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Using the abundant and cost‐effective oleic acid and isosorbide with excellent properties as raw materials, the plasticizers of isosorbide di‐oleate (IDO) and isosorbide di‐epoxidized oleate (IDEO) with good plasticizing effect, low cost and green safety were synthesized by esterification and epoxidation reaction. The molecular structure of the synthesized plasticizers was characterized by FT‐IR and 1H NMR. The PVC shows better flexibility when IDEO or IDO plasticizer is used than commercial DOP. In particular, IDEO‐40 has 34% higher tensile strength and 17% higher elongation at break than DOP‐40. The introduction of epoxy groups on the carbon–carbon double bond of fatty acids meets the high thermal stability of plasticized film. The residual amount of IDEO‐40 is 7.01%, and at a high temperature of 180 °C, it can maintain high heat resistance for more than 220 min and transmittance of over 86%. Moreover, IDEO demonstrates excellent resistance to migration and volatilization. However, PVC films plasticized with IDO display reduced mechanical properties, cold resistance, and resistance to volatilization and migration due to the presence of non‐rotating carbon–carbon double bonds. The results indicate that these bio‐based plasticizers hold promise for practical applications in PVC products, offering improved environmental sustainability and performance characteristics. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) and arginine vasopressin deficiency (AVP‐D) are characterized by polyuria. Marfan syndrome is an autosomal dominant disorder caused by pathogenetic variants in FBN1. Here, we report a patient with type 2 diabetes mellitus, AVP‐D, and Marfan syndrome. Although the coexistence of type 2 diabetes mellitus and AVP‐D is rare, for those patients with type 2 diabetes mellitus, the existence of AVP‐D should be considered when polyuria is not in accordance with the blood glucose levels, especially for those with a low urine specific gravity. Specific symptoms or signs help to identify Marfan syndrome early, and genetic testing of the FBN1 pathogenetic variant helps to make a definitive diagnosis. [ABSTRACT FROM AUTHOR]

Aims: To investigate the exposure–response (E‐R) relationship, including exposure–efficacy and exposure–safety, of ropeginterferon alfa‐2b treatment in patients with polycythaemia vera (PV). Methods: Based on the results of the phase II trial A20‐202 regarding ropeginterferon alfa‐2b in patients with PV, E‐R analyses were performed to evaluate the efficacy and safety of the given dosing regimen. The E‐R analyses were based on logistic and linear regression and the relationship between exposure to ropeginterferon alfa‐2b and key efficacy and safety variables. The key efficacy variables included complete haematologic response (CHR) and reduction of the driver mutation JAK2V617F. The safety variable was treatment‐related adverse events (TRAEs). Results: A clear relationship between the exposure to ropeginterferon alfa‐2b and CHR was observed, with an increase in drug exposure resulting in an increased probability of achieving CHR. Similar CHR probabilities were observed in the third and fourth quantiles of the average concentration at Week 24. The results from the exposure–JAK2V617F model indicated that the JAK2V617F allele burden decreased with increasing exposure to ropeginterferon alfa‐2b and baseline body surface area. Exposure–safety analysis revealed a risk of AEs associated with transaminase abnormalities, which were not associated with clinical significance. Conclusions: Our analyses have shown that patients with PV treated with ropeginterferon alfa‐2b had an increased probability of achieving CHR and a molecular response with acceptable safety risks at the 250–350–500 μg titration dosing regimen. This study has provided the relevant data for the application of a biologics licence of ropeginterferon alfa‐2b for PV treatment in China. [ABSTRACT FROM AUTHOR]

Most current research focusing on the health risk assessments of particulate polycyclic aromatic hydrocarbons (PAHs) have not analyzed the size distributions and human respiratory deposition rates. In the present study, size‐separated particulate matter (PM) was collected in the coastal area of Ningbo using an Anderson eight‐stage air sampler over a 1‐year period (2014–2015). The 16 US Environmental Protection Agency priority PAHs associated with PM were pretreated with rapid solvent extraction and analyzed by gas chromatography–mass spectrometry. The respiratory exposure assessment was determined using the multiple‐path particle dosimetry (MPPD) model. The results show that all PAHs exhibited bimodal distribution with one mode peak in accumulation mode (0.43–0.65 µm) and another mode peak in coarse mode (4.7–5.8 µm). In addition, a low coefficient of divergence of PAHs between PM2.1 and PM2.1−10 indicated a high spatial heterogeneity in source factor contribution and formation mechanism. The deposition fluxes (tracheobronchial + pulmonary) of PM were highest for children in the size range of 3.3 µm < particle diameter (Dp) < 9 µm, while for males and females the highest fluxes occurred in the size range of 1.1 µm < Dp < 2.1 µm. The depositions of coarse PM in children were significantly higher than those in adults. The benzo[a]pyrene equivalent (BaPeq) depositions of dibenz[a,h]anthracene ranged from 1.4e‐04 to 0.015 ng h−1, which were highest among the PAHs. The PAHs on particles with Dp >4.7 µm contributed approximately three times more to children than to males and females. Therefore, the toxicity of coarse PM to children needed attention. The incremental lifetime cancer risks (ILCR) for children, males, and females were estimated to be 2.92 × 10−7, 1.82 × 10−7, and 2.38 × 10−7, respectively, which were below the cancer risk guideline value (10−6). These ILCR values were much lower than the risks calculated without considering particle size distributions and respiratory depositions. The combination of the size‐segregated sampling technique and the MPPD model can effectively avoid the overestimation of human respiratory exposure. Environ Toxicol Chem 2024;43:1364–1377. © 2024 SETAC [ABSTRACT FROM AUTHOR]

Compared to Ir, Ru‐based catalysts often exhibited higher activity but suffered significant and rapid activity loss during the challenging oxygen evolution reaction (OER) in a corrosive acidic environment. Herein, we developed a hybrid MnRuOx catalyst in which the RuO2 microcrystalline regions serve as a supporting framework, and the amorphous MnRuOx phase fills the microcrystalline interstices. In particular, the MnRuOx‐300 catalyst from an annealing temperature of 300 °C contains an optimal amorphous/crystalline heterostructure, providing substantial defects and active sites, facilitating efficient adsorption and conversion of OH−. In addition, the heterostructure leads to a relative increase of the d‐band center close to the Fermin level, thus accelerating electron transfer with reduced charge transfer resistance at the active interface between crystalline and amorphous phases during the OER. The catalyst was further thoroughly evaluated under various operating conditions and demonstrated exceptional activity and stability for the OER, representing a promising solution to replace Ir in water electrolyzers. [ABSTRACT FROM AUTHOR]

