Sex differences in fetal brain functional network topology.

The fetal period is a critical stage in brain development, and understanding the characteristics of the fetal brain is crucial. Although some studies have explored aspects of fetal brain functional networks, few have specifically focused on sex differences in brain network characteristics. We adopted the graph theory method to calculate brain network functional connectivity and topology properties (including global and nodal properties), and further compared the differences in these parameters between male and female fetuses. We found that male fetuses showed an increased clustering coefficient and local efficiency than female fetuses, but no significant group differences concerning other graph parameters and the functional connectivity matrix. Our study suggests the existence of sex-related distinctions in the topological properties of the brain network at the fetal stage of development and demonstrates an increase in brain network separation in male fetuses compared with female fetuses.

Erythrocyte adenosine A2B receptor prevents cognitive and auditory dysfunction by promoting hypoxic and metabolic reprogramming.

Hypoxia drives aging and promotes age-related cognition and hearing functional decline. Despite the role of erythrocytes in oxygen (O2) transport, their role in the onset of aging and age-related cognitive decline and hearing loss (HL) remains undetermined. Recent studies revealed that signaling through the erythrocyte adenosine A2B receptor (ADORA2B) promotes O2 release to counteract hypoxia at high altitude. However, nothing is known about a role for erythrocyte ADORA2B in age-related functional decline. Here, we report that loss of murine erythrocyte-specific ADORA2B (eAdora2b-/-) accelerates early onset of age-related impairments in spatial learning, memory, and hearing ability. eAdora2b-/- mice display the early aging-like cellular and molecular features including the proliferation and activation of microglia and macrophages, elevation of pro-inflammatory cytokines, and attenuation of hypoxia-induced glycolytic gene expression to counteract hypoxia in the hippocampus (HIP), cortex, or cochlea. Hypoxia sufficiently accelerates early onset of cognitive and cochlear functional decline and inflammatory response in eAdora2b-/- mice. Mechanistically, erythrocyte ADORA2B-mediated activation of AMP-activated protein kinase (AMPK) and bisphosphoglycerate mutase (BPGM) promotes hypoxic and metabolic reprogramming to enhance production of 2,3-bisphosphoglycerate (2,3-BPG), an erythrocyte-specific metabolite triggering O2 delivery. Significantly, this finding led us to further discover that murine erythroblast ADORA2B and BPGM mRNA levels and erythrocyte BPGM activity are reduced during normal aging. Overall, we determined that erythrocyte ADORA2B-BPGM axis is a key component for anti-aging and anti-age-related functional decline.

Predicting Two-Photon Absorption Spectra of Octupolar Molecules: A Deep-Learning Approach Based Exclusively on Molecular Structures.

Octupolar molecules possessing a strong two-photon response are vital for numerous advanced applications. However, accurately predicting their two-photon absorption (TPA) spectra requires high-precision quantum chemical calculations, which are computationally expensive due to repeated simulations of molecular excited-state properties. To address this challenge, we introduce a deep learning approach capable of rapidly and accurately forecasting TPA spectra for octupolar molecules. By leveraging the geometric structure as an initial descriptor, we employ a graph neural network to predict the maximum two-photon transition wavelength and cross-section. Our model demonstrates a mean absolute percentage error of less than 4% compared to time-dependent density-functional theory calculations, effectively reproducing experimental observations. Notably, this deep learning technique is nearly 100 000 times faster than comparable quantum calculations, making it an efficient and cost-effective tool for simulating TPA properties of octupolar molecules. Furthermore, this method holds great promise for the high-throughput screening of exceptional TPA materials.

Dendrobium polysaccharide (DOP) ameliorates the LL-37-induced rosacea by inhibiting NF-κB activation in a mouse model.

