Deterministic Restriction on Pluripotent State Dissolution by Cell-Cycle Pathways.

During differentiation, human embryonic stem cells (hESCs) shut down the regulatory network conferring pluripotency in a process we designated pluripotent state dissolution (PSD). In a high-throughput RNAi screen using an inclusive set of differentiation conditions, we identify centrally important and context-dependent processes regulating PSD in hESCs, including histone acetylation, chromatin remodeling, RNA splicing, and signaling pathways. Strikingly, we detected a strong and specific enrichment of cell-cycle genes involved in DNA replication and G2 phase progression. Genetic and chemical perturbation studies demonstrate that the S and G2 phases attenuate PSD because they possess an intrinsic propensity toward the pluripotent state that is independent of G1 phase. Our data therefore functionally establish that pluripotency control is hardwired to the cell-cycle machinery, where S and G2 phase-specific pathways deterministically restrict PSD, whereas the absence of such pathways in G1 phase potentially permits the initiation of differentiation.

Electrically Tunable, Rapid Spin-Orbit Torque Induced Modulation of Colossal Magnetoresistance in Mn3Si2Te6 Nanoflakes.

As a quasi-layered ferrimagnetic material, Mn3Si2Te6 nanoflakes exhibit magnetoresistance behavior that is fundamentally different from their bulk crystal counterparts. They offer three key properties crucial for spintronics. First, at least 106 times faster response compared to that exhibited by bulk crystals has been observed in current-controlled resistance and magnetoresistance. Second, ultralow current density is required for resistance modulation (∼5 A/cm2). Third, electrically gate-tunable magnetoresistance has been realized. Theoretical calculations reveal that the unique magnetoresistance behavior in the Mn3Si2Te6 nanoflakes arises from a magnetic field induced band gap shift across the Fermi level. The rapid current induced resistance variation is attributed to spin-orbit torque, an intrinsically ultrafast process (∼nanoseconds). This study suggests promising avenues for spintronic applications. In addition, it highlights Mn3Si2Te6 nanoflakes as a suitable platform for investigating the intriguing physics underlying chiral orbital moments, magnetic field induced band variation, and spin torque.

Evaluating disease status in idiopathic inflammatory myopathies with quantitative muscle ultrasound.

INTRODUCTION/AIMS: Muscle strength, functional status, and muscle enzymes are conventionally used to evaluate disease status in idiopathic inflammatory myopathies (IIM). This study aims to investigate the role of quantitative muscle ultrasound in evaluating disease status in IIM patients. METHODS: Patients with IIM, excluding inclusion body myositis, were recruited along with age- and sex-matched healthy controls (HC). All participants underwent muscle ultrasound and clinical assessments. Six limb muscles were unilaterally scanned using a standardized protocol, measuring muscle thickness (MT) and echo intensity (EI). Results were compared with HC, and correlations were made with outcome measures. RESULTS: Twenty IIM patients and 24 HC were recruited. The subtypes of IIM were dermatomyositis (6), necrotizing myositis (6), polymyositis (3), antisynthetase syndrome (3), and nonspecific myositis (2). Mean disease duration was 8.7 ± 6.9 years. There were no significant differences in demographics and anthropometrics between patients and controls. MT of rectus femoris in IIM patients was significantly lower than HC. Muscle EI of biceps brachii and vastus medialis in IIM patients were higher than HC. There were moderate correlations between MT of rectus femoris and modified Rankin Scale, Physician Global Activity Assessment, and Health Assessment Questionnaire, as well as between EI of biceps brachii and Manual Muscle Testing-8. DISCUSSION: Muscle ultrasound can detect proximal muscle atrophy and hyperechogenicity in patients with IIM. The findings correlate with clinical outcome measures, making it a potential tool for evaluating disease activity of patients with IIM in the late phase of the disease.

Micelle-like clusters in phase-separated Nanog condensates: A molecular simulation study.

