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Radar reflectivity data is crucial to improve initial field of numerical model. However, the method of Ensemble Kalman Filtering (EnKF) can not directly assimilate radar reflectivity data. We explore a method of modifying the initial thermodynamic field of numerical model by using radar reflectivity data. Two experiments are carried out to reveal the forecast improvement of a squall line occurred in the Eastern China by assimilating reflectivity data. One experiment is assimilating some observational data without radar reflectivity data using EnKF method (hereafter called No-Ref experiment), and the other is modifying the initial thermodynamic field using radar reflectivity data after conducting EnKF experiment (called Ref experiment). Compared with the simulation results of No-Ref experiment, the forecast is improved in Ref experiment. The results show that thermodynamic field adjustment leads to the adjustment of the dynamic field, and plays an important role in the improvement of squall line forecast. [ABSTRACT FROM AUTHOR]

Plant roots employ diverse strategies to acquire soil nutrients, including direct nutrient uptake through absorptive fine roots and root hairs, scavenging nutrients by forming symbioses with mycorrhizal fungi, and mining nutrients by releasing root exudates. However, whether these three strategies are differently coordinated among phylogenetically closely related tree species and how this coordination shifts with stand development remains largely unclear.To fill these knowledge gaps, we measured 13 root morphological, architectural, physiological and mycorrhizal traits tightly related to nutrient‐acquisition of three Pinus species (P. sylvestris var. mongolica, P. densiflora and P. tabuliformis) at young (20‐year‐old) and mature (50‐year‐old) stages planted in nutrient‐impoverished sandy soils, in Northeast China.We found that young trees had thinner absorptive fine roots and a higher specific root length than mature trees across three Pinus species, indicating that roots become morphologically less efficient in 'do it yourself' scavenging nutrients during stand development. Moreover, young stands had greater root length density and root area index, and mature stands had faster root‐exudation rates, suggesting that young stands rely more on expanding soil volumes to scavenge nutrients and mature stands depend more on root exudation to 'mine' nutrients. The three Pinus species exhibited different nutrient‐acquisition strategies at the mature stage; P. densiflora had higher root length density and root area index, and the other two Pinus species had greater ectomycorrhizal colonization rates.Synthesis. Our findings highlight that phylogenetically closely related tree species may exhibit different nutrient‐acquisition strategies and suggest a shift from an extensive nutrient‐acquisition mode depending more on absorptive fine roots to an intensive nutrient‐acquisition mode relying more on root exudation during stand development. [ABSTRACT FROM AUTHOR]

Ischemic stroke is associated with a high mortality rate, and effective treatment strategies are currently lacking. In this study, we aimed to develop a novel nano delivery system to treat ischemic stroke via intranasal administration. A three-factor Box–Behnken experimental design was used to optimize the formulation of liposomes co-loaded with Panax notoginseng saponins (PNSs) and Ginsenoside Rg3 (Rg3) (Lip-Rg3/PNS). Macrophage membranes were coated onto the surface of the optimized liposomes to target the ischemic site of the brain. The double-loaded liposomes disguised by macrophage membranes (MM-Lip-Rg3/PNS) were spherical, in a "shell–core" structure, with encapsulation rates of 81.41% (PNS) and 93.81% (Rg3), and showed good stability. In vitro, MM-Lip-Rg3/PNS was taken up by brain endothelial cells via the clathrin-dependent endocytosis and micropinocytosis pathways. Network pharmacology experiments predicted that MM-Lip-Rg3/PNS could regulate multiple signaling pathways and treat ischemic stroke by reducing apoptosis and inflammatory responses. After 14 days of treatment with MM-Lip-Rg3/PNS, the survival rate, weight, and neurological score of middle cerebral artery occlusion (MCAO) rats significantly improved. The hematoxylin and eosin (H&E) and TUNEL staining results showed that MM-Lip-Rg3/PNS can reduce neuronal apoptosis and inflammatory cell infiltration and protect the ischemic brain. In vivo biological experiments have shown that free Rg3, PNS, and MM-Lip-Rg3/PNS can alleviate inflammation and apoptosis, especially MM-Lip-Rg3/PNS, indicating that biomimetic liposomes can improve the therapeutic effects of drugs. Overall, MM-Lip-Rg3/PNS is a potential biomimetic nano targeted formulation for ischemic stroke therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Bladder cancer (BC) is a common malignant tumor of the urinary system. Despite extensive advances in the treatment of BC, it remains one of the most recurring and life-threatening tumors. At present, there have been increasing reports of studies on the presence of aberrant regulation of RBPs in BC. However, the complex regulatory network of these RBPs in BC remains to be fully elaborated. RBPs have a very high potential in tumor prediction and personalized therapy. Moreover, only with a deep understanding of their regulatory mechanisms, expression characteristics, and potential binding sites, among other issues, will it become possible to apply RBPs to clinical applications. This article aims to summarize the research progress of RBPs in BC. It also attempts to encourage clinicians and researchers to devote attention this field of study and provides a reference for researchers who aspire to pursue a career in this area. RNA-binding proteins (RBPs) are key regulators of transcription and translation, with highly dynamic spatio-temporal regulation. They are usually involved in the regulation of RNA splicing, polyadenylation, and mRNA stability and mediate processes such as mRNA localization and translation, thereby affecting the RNA life cycle and causing the production of abnormal protein phenotypes that lead to tumorigenesis and development. Accumulating evidence supports that RBPs play critical roles in vital life processes, such as bladder cancer initiation, progression, metastasis, and drug resistance. Uncovering the regulatory mechanisms of RBPs in bladder cancer is aimed at addressing the occurrence and progression of bladder cancer and finding new therapies for cancer treatment. This article reviews the effects and mechanisms of several RBPs on bladder cancer and summarizes the different types of RBPs involved in the progression of bladder cancer and the potential molecular mechanisms by which they are regulated, with a view to providing information for basic and clinical researchers. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is an important signaling molecule involved in mediation of salt stress induced physiological responses in plants. In this study, we investigated the effect of NO on Nitraria tangutorum seedlings exposed to salt stress. Exogenous application of NO donor, sodium nitroprusside (SNP) increased fresh weight, shoot and root elongation and decreased electrolyte leakage and malondialdehyde (MDA) content in N. tangutorum seedlings under salt stress. Simultaneously, leaf senescence and root damage induced by salt stress were alleviated. SNP effectively increased NO content both in leaves and roots of plants under salt stress. Meanwhile, SNP activated the ascorbate-glutathione (AsA-GSH) cycle by increasing antioxidants contents, antioxidant enzymes activities, and related genes expression, thereby scavenging reactive oxygen species (ROS) and alleviating oxidative damage caused by salt stress. SNP alleviated salt stress induced ion toxicity by promoting Na+ efflux and ion transporter gene expression and reducing Na+ content and the Na+/K+ ratio. In addition, application of NO specific scavenger cPTIO and mammalian NO synthase inhibitor L -NAME sifnificantly aggravated stress damage in plant under salt stress. These results show the beneficial impacts of NO as a stress-signaling molecule that positively regulates defense response in N. tangutorum to salt stress. • Sodium nitroprusside (SNP) application reduces salt-induced growth inhibition and stress damage in N. tangutorum seedlings. • SNP increases nitric oxide (NO) content both in shoots and roots. • NO alleviates salinity-induced H 2 O 2 and O 2 − generation by activating ascorbate-glutathione cycle. • NO maintains cytoplasmic Na+/K+ homeostasis by regulating ion efflux and ion transporter expression. • NO-induced changes in ROS and Na+/K+ homeostasis are positively correlated with N. tangutorum salt tolerance. [ABSTRACT FROM AUTHOR]