BACKGROUND: Rosacea, a common chronic inflammatory skin disease worldwide, is currently incurable with complex pathogenesis. Dendrobium polysaccharide (DOP) may exert therapeutic effects on rosacea via acting on the NF-κB-related inflammatory and oxidative processes. MATERIALS AND METHODS: In this study, an LL-37-induced rosacea-like mouse model was established. HE staining was used to assess the skin lesions, erythema severity scores, pathological symptoms, and inflammatory cell numbers of mice in each group. The inflammation level was quantitatively analyzed using enzyme-linked immunosorbent assay (ELISA) and reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). The expression levels of TLR4 and p-NF-κB were finally detected. RESULTS: DOP improved skin pathological symptoms of rosacea mice. DOP also alleviated the inflammation of rosacea mice. Moreover, the TLR4/NF-κB pathway was observed to be inhibited in the skin of mice after DOP application. These findings evidenced the anti-inflammatory effects of DOP on the LL-37-induced rosacea mouse model. DOP could inhibit NF-κB activation, suppress neutrophil infiltration, and reduce pro-inflammatory cytokines production, which may be the reason for DOP protecting against rosacea. CONCLUSION: This study may propose an active candidate with great potential for rosacea drug development and lay a solid experimental foundation for promoting DOP application in rosacea therapy.

Diagnostic value of cervical spine ZOOM-DWI in cervical spondylotic myelopathy.

PURPOSE: To investigate the clinical application value of the non-shared incentive diffusion imaging technique (ZOOM-DWI) diagnoses of cervical spondylotic myelopathy (CSM). METHODS: 49 CSM patients who presented from January 2022 to December 2022 were selected as the patient group, and 50 healthy volunteers are recruited as the control group. All subjects underwent conventional MRI and ZOOM-DWI of the cervical spine and neurologic mJOA scores in patients with CSM. The spinal ADC values of segments C2-3, C4-5, C5-6, and C6-7 are measured and analyzed in all subjects, with C5-6 being the most severe level of spinal canal compression in the patient group. In addition, the study also analyzes and compares the relationship between the C5-6 ADC value and mJOA score in the patient group. RESULTS: The mean ADC shows no significantly different levels in the control group. Among the ADC values at each measurement level in the patient group, except for C4-5 and C6-7 segments are not statistically significant, the remaining pair-wise comparisons all show statistically significant differences (F = 24.368, p < 0.001). And these individuals have the highest ADC value at C5-6. The C5-6 ADC value in the patient group is significantly higher compared with the ADC value in the control group (t = 9.414, p < 0.001), with statistical significance. The ADC value at the patient stenosis shows a significant negative correlation with the mJOA score (r = -0.493, p < 0.001). CONCLUSION: Cervical ZOOM-DWI can be applied to diagnose CSM, and spinal ADC value can use as reliable imaging data for diagnosing cervical myelopathy.

Erythrocyte ENT1-AMPD3 Axis is an Essential Purinergic Hypoxia Sensor and Energy Regulator Combating CKD in a Mouse Model.

SIGNIFICANCE STATEMENT: Hypoxia drives kidney damage and progression of CKD. Although erythrocytes respond rapidly to hypoxia, their role and the specific molecules sensing and responding to hypoxia in CKD remain unclear. In this study, we demonstrated in a mouse model that erythrocyte ENT1-AMPD3 is a master energy regulator of the intracellular purinergic hypoxic compensatory response that promotes rapid energy supply from extracellular adenosine, eAMPK-dependent metabolic reprogramming, and O 2 delivery, which combat renal hypoxia and progression of CKD. ENT1-AMPD3-AMPK-BPGM comprise a group of circulating erythroid-specific biomarkers, providing early diagnostic and novel therapeutic targets for CKD. BACKGROUND: Hypoxia drives kidney damage and progression of CKD. Although erythrocytes respond rapidly to hypoxia, their role and the specific molecules sensing and responding to hypoxia in CKD remain unclear. METHODS: Mice with an erythrocyte-specific deficiency in equilibrative nucleoside transporter 1 ( eEnt1-/- ) and a global deficiency in AMP deaminase 3 ( Ampd3-/- ) were generated to define their function in two independent CKD models, including angiotensin II (Ang II) infusion and unilateral ureteral obstruction (UUO). Unbiased metabolomics, isotopic adenosine flux, and various biochemical and cell culture analyses coupled with genetic studies were performed. Translational studies in patients with CKD and cultured human erythrocytes examined the role of ENT1 and AMPD3 in erythrocyte function and metabolism. RESULTS: eEnt1-/- mice display severe renal hypoxia, kidney damage, and fibrosis in both CKD models. The loss of eENT1-mediated adenosine uptake reduces intracellular AMP and thus abolishes the activation of AMPK α and bisphosphoglycerate mutase (BPGM). This results in reduced 2,3-bisphosphoglycerate and glutathione, leading to overwhelming oxidative stress in eEnt1-/- mice. Excess reactive oxygen species (ROS) activates AMPD3, resulting in metabolic reprogramming and reduced O 2 delivery, leading to severe renal hypoxia in eEnt1-/- mice. By contrast, genetic ablation of AMPD3 preserves the erythrocyte adenine nucleotide pool, inducing AMPK-BPGM activation, O 2 delivery, and antioxidative stress capacity, which protect against Ang II-induced renal hypoxia, damage, and CKD progression. Translational studies recapitulated the findings in mice. CONCLUSION: eENT1-AMPD3, two highly enriched erythrocyte purinergic components that sense hypoxia, promote eAMPK-BPGM-dependent metabolic reprogramming, O 2 delivery, energy supply, and antioxidative stress capacity, which mitigates renal hypoxia and CKD progression.