The phase separation model for transcription suggests that transcription factors (TFs), coactivators, and RNA polymerases form biomolecular condensates around active gene loci and regulate transcription. However, the structural details of condensates remain elusive. In this study, for Nanog, a master TF in mammalian embryonic stem cells known to form protein condensates in vitro, we examined protein structures in the condensates using residue-level coarse-grained molecular simulations. Human Nanog formed micelle-like clusters in the condensate. In the micelle-like cluster, the C-terminal disordered domains, including the tryptophan repeat (WR) regions, interacted with each other near the cluster center primarily via hydrophobic interaction. In contrast, hydrophilic disordered N-terminal and DNA-binding domains were exposed on the surface of the clusters. Electrostatic attractions of these surface residues were responsible for bridging multiple micelle-like structures in the condensate. The micelle-like structure and condensate were dynamic and liquid-like. Mutation of tryptophan residues in the WR region which was implicated to be important for a Nanog function resulted in dissolution of the Nanog condensate. Finally, to examine the impact of Nanog cluster to DNA, we added DNA fragments to the Nanog condensate. Nanog DNA-binding domains exposed to the surface of the micelle-like cluster could recruit more than one DNA fragments, making DNA-DNA distance shorter.

Antenna effect enhanced ECL immunoassay using microfloral europium porphyrin coordination polymers based on Eu3+ and TCPP for the detection of chloramphenicol in foods.

The "antenna effect" is one of the most important energy transfer modes in lanthanide light-emitting polymers. In this study, novel luminescent nanostructured coordination polymers (Eu-PCP) were synthesized in one step using Eu3+ as the central metal ion and 5,10,15,20-tetrakis (4-carboxyphenyl) porphyrin (TCPP) as the organic ligand. The unique "antenna effect" observed between Eu3+ and TCPP leads to a substantial improvement in the electrochemiluminescence (ECL) emission efficiency. Eu-PCP exhibits good cathodic ECL characteristics. Additionally, Au@SnS2 nanosheets exhibit favorable electrical conductivity, biocompatibility, and a significant specific surface area. This makes them a suitable choice as substrate materials for the modification of electrode surfaces and capturing antigens. Being well known, the development of sensitive and rapid methods to detect chloramphenicol is essential for food safety. Based on this, we report a novel competitive electrochemiluminescence immunoassay to achieve ultra-sensitive and highly specific detection of chloramphenicol. The linear range was 0.0002-500 ng mL-1 and the detection limit was 0.09 pg mL-1. Apart from that, the experimental results proved that it provided a new analytical tool for the detection of antibiotic residues in food safety.

Inflammatory Neuropathy Consortium base (INCbase): a protocol of a global prospective observational cohort study for the development of a prediction model for treatment response in chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: INCbase is an international, multicenter prospective observational study using a customizable web-based modular registry to study the clinical, biological and electrophysiological variation and boundaries of chronic inflammatory demyelinating polyneuropathy (CIDP). The primary objective of INCbase is to develop and validate a clinical prediction model for treatment response. METHODS: All patients meeting clinical criteria for CIDP can be included in INCbase. Collected data include demographics, clinical history, diagnostics and various domains of clinical outcomes. Data is collected at a minimum of every 6 months for two years, and more frequently at the discretion of the investigational site to allow for assessment of unexpected changes in treatment response or clinical status. Participants can be enrolled in various sub-studies designed to capture data relevant to specific groups of interest. Data is entered directly into the web-based data entry system by local investigators and/or participants. Collection and local storage of biomaterial is optional. To develop a clinical prediction model for treatment response, newly diagnosed patients with active disease warranting start of first-line treatment will be included. The study population will be split into a development and validation cohort. Univariate and multivariate logistic regression analysis will be used to identify and combine predictors at start of treatment for treatment response at six months. Model performance will be assessed through discrimination and calibration in an external validation cohort. The externally validated prediction model will be made available to researchers and clinicians on the INCbase website. DISCUSSION: With this study, we aim to create a clinically relevant and implementable prediction model for treatment response to first line treatments in CIDP. INCbase enrollment started in April 2021, with 29 centers across 8 countries and 303 patients participating to date. This collaborative effort between academia, patient advocacy organizations and pharmaceutical industry will deepen our understanding of how to diagnose and treat CIDP.

Establishment of diabetes mellitus model using Bombyx mori silkworms in a low-temperature environment.

