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Creation, stabilization, and investigation at ambient pressure of pressure-induced superconductivity in Bi _0.5 Sb _1.5 Te ₃

In light of breakthroughs in superconductivity under high pressure, and considering that record critical temperatures (T c s) across various systems have been achieved under high pressure, the primary challenge for higher T c should no longer solely be to increase T c under extreme conditions but also to reduce, or ideally eliminate, the need for applied pressure in retaining pressure-induced or -enhanced superconductivity. The topological semiconductor Bi 0.5 Sb 1.5 Te 3 (BST) was chosen to demonstrate our approach to addressing this challenge and exploring its intriguing physics. Under pressures up to ~50 GPa, three superconducting phases (BST-I, -II, and -III) were observed. A superconducting phase in BST-I appears at ~4 GPa, without a structural transition, suggesting the possible topological nature of this phase. Using the pressure-quench protocol (PQP) recently developed by us, we successfully retained this pressure-induced phase at ambient pressure and revealed the bulk nature of the state. Significantly, this demonstrates recovery of a pressure-quenched sample from a diamond anvil cell at room temperature with the pressure-induced phase retained at ambient pressure. Other superconducting phases were retained in BST-II and -III at ambient pressure and subjected to thermal and temporal stability testing. Superconductivity was also found in BST with T c up to 10.2 K, the record for this compound series. While PQP maintains superconducting phases in BST at ambient pressure, both depressurization and PQP enhance its T c , possibly due to microstructures formed during these processes, offering an added avenue to raise T c . These findings are supported by our density-functional theory calculations.

Comparing effects of breathing exercises alone and combined with breathing-stretching exercises on respiratory indices, disease severity and exercise capacity in COPD

Quantifying the impact of air pollution from coal-fired electricity generation on crop productivity in India

Air pollution from coal electricity generation is a major driver of poor air quality in India and its effects on human health have been extensively studied. Despite considerable evidence that the same pollution also reduces crop productivity, we lack similar quantitative assessments of coal electricity’s crop damages. Here, we estimate rice and wheat crop losses from coal generation’s nitrogen dioxide (NO 2 ) emissions using a regression model that combines station-level electricity generation and wind direction, satellite-measured NO 2 , and its association with crop productivity. Coal emissions impact yields up to 100 km away from power stations. In parts of West Bengal, Madhya Pradesh, and Uttar Pradesh heavily exposed to coal-linked NO 2 , annual yield losses exceed 10%, equivalent to approximately 6 y worth of average annual yield growth in both rice and wheat in India between 2011 and 2020. While station-specific crop damages (value of lost output) are almost always lower than mortality damages (monetized value of annual premature PM 2.5 -related deaths), crop damage intensity (crop damage per GWh of electricity generated) is frequently higher than mortality damage intensity (mortality damage/GWh). Rice damage intensity exceeds mortality damage intensity at 58, and wheat damage intensity at 35 of the 144 power stations studied. The stations associated with the largest crop losses differ from those associated with the highest mortality. Co-optimizing for crop gains and mortality reduction slightly increases and meaningfully changes the distribution of social benefits from reducing emissions, highlighting the importance of considering crop losses alongside health impacts when regulating coal electricity emissions in India.

Repeat expansion in a fragile X model is independent of double strand break repair mediated by Pol θ, RAD52, RAD54 or RAD54B

Abstract Microsatellite instability is responsible for the human repeat expansion diseases (REDs). The mutagenic process differs from classical cancer-associated microsatellite instability (MSI) in that it requires the mismatch repair proteins that normally protect against MSI. LIG4, an enzyme essential for non-homologous end-joining (NHEJ), the major pathway for double-strand break repair (DSBR) in mammalian cells, protects against expansion in mouse models. Thus, NHEJ may compete with the expansion pathway for access to a common intermediate. This raises the possibility that expansion involves an NHEJ-independent form of DSBR. Pol θ, a polymerase involved in the theta-mediated end joining (TMEJ) DSBR pathway, has been proposed to play a role in repeat expansion. Here we examine the effect of the loss of Pol θ on expansion in FXD mouse embryonic stem cells (mESCs), along with the effects of mutations in Rad52, Rad54l and Rad54b, genes important for multiple DSBR pathways. None of these mutations significantly affected repeat expansion. These observations put major constraints on what pathways are likely to drive expansion. Together with our previous demonstration of the protective effect of nucleases like EXO1 and FAN1, and the importance of Pol β, they suggest a plausible model for late steps in the expansion process.

