The effect of regional integration on the efficiency of enterprise resource allocation.

Based on a micro-entity perspective, this paper empirically examines the effect of regional integration on the efficiency of enterprise resource allocation. Firstly, regional integration can significantly reduce the degree of resource mismatch of enterprises and improve the efficiency of resource allocation of enterprises overall. Secondly, regional integration can improve the efficiency of resource allocation of enterprises mainly through three channels, which are alleviating the financing constraints of enterprises, improving the degree of talent agglomeration, and reducing the operating costs of enterprises.

Circadian clock communication during homeostasis and ageing.

Maintaining homeostasis is essential for continued health, and the progressive decay of homeostatic processes is a hallmark of ageing. Daily environmental rhythms threaten homeostasis, and circadian clocks have evolved to execute physiological processes in a manner that anticipates, and thus mitigates, their effects on the organism. Clocks are active in almost all cell types; their rhythmicity and functional output are determined by a combination of tissue-intrinsic and systemic inputs.

Use of Remote Regulatory Assessment (RRA) for Site Evaluations during the COVID-19 Pandemic: The USFDA's Office of Study Integrity and Surveillance (OSIS) Perspective.

Travel restrictions during the novel coronavirus, SARS-CoV-2 (COVID-19) public health emergency affected the U.S. Food and Drug Administration's (FDA) ability to conduct on-site bioavailability/bioequivalence (BA/BE) and Good Laboratory Practice (GLP) nonclinical inspections.

Roles of sensory receptors in non-sensory organs: the kidney and beyond.

Olfactory receptors (ORs), taste receptors and opsins are well-known for their pivotal roles in mediating the senses of smell, taste and sight, respectively. However, in the past two decades, research has shown that these sensory receptors also regulate physiological processes in a variety of non-sensory tissues. Although ORs, taste receptors and opsins have all been shown to have physiological roles beyond their traditional locations, most work in the kidney has focused on ORs.

Genome-wide association studies in lettuce reveal the interplay of seed age, color, and germination under high temperatures.

Thermoinhibition, the suppression of seed germination by high temperatures, is an adaptive trait that ensures successful seedling establishment in natural environments. While beneficial for wild plants, thermoinhibition can adversely affect crop yields due to uneven and reduced germination rates, particularly in the face of climate change. To understand the genetic basis of thermoinhibition, we conducted a comprehensive genetic analysis of a diverse panel of Lactuca spp.

Bacteria use exogenous peptidoglycan as a danger signal to trigger biofilm formation.

For any organism, survival is enhanced by the ability to sense and respond to threats in advance. For bacteria, danger sensing among kin cells has been observed, but the presence or impacts of general danger signals are poorly understood. Here we show that different bacterial species use exogenous peptidoglycan fragments, which are released by nearby kin or non-kin cell lysis, as a general danger signal.

Two decades of bacterial ecology and evolution in a freshwater lake.

Ecology and evolution are considered distinct processes that interact on contemporary time scales in microbiomes. Here, to observe these processes in a natural system, we collected a two-decade, 471-metagenome time series from Lake Mendota (Wisconsin, USA). We assembled 2,855 species-representative genomes and found that genomic change was common and frequent.

Unravelling viral ecology and evolution over 20 years in a freshwater lake.

As freshwater lakes undergo rapid anthropogenic change, long-term studies reveal key microbial dynamics, evolutionary shifts and biogeochemical interactions, yet the vital role of viruses remains overlooked. Here, leveraging a 20 year time series from Lake Mendota, WI, USA, we characterized 1.3 million viral genomes across time, seasonality and environmental factors.

High-density multielectrode arrays bring cellular resolution to neuronal activity and network analyses of corticospinal motor neurons.

Corticospinal motor neurons (CSMN), located in the motor cortex of the brain, are one of the key components of the motor neuron circuitry. They are in part responsible for the initiation and modulation of voluntary movement, and their degeneration is the hallmark for numerous diseases, such as amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia, and primary lateral sclerosis. Cortical hyperexcitation followed by in-excitability suggests the early involvement of cortical dysfunction in ALS pathology.