The equilibrative nucleoside transporter ENT1 is critical for nucleotide homeostasis and optimal erythropoiesis.

The tight regulation of intracellular nucleotides is critical for the self-renewal and lineage specification of hematopoietic stem cells (HSCs). Nucleosides are major metabolite precursors for nucleotide biosynthesis and their availability in HSCs is dependent on their transport through specific membrane transporters. However, the role of nucleoside transporters in the differentiation of HSCs to the erythroid lineage and in red cell biology remains to be fully defined. Here, we show that the absence of the equilibrative nucleoside transporter (ENT1) in human red blood cells with a rare Augustine-null blood type is associated with macrocytosis, anisopoikilocytosis, an abnormal nucleotide metabolome, and deregulated protein phosphorylation. A specific role for ENT1 in human erythropoiesis was demonstrated by a defective erythropoiesis of human CD34+ progenitors following short hairpin RNA-mediated knockdown of ENT1. Furthermore, genetic deletion of ENT1 in mice was associated with reduced erythroid progenitors in the bone marrow, anemia, and macrocytosis. Mechanistically, we found that ENT1-mediated adenosine transport is critical for cyclic adenosine monophosphate homeostasis and the regulation of erythroid transcription factors. Notably, genetic investigation of 2 ENT1null individuals demonstrated a compensation by a loss-of-function variant in the ABCC4 cyclic nucleotide exporter. Indeed, pharmacological inhibition of ABCC4 in Ent1-/- mice rescued erythropoiesis. Overall, our results highlight the importance of ENT1-mediated nucleotide metabolism in erythropoiesis.

Theoretical Insights on the Sensing Performance for Newly-synthesized Two-photon Fluorescent N2H4 Probes Based on Spirobifluorence.

The development of fluorescent probe for hydrazine (N2H4) detection has attracted much attention due to the important role of N2H4 plays in the fields of medicine, agriculture, biology and environments. In this paper, the optical properties and water solubility of two novel two-photon fluorescent molecular probes (Probe1 and Probe2) before and after the reaction with N2H4 are studied by using the density function theory. The results show that electronic distribution and transition dipole moment of the probes are obviously changed after the reaction with N2H4, thus the optical properties of the molecules are influenced and the detection of N2H4 are realized. In addition, photoinduced electron transfer processes for Probe1 and Probe2 in the presence of N2H4 are theoretically characterized, which explains the experimental observations from the microscopic mechanism. Special attention has been paid on the analysis of the two-photon absorption for the probes with the absence and presence of N2H4 by the response theory method. Both probes with good water solubility show large variation on the two-photon absorption cross section when reacts with N2H4. In particular, the two-photon absorption response of Probe2 is more obvious, so it possesses preferable two-photon fluorescence microscopic imaging ability. More importantly, the receptor effect on the sensing performances of the probes are demonstrated, providing a theoretical reference for the design and synthesis on more efficient two-photon fluorescence N2H4 probes. Our study provides necessary information on the response mechanism of the studied chemosensors and helps to establish the relationship between the structure and optical properties of two-photon fluorescence N2H4 probes.

The differential value of radiomics based on traditional T1-weighted sequences in newborns with hyperbilirubinemia.