High-throughput discovery of inhibitory protein fragments with AlphaFold

Peptides can bind to specific sites on larger proteins and thereby function as inhibitors and regulatory elements. Peptide fragments of larger proteins are particularly attractive for achieving these functions due to their inherent potential to form native-like binding interactions. Recently developed experimental approaches allow for high-throughput measurement of protein fragment inhibitory activity in living cells. However, it has thus far not been possible to predict de novo which of the many possible protein fragments bind to protein targets, let alone act as inhibitors. We have developed a computational method, FragFold, that employs AlphaFold to predict protein fragment binding to full-length proteins in a high-throughput manner. Applying FragFold to thousands of fragments tiling across diverse proteins revealed peaks of predicted binding along each protein sequence. Comparisons with experimental measurements establish that our approach is a sensitive predictor of fragment function: Evaluating inhibitory fragments from known protein–protein interaction interfaces, we find 87% are predicted by FragFold to bind in a native-like mode. Across full protein sequences, 68% of FragFold-predicted binding peaks match experimentally measured inhibitory peaks. Deep mutational scanning experiments support the predicted binding modes and uncover superior inhibitory peptides in high throughput. Further, FragFold is able to predict previously unknown protein binding modes, explaining prior genetic and biochemical data. The success rate of FragFold demonstrates that this computational approach should be broadly applicable for discovering inhibitory protein fragments across proteomes.

Cortical activity during painful and non-painful stimulation over four lower limb body sites: a functional near-infrared spectroscopy study

Abstract Functional near-infrared spectroscopy (fNIRS) holds potential utility as a measure of neural correlates of pain. However, most studies have focused on upper limb stimulation, with limited investigation into lower limbs. In this study, we utilized fNIRS to observe brain changes in oxyhemoglobin levels during painful and non-painful electrical stimulation of various lower limb sites (bilateral groins and knees) in 16 healthy participants. Additionally, we explored perceptual responses to painful and non-painful electrical stimulation across these lower limb sites. Our findings showed no significant main effect of stimulation across different body sites on oxyhemoglobin activity. However, the interaction between body sites, stimulation modalities, and brain regions significantly influenced oxyhemoglobin activity. Specifically, we found a decrease of neuro-metabolic activity in prefrontal and bilateral primary somatosensory cortices during painful stimulation of the left groin compared to non-painful stimulation, whereas an increase of neuro-metabolic activity was observed during painful stimulation of the right knee. Our findings also revealed that stimulation intensity was notably lower for bilateral knees compared to the left groin. These findings underscore the potential and feasibility of utilizing fNIRS to investigate pain mechanisms related to stimulation across distinct lower limb regions.

Translation elongation defects activate the <i>Caenorhabditis elegans</i> ZIP-2 bZIP transcription factor–mediated toxin defense

The Caenorhabditis elegans bZIP transcription factor ZIP-2 is activated by toxins or mutations that inhibit translational elongation. The zip-2 DNA-binding protein is encoded in a downstream main open reading frame (mORF), but under normal translation elongation conditions only an upstream overlapping oORF -1 frameshifted from mORF is translated. Mutations or toxins that slow translational elongation, but not inhibitors of translational initiation or termination, activate ZIP-2. An mORF initiation codon mutation does not disrupt the normal zip-2 response to translational elongation defects, suggesting that zip-2 activation does not depend on this ATG. An mORF early termination mutant can be activated by strong translation elongation inhibition, suggesting that translation initiated upstream on oORF +1 frameshifts when elongation is inhibited to the mORF reading frame downstream of the stop codon to activate a fused oORF/mORF ZIP-2 transcription factor. The protein and DNA sequences of zip-2 oORF and mORF are conserved across the Caenorhabditis , suggesting selection for particular codons sensitive to translational elongation defects. Mutations that disrupt the oORF initiation codon constitutively activate zip-2 , but not if the mORF initiation codon is also mutant, showing that zip-2 oORF competes with mORF for translational initiation. oORF initiation codon mutation-activated zip-2 slows C. elegans growth, and this slow growth is suppressed by a zip-2 null mutation. A zip-2 null mutant also strongly suppresses the growth arrest caused by translational elongation inhibitors. Thus, ZIP-2 is both a sensor of translational elongation attack, and a defense regulatory output via its activation of response genes.

