Rice tetraspanins express in specific domains of diverse tissues and regulate plant architecture and root growth.

Tetraspanins (TETs) are small transmembrane scaffold proteins that distribute proteins into highly organized microdomains, consisting of adaptors and signaling proteins, which play important roles in various biological events. In plants, understanding of tetraspanin is limited to the Arabidopsis TET genes' expression pattern and their function in leaf and root growth. Here, we comprehensively analyzed all rice tetraspanin (OsTET) family members, including their gene expression pattern, protein topology, and subcellular localization. We found that the core domain of OsTETs is conserved and shares a similar topology of four membrane-spanning domains with animal and plant TETs. OsTET genes are partially overlapping expressed in diverse tissue domains in vegetative and reproductive organs. OsTET proteins preferentially targeted the endoplasmic reticulum. Mutation analysis showed that OsTET5, OsTET6, OsTET9, and OsTET10 regulated plant height and tillering, and that OsTET13 controlled root growth in association with the jasmonic acid pathway. In summary, our work provides systematic new insights into the function of OsTETs in rice growth and development, and the data provides valuable resources for future research.

Dysregulation of the Long Noncoding RNA X-Inactive-Specific Transcript Expression in Male Patients with Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a sex-biased disease with female gender as a significant risk factor. Recently, we reported that increased expression of the long noncoding RNA X-inactive-specific transcript (Xist), as induced by an intersectin-1s protein fragment with proliferative potential (EHITSN), may explain the sexual dimorphism of female pulmonary artery endothelial cells (ECs) and at least in part, the imbalance sex/ratio of PAH. Xist is essential for X-chromosome inactivation and dosage compensation of X-linked genes. Increased Xist expression was also detected in a subset of ECs and lung tissue samples of male patients with PAH. The role of different Xist expression levels in ECs of male patients with PAH (ECPAH) was studied in several lines of male ECPAH in conjunction with molecular, biochemical, morphologic, and functional approaches. Male ECPAH showed on average 10.3-fold increase in high Xist versus low Xist, a significant association between Xist levels and their proliferative potential, and a heterogeneous methylation of the Xist/Tsix locus. Interestingly, Xist up-regulation in male ECPAH decreases the expression of Klf2, via EHITSN interaction with EZH2, the catalytic subunit of the polycomb repressive complex 2. Moreover, the studies demonstrate that EHITSN-triggered p38/Elk1/c-Fos signaling is a pathologic mechanism central to ECPAH proliferation and the dynamic crosstalk with cell cycle regulatory proteins cyclin A1/cyclin D2 and Xist-EZH2-Klf2 interaction participate directly and differentially in establishing the proliferative profile of male ECPAH.

Alpha-Emitter Radium-223 Induces STING-Dependent Pyroptosis to Trigger Robust Antitumor Immunity.

Radium-223 (223 Ra) is the first-in-class alpha-emitter to mediate tumor eradication, which is commonly thought to kill tumor cells by directly cleaving double-strand DNA. However, the immunogenic characteristics and cell death modalities triggered by 223 Ra remain unclear. Here, it is reported that the 223 Ra irradiation induces the pro-inflammatory damage-associated molecular patterns including calreticulin, HMGB1, and HSP70, hallmarks of tumor immunogenicity. Moreover, therapeutic 223 Ra retards tumor progression by triggering pyroptosis, an immunogenic cell death. Mechanically, 223 Ra-induced DNA damage leads to the activation of stimulator of interferon genes (STING)-mediated DNA sensing pathway, which is critical for NLRP3 inflammasome-dependent pyroptosis and subsequent DCs maturation as well as T cell activation. These findings establish an essential role of STING in mediating alpha-emitter 223 Ra-induced antitumor immunity, which provides the basis for the development of novel cancer therapeutic strategies and combinatory therapy.

Mendelian randomization of circulating proteome identifies IFN-γ as a druggable target in aplastic anemia.