The effects of long non-coding RNAs (lncRNAs) on the proliferation of hypertrophic scars have been described, however, the underlying mechanisms are not well characterized. The present study aimed to investigate the mechanisms of lncRNA H19 in hypertrophic scars. The effects of the lncRNA H19 on the proliferation and apoptosis of hypertrophic scar fibroblasts (HSFs) were analyzed using 5′-ethynyl-2′-deoxyuridine staining, flow cytometry, and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT). The results revealed H19 promoted the proliferation and inhibited the apoptosis in HSF. In addition, the binding associations between H19 and microRNA-194 (miR-194), and miR-194 and insulin-like growth factor I receptor (IGF1R) were identified using bioinformatics screening and verified using dual-luciferase assays. Furthermore, the effects of the IGF1R knockdown on H19-induced HSF phenotypes and regulation over the p38 MAPK pathway were determined. Mechanistically, miR-194 was identified as the downstream effector of the H19-mediated phenotypes of HSFs through its ability to directly target IGF1R, thus modulating the p38 MAPK signaling pathway. In conclusion, the findings suggested that H19 may inhibit the apoptosis and promote the proliferation of HSFs through the miR-194/IGF1R/p38 MAPK signaling axis, thereby contributing to the progression of hypertrophic scars. These findings may provide novel targets for the treatment of hypertrophic scars. [ABSTRACT FROM AUTHOR]

[Display omitted] • TCS exposure induced ADHD-like behaviour in offspring rats. • TCS exposure activated microglia and induced them to release inflammatory cytokines. • TCS mediated the secretion of inflammatory cytokines via the hnRNPA1-PKM2-STAT3 feedback loop. Triclosan (TCS) is an environmental pollutant. In recent years, there has been increasing level of concern regarding the potential toxicity of TCS in animals and humans, especially its effects on the nervous system. However, whether TCS induces ADHD-like behaviour and the mechanism by which it affects neural function are unclear. The impact of 60 days of continuous exposure to TCS on the behaviour of offspring rats was assessed in this research. According to the results of this study, TCS exposure led to ADHD-like behaviour in offspring rats and activated microglia in the prefrontal cortex (PFC), inducing inflammatory factor release. In vitro studies showed that TCS increased the levels of inflammatory cytokines, including interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α, in HMC3 cells. More importantly, we found that TCS regulated the STAT3 pathway by upregulating PKM2 via hnRNPA1. In summary, this study suggested that TCS can induce ADHD-like behaviour in offspring rats and continuously activate HMC3 microglia through the hnRNPA1-PKM2-STAT3 feedback loop, promoting inflammatory cytokine secretion. [ABSTRACT FROM AUTHOR]

Background: Interferon regulatory factor 2 (IRF2) is an important transcription factor, which can regulate the IFN response and plays a role in antiviral innate immunity in teleost. Results: In the present study, the full-length cDNA sequence of IRF2 (CcIRF2) was characterized in common carp (Cyprinus carpio L.), which encoded a protein containing a conserved DNA-binding domain (DBD) and an IRF-associated domain (IAD). Phylogenetic analysis showed that CcIRF2 was most closely related with IRF2 of Ctenopharyngodon idella. CcIRF2 transcripts were detectable in all examined tissues, with higher expression in the gills, spleen and brain. CcIRF2 expression was upregulated in immune-related tissues of common carp upon polyinosinic:polycytidylic acid (poly (I:C)) and Aeromonas hydrophila stimulation and induced by poly (I:C), lipopolysaccharide (LPS), peptidoglycan (PGN) and flagellin in the peripheral blood leucocytes (PBLs) and head kidney leukocytes (HKLs). In addition, overexpression of CcIRF2 decreased the expression of IFN and IFN-stimulated genes (ISGs), and a dual-luciferase reporter assay revealed that CcIRF2 could increase the activation of NF-κB. Conclusions: These results indicate that CcIRF2 participates in antiviral and antibacterial immune response and negatively regulates the IFN response, which provide a new insight into the regulation of IFN system in common carp, and are helpful for the prevention and control of infectious diseases in carp farming. [ABSTRACT FROM AUTHOR]

Reaumuria trigyna, a Tamaricaceae archaic recretohalophyte, is an important feral forage plant in the desert steppe of northwestern China. We identified two significantly differentially expressed leucoanthocyanidin dioxygenase genes (RtLDOX/RtLDOX2) and investigated the function and characteristics of RtLDOX2. RtLDOX2 from R. trigyna was rapidly upregulated by salt, drought, and abscisic acid, consistent with the stress-related cis-regulatory elements in the promoter region. Recombinant RtLDOX2 converted dihydrokaempferol to kaempferol in vitro, and was thus interchangeable with flavonol synthase, a dioxygenase in the flavonoid pathway. Transgenic plants overexpressing RtLDOX2 accumulated more anthocyanin and flavonols under abiotic stresses, speculating that RtLDOX2 may act as a multifunctional dioxygenase in the synthesis of anthocyanins and flavonols. Overexpression of RtLDOX2 enhanced the primary root length, biomass accumulation, and chlorophyll content of salt-, drought-, and ultraviolet-B-stressed transgenic Arabidopsis. Antioxidant enzyme activity; proline content; and expression of antioxidant enzyme, proline biosynthesis, and ion-transporter genes were increased in transgenic plants. Therefore, RtLDOX2 confers tolerance to abiotic stress on transgenic Arabidopsis by promoting the accumulation of anthocyanins and flavonols. This in turn increases reactive oxygen species scavenging and activates other stress responses, such as osmotic adjustment and ion transport, and so improves tolerance to abiotic stresses. [ABSTRACT FROM AUTHOR]

[Display omitted] • 3D compressible nanofiber aerogels composed of PANI-NFs and CNFs were prepared. • PCNFA adsorbent showed superior removal performance on ionic organic pollutants. • Synergistic regeneration of PCNFA and oxidation of dyes was achieved by PDS process. To deal with the challenge in separating nanostructured adsorbents from wastewater and avoid producing highly concentrated wastewater, we developed three-dimensional polyaniline/cellulose nanofiber aerogel (PCNFA) for the applications in organic dye pollutants removal. This new adsorbent was fabricated by a two-step method using the in-situ crosslinking and acid-induced polymerization processes. Owing to the in-situ supramolecular combination of polyaniline nanofibers (PANI-NFs) and carbonylated cellulose nanofibers (CNFs), PCNFAs exhibited the highest compressive stress of 48.2 kPa at a compressive strain of 50% and superior adsorption performance, with the maximum Langmuir adsorption capacity for Acid Red G (ARG, anionic dye) and Methyl Blue (MB, cationic dye) reached around 600.7 and 1369.6 mg g−1, respectively. Moreover, peroxydisulfate (PDS) process was adopted here for the first time to realize the synergistic regeneration of the PCNFA adsorbent and the degradation of dyes by activating PDS on PANI. The adsorption capacity of PCNFA for ARG and MB remained respectively above 84% and 70% after three regeneration cycles in the PDS process and the corresponding COD removal rate achieved around 26% and 60%, respectively. Finally, we explored adsorption and regeneration mechanism showing that the electrostatic and π-π stacking interactions were the driving forces for adsorption, and nonradical reactions may be the main contribution to the oxidation of contaminants and regeneration of PCNFA. The results demonstrated that the fabricated aerogel can be used as an adsorbent for the practical treatment of dyes-containing wastewater and the PDS process provides a promising and viable approach for the regeneration of PANI-based adsorbents. [ABSTRACT FROM AUTHOR]