Demonstration of active neutron interrogation of special nuclear materials using a high-intensity short-pulse-laser-driven neutron source.

Detecting shielded special nuclear material, such as nuclear explosives, is a difficult challenge pursued by non-proliferation, anti-terrorism, and nuclear security programs worldwide. Interrogation with intense fast-neutron pulses is a promising method to characterize concealed nuclear material rapidly but is limited by suitable source availability and proven instrumentation. In this study we have pioneered a demonstration of such an interrogation method using a high-intensity, short-pulse, laser-driven neutron source that offers potential benefits compared to conventional neutron sources.

Real-world evaluation of an evidence-based telemental health program for PTSD symptoms.

Blended care therapy (BCT), which augments live, video-based psychotherapy sessions with asynchronous digital tools, has the potential to increase access to evidence-based treatments for posttraumatic stress disorder (PTSD). However, its effectiveness in diverse, real-world settings is not well-understood. This evaluation aimed to assess clinical outcomes of a BCT program for PTSD symptoms.

Space exploration and risk of Parkinson's disease: a perspective review.

Systemic mitochondrial dysfunction, dopamine loss, sustained structural changes in the basal ganglia including reduced tyrosine hydroxylase, and altered gait- these effects observed in space-flown animals and astronauts mirrors Parkinson's disease (PD). Evidence of mitochondrial changes in space-flown human cells, examined through the lens of PD, suggests that spaceflight-induced PD-like molecular changes are important to monitor during deep space exploration. These changes, may potentially elevate the risk of PD in astronauts.

Characterizing cell-type spatial relationships across length scales in spatially resolved omics data.

Spatially resolved omics (SRO) technologies enable the identification of cell types while preserving their organization within tissues. Application of such technologies offers the opportunity to delineate cell-type spatial relationships, particularly across different length scales, and enhance our understanding of tissue organization and function. To quantify such multi-scale cell-type spatial relationships, we present CRAWDAD, Cell-type Relationship Analysis Workflow Done Across Distances, as an open-source R package.

Design and synthesis of antiproliferative 2-oxoindolin-3-ylidenes incorporating urea function with potential VEGFR-2 inhibitory properties.

Targeted therapy is preferable over other therapeutics due to its limitation of drawbacks and better pharmaceutical outcomes. VEGF and its receptors have been observed to be hyper-activated in many cancer types and are considered promising targets for assigning anticancer agents. The current study is directed towards synthesis of novel antiproliferative 2-oxoindolin-3-ylidenes incorporating urea function with VEGFR-2 properties.

Continental drift triggered the Early Permian aridification of North China.

The boundary between wet and arid climate zones in the Tethys Ocean remains challenging to trace, complicating our understanding of global aridification pattern during the Late Carboniferous to Early Permian transition. The North China Block (NCB), situated in the Tethys Ocean, underwent a transition from humid to arid climate during the Early Permian, providing a rare opportunity to trace this climate boundary across this region. Here, we present paleomagnetic evidence indicating that the NCB underwent rapid northward drift between 290 and 281 million years ago.

Deciphering antioxidant interactions via data mining and RDKit.

Minimizing the oxidation of lipids remains one of the most important challenges to extend the shelf-life of food products and reduce food waste. While most consumer products contain antioxidants, the most efficient strategy is to incorporate combinations of two or more compounds, boosting the total antioxidant capacity. Unfortunately, the reasons for observing synergistic / antagonistic / additive effects in food samples are still unclear, and it is common to observe very different responses even for similar mixtures.

Systemically circulating 17β-estradiol enhances the neuroprotective effect of the smoking cessation drug cytisine in female parkinsonian mice.