The DIN color system is a visually uniform system adopted as the standard by several countries in central Europe. Currently, the conversion method from CIE‐XYZ color system to DIN color system consists of the DIN 6164 method combined with the manual reading method. However, the DIN 6164 method cannot be used for the edges of a chromaticity diagram. The manual reading method can read all areas in a chromaticity diagram; however, it is too inefficient to convert large quantities of data. This study builds on the manual reading method to create a new method entitled the program reading method. Upon comparing the relative error, absolute error and conversion times of all methods, it was determined that the program reading method achieved higher accuracy than that of the manual reading method. The maximum relative error of the program reading method was 3.24%; however, the conversion time for each sample was 0.07 s, which was 3.5 times slower than that of the DIN 6164 method. Based on these findings, this study proposes an automatic conversion method that combines the strengths of both approaches: the DIN 6164 method to be used for interpolable areas and the program reading method to be used for areas that cannot be interpolated. The automatic conversion method outlined in this study provides an efficient, precise and fast way to convert a CIE‐XYZ color system to a DIN color system. [ABSTRACT FROM AUTHOR]

The branch point singularities in the Riemann surface of the parameter space are known as the exceptional points (EPs), at which two or more eigenvalues and their associated eigenvectors simultaneously coalesce. The abrupt bifurcation property around an EP shows a strong spectral response to external perturbations, and hence, is exploited as a new approach to ultrasensitive sensors. Recently, an intriguing proposal for implementing second‐order EPs in optical resonators with external perturbations has shown the superiority of non‐Hermitian degeneracies in the enhancement of sensing. Of particular importance is further improving the sensitivity to even greater extents. To this end, a novel physical mechanism is proposed, namely introducing extra resonances of external Rayleigh scatterers to accomplish strong‐coupling augmentation in sensing. The results, grounded by both theoretical coupled‐mode‐theory calculations and experimental spectral‐domain measurements, show that the EP‐based sensor working at the coherent resonance equips simultaneously substantial perturbation strength and azimuth sensitivity even subjected to extremely weak perturbations. This work paves the way to a new class of highly functional tunable sensors for applications in optics, microwave and acoustics. [ABSTRACT FROM AUTHOR]

Compared to traditional small molecule and antibody drugs, RNA‐based drugs offer a simple design, short research and development cycles, high specificity, broad treatment fields, and long‐term efficacy. As a result, RNA‐based drugs are extensively used to treat genetic diseases, tumors, viral infections, and other illnesses, suggesting that they have the potential to become the third‐largest drug class after small molecule and antibody drugs. Currently, more than 10 small nucleic acid drugs have gained regulatory approval. The commercialization successes of small nucleic acid drugs will stimulate the development of RNA‐based drugs. Small nucleic acid drugs primarily target liver diseases, metabolic diseases, genetic diseases, and tumors, and there is also significant potential for expanding indications in the future. This review provides a brief overview of the advantages and development of small nucleic acid‐based therapeutics and shows a focus on platform technologies such as chemical modifications and delivery systems that have enabled the clinical translation of small nucleic acid‐based therapeutics. Additionally, we summarize the latest clinical progress in small nucleic acid‐based therapeutics for the treatment of various diseases, including rare diseases, liver diseases, metabolic diseases, and tumors. Finally, we highlight the future prospects for this promising treatment approach. [ABSTRACT FROM AUTHOR]

Phosphatidylinositol 4‐kinase beta (PI4KB) is a member of the PI4K family, which is mainly enriched and functions in the Golgi apparatus. The kinase domain of PI4KB catalyzes the phosphorylation of phosphatidylinositol to form phosphatidylinositol 4‐phosphate, a process that regulates various sub‐cellular events, such as non‐vesicular cholesterol and ceramide transport, protein glycosylation, and vesicle transport, as well as cytoplasmic division. In this study, a strain of PI4KB knockout mouse, immunofluorescence, reverse transcription polymerase chain reaction and microinjection were used to characterize the cytological location and biological function of PI4KB in the mouse embryos. we found that knocking down Pi4kb in mouse embryos resulted in embryonic lethality at around embryonic day (E) 7.5. Additionally, we observed dramatic fluctuations in PI4KB expression during the development of preimplantation embryos, with high expression in the 4‐cell and morula stages. PI4KB colocalized with the Golgi marker protein TGN46 in the perinuclear and cytoplasmic regions in early blastomeres. Postimplantation, PI4KB was highly expressed in the epiblast of E7.5 embryos. Treatment of embryos with PI4KB inhibitors was found to inhibit the development of the morula into a blastocyst and the normal progression of cytoplasmic division during the formation of a 4‐cell embryo. These findings suggest that PI4KB plays an important role in mouse embryogenesis by regulating various intracellular vital functions of embryonic cells. [ABSTRACT FROM AUTHOR]

Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late‐stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes‐rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles‐rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early‐stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late‐stage PDAC patients undergoing chemotherapy, lower GPC1 tMV‐mProtein and Exo‐mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis. [ABSTRACT FROM AUTHOR]

Changes in the habitats of species can provide insights into the impact of climate change on their habitats. Species in the genus Morina (Morinoideae) are perennial herbaceous plants that are mainly distributed in the South Asian Mountains and Eastern Mediterranean. In China, there are four species and two varieties of this genus distributed across the Yunnan, Sichuan, Qinghai, and Gansu provinces. This study used the optimal MaxEnt model to simulate past, current, and future potentially suitable habitats of Morina kokonorica and Morina chinensis. Seventy data of M. kokonorica occurrences and 3 of M. chinensis were used in the model to predict potentially suitable habitats. The model prediction results indicated that both M. kokonorica and M. chinensis exhibited trends of northward migration to higher latitudes and westward migration along the Himalayas to higher elevations, suggesting that the northern valleys of Hengduan Mountains and northern and eastern parts of the Himalayas were potential refugia for M. kokonorica, and the potential refugia for M. chinensis was located in the eastern part of Qinghai‐Tibet Plateau. The results of this niche analysis showed that the two species had higher levels of interspecific competition and that the environmental adaptability of M. chinensis was stronger. This research could help further understand the response pattern of Morina to environmental change, to understand the adaptability of species to the environment, and promote the protection of species. [ABSTRACT FROM AUTHOR]