Correlation of epicardial adipose tissue with microvascular obstruction and its effect on new-onset atrial arrhythmias after PCI in STEMI patients

Light’s hidden power: Vacuum fluctuations reshape superconductivity from within

The antidiabetic effect of safflower yellow by regulating the GOAT/ghrelin/GHS-R1a/cAMP/TRPM2 pathway

Yet another twist to the regulation of the TGF-β family ligands

Research on multi-condition optimization of centrifugal compressor impeller meridian profile

The turbocharger, a pivotal technology for energy conservation and emission reduction, offers substantial academic significance, particularly in the in-depth study of its core component: the centrifugal compressor impeller. This research aims to enhance the centrifugal compressor’s overall efficiency by optimizing its impeller meridional profile. By modifying the impeller meridional profile of a certain centrifugal compressor impeller to address the issue of discontinuous curvature, this paper aims to optimize the comprehensive average efficiency under variable speed and variable flow conditions. The optimization goal is to improve the overall average efficiency while maintaining the high pressure ratio based on the prototype scheme. The NSGA-III optimization algorithm is employed for multi-condition optimization, aiming to achieve comprehensive efficiency improvements under multiple operating speeds. The following conclusions are drawn: under multi-speed conditions, the optimized scheme exhibits comprehensive efficiency improvements over the prototype scheme, with an expanded stable operating flow range and maintained high-pressure ratio based on efficiency improvement, without sacrificing the operating flow range. Comparisons of internal flow conditions indicate that the optimized impeller features a smoother meridional passage and a reduced high-entropy region at the outlet, leading to lower entropy values. Additionally, pressure increases on both sides of the impeller blades while pressure differentials diminish, signifying enhanced internal flow conditions.

Wind power data cleaning using RANSAC-based polynomial and linear regression with adaptive threshold

A 5,000-fold increase in the HAT reactivity of a nonheme Fe ^IV =O complex simply by replacing two pyridines of the pentadentate N4Py ligand with pyrazoles

A pentadentate [N5] ligand (N2Py2Pz) based on the classic N4Py ( N,N -bis(2-pyridylmethyl)- N -bis(2-pyridyl)methylamine) framework has been synthesized by replacing the two pyridylmethyl arms with corresponding ( N -methyl)pyrazolylmethyl units to form [ N- bis(1-methyl-2-pyrazolyl)methyl- N -( bis -2-pyridylmethyl)amine] (L1). The oxidation of the iron(II) precursor (N2Py2Pz)Fe II (OTf) 2 ( 1 ) with ( t BuSO 2 )C 6 H 4 IO at 298 K leads to the formation of the [Fe IV (O)(N2Py2Pz)] 2+ intermediate ( 2 ) with a near-IR band at 750 nm (ε M = 250 M −1 cm −1 ) and a t 1/2 ~ 2 min at 298 K. The introduction of the less basic pyrazolylmethyl ligands in place of two pyridylmethyl units generates Fe IV =O intermediate 2 that exhibits a cyclohexane oxidation rate of 0.29 s −1 at 298 K, which is 5,000-fold faster than that observed for the classic Fe IV (O)N4Py parent complex and 40,000-fold more reactive than the least reactive Fe IV (O)N2Py2Q′ complex in this series (Py = pyridine, Q′ = isoquinoline) recently reported by Nordlander.

Severe outcomes of COVID-19 among adults with increased risk conditions: A population-based observational study

Background The individual risk of severe outcomes following COVID-19 is poorly understood in populations with prior immunity. The lack of contemporary estimates limits support of timely diagnosis and antiviral treatment for individuals most likely to benefit. Objective To determine the risk of severe outcomes following COVID-19 within strata of comorbidities, including patients without documented infection. Design Population-based cohort study utilizing electronic medical records and g methods to account for selection bias in the documentation of COVID-19 illnesses. Setting A large health system in northeastern United States Patients Adults with increased risk conditions (90% vaccinated) and COVID-19 from June to December 2022. Measurements Incidence of composite of inpatient admission within 14 days and death within 28 days of COVID-19 diagnosis. Results An estimated 265,248 patients with at least one increased risk condition developed COVID-19, including 76,996 documented cases. Severe outcomes occurred in 3344 (1.3%) patients following COVID-19— 3147 (1.2%) hospitalizations and 376 (0.14%) deaths. In the absence of treatment, individuals with few increased risk conditions (MASS of 3 or less) accounted for 57% of infections and 0.7% developed severe outcomes. In contrast, 2.3% of patients with multiple increased risk conditions (MASS 4 or greater) or severe immunocompromise experienced severe outcomes, including 81% of deaths. The observed risk reduction with antiviral treatment was -0.1% (-0.2 to 0.02%), -0.6% (-0.9 to -0.4%), -1.3% (-2 to -1%), and -1.9% (-3 to -1%) for patients with MASS 3 or less, MASS 4 and 5, MASS 6 or greater, and severe immunocompromise, respectively. Limitations Estimated number COVID-19 cases cannot be directly verified Conclusions Individuals with multiple medical conditions remain at substantial risk for severe outcomes of COVID-19 and benefit from treatment.