Reaumuria trigyna , an endangered recretohalophyte, is a small archaic wild shrub endemic to arid and semiarid plateau regions of Inner Mongolia, China. Based on salt-related transcriptomic data, we isolated a GRX family gene, glutaredoxin like protein (RtGRL1), from R. trigyna that is associated with the removal of active oxygen and regulation of redox status. RtGRL1 encodes a plasma membrane and chloroplast-localized protein induced by salt, cold, drought stress, ABA, and H 2 O 2. In Arabidopsis thaliana , ectopically expressed RtGRL1 positively regulated biomass accumulation, chlorophyll content, germination rate, and primary root length under salt and drought stress. Overexpression of RtGRL1 induced expression of genes related to antioxidant enzymes and proline biosynthesis, thus increasing glutathione biosynthesis, glutathione-dependent detoxification of reactive oxygen species (ROS), and proline content under stress. Changes in RtGRL1 expression consistently affected glutathione/oxidizedglutathione and ascorbate/dehydroascorbate ratios and H 2 O 2 concentrations. Furthermore, RtGRL1 promoted several GSH biosynthesis gene transcripts, decreased leaf Na+ content, and maintained lower Na+/K+ ratios in transgenic A. thaliana compared to wild type plants. These results suggest a critical link between RtGRL1 and ROS modulation, and contribute to a better understanding of the mechanisms governing plant responses to drought and salt stress. • Overexpression of RtGRL1 induced expression of genes related increasing glutathione biosynthesis and proline content under abiotic stress. • RtGRL1 improved plant ability of glutathione-dependent detoxification of reactive oxygen species (H 2 O 2). • RtGRL1 maintained glutathione pool balance and decreased leaf Na+ content, and increased water retention capacity. [ABSTRACT FROM AUTHOR]

To investigate the effect of low-intensity pulsed ultrasound (LIPUS) on the proliferation of human adipose-derived mesenchymal stromal cells (hASCs) and uncovered its stimulation mechanism. LIPUS at 30 mW/cm2 was applied for 5 min/day to promote the proliferation of hASCs. Flow cytometry was used to study the cell surface markers, cell cycle, and apoptosis of hASCs. The proliferation of hASCs was detected by cell counting kit-8, cell cycle assay, and RT-PCR. The expression of hASCs cytokines was determined by ELISA. The differences between transcriptional genes and metabolites were analyzed by transcript analysis and metabolomic profiling experiments. The number of cells increased after LIPUS stimulation, but there was no significant difference in cell surface markers. The results of flow cytometry, RT-PCR, and ELISA after LIPUS was administered showed that the G1 and S phases of the cell cycle were prolonged. The expression of cell proliferation related genes (CyclinD1 and c-myc) and the paracrine function related gene (SDF-1α) were up-regulated. The expression of cytokines was increased, while the apoptosis rate was decreased. The results of transcriptome experiments showed that there were significant differences in 27 genes;15 genes were up-regulated, while 12 genes were down-regulated. The results of metabolomics experiments showed significant differences in 30 metabolites; 7 metabolites were up-regulated, and 23 metabolites were down-regulated. LIPUS at 30 mW/cm2 intensity can promote the proliferation of hASCs cells in an undifferentiating state, and the stem-cell property of hASCs was maintained. CyclinD1 gene, c-myc gene, and various genes of transcription and products of metabolism play an essential role in cell proliferation. This study provides an important experimental and theoretical basis for the clinical application of LIPUS in promoting the proliferation of hASCs cells. [ABSTRACT FROM AUTHOR]

This study investigated the influences of lanthanum (La) exposure on learning and memory and the expression of apoptosis-related proteins in offspring rats. Wistar female rats were randomly divided into a control group (NC) and 0.25%, 0.5% and 1.0% LaCl3 treatment groups, with eight per group. La dye was transmitted to offspring rats through parental blood circulation and breast milk before delactation and through water drinking after delectation. Offspring rats were killed at 14, 28 and 42 days after birth. Hippocampal neurons were observed by microscope, and apoptosis and necrosis were tested. The expression levels of apoptosis-related proteins were detected by Western blot, and Morris water maze experiments were used to measure learning and memory abilities. LaCl3 groups showed longer escape latency periods and swimming distances than the NC group (p < 0.05). The 1.0% LaCl3 group passed across the target quadrants and platforms more times and stayed in the target quadrants for less time, than the NC group (p < 0.05). At 42 days, the apoptosis rate and necrosis in the hippocampus of the 1.0% LaCl3 group were significantly higher than those of other groups. There was a significant difference among LaCl3 groups in terms of protein expressions measured in the hippocampus. In LaCl3 groups, caspase-3 and caspase-9 were significantly higher than in the NC group (p < 0.05). Therefore, La exposure can promote neuronal apoptosis by regulating the protein expressions of Akt, Bcl-2, Bcl-xl, Bax, Bad, caspase-3 and caspase-9, thus damaging learning and memory and the hippocampal neurons of offspring rats. [ABSTRACT FROM AUTHOR]

Nanozymes, or nanomaterials that mimic the behaviors of enzymes, are highly promising materials for biomedical applications because of their excellent chemical stability under harsh conditions, simple preparation method and lower costs compared with natural enzymes. We herein report the intrinsic oxidase-mimicking activity of molybdenum oxide nanoparticles (MoO 3 NPs). MoO 3 NPs catalyzed the oxidation of colorless 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) to green product. The catalytic mechanism of the oxidase-mimicking activity of the MoO 3 NPs was investigated in detail using electron spin resonance and a radical inhibition method. The oxidation of ABTS stems from 1O 2 generated from the interaction between MoO 3 NPs and dissolved oxygen in the solution. Acid phosphatase (ACP) catalyzes the hydrolysis of the ascorbic acid 2-phosphate (AAP) substrate to produce ascorbic acid (AA). AA was found to fade the coloration process of the MoO 3 NP-mediated ABTS oxidation. By combining the oxidase-mimicking property of the MoO 3 NPs and the ACP-catalyzed hydrolysis of AAP, a novel and simple colorimetric method for detecting ACP was established. The linear range for ACP determination is 0.09–7.3 U/L with a detection limit of 0.011 U/L. This new colorimetric method was successfully applied to the detection of ACP in diluted human serum samples and screening of ACP inhibitors. The present study proposes MoO 3 NPs as a new oxidase mimic for establishing various biosensing method. Ascorbic acid (AA), the product of the ACP-AA 2-phosphate (AAP) system, interferes with the oxidation of ABTS and inhibits the oxidase-mimicking property of MoO 3 NPs, based on which a colorimetric ACP detection method has been established. Image 1 • Colorimetric sensor for acid phosphatase detection. • Oxidase-mimicking activity of molybdenum oxide nanoparticles. • Acid phosphatase catalyzes the hydrolysis of the ascorbic acid 2-phosphate. • Ascorbic acid inhibits the catalytic activity of molybdenum oxide nanoparticles. [ABSTRACT FROM AUTHOR]

Reaumuria trigyna (Reaumuria Linn genus, family Tamaricaceae), an endangered dicotyledonous shrub with the features of a recretohalophyte, is endemic to the Eastern Alxa–Western Ordos area of China. Based on R. trigyna transcriptome data and expression pattern analysis of RtWRKYs , RtWRKY23 , a Group II WRKY transcription factor, was isolated from R. trigyna cDNA. RtWRKY23 was mainly expressed in the stem and was induced by salt, drought, cold, ultraviolet radiation, and ABA treatments, but suppressed by heat treatment. Overexpression of RtWRKY23 in Arabidopsis increased chlorophyll content, root length, and fresh weight of the transgenic lines under salt stress. Real-time quantitative PCR (qPCR) analysis and yeast one-hybrid analysis demonstrated that RtWRKY23 protein directly or indirectly modulated the expression levels of downstream genes, including stress-related genes AtPOD , AtPOD22 , AtPOD23 , AtP5CS1 , AtP5CS2 , and AtPRODH2 , and reproductive development-related genes AtMAF5 , AtHAT1 , and AtANT. RtWRKY23 transgenic Arabidopsis had higher proline content, peroxidase activity, and superoxide anion clearance rate, and lower H 2 O 2 and malondialdehyde content than WT plants under salt stress conditions. Moreover, RtWRKY23 transgenic Arabidopsis exhibited later flowering and shorter pods, but little change in seed yield, compared with WT plants under salt stress. Our study demonstrated that RtWRKY23 not only enhanced salt stress tolerance through maintaining the ROS and osmotic balances in plants, but also participated in the regulation of flowering under salt stress. [ABSTRACT FROM AUTHOR]