DNAzyme‐based fluorescent probes for imaging metal ions in living cells have received much attention recently. However, employing in situ metal ions imaging within subcellular organelles, such as nucleus, remains a significant challenge. We developed a three‐stranded DNAzyme probe (TSDP) that contained a 20‐base‐pair (20‐bp) recognition site of a CRISPR/Cas9, which blocks the DNAzyme activity. When Cas9, with its specialized nuclear localization function, forms an active complex with sgRNA within the cell nucleus, it cleaves the TSDP at the recognition site, resulting in the in situ formation of catalytic DNAzyme structure. With this design, the CRISPR/Cas9‐inducible imaging of nuclear Zn2+ is demonstrated in living cells. Moreover, the superiority of CRISPR‐DNAzyme for spatiotemporal control imaging was demonstrated by integrating it with photoactivation strategy and Boolean logic gate for dynamic monitoring nuclear Zn2+ in both HeLa cells and mice. Collectively, this conceptual design expands the DNAzyme toolbox for visualizing nuclear metal ions and thus provides new analytical methods for nuclear metal‐associated biology. [ABSTRACT FROM AUTHOR]

Recently, patients with Mpox breakthrough infection or reinfection were constantly reported. However, the induction, risk factors, and important clinical symptoms of breakthrough infection and reinfection of Mpox virus (MPXV), as well as the factors affecting the effectiveness of Mpox vaccine are not characterized. Herein, a literature review was preformed to summarize the risk factors and important clinical symptoms of patients with Mpox breakthrough infection or reinfection, as well as the factors affecting the effectiveness of smallpox vaccine against Mpox. Results showed that MSM sexual behavior, condomless sexual behavior, multiple sexual partners, close contact, HIV infection, and the presence of comorbidity are important risk factors for Mpox breakthrough infection and reinfection. Genital ulcers, proctitis, and lymphadenopathy are the important clinical symptoms of Mpox breakthrough infection and reinfection. The effectiveness of emergent vaccination of smallpox vaccine for post‐exposure of MPXV is associated with smallpox vaccination history, interval between exposure and vaccination, and history of HIV infection. This review provides a better understanding for the risk factors and important clinical symptoms of Mpox breakthrough infection and reinfection, as well as the formulation of Mpox vaccine vaccination strategies. [ABSTRACT FROM AUTHOR]

Unveiling the intricate relationships between animal movement ecology, feeding behavior, and internal energy budgeting is crucial for a comprehensive understanding of ecosystem functioning, especially on coral reefs under significant anthropogenic stress. Here, herbivorous fishes play a vital role as mediators between algae growth and coral recruitment. Our research examines the feeding preferences, bite rates, inter‐bite distances, and foraging energy expenditure of the Brown surgeonfish (Acanthurus nigrofuscus) and the Yellowtail tang (Zebrasoma xanthurum) within the fish community on a Red Sea coral reef. To this end, we used advanced methods such as remote underwater stereo‐video, AI‐driven object recognition, species classification, and 3D tracking. Despite their comparatively low biomass, the two surgeonfish species significantly influence grazing pressure on the studied coral reef. A. nigrofuscus exhibits specialized feeding preferences and Z. xanthurum a more generalist approach, highlighting niche differentiation and their importance in maintaining reef ecosystem balance. Despite these differences in their foraging strategies, on a population level, both species achieve a similar level of energy efficiency. This study highlights the transformative potential of cutting‐edge technologies in revealing the functional feeding traits and energy utilization of keystone species. It facilitates the detailed mapping of energy seascapes, guiding targeted conservation efforts to enhance ecosystem health and biodiversity. [ABSTRACT FROM AUTHOR]

Summary: Upland rice is a distinctive drought‐aerobic ecotype of cultivated rice highly resistant to drought stress. However, the genetic and genomic basis for the drought‐aerobic adaptation of upland rice remains largely unclear due to the lack of genomic resources. In this study, we identified 25 typical upland rice accessions and assembled a high‐quality genome of one of the typical upland rice varieties, IRAT109, comprising 384 Mb with a contig N50 of 19.6 Mb. Phylogenetic analysis revealed upland and lowland rice have distinct ecotype differentiation within the japonica subgroup. Comparative genomic analyses revealed that adaptive differentiation of lowland and upland rice is likely attributable to the natural variation of many genes in promoter regions, formation of specific genes in upland rice, and expansion of gene families. We revealed differentiated gene expression patterns in the leaves and roots of the two ecotypes and found that lignin synthesis mediated by the phenylpropane pathway plays an important role in the adaptive differentiation of upland and lowland rice. We identified 28 selective sweeps that occurred during domestication and validated that the qRT9 gene in selective regions can positively regulate drought resistance in rice. Eighty key genes closely associated with drought resistance were appraised for their appreciable potential in drought resistance breeding. Our study enhances the understanding of the adaptation of upland rice and provides a genome navigation map of drought resistance breeding, which will facilitate the breeding of drought‐resistant rice and the "blue revolution" in agriculture. [ABSTRACT FROM AUTHOR]

Background: Thalassemia is a common genetic disorder in southwestern China, and an increasing number of cases from eastern China have been recently reported. Here, we developed a rapid, convenient, and accurate assay to evaluate the mutation spectrum of thalassemia in eastern China. Methods: A carrier screening assay for 61 hotspot variants among HBA1/HBA2 and HBB (OMIM: 141800, 141850, and 141900) genes was developed by SNaPshot/high‐throughput ligation‐dependent probe amplification (HLPA) technology. We used this assay to detect the mutation spectrum of thalassemia in individuals from eastern China and compared with the data collected from literatures focused on southern and northern China for variant distribution. Results: Among 4276 tested individuals, 2.62% (112/4276) were α‐thalassemia carriers, with 90 carrying one deletion or mutation and 22 carrying two deletions. 0.40% (17/4276) were β‐thalassemia carriers, and the most common variant of β‐thalassemia was c.126_129delCTTT (29.41%) followed by c.316‐197C>T (23.53%). The genotype distribution in our study was similar to those from southern China populations. Conclusion: The Chinese population from different regions presented comparable mutation spectrum of thalassemia, and the SNaPshot/HLPA technique may serve as a capable assay for a routine genetic test in clinical practice with its accurate, rapid, and inexpensive advantage. [ABSTRACT FROM AUTHOR]