BACKGROUND: On the basis of visual-dependent reading method, radiological recognition and assessment of neonatal hyperbilirubinemia (NH) or acute bilirubin encephalopathy (ABE) on conventional magnetic resonance imaging (MRI) sequences are challenging. Prior studies had shown that radiomics was possible to characterize ABE-induced intensity and morphological changes on MRI sequences, and it has emerged as a desirable and promising future in quantitative and objective MRI data extraction. To investigate the utility of radiomics based on T1-weighted sequences for identifying neonatal ABE in patients with hyperbilirubinemia and differentiating between those with NH and the normal controls. METHODS: A total of 88 patients with NH were enrolled, including 50 patients with ABE and 38 ABE-negative individuals, and 70 age-matched normal neonates were included as controls. All participants were divided into training and validation cohorts in a 7:3 ratio. Radiomics features extracted from the basal ganglia of T1-weighted sequences on magnetic resonance imaging were evaluated and selected to set up the prediction model using the K-nearest neighbour-based bagging algorithm. A receiver operating characteristic curve was plotted to assess the differentiating performance of the radiomics-based model. RESULTS: Four of 744 radiomics features were selected for the diagnostic model of ABE. The radiomics model yielded an area under the curve (AUC) of 0.81 and 0.82 in the training and test cohorts, with accuracy, precision, sensitivity, and specificity of 0.82, 0.80, 0.91, and 0.69 and 0.78, 0.8, 0.8, and 0.75, respectively. Six radiomics features were selected in this model to distinguish those with NH from the normal controls. The AUC for the training cohort was 0.97, with an accuracy of 0.92, a precision of 0.92, a sensitivity of 0.93, and a specificity of 0.90. The performance of the radiomics model was confirmed by testing the test cohort, and the AUC, accuracy, precision, sensitivity, and specificity were 0.97, 0.92, 0.96, 0.89, and 0.95, respectively. CONCLUSIONS: The proposed radiomics model based on traditional TI-weighted sequences may be used effectively for identifying ABE and even differentiating patients with NH from the normal controls, which can provide microcosmic information beyond experience-dependent vision and potentially assist in clinical diagnosis and treatment.

Establishment of protoplasts transient expression system in Pinellia ternata (Thunb.) Breit.

OBJECTIVE: In this study, we established an efficient and rapid transient expression system in the protoplasts of Pinellia ternata (Thunb.) Breit. (P. ternata). RESULTS: The protoplasts of P. ternata were prepared from plant leaves as the source material by digesting them with the combination of 20 g·l-1 cellulase and 15 g·l-1 macerozyme for 6 h. Based on the screening of PEG concentration, the conditions for PEG-mediated protoplast transformation were improved, and the highest transformation efficiency was found for 40% PEG 4000. Furthermore, we used the subcellular protein localization technique in P. ternata protoplasts to allow further validation of transient expression system. CONCLUSIONS: We present the method that can be applicable for studying both gene verification and expression in P. ternata protoplasts, thus allowing for engineering the improved varieties of P. ternata through molecular plant breeding techniques. This method can also be widely applicable for analyzing protein interactions, detecting promoter activity, for somatic cell fusion in plant breeding, as well as for other related studies.

Variable Rate Point Cloud Geometry Compression Method.

With the development of 3D sensors technology, 3D point cloud is widely used in industrial scenes due to their high accuracy, which promotes the development of point cloud compression technology. Learned point cloud compression has attracted much attention for its excellent rate distortion performance. However, there is a one-to-one correspondence between the model and the compression rate in these methods. To achieve compression at different rates, a large number of models need to be trained, which increases the training time and storage space. To address this problem, a variable rate point cloud compression method is proposed, which enables the adjustment of the compression rate by the hyperparameter in a single model. To address the narrow rate range problem that occurs when the traditional rate distortion loss is jointly optimized for variable rate models, a rate expansion method based on contrastive learning is proposed to expands the bit rate range of the model. To improve the visualization effect of the reconstructed point cloud, a boundary learning method is introduced to improve the classification ability of the boundary points through boundary optimization and enhance the overall model performance. The experimental results show that the proposed method achieves variable rate compression with a large bit rate range while ensuring the model performance. The proposed method outperforms G-PCC, achieving more than 70% BD-Rate against G-PCC, and performs about, as well as the learned methods at high bit rates.

A Feature-Trajectory-Smoothed High-Speed Model for Video Anomaly Detection.