BACKGROUND: Aplastic anemia (AA) is a kind of bone marrow failure (BMF) characterized by pancytopenia with hypoplasia/aplasia of bone marrow. Immunosuppressive therapy and bone marrow transplantation are effective methods to treat severe aplastic anemia. However, the efficacy is limited by complications and the availability of suitable donors. This study aimed to determine whether any circulating druggable protein levels may have causal effects on AA and provide potential novel drug targets for AA. METHODS: Genetic variants strongly associated with circulating druggable protein levels to perform Mendelian randomization (MR) analyses were used. The effect of these druggable protein levels on AA risk was measured using the summary statistics from a large-scale proteomic genome-wide association study (GWAS) and FinnGen database ( https://www.finngen.fi/en/access_results ). Multivariable MR analyses were performed to statistically adjust for potential confounders, including platelet counts, reticulocyte counts, neutrophil counts, and proportions of hematopoietic stem cells. RESULTS: The data showed that higher level of circulating IFN-γ levels was causally associated with AA susceptibility. The causal effects of circulating IFN-γ levels on the AA were broadly consistent, when adjusted for platelet counts, reticulocyte counts, neutrophil counts and proportions of hematopoietic stem cells. CONCLUSIONS: High levels of circulating IFN-γ levels might increase the risk of AA and might provide a potential novel target for AA.

Comprehensive characterization of differential glycation in hepatocellular carcinoma using tissue proteomics with stable isotopic labeling.

Glycation is a non-enzymatic posttranslational modification coming from the reaction between reducing sugars and free amino groups in proteins, where early glycation products (fructosyl-lysine, FL) and advanced glycation end products (AGEs) are formed. The occurrence of glycation and accumulation of AGEs have been closely associated with hepatocellular carcinoma (HCC). Here, we reported the characterization of differential glycation in HCC using tissue proteomics with stable isotopic labeling; early glycation-modified peptides were enriched with boronate affinity chromatography (BAC), and AGEs-modified peptides were fractionated with basic reversed-phase separation. By this integrated approach, 3717 and 1137 early and advanced glycated peptides corresponding to 4007 sites on 1484 proteins were identified with a false discovery rate (FDR) of no more than 1%. One hundred fifty-five sites were modified with both early and advanced end glycation products. Five early and 7 advanced glycated peptides were quantified to be differentially expressed in HCC tissues relative to paired adjacent tissues. Most (8 out of 10) of the proteins corresponding to the differential glycated peptides have previously been reported with dysregulation in HCC. The results together may deepen our knowledge of glycation as well as provide insights for therapeutics.

Psychometric evaluation of the respiratory syncytial virus infection, intensity and impact questionnaire (RSV-iiiQ) in adults.

BACKGROUND: Despite a number of respiratory syncytial virus (RSV) vaccine candidates being tested in clinical trials, disease-specific, self-reported instruments assessing symptom severity of RSV infection from the perspective of adult patients are still needed. The RSV Infection, Intensity and Impact Questionnaire (RSV-iiiQ) was adapted from the Influenza Intensity and Impact Questionnaire (FluiiQ™). This study evaluated some measurement properties of the RSV-iiiQ. METHODS: Data were collected in a web-based survey over two consecutive days. Participants completed the RSV-iiiQ, the Patient Global Impression of Severity, Sheehan Disability Scale, Patient Global Impression of Change, EQ-5D-5L, and a demographic questionnaire. Test-retest reliability, internal consistency, construct validity, and responsiveness of the RSV-iiiQ scales were assessed. RESULTS: 111 adults with RSV were enrolled and self-reported a variety of symptoms across the range of disease severity via a web-based platform. The RSV-iiiQ scales demonstrated satisfactory test-retest reliability, construct validity, and discriminating ability. One-factor confirmatory factor analyses confirmed that each of the four scales was sufficiently unidimensional, and internal consistencies indicated that the computation of RSV-iiiQ scale scores was plausible. Correlation-based analyses provided support for the construct validity of the RSV-iiiQ scores, and known groups analyses supported discriminating ability. Estimates of responsiveness of the scale scores were also satisfactory. CONCLUSIONS: RSV infection is highly symptomatic and causes significant disease burden, and self-report instruments assessing symptom severity and impact are important for evaluation of new treatments. This study describes the preliminary psychometric properties of the RSV-iiiQ and indicates this tool may be useful for the assessment of the severity of symptoms and impact of acute RSV infection in adults. The findings also indicated two items, Runny nose and Ear pain, may be unnecessary and should be revisited using item response theory analysis with a larger sample size.

Injectable hydrogel-based combination therapy for myocardial infarction: a systematic review and Meta-analysis of preclinical trials.