Thermal spraying ceramic coatings have been widely used to prevent wear damage. However, the poor lubricating ability seriously restricted their application. In this article, zirconia stabilized by 8 wt% yttria (8YSZ)‐C composite coating is prepared with the combination of in‐situ synthesis carbon microspheres in the pores of as‐sprayed 8YSZ coating by hydrothermal reaction. The chemical constituents and morphologies of the synthesized powders and the composite coatings are analyzed by scanning electron microscope (SEM) and X‐ray diffraction (XRD). The microstructure and tribological behaviors of the composite coating are studied by SEM, TEM. and Raman analysis. The influence of humidity on the structural evolution of carbon microspheres during sliding wear process is discussed. The results show that the synthetic C powders exhibit a typical spherical structure. Meanwhile, carbon microspheres adhere to the pores of the 8YSZ coating. The friction and wear experiments in different humidity show that the re‐graphitization of amorphous carbon becomes extremely obvious with the increase of humidity. Under the 80% humidity, an ordered graphene nanoscroll structure is formed, resulting in the optimization of the tribological properties. Furthermore, the friction coefficient of composite coating is reduced to 0.18, and its wear rate is about 1 times lower than that of under the 10% humidity. [ABSTRACT FROM AUTHOR]

Negative Poisson's ratio as the anomalous characteristic generally exists in artificial architectures, such as re‐entrant and honeycomb structures. The structures with negative Poisson's ratio have attracted intensive attention due to their unique auxetic effect and many promising applications in shear‐resistant and energy absorption fields. However, experimental observation of negative Poisson's ratio in natural materials barely happens, although various 2D layered materials are predicted in theory. Herein, the anisotropic Raman response and the intrinsic intralayer negative Poisson's ratio of 2D natural black arsenic (b‐As) via strain engineering strategy are reported. The results are evident by the detailed Raman spectrum of b‐As under uniaxial strain together with density functional theory calculations. It is found that b‐As is softer along the armchair than zigzag direction. The anisotropic mechanical features and van der Waals interactions play essential roles in strain‐dependent Raman shifts and negative Poisson's ratio in the natural b‐As along zigzag direction. This work may shed a light on the mechanical properties and potential applications of 2D puckered materials. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Secondary alcohols bearing both axial and central chirality comprise attractive biological activity and exhibit excellent chiral induction in asymmetric reactions. However, only very limited asymmetric catalytic approaches were developed for their synthesis. We herein describe visible light‐mediated cobalt‐catalyzed asymmetric reductive Grignard‐type addition of aryl iodides with axially prochiral biaryl dialdehydes leading to the direct construction of axially chiral secondary alcohols. Preliminary mechanistic studies indicate that efficient kinetic recognition of diastereomers might occur for axially prochiral dialdehydes to improve the stereoselectivity, which might open a new avenue for the challenging cascade construction of multiple chiral elements. This protocol features excellent enantio‐ and diastereoselectivity, green and mild conditions, simple operation, and broad substrate scope, providing a modular platform for the synthesis of secondary axially chiral alcohols. [ABSTRACT FROM AUTHOR]

Regenerative medicine in tissue engineering often relies on stem cells and specific growth factors at a supraphysiological dose. These approaches are costly and may cause severe side effects. Herein, therapeutic small extracellular vesicles (t‐sEVs) endogenously loaded with a cocktail of human vascular endothelial growth factor A (VEGF‐A) and human bone morphogenetic protein 2 (BMP‐2) mRNAs within a customized injectable PEGylated poly (glycerol sebacate) acrylate (PEGS‐A) hydrogel for bone regeneration in rats with challenging femur critical‐size defects are introduced. Abundant t‐sEVs are produced by a facile cellular nanoelectroporation system based on a commercially available track‐etched membrane (TM‐nanoEP) to deliver plasmid DNAs to human adipose‐derived mesenchymal stem cells (hAdMSCs). Upregulated microRNAs associated with the therapeutic mRNAs are enriched in t‐sEVs for enhanced angiogenic–osteogenic regeneration. Localized and controlled release of t‐sEVs within the PEGS‐A hydrogel leads to the retention of therapeutics in the defect site for highly efficient bone regeneration with minimal low accumulation in other organs. [ABSTRACT FROM AUTHOR]

The research presented in this paper introduces a novel environmental energy‐harvesting technology that harnesses electricity from the evaporation of water using porous structural materials. Specifically, a strategy employing paper‐based hydroelectric generators (p‐HEGs) is proposed to capture the energy produced during water evaporation and convert it into usable electricity. The p‐HEGs offer several advantages, including simplicity in fabrication, low cost, and reusability. To evaluate their effectiveness, the water evaporation‐induced electrical output performance of four different p‐HEGs are compared. Among the variants tested, the p‐HEG combining wood pulp and polyester fiber exhibits the best output performance. At room temperature, this particular p‐HEG generates a short‐circuit current and open‐circuit voltage of ≈0.4 µA and 0.3 V, respectively, thereby demonstrating excellent electrical stability. Furthermore, the electrical current and voltage generated by the p‐HEG through water evaporation are able to power an LED light, both individually and in series and parallel connections. This study delves into the potential of electricity harvesting from water evaporation and establishes it as a viable method for renewable energy applications. [ABSTRACT FROM AUTHOR]

Aim: The pathogenesis of ankylosing spondylitis (AS) seems to be associated with genetics, the environment, heredity, and oxidative stress. Single nucleotide polymorphisms (SNPs) in the displacement loop (D‐loop) region of mitochondrial DNA (mtDNA) and mtDNA copy number were investigated for their correlation with AS patients. Methods: This study included 83 AS patients and 100 healthy controls from the Second Hospital of Hebei Medical University. DNAs were extracted from blood samples for polymerase chain reaction analysis and quantitative real‐time polymerase chain reaction analysis. Plasma reactive oxygen species (ROS) levels were measured by fluorescent probe technology. Results: The distribution frequencies of the minor alleles of nucleotides 16304C (p =.037), 16311C (p =.027), and 152C (p =.034) were remarkably higher in AS patients than in healthy controls, which indicated that the16304C, 16311C, and 152C alleles were correlated with an increased risk of AS. Simultaneously, mtDNA copy number was statistically higher in patients with AS compared with controls (1.450 ± 0.876 versus 0.835 ± 0.626, p <.001). We also observed an increased ROS generation in AS patients compared with controls (27 066.169 ± 18 364.819 versus 14 758.330 ± 5854.946, p <.001) subsequently. In addition, the AS susceptible SNP 16311C is associated with high ROS levels (35 065.177 ± 26 999.934 vs. 25 005.818 ± 14 999.495, p =.043). Conclusion: Our study demonstrated that SNPs in the mtDNA D‐loop could be AS risk biomarkers with the potential to promote oxidative stress levels; mtDNA copy number‐induced mitochondrial dysfunction may also be involved in AS pathogenesis. [ABSTRACT FROM AUTHOR]