Post-harvest browning, decay, lignification, and other adverse physiological effects limit the shelf-life of mung bean sprouts at ambient temperature. In this study, vacuum packing at pressures of 0, ↓0.02, ↓0.04, and ↓0.06 mPa at 20 °C, and the optimum pressure of ↓0.04 mPa at 4 °C for maintenance of sprouts, was investigated. Chlorogenic acid was identified as the main phenolic compound leading to the browning of mung bean sprouts, along with total flavonoids, total phenols, rutin, and o -phthalic acid. Among these, flavonoids were identified as being the main substrate for polyphenol oxidase (PPO) activity. Moderate vacuum packing combined with low temperature storage inhibited PPO, as well as peroxidase (POD) and superoxide dismutase activities, which was associated with a slower rate of browning. In addition, these storage conditions reduced the activity of phenylalanine ammonia lyase (PAL), thereby suppressing the synthesis of phenolic substrates used in the browning reaction. Moderate vacuum packing combined with low temperature storage also maintained the activities of the cell wall-degrading enzymes cellulase and xylanase, and suppressed POD and PAL activities. Together, these effects would be expected to lead to a decrease in cellulose, hemicellulose, and lignin levels, ultimately restricting sprout elongation and maintaining the firmness of the sprouts. [ABSTRACT FROM AUTHOR]

Improving the ability of implants to integrate with natural bone tissue at the initial stage of implantation remains a huge challenge because bone-to-implant interfaces are often accompanied by abnormal microenvironments with infection, reactive oxygen species (ROS) and unbalanced bone homeostasis. In this study, a multifunctional coating was fabricated on the basis of gallium (III)-phenolic networks. It is easily obtained by immersing the implants into a mixed solution of tannic acids (TAs) and gallium ions. The thickness of the coating can be precisely controlled by adjusting the number and time of immersion experiments. The resulting coating displays excellent near-infrared photothermal property. As the coating degrades, TAs and gallium ions with low concentration are released from the coating, which is more rapid in acidic and oxidative stress microenvironments. Photothermal performance as well as released TAs and gallium ions give the coating outstanding broad-spectrum antibacterial ability. Furthermore, the coating effectively reduces intracellular ROS of osteoblasts. In vitro and in vivo experiments demonstrate the capability of the coating enhancing implants' osseointegration via pro-osteogenesis and inhibiting osteoclastogenesis. The findings imply that gallium (III)-phenolic coating holds great promise to promote implant osseointegration by rescuing abnormal microenvironments of infection, oxidative stress and unbalanced bone homeostasis. [ABSTRACT FROM AUTHOR]

Reaumuria trigyna is an endangered recretohalophyte and a small xeric shrub that is endemic to the eastern Alxa and western Ordos areas of Inner Mongolia, China. Using transcriptome data, we identified a 1662-bp open reading frame encoding a 553-amino-acid protein corresponding to a Na + /H + antiporter (RtNHX1) from R . trigyna . RtNHX1 was rapidly up-regulated by NaCl and exogenous abscisic acid treatment and had different tissue-specific expression patterns before and after salt-stress treatment. Overexpression of RtNHX1 enhanced seed germination, biomass accumulation, chlorophyll content, and root elongation in transgenic Arabidopsis plants under salt stress and rescued the salt-sensitive deficiencies of the nhx1 mutant. POD and CAT enzyme activities, proline content, and RWC all increased significantly in salt-stressed transgenic Arabidopsis plants, whereas MDA content did not. Additionally, there was a corresponding upregulation of some antioxidant-enzyme, proline biosynthesis and other stress responsive genes ( AtPOD1 , AtCAT1 , AtP5CS1 , AtP5CS2 , AtRD29A , AtRD29B , AtKIN1 , and AtABI2 ). The transgenic Arabidopsis plants accumulated more K + and less Na + in their leaves and had lower Na + /K + ratios than WT plants. This was reflected in the upregulation of some ion transport-related genes ( AtAVP1 , AtSOS1 , AtKUP6 , and AtKUP8 ). When RtNHX1 was expressed in the AXT3 yeast strain, the accumulation of Na + and K + in the vacuole increased and the Na + /K + ratio decreased. These results reveal that R . trigyna RtNHX1 is a functional antiporter that sequesters Na + and K + in the vacuole and could confer salt tolerance on transgenic Arabidopsis plants by maintaining Na + /K + homeostasis and enhancing osmotic and antioxidant regulatory capacity. These results suggest that RtNHX1 may be a good target for improving salt tolerance in plants. [ABSTRACT FROM AUTHOR]

Reaumuria trigyna ( R. trigyna ) is an endangered small shrub endemic to the Eastern Alxa–Western Ordos area in Inner Mongolia, China. Based on R. trigyna transcriptome data, the Group I WRKY transcription factor gene RtWRKY1 was cloned from R. trigyna . The full-length RtWRKY1 gene was 2100 bp, including a 1261-bp open reading frame (ORF) encoding 573 amino acids. RtWRKY1 was mainly expressed in the stem and was induced by salt, cold stress, and ABA treatment. Overexpression of RtWRKY1 in Arabidopsis significantly enhanced the chlorophyll content, root length, and fresh weight of the transgenic lines under salt stress. RtWRKY1 transgenic Arabidopsis exhibited higher proline content, GSH-PX, POD, SOD, and CAT activities, and lower MDA content, Na + content, and Na + /K + ratio than wild-type Arabidopsis under salt stress conditions. Salt stress affected the expression of ion transport, proline biosynthesis, and antioxidant related genes, including AtAPX1 , AtCAT1 , AtSOD1 , AtP5CS1 , AtP5CS2 , AtPRODH1 , AtPRODH2 , and AtSOS1 in transgenic lines. RtWRKY1 confers tolerance to salt stress in transgenic Arabidopsis by regulating plant growth, osmotic balance, Na + /K + homeostasis, and the antioxidant system. [ABSTRACT FROM AUTHOR]

Reaumuria trigyna is a typical, native desert halophyte that grows under extreme conditions in Inner Mongolia. In a previous transcriptomic profiling analysis, flavonoid pathway-related genes in R. trigyna showed significant differences in transcript abundance under salt stress. Leucoanthocyanidin dioxygenase (LDOX, EC 1.14.11.19) is one of three dioxygenases in the flavonoid pathway that catalyzes the formation of anthocyanidins from leucoanthocyanidins. In this study, we cloned the full-length cDNA of R. trigyna LDOX ( RtLDOX ), and found RtLDOX recombinant protein was able to replace flavanone-3-hydroxylase (F3H, EC 1.14.11.9), another dioxygenase in the flavonoid pathway, to convert naringenin to dihydrokaempferol in vitro . R. trigyna LDOX can complement the Arabidopsis LDOX mutant transparent testa11 ( tt11-11 ), which has reduced proanthocyanin (PA) and anthocyanin levels in seeds, to accumulate these two compounds. Thus, RtLDOX acts as a multifunctional dioxygenase to effect the synthesis of PA and anthocyanins and can perform F3H dioxygenase activities in the flavonoid biosynthesis pathway. The RtLDOX promoter harbored many cis -acting elements that might be recognized and bound by transcription factors related to stress response. RtLDOX expression was strongly increased under salt stress, and RtLDOX transgenic Arabidopsis mutant under NaCl stress accumulated the content of flavonoids leading to an increased antioxidant activities and plant biomass. These results suggest that RtLDOX as a multifunctional dioxygenase in flavonoid biosynthesis involves in enhancing plant response to NaCl stress. [ABSTRACT FROM AUTHOR]