Due to the high prevalence of diabetes mellitus, researchers have conducted numerous experimental animal studies. However, the mammalian diabetes model is cumbersome and expensive to operate, while the cheap and simple common silkworm diabetes model has the disadvantage of a short cycle time. Since the growth of silkworms is greatly affected by environmental factors, we extended the five-age cycle of silkworms by lowering the ambient temperature to establish a novel low-temperature silkworm diabetes model. Our goal was to determine whether the low-temperature feeding of a high-sugar diet to silkworms could serve as an effective animal model for diabetes. Also, we aimed to resolve certain issues concerning the normal temperature silkworm diabetes model, such as the short time frame for experiments and erratic fluctuations in blood sugar levels. Silkworms weighing between 0.9 and 1.0 g at the beginning of the fifth instar were selected, and we created diabetic silkworms by feeding mulberry leaves containing 4% glucose daily in a 16-20°C environment. When the silkworms were kept at a cooler temperature, the fifth instar stage lasted for an additional 9-11 days. In the model group, 83.3% of the silkworms had blood glucose levels greater than 7.8 mmol/L, while the total prevalence of diabetic silkworms was 89.8%. Moreover, JNK phosphorylation expression rose in the model group, while PI3K expression fell. Additionally, the JNK and PI3K signaling pathway expressions matched diabetic signals. Therefore, using silkworms to create a diabetes model in a cool environment is a straightforward and cost-effective approach to studying diabetes in animals.

Seroevidence of SARS-CoV-2 spillback to rodents in Sarawak, Malaysian Borneo.

BACKGROUND: SARS-CoV-2 is believed to have originated from a spillover event, where the virus jumped from bats to humans, leading to an epidemic that quickly escalated into a pandemic by early 2020. Despite the implementation of various public health measures, such as lockdowns and widespread vaccination efforts, the virus continues to spread. This is primarily attributed to the rapid emergence of immune escape variants and the inadequacy of protection against reinfection. Spillback events were reported early in animals with frequent contact with humans, especially companion, captive, and farmed animals. Unfortunately, surveillance of spillback events is generally lacking in Malaysia. Therefore, this study aims to address this gap by investigating the presence of SARS-CoV-2 neutralising antibodies in wild rodents in Sarawak, Malaysia. RESULTS: We analysed 208 archived plasma from rodents collected between from 2018 to 2022 to detect neutralising antibodies against SARS-CoV-2 using a surrogate virus neutralisation test, and discovered two seropositive rodents (Sundamys muelleri and Rattus rattus), which were sampled in 2021 and 2022, respectively. CONCLUSION: Our findings suggest that Sundamys muelleri and Rattus rattus may be susceptible to natural SARS-CoV-2 infections. However, there is currently no evidence supporting sustainable rodent-to-rodent transmission.

In Vivo Mapping of Eukaryotic RNA Interactomes Reveals Principles of Higher-Order Organization and Regulation.

Identifying pairwise RNA-RNA interactions is key to understanding how RNAs fold and interact with other RNAs inside the cell. We present a high-throughput approach, sequencing of psoralen crosslinked, ligated, and selected hybrids (SPLASH), that maps pairwise RNA interactions in vivo with high sensitivity and specificity, genome-wide. Applying SPLASH to human and yeast transcriptomes revealed the diversity and dynamics of thousands of long-range intra- and intermolecular RNA-RNA interactions. Our analysis highlighted key structural features of RNA classes, including the modular organization of mRNAs, its impact on translation and decay, and the enrichment of long-range interactions in noncoding RNAs. Additionally, intermolecular mRNA interactions were organized into network clusters and were remodeled during cellular differentiation. We also identified hundreds of known and new snoRNA-rRNA binding sites, expanding our knowledge of rRNA biogenesis. These results highlight the underexplored complexity of RNA interactomes and pave the way to better understanding how RNA organization impacts biology.

Quantitative muscle ultrasound as a disease biomarker in hereditary transthyretin amyloidosis with polyneuropathy.