Extreme two-phase change of ionospheric electron temperature overshoot during geomagnetic storms

Abstract An intense surge in the equatorial electron temperature (Te) at sunrise, known as the morning Te overshoot, has been one of the defining ionospheric features since its discovery early in the Space Age. Despite decades of study, the behavior of the morning overshoot during geomagnetic storms remains poorly understood. We report a two-stage response of the morning Te overshoot to geomagnetic activity, uncovered by a neural network model. Electron temperatures show an initial enhancement during the storm’s main phase, followed by a drastic depletion exceeding 1000 K and disappearance of the overshoot in the recovery phase. This two-phase change aligns with the early influence of westward prompt penetration electric field, overtaken by the development of the eastward disturbance dynamo later in the storm. These electric field changes affect vertical plasma drifts that redistribute electron densities, modifying ionospheric cooling rates. Our findings provide new insights into the dynamics of one of the most widely studied ionospheric features and showcase the potential of new-generation digital twin models of near-Earth space environment to reveal previously unrecognized physical patterns.

Co-zorbs: Motile, multispecies biofilms aid transport of diverse bacterial species

Biofilms are three-dimensional structures containing one or more bacterial species embedded in extracellular polymeric substances. Although most biofilms are stationary, Flavobacterium johnsoniae forms a motile spherical biofilm called a zorb, which is propelled by its base cells and contains a polysaccharide core. Here, we report the formation of spatially organized, motile, multispecies biofilms, designated “co-zorbs,” that are distinguished by a core–shell structure. F. johnsoniae forms zorbs whose cells collect other bacterial species and transport them to the zorb core, forming a co-zorb. Live imaging revealed that co-zorbs also form in zebrafish, thereby demonstrating a different type of bacterial movement in vivo. This finding opens different avenues for understanding community behaviors, the role of biofilms in bulk bacterial transport, and collective strategies for microbial success in various environments.

Bacterial targets of fecal host miRNAs in high-fat diet-fed mice

The gut microbiome composition is intricately linked to the host’s health status, yet the mechanisms underlying its interaction with the host are not fully understood. MicroRNAs (miRNAs), facilitating intercellular communication, are found in bodily fluids, including the intestinal content, where they may affect the microbiome. However, their role in type 2 diabetes (T2D)-associated microbiome and treatment implications are not explored. Our study investigated how host miRNAs may influence gut microbiome changes related to metformin treatment in a T2D mouse model. Analyzing fecal and gut mucosal samples via small RNA sequencing, we correlated results with microbiome sequencing data, identifying miRNA-microbiome correlations, bacterial targets, and proteins targeted in these bacteria. Significant differences in miRNA expression based on diet and intestinal location were noted, with minor effects from metformin treatment in the proximal small intestine of non-diabetic male mice. Key fecal miRNAs targeting bacteria included mmu-miR-5119, mmu-miR-5126, mmu-miR-6538, and mmu-miR-2137, primarily affecting Oscillospiraceae_NOV, Lachnospiraceae_NOV, and Bacteroides. Our analysis of targeted proteins revealed diverse biological and molecular effects. Further research into miRNA-bacteria interactions could lead to new strategies for manipulating the gut microbiome in T2D and beyond.

A novel lncRNA enhances autophagy to suppress extracellular matrix via modulating TP53INP1 in human trabecular meshwork cells under oxidative stress

Spatiotemporal distribution of the North American Indigenous population prior to European contact

We examine spatiotemporal trends in the pre-European-contact Indigenous population of North America using radiocarbon ( 14 C) dates of the past 2000 y. At a continental scale, the Indigenous population of the past ~14,000 y peaked at ~1150 CE and then declined until a brief recovery shortly before 1500 CE, after which 14 C probability declines precipitously. After testing, we reject the hypothesis that the 1150 CE peak and decline is a result of 14 C sampling issues. We then examine the 14 C record of the past 2000 y in each of 18 watersheds where we find peaks ranging from ~800 to 770 CE to after European contact, with the majority, in the interior of the continent, declining ~1080 to 1300 CE. Although all Indigenous populations declined after European contact, that of a large portion of the country (the Great Lakes, New England, the Mid-Atlantic, the Central Plains, the Northwest, and California) did not decline until after contact.