Physochlaina physaloides (L.) G. Don is a Physochlaina species of the Solanaceae family and is cultivated extensively as a medicinal plant in Inner Mongolia, China. Its root extracts have been found to treat a variety of diseases, including cancer. The aim of this study is to isolate and identify the bioactive compounds of roots of Physochlaina physaloides (L.) G. Don, and elucidate their cytotoxic effects and related mechanisms. The ethyl acetate (EtOAc) and n-butanol (n-BuOH) components of crude root extract displayed marked cytotoxicity against Hep-G2 and HGC-27 cells. Two compounds—physochloside B and physochloside C—with new skeletons from the n-BuOH fraction and three known compounds (3−5) from the EtOAc fraction were isolated. The cell viability and flow cytometer assay showed that physochlosides B and C exhibited the strongest cytotoxicity of these compounds, including cell cycle blockage and apoptosis at the sub-G1 phase in HGC-27 and Hep-G2 cells, with less severe toxicity to normal cells (GES-1 and L02 cells). Based on the Western blotting results, physochlosides B and C suppressed β-catenin and p-GSK3β expression and downregulated cyclin D1 and C-myc, which are targets of the Wnt/β-catenin pathway, suggesting the involvement of Wnt/β-catenin pathway in the inhibition of HGC-27 and Hep-G2 cells. Above findings indicate a role of physochlosides B and C from Physochlaina physaloides (L.) G. Don roots in suppressing gastric and liver cancer cells. [Display omitted] • Root fractions of Physochlaina physaloides have cytotoxicities against HGC-27 and Hep G2 cells. • Two compounds with new skeleton (physochloside B and physochloside C) were isolated from root fractions. • Physochloside B and physochloside C promote apoptosis of HGC-27 and Hep G2 cells. • Physochloside B and physochloside C induced cell cycle arrest by inhibiting the Wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]

• The 3D bifunctional electrode was constructed via in-situ growth of MOF-74(Ni) and electrochemical deposition of NiCo LDH. • CC@MOF-74(NiO)@NiCo LDH demonstrates an ultra-high area specific capacitance, superior rate capability for supercapacitor. • The electrode also exhibits ultra-low detection limit, wide detection range for glucose detection. • The synergistic effect of unique structure and bimetal promote the diffusion of ions and reduce mass transfer resistance. The 3D self-supporting multistage structure CC@MOF-74(NiO)@NiCo LDH electrode was successfully synthesized, which demonstrated ultra-high specific capacitance, cyclic stability, excellent electrocatalytic performance and selectivity, providing a new reference for the research of bifunctional materials in the field of supercapacitors and non-enzymatic glucose sensors. [Display omitted] The bifunctional electrode materials for supercapacitors and non-enzymatic glucose sensors have attracted the researchers' great interest due to their excellent electrochemical performance. In this work, three-dimensional self-supporting multistage structure CC@MOF-74(NiO)@NiCo LDH electrode has been successfully prepared through a facile hydrothermal and electrochemical deposition method. Benefiting from the unique three-dimensional flower-like multistage structure, the optimized CC@MOF-74(NiO)@NiCo LDH electrode exhibits an excellent specific capacitance of 9.73 F cm−2 and a superior rate capability of 77.65% at a high current density of 50 mA cm−2. Besides, the material has a superior capacitance retention rate of 84.09% after 5000 cycles. Furthermore, the fabricated CC@MOF-74(NiO)@NiCo LDH//CC@NiCo 2 O 4 @NiFe LDH ASC device exhibits a high energy density of 22.85 Wh kg−1 and the power density of 1750 W kg−1 at the current density of 10 mA cm−2. Moreover, the as-prepared CC@MOF-74(NiO)@NiCo LDH shows an outstanding electrocatalytic performance in glucose detection, including a high sensitivity of 1699 μA mM−1 cm−2, a low detection limit of 278 nM (S/N = 3) and a wide linear range of 10 μM–1.1 mM and 1.5–9 mM. The electrode also has good long-term stability and remains 93.29% of the original current density after 35 days. The unique three-dimensional flower-like structure of MOF-74 and two-dimensional layered double hydroxides (LDHs) nanosheets structure provide a larger specific surface area and improve the conductivity of the MOF-74(NiO). Furthermore, the synergistic effect of the bimetal Ni-Co provides more active sites for electrochemical reactions and shortens the ion transport path. Accordingly, the fabricated CC@MOF-74(NiO)@NiCo LDH has great potential application prospects in the field of supercapacitors and non-enzymatic glucose sensors. [ABSTRACT FROM AUTHOR]

Plant specialised metabolites constitute a layer of chemical defence. Classes of the defence compounds are often restricted to a certain taxon of plants, e.g. benzoxazinoids (BX) are characteristically detected in grasses. BXs confer wide-range defence by controlling herbivores and microbial pathogens and are allelopathic compounds. In the crops maize, wheat and rye high concentrations of BXs are synthesised at an early developmental stage. By transfer of six Bx -genes (Bx1 to Bx5 and Bx8) it was possible to establish the biosynthesis of 2,4-dihydroxy-1,4-benzoxazin-3-one glucoside (GDIBOA) in a concentration of up to 143 nmol/g dry weight in Arabidopsis thaliana. Our results indicate that inefficient channeling of substrates along the pathway and metabolisation of intermediates in host plants might be a general drawback for transgenic establishment of specialised metabolite biosynthesis pathways. As a consequence, BX levels required for defence are not obtained in Arabidopsis. We could show that indolin-2-one (ION), the first specific intermediate, is phytotoxic and is metabolised by hydroxylation and glycosylation by a wide spectrum of plants. In Arabidopsis, metabolic stress due to the enrichment of ION leads to elevated levels of salicylic acid (SA) and in addition to its intrinsic phytotoxicity, ION affects plant morphology indirectly via SA. We could show that Bx3 has a crucial role in the evolution of the pathway, first based on its impact on flux into the pathway and, second by C3-hydroxylation of the phytotoxic ION. Thereby BX3 interferes with a supposedly generic detoxification system towards the non-specific intermediate. Benzoxazinoid biosynthesis in transgenic Arabidopsis is impaired by modification of intermediates leading to metabolic stress. [Display omitted] • Transfer of six maize genes enabled benzoxazinoid (BX) biosynthesis in Arabidopsis. • The phytotoxic BX pathway intermediate indolinone causes morphological changes. • Plants detoxify indolinone by hydroxylation and glucosylation. • Metabolisation of indolinone and content of salicylic acid are interdependent. • Acquisition of BX3 function might be a prerequisite in the evolution of the pathway. [ABSTRACT FROM AUTHOR]

• Reaumuria trigyna is a halophyte useful for uncovering the mechanism of plant salt tolerance. • Methyl jasmonate upregulated RtNAC100 expression. • RtNAC100 interacted with RtRbohE/SAG12 , accelerating salt-induced programmed cell death. • RtNAC100 promoted reactive oxygen species, Ca2+, and Na+ accumulation and increased the Na+/K+ ratio. NAM, ATAF1/2, and CUC2 (NAC) proteins regulate plant responses to salt stress. However, the molecular mechanisms by which NAC proteins regulate salt-induced programmed cell death (PCD) are unclear. We identified 56 NAC genes, 35 of which had complete open reading frames with complete NAM domain, in the R. trigyna transcriptome. Salt stress and methyl jasmonate (MeJA) mediated PCD-induced leaf senescence in R. trigyna seedlings. Salt stress accelerated endogenous JA biosynthesis, upregulating RtNAC100 expression. This promoted salt-induced leaf senescence in R. trigyna by regulating RtRbohE and RtSAG12/20 and enhancing ROS accumulation. Transgenic assays showed that RtNAC100 overexpression aggravated salt-induced PCD in transgenic lines by promoting ROS and Na+ accumulation, ROS-Ca2+ hub activation, and PCD-related gene expression. Therefore, RtNAC100 induces PCD via the MeJA signaling pathway in R. trigyna under salt stress. [ABSTRACT FROM AUTHOR]