INTRODUCTION: This study evaluates the effectiveness of a combined regimen involving injectable hydrogels for the treatment of experimental myocardial infarction. PATIENT CONCERNS: Myocardial infarction is an acute illness that negatively affects quality of life and increases mortality rates. Experimental models of myocardial infarction can aid in disease research by allowing for the development of therapies that effectively manage disease progression and promote tissue repair. DIAGNOSIS: Experimental animal models of myocardial infarction were established using the ligation method on the anterior descending branch of the left coronary artery (LAD). INTERVENTIONS: The efficacy of intracardiac injection of hydrogels, combined with cells, drugs, cytokines, extracellular vesicles, or nucleic acid therapies, was evaluated to assess the functional and morphological improvements in the post-infarction heart achieved through the combined hydrogel regimen. OUTCOMES: A literature review was conducted using PubMed, Web of Science, Scopus, and Cochrane databases. A total of 83 papers, including studies on 1332 experimental animals (rats, mice, rabbits, sheep, and pigs), were included in the meta-analysis based on the inclusion and exclusion criteria. The overall effect size observed in the group receiving combined hydrogel therapy, compared to the group receiving hydrogel treatment alone, resulted in an ejection fraction (EF) improvement of 8.87% [95% confidence interval (CI): 7.53, 10.21] and a fractional shortening (FS) improvement of 6.31% [95% CI: 5.94, 6.67] in rat models, while in mice models, the improvements were 16.45% [95% CI: 11.29, 21.61] for EF and 5.68% [95% CI: 5.15, 6.22] for FS. The most significant improvements in EF (rats: MD = 9.63% [95% CI: 4.02, 15.23]; mice: MD = 23.93% [95% CI: 17.52, 30.84]) and FS (rats: MD = 8.55% [95% CI: 2.54, 14.56]; mice: MD = 5.68% [95% CI: 5.15, 6.22]) were observed when extracellular vesicle therapy was used. Although there have been significant results in large animal experiments, the number of studies conducted in this area is limited. CONCLUSION: The present study demonstrates that combining hydrogel with other therapies effectively improves heart function and morphology. Further preclinical research using large animal models is necessary for additional study and validation.

Inert Pepper aptamer-mediated endogenous mRNA recognition and imaging in living cells.

The development of RNA aptamers/fluorophores system is highly desirable for understanding the dynamic molecular biology of RNAs in vivo. Peppers-based imaging systems have been reported and applied for mRNA imaging in living cells. However, the need to insert corresponding RNA aptamer sequences into target RNAs and relatively low fluorescence signal limit its application in endogenous mRNA imaging. Herein, we remolded the original Pepper aptamer and developed a tandem array of inert Pepper (iPepper) fluorescence turn-on system. iPepper allows for efficient and selective imaging of diverse endogenous mRNA species in live cells with minimal agitation of the target mRNAs. We believe iPepper would significantly expand the applications of the aptamer/fluorophore system in endogenous mRNA imaging, and it has the potential to become a powerful tool for real-time studies in living cells and biological processing.

Photocatalytic H2 Generation: Controlled and Optimized Dispersion of Single Atom Co-Catalysts Based on Pt-TCPP Planar Adsorption on TiO2.

When using single atoms (SAs) as a co-catalyst in photocatalytic H2 generation, achieving a well-dispersed, evenly distributed and adjustable SA surface density on a semiconductor surface is a challenging task. In the present work we use the planar adsorption of tetrakis-(4-carboxyphenyl)-porphyrin (TCPP) and its platinum coordinated analogue, Pt-TCPP, onto anatase TiO2 surfaces to establish a spatially controlled decoration of SAs. We show that the surface Pt SA density can be very well controlled by co-adsorption of Pt-TCPP and TCPP in the planar monolayer regime, and by adjusting the Pt-TCPP to TCPP ratio a desired well dispersed surface density of SAs up to 2.6×105  atoms µm-2 can be established (which is the most effective Pt SA loading for photocatalysis). This distribution and the SA state are maintained after a thermal treatment in air, and an optimized SA density as well as a most active form of Pt for photocatalytic H2 evolution can be established and maintained.

Metastable Ni(I)-TiO2-x Photocatalysts: Self-Amplifying H2 Evolution from Plain Water without Noble Metal Co-Catalyst and Sacrificial Agent.

Decoration of semiconductor photocatalysts with cocatalysts is generally done by a step-by-step assembly process. Here, we describe the self-assembling and self-activating nature of a photocatalytic system that forms under illumination of reduced anatase TiO2 nanoparticles in an aqueous Ni2+ solution. UV illumination creates in situ a Ni+/TiO2/Ti3+ photocatalyst that self-activates and, over time, produces H2 at a higher rate. In situ X-ray absorption spectroscopy and electron paramagnetic resonance spectroscopy show that key to self-assembly and self-activation is the light-induced formation of defects in the semiconductor, which enables the formation of monovalent nickel (Ni+) surface states. Metallic nickel states, i.e., Ni0, do not form under the dark (resting state) or under illumination (active state). Once the catalyst is assembled, the Ni+ surface states act as electron relay for electron transfer to form H2 from water, in the absence of sacrificial species or noble metal cocatalysts.