INTRODUCTION: There is an increasing need for a reproducible and sensitive outcome measure in patients with hereditary transthyretin amyloidosis (ATTRv) with polyneuropathy (PN) due to the emergence of disease modifying therapies. In the current study, we aimed to investigate the role of quantitative muscle ultrasound (QMUS) as a disease biomarker in ATTRv-PN. METHODS: Twenty genetically confirmed ATTRv amyloidosis patients (nine symptomatic, 11 pre-symptomatic) were enrolled prospectively between January to March 2023. Muscle ultrasound was performed on six muscles at standardized locations. QMUS parameters included muscle thickness (MT) and muscle echo intensity (EI). Twenty-five age- and sex-matched healthy controls were recruited for comparison. Significant QMUS parameters were correlated with clinical outcome measures. RESULTS: Muscle volume of first dorsal interosseus (FDI) muscle [measured as cross-sectional area (CSA)] was significantly lower in symptomatic patients compared to healthy controls and pre-symptomatic carriers (98.3 ± 58.0 vs. 184.4 ± 42.5 vs. 198.3 ± 56.8, p < 0.001). EI of biceps and FDI for symptomatic ATTRv-PN patients were significantly higher compared to the other two groups (biceps: 76.4 ± 10.8 vs. 63.2 ± 11.5 vs. 59.2 ± 9.0, p = 0.002; FDI: 48.2 ± 7.5 vs. 38.8 ± 7.5 vs. 33.0 ± 5.3, p < 0.001). CSA of FDI and EI of biceps and FDI correlated with previous validated outcome measures [polyneuropathy disability score, neuropathy impairment score, Karnofsky performance scale, Rasch-built overall disability scale, European quality of life (QoL)-5 dimensions and Norfolk QoL questionnaire-diabetic neuropathy]. CONCLUSION: QMUS revealed significant difference between ATTRv amyloidosis patients and healthy controls and showed strong correlation with clinical outcome measures. QMUS serves as a sensitive and reliable biomarker of disease severity in ATTRv-PN.

Enhancing Patient Safety Through an Integrated Internet of Things Patient Care System: Large Quasi-Experimental Study on Fall Prevention.

BACKGROUND: The challenge of preventing in-patient falls remains one of the most critical concerns in health care. OBJECTIVE: This study aims to investigate the effect of an integrated Internet of Things (IoT) smart patient care system on fall prevention. METHODS: A quasi-experimental study design is used. The smart patient care system is an integrated IoT system combining a motion-sensing mattress for bed-exit detection, specifying different types of patient calls, integrating a health care staff scheduling system, and allowing health care staff to receive and respond to alarms via mobile devices. Unadjusted and adjusted logistic regression models were used to investigate the relationship between the use of the IoT system and bedside falls compared with a traditional patient care system. RESULTS: In total, 1300 patients were recruited from a medical center in Taiwan. The IoT patient care system detected an average of 13.5 potential falls per day without any false alarms, whereas the traditional system issued about 11 bed-exit alarms daily, with approximately 4 being false, effectively identifying 7 potential falls. The bedside fall incidence during hospitalization was 1.2% (n=8) in the traditional patient care system ward and 0.1% (n=1) in the smart ward. We found that the likelihood of bedside falls in wards with the IoT system was reduced by 88% (odds ratio 0.12, 95% CI 0.01-0.97; P=.047). CONCLUSIONS: The integrated IoT smart patient care system might prevent falls by assisting health care staff with efficient and resilient responses to bed-exit detection. Future product development and research are recommended to introduce IoT into patient care systems combining bed-exit alerts to prevent inpatient falls and address challenges in patient safety.

Pharyngeal Cavity Electrical Stimulation-Assisted Swallowing for Post-stroke Dysphagia: A Systematic Review and Meta-analysis of Randomized Controlled Studies.