Aim: To provide a systematic review of the qualitative literature on self‐reported barriers to self‐management in pregnant women with gestational diabetes mellitus (GDM). Design: Systematic review. Methods: This systematic review followed the Joanna Briggs Institute meta‐aggregation approach and was evaluated using the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research. Qualitative studies on the barriers to self‐management among GDM pregnancy survivors conducted until 17 May 2022, were searched. Results: A total of 30 studies were included, of which seven were in Chinese and 23 were in English, and 10 findings resulted in three themes: (a) Knowledge and belief, (b) Skills and abilities and (c) Environment and social support. By summarizing the self‐reported barriers to self‐management in patients with GDM and recommends precise interventions for these barriers, thereby saving health resources and helping to increase their willingness and ability to engage in self‐management. [ABSTRACT FROM AUTHOR]

Glechoma longituba has been frequently used in treating urolithiasis and cholelithiasis due to the presence of flavonoids, which are its major bioactive constituents. However, research on the molecular background of flavonoid biosynthesis in G. longituba is limited. In this study, we used single‐molecule real‐time combined with next‐generation sequencing technologies to construct the complete transcriptome of G. longituba. We identified 404,648 non‐redundant transcripts, including 249,697 coding sequences, 197,811 simple sequence repeats, 174,846 long noncoding RNA, and 176,554 coding RNA. Moreover, we functionally annotated 346,218 isoforms (85.56%) and identified 86,528 differentially expressed genes. We also identified 55 non‐redundant full‐length isoforms related to the flavonoid biosynthetic pathway. Pearson correlation analysis revealed that the expression levels of some key genes of the flavonoid biosynthesis pathway were significantly positively correlated with the flavonoid metabolites. Furthermore, we performed bioinformatics analysis (sequence and structural) of isoform_47029 (encoding flavanone 3‐hydroxylase) and isoform_53692 (encoding flavonol synthase) to evaluate their potential biological functions. Finally, we validated gene expression levels of 12 flavonoid‐related key enzyme genes using quantitative real‐time PCR. Overall, this study provides full‐length transcriptome information on G. longituba for the first time and valuable molecular resources for further research on the medicinal properties of this plant. [ABSTRACT FROM AUTHOR]

Climate change and the resulting natural vegetation succession can alter vegetation productivity. However, the mechanisms underlying future productivity changes under the two influences remain unclear. Here, we used the comprehensive sequence classification system to simulate changes in global potential natural vegetation under different climate scenarios (SSP1‐2.6, SSP2‐4.5, SSP3‐7.0, and SSP5‐8.5), and combined the Carnegie–Ames–Stanford Approach model with random forest to assess the response of net primary productivity (NPP) to climate change and vegetation succession from 2020 to 2100. Except for SSP126, terrestrial NPP in 2100 decreased by 0.86, 2.39, and 2.54 Pg C·a−1 versus 2020 under SSP2‐4.5, SSP5‐8.5, and SSP3‐7.0, respectively. Forest was the primary contributor to terrestrial NPP changes. The total forest area was projected to increase under all scenarios, with SSP2‐4.5 showing the largest increase (358.57 × 104 km2). However, expanding forest regions exhibited a relatively low mean NPP, while stable regions demonstrated a declining pattern. Consequently, forest NPP increased under SSP1‐2.6 but decreased by 4.03, 3.43, and 0.82 Pg C·a−1 in 2100 versus 2020 under SSP5‐8.5, SSP3‐7.0, and SSP2‐4.5, respectively. In comparison, grassland and desert exerted minor influence on terrestrial NPP changes, their total NPP decreased only under the SSP1‐2.6 scenario. The grassland area decreased, but the mean NPP increased, whereas the desert area expanded, resulting in consistent changes in both total and mean NPP. Our results analyzed the effects of climate change and vegetation distribution under its influence on the change of NPP, which can deepen our understanding of their relationship. Plain Language Summary: Climate change can affect global terrestrial vegetation net primary productivity (NPP) both directly and indirectly by influencing vegetation succession, however, the process of NPP change remains uncertain. Combining the comprehensive sequential classification system, Carnegie‐Ames‐Stanford Approach model, and the random forest, we predicted the distribution of potential natural vegetation (PNV) and changes in NPP from 2020 to 2100, and analyzed the mechanisms of NPP change under climate change and vegetation succession. The global terrestrial NPP was predicted to decline under the scenario of sharper temperature increase in the future, with the largest contribution from the forest NPP change. Moreover, under the scenario of sharper temperature increase, the increase in forest area but the decrease in mean NPP was predicted to lead to a decrease in total NPP. Grassland and desert showed an increase in total NPP, but their area as well as mean NPP changes were opposite. Globally, for various PNVs on the land, varied reasons accounted for changes in total NPP. Overall, our results contribute toward better understanding of the relationship between future climate change and terrestrial vegetation ecosystems. Key Points: In the four climate scenarios, vegetation underwent mutual succession, yet all exhibited forest and desert expanded and grassland shrankFrom 2020 to 2100, global terrestrial net primary productivity mainly declines when affected by climate change and vegetation successionNet primary productivity of various vegetations has varying mechanisms of change in response to climate change and vegetation succession [ABSTRACT FROM AUTHOR]

Vitamin D‐regulating action of PPARγ on obesity has been confirmed on adipocyte differentiation. However, it is not clear whether vitamin D affects the morphological size of mature adipocytes by influencing the expression of PPARγ in vivo. Our hypothesis was that Vitamin D3 (VitD3) inhibits the growth of adipocyte size by suppressing PPARγ expression in white adipocytes of obese mice. Five‐week‐old male C57BL/6J mice were randomly divided into normal diet and high‐fat diet groups. After 10 weeks, the body weight between the two groups differed by 26.91%. The obese mice were randomly divided into a high‐fat diet, solvent control, low‐dose VitD3 (5000 IU/kg·food), medium‐dose VitD3 (7500 IU/kg·food), high‐dose VitD3 (10,000 IU/kg·food), and PPAR γ antagonist group, and the intervention lasted for 8 weeks. Diet‐induced obesity (DIO) mice fed high‐dose VitD3 exacerbated markers of adiposity (body weight, fat mass, fat mass rate, size of white and brown adipocytes, mRNA, and protein levels of ATGL and Fsp27), and the protein level of ATGL and Fsp27 decreased in the low‐dose group. In conclusion, high‐dose VitD3 possibly via inhibiting the ATGL expression, thereby inhibiting lipolysis, increasing the volume of adipocytes, and decreasing their fat‐storing ability resulted in decreased Fsp27 expression. Therefore, long‐term high‐dose oral VitD3 may not necessarily improve obesity, and we need more clinical trials to explore the intervention dose and duration of VitD3 in the treatment of VitD3 deficiency in obese patients. [ABSTRACT FROM AUTHOR]