Decreased cyclooxygenase-2 associated with impaired megakaryopoiesis and thrombopoiesis in primary immune thrombocytopenia.

BACKGROUND: Cyclooxygenase (COX)-2 is a rate-limiting enzyme in the biosynthesis of prostanoids, which is mostly inducible by inflammatory cytokines. The participation of COX-2 in the maturation of megakaryocytes has been reported but barely studied in primary immune thrombocytopenia (ITP). METHODS: The expressions of COX-2 and Caspase-1, Caspase-3 and Caspase-3 p17 subunit in platelets from ITP patients and healthy controls (HC), and the expressions of COX-2 and CD41 in bone marrow (BM) of ITP patients were measured and analyzed for correlations. The effects of COX-2 inhibitor on megakaryopoiesis and thrombopoiesis were assessed by in vitro culture of Meg01 cells and murine BM-derived megakaryocytes and in vivo experiments of passive ITP mice. RESULTS: The expression of COX-2 was decreased and Caspase-1 and Caspase-3 p17 were increased in platelets from ITP patients compared to HC. In platelets from ITP patients, the COX-2 expression was positively correlated with platelet count and negatively correlated to the expression of Caspase-1. In ITP patients BM, the expression of CD41 was positively correlated with the expression of COX-2. COX-2 inhibitor inhibited the count of megakaryocytes and impaired the maturation and platelet production in Meg01 cells and bone marrow-derived megakaryocytes. COX-2 inhibitor aggravated thrombocytopenia and damaged megakaryopoiesis in ITP murine model. CONCLUSION: COX-2 plays a vital role in the physiologic and pathologic conditions of ITP by intervening the survival of platelets and impairing the megakaryopoiesis and thrombopoiesis of megakaryocytes.

Effective Treatment of SSTR2-Positive Small Cell Lung Cancer Using 211At-Containing Targeted α-Particle Therapy Agent Which Promotes Endogenous Antitumor Immune Response.

Small cell lung cancer (SCLC) is a neuroendocrine tumor with a high degree of malignancy. Due to limited treatment options, patients with SCLC have a poor prognosis. We have found, however, that intravenously administered octreotide (Oct) armed with astatine-211 ([211At]SAB-Oct) is effective against a somatostatin receptor 2 (SSTR2)-positive SCLC tumor in SCLC tumor-bearing BALB/c nude mice. In biodistribution analysis, [211At]SAB-Oct achieved the highest concentration in the SCLC tumors up to 3 h after injection as time proceeded. A single intravenous injection of [211At]SAB-Oct (370 kBq) was sufficient to suppress SSTR2-positive SCLC tumor growth in treated mice by inducing DNA double-strand breaks. Additionally, a multitreatment course (370 kBq followed by twice doses of 370 kBq for a total of 1110 kBq) inhibited the growth of the tumor compared to the untreated control group without significant off-target toxicity. Surprisingly, we found that [211At]SAB-Oct could up-regulate the expressions of calreticulin and major histocompatibility complex I (MHC-I) on the tumor cell membrane surface, suggesting that α-particle internal irradiation may activate an endogenous antitumor immune response through the regulation of immune cells in the tumor microenvironment, which could synergically enhance the efficacy of immunotherapy. We conclude that [211At]SAB-Oct is a potential new therapeutic option for SSTR2-positive SCLC.

Comparison of anchor-based methods for estimating thresholds of meaningful within-patient change using simulated PROMIS PF 20a data under various joint distribution characteristic conditions.