• LaCl 3 poisoning can decrease the expressions of PI3K, p-AKT, p-mTOR, HIF-1α, and VEGF in the hippocampus of offspring rats. • LaCl 3 poisoning can induce developmental injuries and cell apoptosis in hippocampal neurons of offspring rats. • LaCl 3 poisoning can decrease the learning and memory abilities of offspring rats. This study examined the effects of the AKT/mTOR/HIF-1α signaling pathway on learning and memory in offspring rats induced by lanthanum from neuroethology and molecular biology perspectives. 32 pregnant adult Wistar rats were divided into four groups randomly: control group (NC), 0.25%, 0.5% and 1.0% LaCl 3 groups (n = 8). All rats were poisoned through free drinking from day 0 of pregnancy to postnatal day 21 (suckling period). All offspring rats were poisoned through free drinking from delactation to postnatal day 48. Offspring rats aged 49-days-old were used as sampling objects to construct an LaCl 3 poisoning model of offspring rats. Changes in hippocampal neurons, apoptosis of hippocampal neurons, learning and memory abilities of LaCl 3 -poisoned animals were measured by Nissl staining, TUNEL method and the shuttle box test, respectively. Expressions of PI3K, AKT, and mTOR, HIF-1α, and VEGF in the hippocampus were tested by qPCR and Western blot. Distributions of PI3K and p-AKT in hippocampal neurons were observed through the immunohistochemical method. With increasing LaCl 3 dose, lightning strike time and active avoidance incubation period of offspring rats in the different LaCl 3 groups were significantly prolonged. The Nissl body positive neurons of hippocampal neurons gradually declined while apoptosis in cells increased. The expressions of both mRNA (PI3K, AKT, mTOR, HIF-1α, VEGF) and proteins (PI3K, p-AKT, p-mTOR, HIF-1α, VEGF) in the hippocampus of the LaCl 3 groups were significantly lower than those of NC group (p < 0.05). LaCl 3 poisoning can induce developmental injuries in hippocampal neurons and can increase cell apoptosis. As a result, learning and memory abilities of offspring rats, as well as the expressions of PI3K/AKT/mTOR, are decreased, thus inhibiting activation of HIF-1α and influencing the expression of the downstream VEGF gene. [ABSTRACT FROM AUTHOR]

Tetraena mongolica Maxim is a species of Zygophyllaceae endemic to China. Because few insect pests affect its growth and flowering, we speculated that this plant produces defensive chemicals that are insect repellents or antifeedants. The effects of different fractions from crude stem and leaf extracts on Pieris rapae were examined. The results confirmed that the ethyl acetate (EtOAc) fraction from the stems had insecticidal potential. Five compounds were isolated from the EtOAc fraction: a volatile oil [bis(2-ethylhexyl) benzene-1,2-dicarboxylate (1)], three triterpenoids 2 E -3β-(3,4-dihydroxycinnamoyl)-erythrodiol (2), 2 Z -3β-(3,4-dihydroxycinnamoyl)-erythrodiol (3), and 2 E -3β-(3,4-dihydroxyphenyl)-2-propenoate (4)], and one steroid [β-sitosterol (5)]. Compounds 1 – 5 exhibited different degrees of insecticidal activity, including antifeedant and growth-inhibition effects. Compounds 1 – 5 inhibited the activity of carboxylesterase (CarE) and acetylcholinesterase (AChE) to different degrees. Compound 1 had the strongest antifeedant and growth-inhibition effects, and significantly inhibited the activity of CarE and AChE. Our results indicate that compounds 1 – 4 are the major bioactive insecticidal constituents of Tetraena mongolica. This work should facilitate the development and application of plant-derived botanical pesticides. Unlabelled Image • Five compounds were isolated from the EtOAc fraction from the stem of Tetraena mongolica had insecticidal potential. • The volatile oil had the strongest insecticidal activity, and significantly inhibited the activity of CarE and AChE. • Three triterpenoids had insecticidal activity, and significantly inhibited the activity of AChE. [ABSTRACT FROM AUTHOR]

Timely and reliable detection of foodborne bacterial pathogen is crucial for reducing disease burden in low- and middle-income countries. However, laboratory-based methods are often inaccessibility in resource-limited settings. Here, we developed a single-tube assay and a low-cost palm-sized device for on-site detection of the representative foodborne bacterial pathogen, Salmonella Enteritidis. Our assay incorporates the advantages of protein-nucleic acid signal transduction, EXPonential Amplification Reaction (EXPAR), and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 12a (Cas12a). After systematically investigating the compatibility of these components, we developed a "three-in-one" integration reaction, termed ST-EXPAR-CRISPR assay. This assay requires only one tube, one controlled temperature (39 °C) and simple operation, eliminating the need for bacterial isolation, nucleic acid extraction, or washing steps. ST-EXPAR-CRISPR assay is capable of detecting as few as 37 CFU/mL of target bacterium. Using our kit and portable device, untrained volunteers successfully detected contamination in food samples outdoors. The simplicity of the detection process and minimal hardware requirements make our assay highly promising for application in point-of-care and on-site scenarios. Moreover, the ST-EXPAR-CRISPR assay can be easily modified to detect other targets by changing the nucleic acid sequence with low research and development cost, potentially reducing the global disease burden., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jia Wei reports financial support was provided by Science and Technology Developing Foundation of Jilin Province. Bo Pang and Jinhua Li report financial support was provided by National Natural Science Foundation of China. Bo Pang report financial support was provided by Jilin University Interdisciplinary Project for Junior Teachers and Students. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The genus Camphora encompasses species of significant ecological and economic importance, such as C. parthenoxylon and C. officinarum , which exhibit distinct phenotypic traits and stress responses. This study seeks to elucidate the molecular basis of cold tolerance through comparative transcriptomic analysis complemented by physiological characterization. RNA sequencing revealed 6123 differentially expressed genes between the two species, with enriched pathways related to cold stress, oxidative stress, carotenoid biosynthesis, and photosynthesis. Key genes, such as annexin D5, chlorophyll a/b-binding protein, early light-induced protein 1, 9-cis-epoxycarotenoid dioxygenase, were identified as critical regulators of frost resistance, photosynthetic efficiency, and carotenoid biosynthesis. Functional enrichment analyses highlighted the involvement of signal transduction, membrane stabilization, and secondary metabolism in adaptive responses. Physiological assays supported these findings, showing higher chlorophyll and carotenoid content and enhanced antioxidative enzyme activities in C. parthenoxylon . These results provide valuable insights into the genetic and biochemical mechanisms underlying stress adaptation in Camphora species and offer promising targets for enhancing resilience in economically valuable plants.

African swine fever virus (ASFV) is the causative agent of African swine fever (ASF), a severe hemorrhagic disease with a mortality rate reaching 100%. Despite extensive research on ASFV mechanisms, no safe and effective vaccines or antiviral treatments have been developed. Live attenuated vaccines generated via gene deletion are considered to be highly promising. We developed a novel recombinant ASFV strain by deleting MGF360-10L and MGF505-7R , significantly reducing virulence in pigs. In the inoculation experiment, pigs were infected with 10 4 50% hemadsorption doses (HAD 50 ) of the mutant strain. All the animals survived the observation period without showing ASF-related clinical signs. Importantly, no significant viral infections were detected in the cohabitating pigs. In the virus challenge experiment, all pigs succumbed after being challenged with the parent strain. RNA-seq analysis showed that the recombinant virus induced slightly higher expression of natural immune factors than the parent ASFV; however, this level was insufficient to provide immune protection. In conclusion, our study demonstrates that deleting MGF360-10L and MGF505-7R from ASFV CN/GS/2018 significantly reduces virulence but fails to provide protection against the parent strain.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons and the accumulation of alpha-synuclein. Glutathione (GSH), a key antioxidant, is significantly depleted in PD patients. This study presents a dual-mode detection strategy for selectively determining GSH using a single probe. A series of "turn-on" electrochemical and fluorescent probes were developed, with resorufin (Re) serving as the reporting unit and featuring specific GSH recognition sites. Among these, the 7-(3,5-dinitrophenoxy)-3 H -phenoxazin-3-one (Re-DNP) probe was selected for its high selectivity as both a fluorescent and electrochemical probe. Its response to GSH was superior in comparison to that observed for hydrogen sulfide (H 2 S) and cysteine (Cys). For electrochemical detection using screen-printed carbon electrode (SPCE)/carbon nanotube (CNT) modified electrodes, the detection limit for GSH was 5 μM, with a linear range of 25-500 μM. In fluorescence detection, the probe produced a 78-fold increase in emission at 630 nm in the presence of GSH, with a strong linear correlation between fluorescence intensity and GSH concentration in the range of 10-700 μM, and a detection limit of 2 μM. When applied to real clinical serum samples, the probe demonstrated significantly lower GSH levels in both PD mice and human patients compared to healthy controls. This dual-mode detection method provides a sensitive and accurate tool for GSH detection, with potential applications in understanding GSH's role in PD and related neurodegenerative diseases.