Aging has been considered as a risk factor in many diseases, thus, comprehensively understanding the cellular and molecular mechanisms of delayed aging is important. Here we investigated whether Krüppel‐like factor 14 (KLF14) is a suppressor of cellular senescence and aging. In our research, KLF14 levels significantly decreased not only in the lymphocytes of healthy people but also in the cells and tissues of mice with aging. We performed in vitro and in vivo experiments on cells and mice to reveal the function of KLF14 in aging. KLF14 deficiency facilitates cellular senescence and aging‐related pathologies in C57BL/6J mice, whereas KLF14 overexpression attenuates cellular senescence. Mechanistically, KLF14 delays aging by binding to the POLD1 promoter to positively regulate POLD1 expression. Remarkably, cellular senescence mediated by KLF14 downregulation could be alleviated by POLD1 expression. In addition, perhexiline, an agonist of KLF14, could delay cellular senescence and aging‐related pathologies in senescence‐accelerated P8 mice by inducing POLD1 expression, as perhexiline could enhance the effect of KLF14's transcription activation to POLD1 by elevating the binding level of KLF14 to the POLD1 promoter. Our data indicate that KLF14 might be a critical element in aging by upregulating POLD1 expression, indicating that the activation of KLF14 may delay aging and aging‐associated diseases. [ABSTRACT FROM AUTHOR]

Water evaporation is a ubiquitous natural process for collecting thermal energy from the environment. Carbon nanomaterial‐based aerogels are good candidates for use as hydroelectric generators (HEGs), permitting substantial interaction with water through electronic coupling, and have been considered for application in evaporation‐induced electricity generation. However, the water transport and electricity generation ability of the aerogels are affected by their pore structures. Inspired by the directional transport of the water vessel elements of the xylem, a biomimetic partially reduced graphene oxide aerogel (prGO) with an aligned porous structure is prepared, assisted by directional ice templating. The as‐prepared prGO aerogel presents a high capillary water transport rate and can efficiently transport water to the top, which is the basis for efficient current generation. This biomimetic prGO is scalable, providing an avenue for assembling other low‐dimensional carbon materials into high current output HEGs. [ABSTRACT FROM AUTHOR]

In this study, five new chitosan oligosaccharide quaternary ammonium derivatives bearing quinoline are synthesized by reaction between 6‐O‐chloroacetyl‐2‐N, N, N‐trimethyl quaternary ammonium salt chitosan oligosaccharide (CTCOS, compound 1) and quinoline derivatives. The derivatives are characterized by analytical techniques including Fourier Transform Infrared (FTIR), 1H Nuclear Magnetic Resonance (1H NMR) spectroscopy, and elemental analysis. The obtained results confirm that quinoline groups are successfully introduced into the CTCOS molecule. Meanwhile, the antioxidant activities of the prepared chitosan oligosaccharide derivatives are evaluated in vitro. The experimental results show that the derivatives have excellent free radical scavenging ability. The free radical scavenging abilities are all over 75% at the concentration of 1.6 mg mL−1. Moreover, antibacterial tests show that derivative 2e has the best antibacterial activities. Its minimum inhibitory concentration (MIC) value and minimum bactericidal concentration (MBC) value against Staphylococcus aureus and Escherichia coli are 0.0625 and 0.03125 mg mL−1, respectively. In addition, the cytotoxicity of chitosan oligosaccharide and its derivatives is examined by MTT colorimetric assay in RAW 264.7 macrophages, observing that all derivatives are non‐cytotoxic. Consequently, the findings indicate that the enhanced antioxidant activity, antibacterial activity, and biocompatibility of these chitosan oligosaccharide derivatives can enlarge the scope of the application of chitosan oligosaccharides, particularly as antioxidant and antibacterial agents in food packaging, pharmaceutical, cosmetics industries, and other fields. [ABSTRACT FROM AUTHOR]

Since there are many SNPs in this region in humans, we will not be surprised that those SNPs with more sizeable side chains might also disrupt the enzyme activity and be implicated in metabolic disorders and abnormal drug metabolism, and therefore, should be considered for precision medicine. Dear Editor, Cytochrome P450s (CYPs) are a superfamily of heme-containing enzymes that play critical roles in oxidizing endogenous metabolites and xenobiotics.[1] They are membrane-anchored enzymes, and the transmembrane domains are involved in the electron transfer and the access of substrate and water during the catalytic cycle.[[2], [4]] Mutations of human CYPs cause metabolic disorders and abnormal drug metabolism.[5] Because their amino acid sequences are remarkably diverse, the existing work on different human CYPs is seemingly unrelated. (A-C) The enzyme activities of the wild-type (WT) and mutants of CYP21A2 (A), CYP7A1 (B), and CYP2A6 (C) were revealed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Metabolic profiling showed that the conversion of Gly to Ala in both positions of the I-helix kink (G292A and G293A) reduced CYP21A2 activity to about 60% of the WT activity, whereas substituents with more sizeable side chains more profoundly inhibited the enzyme function. [Extracted from the article]

Low energy electron beam (E‐Beam) curing process has been considered a promising fabrication technology in high‐efficiency and low‐cost OOA curing, but still not been widely used in industrial applications, mainly limited by the poor mechanical properties of the CFRP resulting from the poor toughness of the low‐energy E‐Beam curable resin. This paper extended the excellent effect of carbon nanotubes (CNTs) toughened resin to the E‐Beam curable resin system, and focused on the influence law and mechanism of CNTs on the curing characteristics of the resin. Theoretical analysis showed that the carboxylated CNTs affect the curing characteristics by participating in the chain transfer link of the cationic curing process. According to the DSC experimental results, the activation energy of the curing reaction of the resin were reduced from 136.2 kJ·mol−1 without adding CNTs to 123.9 kJ·mol−1, 118.3 kJ·mol−1, 112.8 kJ·mol−1 and 105.8 kJ·mol−1 at 0.25 wt.%, 0.5 wt.%, 0.75 wt.% and 1 wt.% of CNTs adding amount respectively, due to which the curing degree of the E‐Beam curable CFRPs were improved with the increase of CNTs contents. Considering the E‐Beam dose attenuation and its influence on curing characteristics, prepregs were irradiated single‐sided or both sided for efficient preparation of E‐Beam cured CFRP components subsequently, for which the curing degree along the prepreg thickness were investigated through the curing reaction kinetic models and DSC experiments. This study will provide research basis for parameter optimization of CNTs contents, and performance improvement of E‐Beam cured CNTs/CFRP. [ABSTRACT FROM AUTHOR]