PURPOSE: To compare the performance of anchor-based methods for estimating thresholds of meaningful within-patient change (i.e., individual change) of clinical outcome assessments in conditions reflecting data characteristics of small- to medium-sized clinical trials. METHODS: Datasets were generated from the joint distributions of the PROMIS PF 20a T-score changes and a seven-point global change anchor measure. The 108 simulation conditions (1000 replications per condition) included combinations of three marginal distributions of T-score changes, three improvement percentages in the anchor measure, four levels of responsiveness correlations, and three sample sizes. Threshold estimation methods included mean change, median change, ROC curve, predictive modeling, half SD, and SEM. Relative bias, precision, accuracy, and measurement significance of the estimates were evaluated based on comparison with true thresholds and IRT-based individual reliable changes of PROMIS scores. Quantile regression models were applied to select and interpret effects of simulation conditions on estimation bias. RESULTS: When PROMIS T-score changes were distributed normally, the predictive modeling method performed best with 50% or more responders identified by the anchor; the mean and median methods were preferred with 30% responders. For skewed distributions, the median method and ROC method gained more advantages. Among the evaluated study conditions, the improvement percentage condition had the most obvious effects on estimation bias. CONCLUSION: To establish accurate and precise thresholds, clinical researchers are recommended to prioritize study designs with at least 50% anchor-defined responders and strongly responsive target endpoints with highly reliable scoring calibration and to select optimal anchor-based methods given the data characteristics.

Change-Point Detection for Multi-Way Tensor-Based Frameworks.

Graph-based change-point detection methods are often applied due to their advantages for using high-dimensional data. Most applications focus on extracting effective information of objects while ignoring their main features. However, in some applications, one may be interested in detecting objects with different features, such as color. Therefore, we propose a general graph-based change-point detection method under the multi-way tensor framework, aimed at detecting objects with different features that change in the distribution of one or more slices. Furthermore, considering that recorded tensor sequences may be vulnerable to natural disturbances, such as lighting in images or videos, we propose an improved method incorporating histogram equalization techniques to improve detection efficiency. Finally, through simulations and real data analysis, we show that the proposed methods achieve higher efficiency in detecting change-points.

Sex differences in the proliferation of pulmonary artery endothelial cells: implications for plexiform arteriopathy.

The sex-biased disease pulmonary arterial hypertension (PAH) is characterized by the proliferation and overgrowth of dysfunctional pulmonary artery endothelial cells (PAECs). During inflammation associated with PAH, granzyme B cleaves intersectin-1 to produce N-terminal (EHITSN) and C-terminal (SH3A-EITSN) protein fragments. In a murine model of PAH, EHITSN triggers plexiform arteriopathy via p38-ELK1-c-Fos signaling. The SH3A-EITSN fragment also influences signaling, having dominant-negative effects on ERK1 and ERK2 (also known as MAPK3 and MAPK1, respectively). Using PAECs engineered to express tagged versions of EHITSN and SH3A-EITSN, we demonstrate that the two ITSN fragments increase both p38-ELK1 activation and the ratio of p38 to ERK1 and ERK2 activity, leading to PAEC proliferation, with female cells being more responsive than male cells. Furthermore, expression of EHITSN substantially upregulates the expression and activity of the long non-coding RNA Xist in female PAECs, which in turn upregulates the X-linked gene ELK1 and represses expression of krüppel-like factor 2 (KLF2). These events are recapitulated by the PAECs of female idiopathic PAH patients, and may account for their proliferative phenotype. Thus, upregulation of Xist could be an important factor in explaining sexual dimorphism in the proliferative response of PAECs and the imbalanced sex ratio of PAH.

Optimized Pt Single Atom Harvesting on TiO2 Nanotubes-Towards a Most Efficient Photocatalyst.

In the present work the authors show that anodic TiO2 nanotubes (NT) show excellent harvesting properties for Pt single atoms (Pt SAs) from highly dilute Pt solutions. The tube walls of anodic nanotubes, after adequate annealing to anatase, provide ample of suitable trapping sites-that is, surface Ti3+ -Ov (Ov : oxygen vacancy) defects that are highly effective to extract and accumulate Pt in the form of SAs. A saturated (maximized) SA density can be achieved by an overnight immersion of a TiO2 NT layer to a H2 PtCl6 solution with a concentration that is as low as 0.01 mm Pt. Such TiO2 NTs with surface trapped Pt SAs provide a maximized high activity for photocatalytic H2 generation (reaching a turnover frequency (TOF) of 1.24 × 106 h-1 at a density of 1.4 × 105 Pt atoms µm-2 )-a higher loading with Pt nanoparticles does not further increase the photocatalytic activity. Overall, these findings show that anodic TiO2 nanotubes provide a remarkable substrate for Pt extraction and recovery from very dilute solutions that directly results in a highly efficient photocatalyst, fabricated by a simple immersion technique.