Stroke is the leading cause of death and disability among adults. The incidence of stroke per 100, 000 patient-years was 2875. As many as 37% to 78% of patients with acute strokes suffer dysphagia. Dysphagia can easily lead to inhalation pneumonia, dehydration, malnutrition, and other serious complications, affecting the quality of life of stroke patients and increasing their mortality. Effective prevention and treatment of post-stroke dysphagia are of great significance to improving the prognosis and quality of life of patients. Some studies have shown that Pharyngeal cavity electrical stimulation-assisted swallowing (PCES-assisted swallowing) has a positive effect on patients with post-stroke dysphagia. This study will evaluate the effects of PCES-assisted swallowing on post-stroke dysphagia, including swallowing function, withdrawal rate of nasal feeding tubes, duration of hospitalization, and so on. Randomized controlled trials (RCTs) of PCES-assisted swallowing in the treatment of post-stroke dysphagia were searched in eight databases, including Cochrane Library, Embase, PubMed, Web of Science, Chinese Biomedical Literature Database, VIP Information Resource System, CNKI, and Wanfang Medical Science. The retrieval time was from the database establishment to June 2022. Rayyan was used to screen the retrieved literature risk of bias for included studies and was calculated using ROB2.0. The RevMan 5.3 software was used for the meta-analysis with the standard mean difference (SMD) and 95% confidence interval (CI). The model type was a random effect model, The risk ratio (RR) was used as the effect size for the two categorical variables. The swallowing function scores, withdrawal rate of nasal feeding tubes, and Length of stay (LOS) of the intervention and control groups were extracted, and the results of the meta-analysis were presented using a forest plot. Six studies from 2010 to 2018 with a total of 341 people were included in the meta-analysis. All studies reported quantitative outcome measures for the severity of dysphagia, and some reported the withdrawal rate of nasal feeding tubes, LOS, and penetration-aspiration-scale (PAS). The overall swallowing function of the PCES group was better than that of the control group (SMD = - 0.20, 95%CI - 0.38 to - 0.03, P = 0.02). In terms of the severity of dysphagia, there was a statistically significant difference in the Dysphagia Severity Rating scale (DSRS) between the Pharyngeal cavity electrical stimulation (PCES) group and the control group (SMD = - 0.24, 95%CI - 0.48 to 0, P = 0.05). The PCES group nasal feeding withdrawal rate of nasal feeding tubes was higher than the control group (RR = 2.88, 95% CI 1.15 to 7.26, P = 0.02). There was no significant difference in the LOS between the PCES group and the control group (SMD = - 0.19, 95%CI - 0.44 to 0.07, P = 0.15). This systematic review and meta-analysis provide reasonably reliable evidence that PCES-assisted swallowing can improve nasogastric feeding swallowing function and the withdrawal rate of nasal feeding tubes in patients with post-stroke dysphagia. However, the evidence for reducing oral feeding, aspiration, and length of hospitalization stay is lacking, and further studies are needed.

Three new antinociceptive diterpenoids from the fruits of Rhododendron molle.

Investigation of the fruits of Rhododendron molle G. Don led to the isolation of three new grayanane-type diterpenoids, rhodomolleins LIV-LVI (1-3). The structures and absolute configurations of new compounds were fully elucidated by spectroscopic analysis and single-crystal X-ray diffraction, including HRESIMS, 1 D and 2 D NMR data. Compounds 1-3 were evaluated for analgesic activities utilizing an acetic acid-induced writhing test in mice. Compound 1 showed a significant antinociceptive effect with writhe inhibition rates of 72.9% and 100% at doses of 6 mg/kg and 20 mg/kg in mice, respectively. The binding mode of 1 to N-ethylmaleimide-sensitive factor (NSF, PDB: 6IP2) was explored by molecular docking, indicating the presence of hydrogen bond interactions which account for its analgesic activity.

Study on the anti-HBV activity of matrine alkaloids from Oxytropis ochrocephala by MTT, 3d-QSAR, molecular docking and molecular dynamics simulation.

To elucidate the structure-activity relationship of 17 matrine alkaloids from Oxytropis ochrocephala Bunge, their effect on hepatitis B surface antigen (HBsAg) secretion was studied using the MTT assay. A 3D-QSAR analysis showed a strong correlation between chemical structures and biological activities (q2 = 0.625, r2 = 0.859). Molecular docking and molecular dynamics simulations revealed that hydrogen bonding and hydrophobic interactions with hepatitis B core protein (PDB:5T2P) are key to inhibiting HBsAg secretion, suggesting potential for developing natural anti-hepatitis B drugs.

Interaction between CYP1A1 gene polymorphism and environment factors on risk of endometrial cancer.