The identification a signature comprising a group of genes as markers of cancer response to chemoradiotherapy would be more appropriate and effective for predicting chemoradiotherapy efficacy. This study investigated the differentially expressed genes (DEGs) related to chemoradiotherapy resistance and established a multigene expression model for predicting the sensitivity of rectal cancer to chemoradiotherapy in rectal cancer patients, elucidated the mechanism of resistance to synchronized chemoradiotherapy. The genome-wide expression profiling microarray were performed in the tissues of 81 rectal cancer patients before neoadjuvant therapy to analyze and discover DEGs related to chemoradiotherapy resistance, and the results were verified in 45 rectal cancer patients, and finally a 20-gene signature was proposed to be a predictor of chemoradiotherapy response. Molecular biology experiments revealed that zinc finger protein 37A (ZNF37A) downregulation leads to therapeutic resistance. This study identified a 20-gene signature with group of genes can help predict the response to chemoradiotherapy of rectal cancer patients. ZNF37A demonstrated a statistically significant correlation with sensitivity to chemoradiotherapy and survival in patients with LARC who underwent chemoradiotherapy. The findings revealed that ZNF37A bound to the tumor necrosis factor receptor superfamily member 6B (TNFRSF6B) promoter region, thereby suppressing its transcriptional activity. Reduced expression of ZNF37A induces chemoradiation resistance by inhibiting apoptosis in colorectal cancer (CRC) cells. TNFRSF6B Knockdown restored the sensitivity of CRC to chemoradiotherapy. ZNF37A is an effective modulator of chemoradiotherapy response in rectal cancer. These findings elucidate the molecular mechanism underlying chemoradiotherapy resistance and provide potential applications for individualized clinical therapy., Competing Interests: Declaration of competing interest Ying Huang, Jing Jin, Ningxin Ren, Hongxia Chen, Yan Qiao, Shuangmei Zou, Xin Wang, Linlin Zheng, Ye-Xiong Li, Wen Tan and Dongxin Lin are the authors of manuscript entitled “ZNF37A downregulation promotes TNFRSF6B expression and leads to therapeutic resistance to concurrent chemoradiotherapy in rectal cancer patients”. These authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: The dense and fibrotic nature of the pancreatic tumor microenvironment significantly contributes to tumor invasion and metastasis. This challenging environment acts as a formidable barrier, hindering effective drug penetration and delivery, which ultimately limits the efficacy of conventional cancer treatments. Gold nanoparticles (AuNPs) have emerged as promising nanocarriers to overcome the extracellular matrix barrier; however, their limited targeting precision, poor delivery efficiency, and insufficient photothermal conversion present challenges., Methods: We developed triphenyl phosphonium-functionalized high-branch gold nanoparticles, denoted as Dox@TPAu, to enhance drug delivery and targeting capabilities. The targeted penetration, biopharmaceutical and pharmacokinetic properties of Dox@TPAu were characterized, and the synergistic therapeutic effect was evaluated by the BxPC-3 xenograft tumor mouse model., Results: Dox@TPAu exhibits superior photothermal conversion efficiency (91.0%) alongside a high drug loading efficiency (26%) and effective photo-triggered drug-release potential. This Dox@TPAu drug delivery system adeptly accumulates at tumor sites due to its unique properties, enabling targeted localization within cancer cells and the mitochondria of stromal fibroblasts. This localization disrupts mitochondrial function and transfer-processes crucial for energy production, metabolism, and cell signaling within the tumor microenvironment. Pharmacokinetic analyses revealed an optimal spatiotemporal distribution of Dox@TPAu at the tumor site. This strategic accumulation enables precise disruption of both the physical barrier and cancer cells, enhancing treatment efficacy through near-infrared light-triggered local chemo-photothermal synergistic therapy., Conclusion: Our findings demonstrate that this innovative strategy effectively leverages the unique properties of mitochondria-targeting, virus-like AuNPs for precise and efficient stromal depletion, presenting a promising approach to enhance the efficacy of pancreatic cancer treatment., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Meng et al.)

Identifying biomarkers for predicting radiotherapy efficacy is crucial for optimizing personalized treatments. We previously reported that rs1553867776 in the miR-4274 seed region can predict survival in patients with rectal cancer receiving postoperative chemoradiation therapy. Hence, to investigate the molecular mechanism of the genetic variation and its impact on the radiosensitivity of colorectal cancer (CRC), in this study, bioinformatics analysis is combined with functional experiments to confirm peroxisomal biogenesis factor 5 (PEX5) as a direct target of miR-4274. The miR-4274 rs1553867776 variant influences the binding of miR-4274 and PEX5 mRNA, which subsequently regulates PEX5 protein expression. The interaction between PEX5 and Ku70 was verified by co-immunoprecipitation and immunofluorescence. A xenograft tumor model was established to validate the effects of miR-4274 and PEX5 on CRC progression and radiosensitivity in vivo. The overexpression of PEX5 enhances radiosensitivity by preventing Ku70 from entering the nucleus and reducing the repair of ionizing radiation (IR)-induced DNA damage by the Ku70/Ku80 complex in the nucleus. In addition, the enhanced expression of PEX5 is associated with increased IR-induced ferroptosis. Thus, targeting this mechanism might effectively increase the radiosensitivity of CRC. These findings offer novel insights into the mechanism of cancer radioresistance and have important implications for clinical radiotherapy., (© 2024. Higher Education Press.)