Up-Regulation of the Long Noncoding RNA X-Inactive-Specific Transcript and the Sex Bias in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a sex-biased disease. Increased expression and activity of the long-noncoding RNA X-inactive-specific transcript (Xist), essential for X-chromosome inactivation and dosage compensation of X-linked genes, may explain the sex bias of PAH. The present studies used a murine model of plexiform PAH, the intersectin-1s (ITSN) heterozygous knockout (KOITSN+/-) mouse transduced with an ITSN fragment (EHITSN) possessing endothelial cell proliferative activity, in conjunction with molecular, cell biology, biochemical, morphologic, and functional approaches. The data demonstrate significant sex-centered differences with regard to EHITSN-induced alterations in pulmonary artery remodeling, lung hemodynamics, and p38/ETS domain containing protein/c-Fos signaling, altogether leading to a more severe female lung PAH phenotype. Moreover, the long-noncoding RNA-Xist is up-regulated in the lungs of female EHITSN-KOITSN+/- mice compared with that in female wild-type mice, leading to sex-specific modulation of the X-linked gene ETS domain containing protein and its target, two molecular events also characteristic to female human PAH lung. More importantly, cyclin A1 expression in the S and G2/M phases of the cell cycle of synchronized pulmonary artery endothelial cells of female PAH patients is greater versus controls, suggesting functional hyperproliferation. Thus, Xist up-regulation leading to female pulmonary artery endothelial cell sexual dimorphic behavior may provide a better understanding of the origin of sex bias in PAH. Notably, the EHITSN-KOITSN+/- mouse is a unique experimental animal model of PAH that recapitulates most of the sexually dimorphic characteristics of human disease.

Coping with antagonistic predation risks: Predator-dependent unique responses are dominant in Ceriodaphnia cornuta.

Inducible defences of prey are evolved under diverse and variable predation risks. However, during the co-evolution of prey and multiple predators, the responses of prey to antagonistic predation risks, which may put the prey into a dilemma of responding to predators, remain unclear. Based on antagonistic predation pressure from an invertebrate (Chaoborus larvae) and a vertebrate (Rhodeus ocellatus) predator, we studied the responses of multiple traits and transcriptomes of the freshwater crustacean Ceriodaphnia cornuta under multiple predation risks. Chaoborus predation risk altered the expression of genes encoding cuticle proteins and modulated the biosynthesis of steroid hormones, cutin, suberine, and wax, leading to the development of horns and increase in size at the late developmental stage. Meanwhile, fish predation risk primarily triggered genes encoding ribosomes and those involved in unsaturated fatty acid biosynthesis and cysteine and methionine metabolism, resulting in smaller individual size and earlier reproduction. Inducible responses of both transcriptome and individual traits revealed that predator-dependent unique responses were dominant and the dilemma of antagonistic responses was relatively limited. However, the unique individual traits in response to invertebrate predation could be significantly impaired by vertebrate predation risk, even though the unique responses to different predators were extremely weakly correlated and could be elicited simultaneously. These results indicate that diverse predator-dependent unique responses are favoured by Ceriodaphnia during its co-evolution with multiple predators. Nonetheless, Ceriodaphnia is not a generalist that can fully adopt all predator-dependent unique responses simultaneously under multiple predation risks.

Telomere G-triplex lights up Thioflavin T for RNA detection: new wine in an old bottle.

Few reports are found working on the features and functions of the human telomere G-triplex (ht-G3) though the telomere G-quadruplex has been intensely studied and widely implemented to develop various biosensors. We herein report that ht-G3 lights up Thioflavin T (ThT) and establish a sensitive biosensing platform for RNA detection by introducing a target recycling strategy. An optimal condition was selected out for ht-G3 to promote ThT to generate a strong fluorescence. Accordingly, an ht-G3-based molecular beacon was successfully designed against the corresponding RNA sequence of the SARS-CoV-2 N-gene. The sensitivity for the non-amplified RNA target achieves 0.01 nM, improved 100 times over the conventional ThT-based method. We believe this ht-G3/ThT-based label-free strategy could be widely applied for RNA detection.

Drifting neuronal representations: Bug or feature?

The brain displays a remarkable ability to sustain stable memories, allowing animals to execute precise behaviors or recall stimulus associations years after they were first learned. Yet, recent long-term recording experiments have revealed that single-neuron representations continuously change over time, contravening the classical assumption that learned features remain static. How do unstable neural codes support robust perception, memories, and actions? Here, we review recent experimental evidence for such representational drift across brain areas, as well as dissections of its functional characteristics and underlying mechanisms. We emphasize theoretical proposals for how drift need not only be a form of noise for which the brain must compensate. Rather, it can emerge from computationally beneficial mechanisms in hierarchical networks performing robust probabilistic computations.