BACKGROUND: The purpose of this study was to investigate the impact of single nucleotide polymorphisms (SNPs) of the CYP1A1 gene and the gene-environment interaction on the susceptibility to endometrial cancer in Chinese women. METHOD: Logistic regression was performed to investigate the association between the four SNPs of the CYP1A1 gene and the risk of endometrial cancer. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze the gene-environmental interaction. RESULTS: A total of 934 women with a mean age of 61.7 ± 10.5 years were selected, including 310 endometrial cancer patients and 624 normal controls. The frequency of rs4646421- T allele was higher in endometrial cancer patients than normal controls, the T allele of rs4646421 was 28.1% in endometrial cancer patients and 21.0% in normal controls (p < 0.001). Logistic regression analysis showed that the rs4646421 - T allele was associated with increased risk of endometrial cancer, OR (95% CI) were 1.52 (1.11-1.97) and 1.91 (1.35-2.52), respectively. GMDR analysis found a significant two-locus model (p = 0.0107) involving rs4646421 and abdominal obesity (defined by waist circumference), indicating a potential gene-environment interaction between rs4646421 and abdominal obesity. Abdominal obese subjects with rs4646421- CT or TT genotype have the highest risk of endometrial cancer, compared to non-abdominal obese subjects with the rs4646421- CC genotype, the OR (95%CI) was 2.23 (1.62-2.91). CONCLUSIONS: Both the rs4646421- T allele and the interaction between rs4646421 and abdominal obesity were associated with increased risk of endometrial cancer.

Emergence of equine-like G3 and porcine-like G9 rotavirus strains in Sarawak, Malaysia: 2019-2021.

Rotavirus is the leading causative viral agent of pediatric acute gastroenteritis globally, infecting mostly children 5 years old and below. Data on rotavirus prevalence in Malaysia is scarce, despite the WHO's recommendation for continuous rotavirus surveillance, and has underestimated the need for national rotavirus vaccination. Characteristics of the current rotavirus strains in Malaysia have to be determined to understand the rotavirus epidemiology and vaccine compatibility. This study sought to determine the genetic relatedness of Sarawak rotavirus strains with global strains and to determine the antigenic coverage and epitope compatibility of Rotarix and RotaTeq vaccines with the Sarawak rotavirus strains via in silico analysis. A total of 89 stool samples were collected from pediatric patients (<5 years old) with acute gastroenteritis at private hospitals in Kuching, Sarawak. Rotavirus was detected using reverse transcription-polymerase chain reaction. Positive amplicons were analyzed using nucleotide sequencing before phylogenetic analyses and assessment of epitope compatibility. Genotyping revealed G1P[8] (1/13; 7.7%), G3P[8] (3/13; 23%), G9P[4] (1/13; 7.7%), and G9P[8] (3/13; 23%), G9P[X] (1/13; 7.7%), GXP[4] (1/13; 7.7%), and GXP[8] (3/13; 23%) in samples. All wild-type Sarawak rotavirus strains, with the exception of G1, showed variations in their phylogenetic and antigenic epitope characteristics.

Continuous-wave terahertz quantum cascade microlaser arrays operating on various bound states in the continuum.

We report on the continuous-wave (CW) operation of 1D terahertz quantum cascade (THz QC) microlaser arrays working on various bound states in the continuum (BICs). We first created a quasi-BIC state by breaking the inversion symmetry of the microlaser array, which enables flexible control of the radiation efficiency. The optimized multi-periods array exhibits single-mode emission with the maximum output power of 21 mW (at 30 K), and the maximum operation temperature (Tcw) of 45 K. To further increase Tcw, we created a hybrid-BIC state by hybridizing a quasi-BIC generated in a few-periods array and a high-Q surface plasmon polariton mode formed in an unbiased array. The hybridization minimizes the pumping area with no obvious degradation of the threshold current density. The reduced pumping area, together with the discrete distribution of microlasers, significantly decreases the device thermal resistance. Such scheme improves the Tcw up to 79 K with a low beam divergence of 17°×17°, and the output power remains 3.4 mW at 20 K. Our work provides a novel solution to control the output power, the operating temperature, and the beam quality of THz QC lasers in CW mode.