Aim: To determine the associated factors of professional identity among intensive care unit (ICU) nurses during the COVID‐19 pandemic in China. Design: Multicentre cross‐sectional study. Methods: This study invited 348 ICU nurses in five hospitals in China from May to July 2020. Online self‐report questionnaires were adopted to collect their demographic and occupational characteristics, perceived professional benefits and professional identity. Based on univariate and multiple linear regression analysis, a path analysis was performed to determine the associated factors' effects on professional identity. Results: The mean score of professional identity was 102.38 ± 16.46. Perceived professional benefits, doctor recognition level and family support level were associated with ICU nurses' professional identity. The path analysis revealed that perceived professional benefits and doctor recognition level had direct effects on professional identity. In addition, doctor recognition level and family support level had indirect effects on professional identity through the mediation of perceived professional benefits. [ABSTRACT FROM AUTHOR]

Aim: Climate and land use changes are two major pervasive and growing global causes of rapid changes in the distribution patterns of biodiversity, challenging the future effectiveness of protected areas (PAs), which were mainly designed based on a static view of biodiversity. Therefore, evaluating the effectiveness of protected areas for protecting the species threatened by climate and land use change is critical for future biodiversity conservation. Location: China. Methods: Here, using distributions of 200 Chinese Theaceae species and ensemble species distribution models, we identified species threatened by future climate and land use change (i.e. species with predicted loss of suitable habitat ≥30%) under scenarios incorporating climate change, land use change and dispersal. We then estimate the richness distribution patterns of threatened species and identify priority conservation areas and conservation gaps of the current PA network. Results: Our results suggest that 36.30%–51.85% of Theaceae species will be threatened by future climate and land use conditions and that although the threatened species are mainly distributed at low latitudes in China under both current and future periods, the mean richness of the threatened species per grid cell will decline by 0.826–3.188 species by the 2070s. Moreover, we found that these priority conservation areas are highly fragmented and that the current PA network only covers 14.21%–20.87% of the 'areas worth exploring' and 6.91%–7.91% of the 'areas worth attention'. Main Conclusions: Our findings highlight the necessity of establishing new protected areas and ecological corridors in priority conservation areas to protect the threatened species. Moreover, our findings also highlight the importance of taking into consideration the potential threatened species under future climate and land use conditions when designating priority areas for biodiversity conservation. [ABSTRACT FROM AUTHOR]

Background: As one of the modal antibiotics in life, the abuse of tetracycline (TC) caused great risks to the ecological environment and health. Cost‐effective removal method of TC in the medical wastewater was a developmental research direction with great potential. Results: In this work, a novel material, modified kaolin/β‐cyclodextrin (β‐CD) coated A (A is a special oxidant made from our laboratory, which is mainly composed of potassium ferrate) was synthesized and characterized. Meanwhile, the removal efficiencies and influencing factors of TC in novel material activation reaction systems were systematically studied. The specific surface area of modified kaolin (MMK) can reach up to 431.82 m2/g after acid and calcination modification. The results of SEM, TEM, XRD, and FT‐IR showed the significant increase in specific surface area of MMK was the complete destruction of kaolin structure and the leaching of aluminum. β‐CD was selected to coat A to attenuate the rapid release of A in water. The optimal coat molar ratio of β‐CD and A was 10: 1 (β‐CD:A). MMK/β‐CD‐A was used to treat the simulated TC wastewater, the removal efficiency was 95.6 % within 90 min when the concentration of TC was 0.22 mmol/L. The removal mechanism of TC with MMK/β‐CD‐A was the adsorption effect from MMK and the oxidation effect from β‐CD‐A. Conclusion: This work could provide useful information for developing a simple and effective technology to treat TC in medical wastewater. © 2023 Society of Chemical Industry (SCI). [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) is an autosomal recessive and often fatal neurological disease. However, very little is known about the attitudes toward SMA carrier screening among Chinese pregnant people. In this study, pregnant women in Eastern China who were undergoing routine chromosomal screening programs were invited to view an educational video about SMA and complete a 26‐item survey regarding their attitudes toward SMA screening by scanning a specific quick response code. A total of 1673 questionnaires were collected, and 81.1% of respondents were willing to undergo self‐funded screening. If the screening program were included in the medical insurance, 97.8% of respondents were willing to accept screening. The important reasons for supporting SMA screening were a belief that it could help them make better reproductive decisions and avoid having a child with SMA. The key reason for declining SMA screening was not having a family history of genetic diseases. A higher score for SMA genetics knowledge was associated with a greater willingness to undergo SMA screening. We concluded that pregnant women in Eastern China had positive attitudes toward SMA carrier screening. Improving genetic knowledge and including the screening program in medical insurance would support the widespread implementation of SMA carrier screening. Steps should be taken to offer SMA carrier screening along with pre‐ and posttest education and genetic counseling to raise awareness and reduce misconceptions regarding SMA. [ABSTRACT FROM AUTHOR]

The ion channels in sperm tail play an important role in triggering key physiological reactions, e.g., progressive motility, hyperactivation, required for successful fertilization. Among them, CatSper and KSper have been shown to be important ion channels for the transport of Ca2+ and K+. Moreover, the voltage‐gated proton channel Hv1, the sperm‐specific sodium‐hydrogen exchanger (sNHE), the epithelial sodium channel (ENaC), members of the temperature‐sensitive TRP channel family, and the cystic fibrosis transmembrane regulator (CFTR) are also found in the flagellum. This review focuses on the latest advances in ion channels located at the flagellum, describes how they affect sperm physiological function, and summarizes some primary mutual regulation mechanism between ion channels, including PH, membrane potential, and cAMP. These ion channels may be promising targets for clinical application in infertility. [ABSTRACT FROM AUTHOR]

We aimed to develop a new biocompatible gastrin‐releasing peptide receptor (GRPR) targeted optical probe, IRDye800‐RM26, for fluorescence image‐guided surgery (FGS) of brain malignancies in near‐infrared window II (NIR‐II) imaging. We developed a novel GRPR targeting probe using a nine‐amino‐acid bombesin antagonist analog RM26 combined with IRDye800CW, and explored the fluorescent probe according to optical properties. Fluorescence imaging characterization in NIR‐I/II region was performed in vitro and in vivo. Following simulated NIR‐II image‐guided surgery, we obtained time‐fluorescent intensity curves and time‐signal and background ratio curves. Further, we used histological sections of brain from tumor‐beating mice model to compare imaging specificity between 5‐aminolevulinic acid (5‐ALA) and IRDye800‐RM26, and evaluated biodistribution and biocompatibility. IRDye800‐RM26 had broad emission ranging from 800 to 1200 nm, showing considerable fluorescent intensity in NIR‐II region. High‐resolution NIR‐II imaging of IRDye800‐RM26 can enhance the advantages of NIR‐I imaging. Dynamic and real time fluorescence imaging in NIR‐II region showed that the probe can be used to treat brain malignancies in mice between 12 and 24 h post injection. Its specificity in targeting glioblastoma was superior to 5‐ALA. Biodistribution analysis indicated IRDye800‐RM26 excretion in the kidney and liver. Histological and blood test analyses did not reveal acute severe toxicities in mice treated with effective dose (40 μg) of the probe for NIR‐II imaging. Because of the considerable fluorescent intensity in NIR‐II region and high spatial resolution, biocompatible and excretable IRDye800‐RM26 holds great potentials for FGS, and is essential for translation into human use. [ABSTRACT FROM AUTHOR]