High-speed detection of abnormal frames in surveillance videos is essential for security. This paper proposes a new video anomaly-detection model, namely, feature trajectory-smoothed long short-term memory (FTS-LSTM). This model trains an LSTM autoencoder network to generate future frames on normal video streams, and uses the FTS detector and generation error (GE) detector to detect anomalies on testing video streams. FTS loss is a new indicator in the anomaly-detection area. In the training stage, the model applies a feature trajectory smoothness (FTS) loss to constrain the LSTM layer. This loss enables the LSTM layer to learn the temporal regularity of video streams more precisely. In the detection stage, the model utilizes the FTS loss and the GE loss as two detectors to detect anomalies. By cascading the FTS detector and the GE detector to detect anomalies, the model achieves a high speed and competitive anomaly-detection performance on multiple datasets.

Dendrobium officinale Polysaccharide (DOP) Promotes Hair Regrowth in Testosterone-Induced Bald Mice.

BACKGROUND: Androgenetic alopecia can affect up to 70% of males and 40% of females; however, certain therapeutic medications offer partial and transitory improvement but with major side effects. Dendrobium officinale polysaccharide (DOP) has been reported to improve androgen-related hair loss in mice, but the molecular mechanism remains unclear. OBJECTIVES: To explore the effects of DOP on androgenetic alopecia. METHODS: In this study, testosterone was subcutaneously administered to shave dorsa skin of mice to establish androgenetic alopecia; the effects of DOP in androgenetic alopecia were explored by DOP administration. RESULTS: Testosterone treatment extended the time of skin growing dark and hair growing, decreased the mean numbers of follicles in skin tissues, decreased ß-catenin and cyclin D1 levels, and elevated testosterone, DHT (dihydrotestosterone), and 5α-reductase levels. In contrast, DOP administration shortened skin growing dark and hair growing times, promoted follicle cell proliferation, increased follicle numbers, increased ß-catenin and cyclin D1 levels, and decreased testosterone, DHT, and 5α-reductase levels. CONCLUSION: DOP application significantly improved testosterone-induced hair follicle miniaturization and hair loss, possibly through affecting the Wnt signaling and hair follicle stem cell functions. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Facile Synthesis of P-Doped ZnIn2S4 with Enhanced Visible-Light-Driven Photocatalytic Hydrogen Production.

ZnIn2S4 (ZIS) is widely used in the field of photocatalytic hydrogen production due to its unique photoelectric properties. Nonetheless, the photocatalytic performance of ZIS usually faces problems of poor conductivity and rapid recombination of charge carriers. Heteroatom doping is often regarded as one of the effective strategies for improving the catalytic activity of photocatalysts. Herein, phosphorus (P)-doped ZIS was prepared by hydrothermal method, whose photocatalytic hydrogen production performance and energy band structure were fully studied. The band gap of P-doped ZIS is about 2.51 eV, which is slightly smaller than that of pure ZIS. Moreover, due to the upward shift of its energy band, the reduction ability of P-doped ZIS is enhanced, and P-doped ZIS also exhibits stronger catalytic activity than pure ZIS. The optimized P-doped ZIS exhibits a hydrogen production rate of 1566.6 µmol g-1 h-1, which is 3.8 times that of the pristine ZIS (411.1 µmol g-1 h-1). This work provides a broad platform for the design and synthesis of phosphorus-doped sulfide-based photocatalysts for hydrogen evolution.

Monodisperse MoS2/Graphite Composite Anode Materials for Advanced Lithium Ion Batteries.

Traditional graphite anode material typically shows a low theoretical capacity and easy lithium decomposition. Molybdenum disulfide is one of the promising anode materials for advanced lithium-ion batteries, which possess low cost, unique two-dimensional layered structure, and high theoretical capacity. However, the low reversible capacity and the cycling-capacity retention rate induced by its poor conductivity and volume expansion during cycling blocks further application. In this paper, a collaborative control strategy of monodisperse MoS2/graphite composites was utilized and studied in detail. MoS2/graphite nanocomposites with different ratios (MoS2:graphite = 20%:80%, 40%:60%, 60%:40%, and 80%:20%) were prepared by mechanical ball-milling and low-temperature annealing. The graphite sheets were uniformly dispersed between the MoS2 sheets by the ball-milling process, which effectively reduced the agglomeration of MoS2 and simultaneously improved the electrical conductivity of the composite. It was found that the capacity of MoS2/graphite composites kept increasing along with the increasing percentage of MoS2 and possessed the highest initial discharge capacity (832.70 mAh/g) when MoS2:graphite = 80%:20%. This facile strategy is easy to implement, is low-cost, and is cosmically produced, which is suitable for the development and manufacture of advance lithium-ion batteries.

