks, and designed a speller in a dry electrode environment. Results Seven subjects participated and completed the experiments. The results showed that the accuracy of the brain-controlled switch designed in this study was up to 94.64%, and all the subjects could use the speller flexibly. The designed 60-character speller based on the TSFC-SSVEP stimulus paradigm has an accuracy rate of 90.18% and an information transmission rate (ITR) of 117.05 bits/min. All subjects can output the specified characters in a short time. Discussion This study designed and implemented a multi-instruction SSVEP speller based on dry electrode. Through the combination of EOG and SSVEP signals, the speller can be flexibly controlled. The frequency of SSVEP stimulation sub-block is recoded in time and space by TSFC-SSVEP stimulation paradigm, which greatly improves the number of output instructions of BCI system in dry electrode environment. This work only uses FBCCA algorithm to test the stimulus paradigm, which requires a long stimulus time. In the future, we will use trained algorithms to study stimulus paradigm to improve its overall performance.
Modeling the acceptability of BCIs for motor rehabilitation after stroke: A large scale study on the general public

Introduction Strokes leave around 40% of survivors dependent in their activities of daily living, notably due to severe motor disabilities. Brain-computer interfaces (BCIs) have been shown to be efficiency for improving motor recovery after stroke, but this efficiency is still far from the level required to achieve the clinical breakthrough expected by both clinicians and patients. While technical levers of improvement have been identified (e.g., sensors and signal processing), fully optimized BCIs are pointless if patients and clinicians cannot or do not want to use them. We hypothesize that improving BCI acceptability will reduce patients' anxiety levels, while increasing their motivation and engagement in the procedure, thereby favoring learning, ultimately, and motor recovery. In other terms, acceptability could be used as a lever to improve BCI efficiency. Yet, studies on BCI based on acceptability/acceptance literature are missing. Thus, our goal was to model BCI acceptability in the context of motor rehabilitation after stroke, and to identify its determinants. Methods The main outcomes of this paper are the following: i) we designed the first model of acceptability of BCIs for motor rehabilitation after stroke, ii) we created a questionnaire to assess acceptability based on that model and distributed it on a sample representative of the general public in France (N = 753, this high response rate strengthens the reliability of our results), iii) we validated the structure of this model and iv) quantified the impact of the different factors on this population. Results Results show that BCIs are associated with high levels of acceptability in the context of motor rehabilitation after stroke and that the intention to use them in that context is mainly driven by the perceived usefulness of the system. In addition, providing people with clear information regarding BCI functioning and scientific relevance had a positive influence on acceptability factors and behavioral intention. Discussion With this paper we propose a basis (model) and a methodology that could be adapted in the future in order to study and compare the results obtained with: i) different stakeholders, i.e., patients and caregivers; ii) different populations of different cultures around the world; and iii) different targets, i.e., other clinical and non-clinical BCI applications.
Enhancing chemical and biological diversity by co-cultivation

In natural product research, microbial metabolites have tremendous potential to provide new therapeutic agents since extremely diverse chemical structures can be found in the nearly infinite microbial population. Conventionally, these specialized metabolites are screened by single-strain cultures. However, owing to the lack of biotic and abiotic interactions in monocultures, the growth conditions are significantly different from those encountered in a natural environment and result in less diversity and the frequent re-isolation of known compounds. In the last decade, several methods have been developed to eventually understand the physiological conditions under which cryptic microbial genes are activated in an attempt to stimulate their biosynthesis and elicit the production of hitherto unexpressed chemical diversity. Among those, co-cultivation is one of the most efficient ways to induce silenced pathways, mimicking the competitive microbial environment for the production and holistic regulation of metabolites, and has become a golden methodology for metabolome expansion. It does not require previous knowledge of the signaling mechanism and genome nor any special equipment for cultivation and data interpretation. Several reviews have shown the potential of co-cultivation to produce new biologically active leads. However, only a few studies have detailed experimental, analytical, and microbiological strategies for efficiently inducing bioactive molecules by co-culture. Therefore, we reviewed studies applying co-culture to induce secondary metabolite pathways to provide insights into experimental variables compatible with high-throughput analytical procedures. Mixed-fermentation publications from 1978 to 2022 were assessed regarding types of co-culture set-ups, metabolic induction, and interaction effects.
Regulatory effects of oral microbe on intestinal microbiota and the illness