Ranunculus japonicus Thunb. is a traditional Chinese herb. Plants in the genus Ranunculus are generally rich in flavonoids, which have antibacterial, anti‐infective, and other pharmacological effects. However, owing to the lack of reference genomes, little is known about the flavonoid biosynthetic pathway in R. japonicus. In this study, PacBio isoform sequencing (PacBio iso‐seq) and DNA nanoball sequencing (DNB‐seq) were combined to build a full‐length transcriptome database for three different tissues of R. japonicus. A total of 395,402 full‐length transcripts were obtained, of which 308,474 were successfully annotated. A Kyoto Encyclopedia of Genes and Genomes analysis identified 29 differentially expressed genes encoding nine key enzymes for flavonoid biosynthesis. Correlation analysis indicated that flavanone 3‐hydroxylase and flavonol synthase genes might have key roles in the accumulation of flavonoid substances in the different tissues of R. japonicus. The structures of chalcone synthase and chalcone isomerase enzymes were spatially modeled. Reverse‐transcription quantitative PCR was used to verify gene expression levels of key enzymes associated with flavonoid biosynthesis. In addition, 22 MYB transcription factors involved in flavonoid biosynthesis and phenylpropanoid biosynthesis were discovered. The reliable transcriptomic data from this study provide genetic information about R. japonicus as well as insights into the molecular mechanism of flavonoid biosynthesis. The results also provide a basis for developing the medicinal value R. japonicus. [ABSTRACT FROM AUTHOR]

The migration and selective localization of graphene nanoplatelets (GNPs) in a polypropylene/high melt strength polypropylene (PP/HMSPP) blend under elongational and shear forces are studied. The effects of elongational flow upon the elongational rheology, X‐ray diffraction patterns, thermal properties, and mechanical properties are investigated. The results show that the elongational viscosity and melt strength of HMSPP are higher than those of PP under elongational flow, whereby HMSPP shows elongational strain hardening behavior, and the migrating of GNPs from the PP to the HMSPP phase is hindered. As a result, the GNPs are constrained to remain at the interface between the two phases. In addition, the elongational force can exfoliate GNPs more effectively, and the orientation of GNPs along the phase interface will reduce the migration rate of GNPs at the interface, while precisely controlling the location of the GNPs at the phase interface. Thus, more thermal conductivity pathways are constructed and, hence, the thermal conductivity of the PP/HMSPP/GNPs composite prepared under elongational flow is higher than that prepared under shear flow. The present work provides a new method for the preparation of highly thermally conductive polymer composites. [ABSTRACT FROM AUTHOR]

Aim: Multiple sclerosis (MS) is an autoimmune disease, and its typical characteristics are neuroinflammation and the demyelination of neurons in the central nervous system (CNS). Sterile alpha and TIR motif containing 1 (SARM1) is an essential factor mediating axonal degeneration and SARM1 deletion reduces the neuroinflammation in spinal cord injury. This study aimed to explore the roles of SARM1 and its underlying mechanisms in MS. Methods: Experimental autoimmune encephalomyelitis (EAE, a model of MS) model was established. Immunostaining, western blot, electron microscope, and HE staining were used to examine the pathological manifestations such as inflammation, demyelination, and neuronal death in SARM1f/f EAE mice and SARM1Nestin‐CKO EAE mice. In addition, RNA‐seq, real‐time PCR and double‐immunostaining were used to examine the underlying mechanism of SARM1 in EAE mice. Results: SARM1 was upregulated in neurons of the spinal cords of EAE mice. SARM1 knockout in CNS ameliorated EAE with less neuroinflammation, demyelination, and dead neurons. Mechanically, SARM1 knockout resulted in the reduction of insulin‐like growth factor (IGF)‐binding protein 2 (IGFBP2) in neurons of EAE mice, which might inhibit the neuroinflammation through inhibiting NF‐κB signaling. Finally, activation of NF‐κB partially aggravated the neuroinflammation and demyelination deficits of SARM1Nestin‐CKO EAE mice. Conclusions: These results identified the unknown role of SARM1 in the promotion of neuroinflammation and demyelination and revealed a novel drug target pathway of SARM1/IGFBP2/NF‐κB for MS. [ABSTRACT FROM AUTHOR]

Mitofusin‐2 (MFN2) is a transmembrane GTPase that regulates mitochondrial fusion and thereby modulates mitochondrial function. However, the role of MFN2 in lung adenocarcinoma remains controversial. Here, we investigated the effect of MFN2 regulation on mitochondria in lung adenocarcinoma. We found that MFN2 deficiency resulted in decreased UCP4 expression and mitochondrial dysfunction in A549 and H1975 cells. UCP4 overexpression restored ATP and intracellular calcium concentration, but not mtDNA copy number, mitochondrial membrane potential or reactive oxygen species level. Furthermore, mass spectrometry analysis identified 460 overlapping proteins after independent overexpression of MFN2 and UCP4; these proteins were significantly enriched in the cytoskeleton, energy production, and calponin homology (CH) domains. Moreover, the calcium signaling pathway was confirmed to be enriched in KEGG pathway analysis. We also found by protein–protein interaction network analysis that PINK1 may be a key regulator of MFN2‐ and UCP4‐mediated calcium homeostasis. Furthermore, PINK1 increased MFN2/UCP4‐mediated intracellular Ca2+ concentration in A549 and H1975 cells. Finally, we demonstrated that low expression levels of MFN2 and UCP4 in lung adenocarcinoma are associated with poor clinical prognosis. In conclusion, our data suggest not only a potential role of MFN2 and UCP4 in co‐regulating calcium homeostasis in lung adenocarcinoma but also their potential use as therapeutic targets in lung cancer. [ABSTRACT FROM AUTHOR]