Biochemical and transcriptomic analyses of the symbiotic interaction between Cremastra appendiculata and the mycorrhizal fungus Coprinellus disseminatus.

BACKGROUND: Cremastra appendiculata is a rare terrestrial orchid with a high market value as an ornamental and medicinal plant. However, the species depends entirely on fungi for seed germination under natural conditions. In a previous study, we have successfully isolated and identified the mycorrhizal fungus Coprinellus disseminatus which was able to induce the germination of C. appendiculata seeds. We then speculated that C. disseminatus may do so by breaking the testa imposed dormancy of the seeds. In this study, biochemical and transcriptomic analyses were used to characterize the germination of C. appendiculata seeds, collected at different stages of germination, as affected by C. disseminatus. RESULTS: The lignocellulose in the seeds coat of C. appendiculata was degraded by the mycorrhizal fungus resulting in facilitated absorption of water. The rate of decline in lignin content was 67 and 73% at 6 and 12 days after sowing, respectively. The water content increased from 13 to 90% during symbiosis. A total of 15,382 genes showing significantly different levels of expression (log2 FPKM≥2.0, Qvalue≤0.05) were successfully identified among all libraries, where the highest number of DEGs was shared between 6 days versus 0 day after symbiotic germination. Gene annotation results suggested that 15 key genes related water-status, such as DHN gene family and Xero 1 were down-regulated. The genes zeaxanthin epoxidase ZEP, 9-cis-epoxycarotenoid dioxygenase NCED3 and ß-carotene hydroxylase involved in the biosynthesis of abscisic acid (ABA) were significantly down-regulated in 6 days as compared to 0 day after symbiotic germination. CONCLUSIONS: This work demonstrates that mycorrhizal fungus C. disseminatus can stimulate C. appendiculata seeds germination through a mechanism of breaking the testa imposed dormancy and inducing water absorption of the embryo.

Erythrocyte Metabolic Reprogramming by Sphingosine 1-Phosphate in Chronic Kidney Disease and Therapies.

RATIONALE: Hypoxia promotes renal damage and progression of chronic kidney disease (CKD). The erythrocyte is the only cell type for oxygen (O2) delivery. Sphingosine 1-phosphate (S1P)-a highly enriched biolipid in erythrocytes-is recently reported to be induced under high altitude in normal humans to enhance O2 delivery. However, nothing is known about erythrocyte S1P in CKD. OBJECTIVE: To investigate the function and metabolic basis of erythrocyte S1P in CKD with a goal to explore potential therapeutics. METHODS AND RESULTS: Using erythrocyte-specific SphK1 (sphingosine kinase 1; the only enzyme to produce S1P in erythrocytes) knockout mice (eSphK1-/-) in an experimental model of hypertensive CKD with Ang II (angiotensin II) infusion, we found severe renal hypoxia, hypertension, proteinuria, and fibrosis in Ang II-infused eSphk1-/- mice compared with controls. Untargeted metabolomics profiling and in vivo U-13C6 isotopically labeled glucose flux analysis revealed that SphK1 is required for channeling glucose metabolism toward glycolysis versus pentose phosphate pathway, resulting in enhanced erythroid-specific Rapoport-Luebering shunt in Ang II-infused mice. Mechanistically, increased erythrocyte S1P functioning intracellularly activates AMPK (AMP-activated protein kinase) 1α and BPGM (bisphosphoglycerate mutase) by reducing ceramide/S1P ratio and inhibiting PP2A (protein phosphatase 2A), leading to increased 2,3-bisphosphoglycerate (an erythrocyte-specific metabolite negatively regulating Hb [hemoglobin]-O2-binding affinity) production and thus more O2 delivery to counteract kidney hypoxia and progression to CKD. Preclinical studies revealed that an AMPK agonist or a PP2A inhibitor rescued the severe CKD phenotype in Ang II-infused eSphK1-/- mice and prevented development of CKD in the control mice by inducing 2,3-bisphosphoglycerate production and thus enhancing renal oxygenation. Translational research validated mouse findings in erythrocytes of hypertensive CKD patients and cultured human erythrocytes. CONCLUSIONS: Our study elucidates the beneficial role of eSphk1-S1P in hypertensive CKD by channeling glucose metabolism toward Rapoport-Luebering shunt and inducing 2,3-bisphosphoglycerate production and O2 delivery via a PP2A-AMPK1α signaling pathway. These findings reveal the metabolic and molecular basis of erythrocyte S1P in CKD and new therapeutic avenues.