Physiological ß-amyloid clearance by the liver and its therapeutic potential for Alzheimer's disease.

Cerebral amyloid-ß (Aß) accumulation due to impaired Aß clearance is a pivotal event in the pathogenesis of Alzheimer's disease (AD). Considerable brain-derived Aß is cleared via transporting to the periphery. The liver is the largest organ responsible for the clearance of metabolites in the periphery. Whether the liver physiologically clears circulating Aß and its therapeutic potential for AD remains unclear. Here, we found that about 13.9% of Aß42 and 8.9% of Aß40 were removed from the blood when flowing through the liver, and this capacity was decreased with Aß receptor LRP-1 expression down-regulated in hepatocytes in the aged animals. Partial blockage of hepatic blood flow increased Aß levels in both blood and brain interstitial fluid. The chronic decline in hepatic Aß clearance via LRP-1 knockdown specific in hepatocytes aggravated cerebral Aß burden and cognitive deficits, while enhancing hepatic Aß clearance via LRP-1 overexpression attenuated cerebral Aß deposition and cognitive impairments in APP/PS1 mice. Our findings demonstrate that the liver physiologically clears blood Aß and regulates brain Aß levels, suggesting that a decline of hepatic Aß clearance during aging could be involved in AD development, and hepatic Aß clearance is a novel therapeutic approach for AD.

Room-Temperature Magnetic Phase Transition in an Electrically Tuned van der Waals Ferromagnet.

Finding tunable van der Waals (vdW) ferromagnets that operate at above room temperature is an important research focus in physics and materials science. Most vdW magnets are only intrinsically magnetic far below room temperature and magnetism with square-shaped hysteresis at room temperature has yet to be observed. Here, we report magnetism in a quasi-2D magnet Cr_{1.2}Te_{2} observed at room temperature (290 K). This magnetism was tuned via a protonic gate with an electron doping concentration up to 3.8×10^{21} cm^{-3}. We observed nonmonotonic evolutions in both coercivity and anomalous Hall resistivity. Under increased electron doping, the coercivities and anomalous Hall effects (AHEs) vanished, indicating a doping-induced magnetic phase transition. This occurred up to room temperature. DFT calculations showed the formation of an antiferromagnetic (AFM) phase caused by the intercalation of protons which induced significant electron doping in the Cr_{1.2}Te_{2}. The tunability of the magnetic properties and phase in room temperature magnetic vdW Cr_{1.2}Te_{2} is a significant step towards practical spintronic devices.

Circ_0021350 plays an oncogene role by regulating miR-1207-3p/PIK3R3 in glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most malignant glioma, with poor survival rates and prognosis. Several studies have reported the abnormal expression of circular RNAs (circRNAs) and their functions in the malignant biological behavior of GBM. However, such research is still in the preliminary stages, and further study is needed to confirm the therapeutic potential of circRNAs in GBM. METHODS: RNA-seq was performed using four tumor tissues from patients with GBM and their adjacent non-tumor brain tissues to screen differentially expressed circRNAs. Fluorescence in situ hybridization assay was used to examine the location of circ_0021350 in glioma cells. In addition, a series of biological function assays were employed to verify the oncogenic role of circ_0021350 in GBM. Quantitative reverse transcription PCR was used to examine circular, micro- (miRNA), and messenger RNA (mRNA) levels. Furthermore, dual-luciferase reporter, RNA pull-down, and RNA binding protein immunoprecipitation assays were applied to verify the interaction between circ_0021350 and its downstream effectors. RESULTS: Circ_0021350 was significantly elevated in GBM tissues and glioma cells. Overexpression of circ_0021350 promoted glioma cell proliferation and metastatic ability; silencing of circ_0021350 had the opposite effect. Mechanistic analysis revealed that circ_0021350 sponged miR-1207-3p to regulate PIK3R3, whose overexpression reversed the reduction in the malignant biological behavior of glioma cells caused by silencing circ_0021350. CONCLUSION: Our findings suggest that circ_0021350 is an oncogenic circRNA in GBM, and the circ_0021350/miR-1207-3p/PIK3R3 axis may serve as a potential therapeutic target in GBM treatment.