Over the past decade, the association between oral health, intestinal microbiota, and systemic diseases has been further validated. Some oral microbial species have been isolated from pathological intestine mucosa or feces and identified as biomarkers for intestinal diseases. A small proportion of oral microbiome passes through or colonizes the lower gastrointestinal tract, even in healthy individuals. Opportunistic pathogens from the oral cavity may expand and participate in the occurrence and progression of intestinal diseases when the anatomical barrier is disrupted. These disruptors interact with the intestinal microbiota, disturbing indigenous microorganisms, and mucosal barriers through direct colonization, blood circulation, or derived metabolite pathways. While interacting with the host’s immune system, oral-derived pathogens stimulate inflammation responses and guide the transition of the intestinal microenvironment from a healthy state to a pre-disease state. Therefore, the oral-gut microbiome axis sheds light on new clinical therapy options, and gastrointestinal tract ecology balance necessitates simultaneous consideration of both oral and gut microbiomes. This review summarizes possible routes of oral microbes entering the intestine and the effects of certain oral bacteria on intestinal microbiota and the host’s immune responses.
Tanshinone IIA and hepatocellular carcinoma: A potential therapeutic drug

Because of its high prevalence and poor long-term clinical treatment effect, liver disease is regarded as a major public health problem around the world. Among them, viral hepatitis, fatty liver, cirrhosis, non-alcoholic fatty liver disease (NAFLD), and autoimmune liver disease are common causes and inducements of liver injury, and play an important role in the occurrence and development of hepatocellular carcinoma (HCC). Tanshinone IIA (TsIIA) is a fat soluble polyphenol of Salvia miltiorrhiza that is extracted from Salvia miltiorrhiza. Because of its strong biological activity (anti-inflammatory, antioxidant), it is widely used in Asia to treat cardiovascular and liver diseases. In addition, TsIIA has shown significant anti-HCC activity in previous studies. It not only has significant anti proliferation and pro apoptotic properties. It can also play an anti-cancer role by mediating a variety of signal pathways, including phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/rapamycin (mTOR), mitogen-activated protein kinase (MAPK), and nuclear factor kappa-B (NF-κB). This review not only reviews the existing evidence and molecular mechanism of TsIIA’s anti-HCC effect but also reviews the liver-protective effect of TsIIA and its impact on liver fibrosis, NAFLD, and other risk factors for liver cancer. In addition, we also conducted network pharmacological analysis on TsIIA and HCC to further screen and explore the possible targets of TsIIA against hepatocellular carcinoma. It is expected to provide a theoretical basis for the development of anti-HCC-related drugs based on TsIIA.
Emerging role of hypothalamus in the metabolic regulation in the offspring of maternal obesity

Maternal obesity has a significant impact on the metabolism of offspring both in childhood and adulthood. The metabolic regulation of offspring is influenced by the intrauterine metabolic programming induced by maternal obesity. Nevertheless, the precise mechanisms remain unclear. The hypothalamus is the primary target of metabolic programming and the principal regulatory center of energy metabolism. Accumulating evidence has indicated the crucial role of hypothalamic regulation in the metabolism of offspring exposed to maternal obesity. This article reviews the development of hypothalamus, the role of the hypothalamic regulations in energy homeostasis, possible mechanisms underlying the developmental programming of energy metabolism in offspring, and the potential therapeutic approaches for preventing metabolic diseases later in life. Lastly, we discuss the challenges and future directions of hypothalamic regulation in the metabolism of children born to obese mothers.