The smoking cessation drug cytisine exerts neuroprotection in substantia nigra pars compacta (SNc) dopaminergic (DA) neurons of female but not male 6-hydroxydopamine (6-OHDA) lesioned parkinsonian mice. To address the important question of whether circulating 17β-estradiol mediates this effect, we employ two mouse models aimed at depleting systemically circulating 17β-estradiol: (i) bilateral ovariectomy (OVX), and (ii) aromatase inhibition with systemically administered letrozole. In both models, depleting systemically circulating 17β-estradiol in female 6-OHDA lesioned parkinsonian mice results in the loss of cytisine-mediated neuroprotection as measured using apomorphine-induced contralateral rotations and SNc DA neurodegeneration.

Synthesis and characterization of innovative GA@Ag-CuO nanocomposite with potent antimicrobial and anticancer properties.

Cancer and microbial infections place a significant burden on the world's health systems and can increase the rate of disease and mortality. In the current study, a novel nanocomposite based on Gum Arabic, silver and copper oxide nanoparticles (GA@Ag-CuO nanocomposite) was synthesized to overcome the problem of microbial infection and in cancer treatment. Characterization using UV-Vis.

Effects of RARα ligand binding domain mutations on breast fibroepithelial tumor function and signaling.

Point mutations in the ligand binding domain of retinoic acid receptor alpha (RARα) are linked to breast fibroepithelial tumor development, but their role in solid tumorigenesis is unclear. In this study, we assessed the functional effects of known RARα mutations on retinoic acid signaling using biochemical and cellular assays. All tested mutants exhibited reduced transcriptional activity compared to wild-type RARα and showed a dominant negative effect, a feature associated with developmental defects and tumor formation.

Radiological markers of CSF α-synuclein aggregation in Parkinson's disease patients.

Alpha-synuclein (αS) aggregation is a widely regarded hallmark of Parkinson's disease (PD) and can be detected through synuclein amplification assays (SAA). This study investigated the association between cerebrospinal fluid (CSF) radiological measures in 41 PD patients (14 iPD, 14 GBA1-PD, 13 LRRK2-PD) and 14 age-and-sex-matched healthy controls. Quantitative measures including striatal binding ratios (SBR), whole-brain and deep gray matter volumes, neuromelanin-MRI (NM-MRI), functional connectivity (FC), and white matter (WM) diffusion-tensor imaging (DTI) were calculated.

Variation in a single allele drives divergent yield responses to elevated CO between rice subspecies.

Rising atmospheric CO generally increases yield of indica rice, one of the two main Asian cultivated rice subspecies, more strongly than japonica rice, the other main subspecies. The molecular mechanisms driving this difference remain unclear, limiting the potential of future rice yield increases through breeding efforts. Here, we show that between-species variation in the DNR1 (DULL NITROGEN RESPONSE1) allele, a regulator of nitrate-use efficiency in rice plants, explains the divergent response to elevated atmospheric CO (eCO) conditions.

regionalpcs improve discovery of DNA methylation associations with complex traits.

We have developed the regionalpcs method, an approach for summarizing gene-level methylation. regionalpcs addresses the challenge of deciphering complex epigenetic mechanisms in diseases like Alzheimer's disease. In contrast to averaging, regionalpcs uses principal components analysis to capture complex methylation patterns across gene regions.

Ionizable polymeric micelles (IPMs) for efficient siRNA delivery.

Lipid nanoparticles (LNPs) are widely used for nucleic acid delivery but face challenges like limited targeting and accelerated blood clearance (ABC) effect. We design three ionizable oligomers (IOs) that, with polylactide-polyethylene glycol (PLA-PEG), form a potential siRNA delivery system, named Ionizable Polymeric Micelles (IPMs). The siRNA encapsulated IPMs escape from lysosomes upon cellular uptake, and silence the target gene.

Deeper response predicts better outcomes in high-risk-smoldering-myeloma: results of the I-PRISM phase II clinical trial.

Early therapeutic intervention in high-risk smoldering multiple myeloma (HR-SMM) has shown benefits, however, no studies have assessed whether biochemical progression or response depth predicts long-term outcomes. The single-arm I-PRISM phase II trial (NCT02916771) evaluated ixazomib, lenalidomide, and dexamethasone in 55 patients with HR-SMM. The primary endpoint, median progression-free survival (PFS), was not reached (NR) (95% CI: 57.