Versatile Dicyanomethylene-Based Fluorescent Probes for the Detection of ß-Amyloid in Alzheimer's Disease: A Theoretical Perspective.

Motivated by the growing demand for target chemosensors designed with diagnostic or therapeutic capability for fibrils related to amyloidosis diseases, we investigated in the present work the response mechanism of dicyanomethylene-based fluorescent probes for amyloid fibril using a combined approach, including molecular docking, quantum mechanics/molecular mechanics (QM/MM), and the quantum chemical method. Various binding modes for the probes in ß-amyloid (Aß) are discussed, and the fibril environment-induced molecular optical changes at the most stable site are compared to the fibril-free situation in aqueous environments. The results reveal that the fluorescence enhancement for the probes in Aß observed experimentally is an average consequence over multiple binding sites. In particular, the conformational difference, including conjugation length and donor effect, significantly contributes to the optical property of the studied probes both in water and fibril. To further estimate the transition nature of the molecular photoabsorption and photoemission processes, the hole-electron distribution and the structural variation on the first excited state of the probes are investigated in detail. On the basis of the calculations, structure-property relationships for the studied chemosensors are established. Our computational approach with the ability to elucidate the available experimental results can be used for designing novel molecular probes with applications to Aß imaging and the early diagnosis of Alzheimer's disease.

Crystallization and Structural Properties of Oleogel-Based Margarine.

Interest in oleogel as a promising alternative to traditional hydrogenated vegetable oil has increasingly grown in recent years due to its low content of saturated fatty acids and zero trans fatty acids. This study aimed to develop wax-based margarine to replace traditional commercial margarine. The wax-based margarine was prepared and compared with commercial margarine in texture, rheology, and microscopic morphology. The possibility of preparing margarine at room temperature (non-quenched) was also explored. The results showed that the hardness of oleogel-based margarine increased as the BW concentration increased. Denser droplets and crystal network structure were observed with the increase in BW content. XRD patterns of oleogel-based margarine with different content BW were quite similar and structurally to the ß' form. However, the melting temperature of oleogel-based margarine was over 40 °C at each concentration, which represented a poor mouth-melting characteristic. In addition, the unique, improved physical properties of oleogel-based margarine were obtained with binary mixtures of China lacquer wax (ZLW) and Beeswax (BW), due to the interaction of the ZLW and BW crystal network. The rapid cooling process improved the spreadability of oleogel-based margarine. The margarine prepared by 5% BW50:ZLW50 had similar properties to commercial margarine in texture and melting characteristics (37 °C), which had the potential to replace commercial margarine.

Shp2-mediated MAPK pathway regulates ΔNp63 in epithelium to promote corneal innervation and homeostasis.

Corneal nerve fibers serving sensory, reflex, and neurotrophic functions sustain corneal homeostasis and transparency to promote normal visual function. It is not known whether corneal epithelium is also important for the corneal innervation. Herein, we generated a compound transgenic mouse strain, K14rtTA;tetO-Cre (TC);Shp2flox/flox, in which Shp2 was conditionally knocked out from K14-positive cells including corneal epithelium (Shp2K14ce-cko) upon doxycycline (dox) administration. Our data reveal that Shp2K14ce-cko caused corneal denervation. More specifically, corneal epithelium thickness and corneal sensitivity reduced dramatically in Shp2K14ce-cko mice. In addition, corneal epithelial wound healing after debridement was delayed substantially in the mutant mice. These defects manifested in Shp2K14ce-cko mice resemble the symptoms of human neurotrophic keratopathy. Our in vitro study shows that neurite outgrowth of the mouse primary trigeminal ganglion cells (TGCs) was inhibited when as cocultured with mouse corneal epithelial cells (TKE2) transfected by Shp2-, Mek1/2-, or ∆Np63-targeted siRNA but not by Akt1/2-targeted siRNA. Furthermore, ∆Np63 RNA interference downregulated Ngf expression in TKE2 cells. Cotransfection experiments reveal that Shp2 tightly monitored ΔNp63 protein levels in HEK293 and TKE2 cells. Taken together, our data suggest that the Shp2-mediated MAPK pathway regulated ΔNp63, which in turn positively regulated Ngf in epithelium to promote corneal innervation and epithelial homeostasis.