In recent years, exposure to triclosan (TCS) has been linked to an increase in psychiatric disorders. Nonetheless, the precise mechanisms of this occurrence remain elusive. Therefore, this study developed a long-life TCS-exposed rat model, an SH-SY5Y cell model, and an atomoxetine hydrochloride (ATX) treatment model to explore and validate the neurobehavioral mechanisms of TCS from multiple perspectives. In the long-life TCS-exposed model, pregnant rats received either 0 mg/kg (control) or 50 mg/kg TCS by oral gavage throughout pregnancy, lactation, and weaning of their offspring (up to 8 weeks old). In the ATX treatment model, weanling rats received daily injections of either 0 mg/kg (control) or 3 mg/kg ATX via intraperitoneal injection until they reached 8 weeks old. Unlike the TCS model, ATX exposure only occurred after the pups were weaned. The results indicated that long-life TCS exposure led to attention-deficit hyperactivity disorder (ADHD)-like behaviors in male offspring rats accompanied by dopamine-related mRNA and protein expression imbalances in the prefrontal cortex (PFC). Moreover, in vitro experiments also confirmed these findings. Mechanistically, TCS reduced dopamine (DA) synthesis, release, and transmission, and increased reuptake in PFC, thereby reducing synaptic gap DA levels and causing dopaminergic deficits. Additional experiments revealed that increased DA concentration in PFC by ATX effectively alleviated TCS-induced ADHD-like behavior in male offspring rats. These findings suggest that long-life TCS exposure causes ADHD-like behavior in male offspring rats through dopaminergic deficits. Furthermore, ATX treatment not only reduce symptoms in the rats, but also reveals valuable insights into the neurotoxic mechanisms induced by TCS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Multiplex PCR is a critical step when preparing amplicon library for next-generation sequencing. However, there are several challenges related to multiplex PCR including poor uniformity, nonspecific amplification, and primer-dimers. To address these issues, we propose a novel solution strategy that involves using a low cycle number (<10 cycles) in multiplex PCR and then employing carrier DNAs and magnetic beads for the selection of targeted products. This technique improves the amplicon uniformity while also reducing primer-dimers and PCR artifacts. To evaluate our technique, we initially utilized 120 DNA fragments from mouse genome containing single nucleotide polymorphism (SNP) sites. Sequencing results demonstrated that with only 7 cycles of multiplex PCR, 95.8% of the targeted SNP sites were mapped, with a coverage of at least 1×. The average sequencing depth of all amplicons was 1705.79 ± 1205.30×; 87% of them reached a coverage depth that exceeded 0.2-fold of the average sequencing depth. Our method had a greater uniformity (87%) when compared to Hi-Plex PCR (53.3%). Furthermore, we validated our strategy by randomly selecting 90 primer pairs twice from the initial set of 120 primer-pairs. Next, we used the same protocol to prepare amplicon libraries. The two groups had an average sequencing depth of 1013.30 ± 585.57× and 219.10 ± 158.27×, respectively; over 84% of the amplicons had a sequencing depth that exceeded 0.2-fold of average depth. These results suggest that the use of a low cycle number in multiplex PCR is a cost-effective and efficient approach for the preparation of amplicon libraries., (© 2024 Wiley‐VCH GmbH.)

Hepatocellular carcinoma (HCC) is a life-threatening disease that presents diagnostic challenges due to the absence of reliable biomarkers. Recently, plasma proteomics and glycoproteomics have emerged as powerful tools for identifying potential diagnostic biomarkers for various diseases. In this study, we conducted a comprehensive proteomic and glycoproteomic analysis of plasma samples from 11 HCC patients and 11 healthy control (HC) individuals. We identified 20 differentially expressed (DE) proteins and 32 DE intact glycosylated peptides (IGPs) that can effectively differentiate between HCC patients and HC samples. Our findings demonstrate that IGP profiles had better predictive power than protein profiles for screening HCC. Pathways associated with DE proteins and IGPs were identified. It was reported that the protein expression level of galectin 3 binding protein (LGALS3BP) and its N-linked glycosylation at the N398 and N551 sites might serve as valuable candidates for HCC diagnosis. These results highlight the importance of N-glycoproteomics in advancing our understanding of HCC and suggest possible candidates for the future diagnosis of this disease., (© 2024 Wiley‐VCH GmbH.)

Purpose: Ginsenoside Rg3 (Rg3) and Panax notoginseng saponins (PNS) can be used for ischemic stroke treatment, however, the lack of targeting to the ischemic region limits the therapeutic effect. To address this, we leveraged the affinity of macrophage membrane proteins for inflamed brain microvascular endothelial cells to develop a macrophage membrane-cloaked liposome loaded with Rg3 and PNS (MM-Lip-Rg3/PNS), which can precisely target brain lesion region through intranasal administration., Methods: MM-Lip-Rg3/PNS was prepared by co-extrusion method and was performed by characterization, stability, surface protein, and morphology. The cellular uptake, immune escape ability, and blood-brain barrier crossing ability of MM-Lip-Rg3/PNS were studied in vitro. The in vivo brain targeting, biodistribution and anti-ischemic efficacy of MM-Lip-Rg3/PNS were evaluated in MACO rats, and we determined the diversity of the nasal brain pathway through the olfactory nerve blockade model in rats. Finally, the pharmacokinetics and brain targeting index of MM-Lip-Rg3/PNS were investigated., Results: Our results indicated that MM-Lip-Rg3/PNS was spherical with a shell-core structure. MM-Lip-Rg3/PNS can avoid mononuclear phagocytosis, actively bind to inflammatory endothelial cells, and have the ability to cross the blood-brain barrier. Moreover, MM-Lip-Rg3/PNS could specifically target ischemic sites, even microglia, increase the cumulative number of drugs in the brain, improve the inflammatory environment of the brain, and reduce the infarct size. By comparing olfactory nerve-blocking rats with normal rats, it was found that there are direct and indirect pathways for nasal entry into the brain. Pharmacokinetics demonstrated that MM-Lip-Rg3/PNS exhibited stronger brain targeting and prolonged drug half-life., Conclusion: MM-Lip-Rg3/PNS might contribute to the accumulation of Rg3 and PNS in the ischemic brain area to improve treatment efficacy. This biomimetic nano-drug delivery system provides a new and promising strategy for the treatment of ischemic stroke., Competing Interests: The authors declare no competing interests in this work., (© 2024 Liu et al.)

Background: As an indicator of tumor invasiveness, microvascular invasion (MVI) is a crucial risk factor for postoperative relapse, metastasis, and unfavorable prognosis in hepatocellular carcinoma (HCC). Nevertheless, the genetic mechanisms underlying MVI, particularly for Chinese patients, remain mostly uncharted., Methods: We applied deep targeted sequencing on 66 Chinese HCC samples. Focusing on the telomerase reverse transcriptase (TERT) promoter (TERTp) and TP53 co-mutation (TERTp+/TP53+) group, gene set enrichment analysis (GSEA) was used to explore the potential molecular mechanisms of the TERTp+/TP53+ group on tumor progression and metastasis. Additionally, we evaluated the tumor immune microenvironment of the TERTp+/TP53+ group in HCC using multiplex immunofluorescence (mIF) staining., Results: Among the 66 HCC samples, the mutated genes that mostly appeared were TERT, TP53, and CTNNB1. Of note, we found 10 cases with TERTp+/TP53+, of which nine were MVI-positive and one was MVI-negative, and there was a co-occurrence of TERTp and TP53 (p < 0.05). Survival analysis demonstrated that patients with the TERTp+/TP53+ group had lower the disease-free survival (DFS) (p = 0.028). GSEA results indicated that telomere organization, telomere maintenance, DNA replication, positive regulation of cell cycle, and negative regulation of immune response were significantly enriched in the TERTp+/TP53+ group (all adjusted p-values (p.adj) < 0.05). mIF revealed that the TERTp+/TP53+ group decreased CD8 + T cells infiltration (p = 0.25) and enhanced PDL1 expression (p = 0.55)., Conclusions: TERTp+/TP53+ was significantly enriched in MVI-positive patients, leading to poor prognosis for HCC patients by promoting proliferation of HCC cell and inhibiting infiltration of immune cell surrounding HCC. TERTp+/TP53+ can be utilized as a potential indicator for predicting MVI-positive patients and poor prognosis, laying a preliminary foundation for further exploration of co-mutation in HCC with MVI and clinical treatment., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The stomata regulate CO 2 uptake and efficient water usage, thereby promoting drought stress tolerance. NAC proteins (NAM, ATAF1/2, and CUC2) participate in plant reactions following drought stress, but the molecular mechanisms underlying NAC-mediated regulation of stomatal movement are unclear. In this study, a novel NAC gene from Reaumuria trigyna , RtNAC055 , was found to enhance drought tolerance via a stomatal closure pathway. It was regulated by RtMYC2 and integrated with jasmonic acid signaling and was predominantly expressed in stomata and root. The suppression of RtNAC055 could improve jasmonic acid and H 2 O 2 production and increase the drought tolerance of transgenic R. trigyna callus. Ectopic expression of RtNAC055 in the Arabidopsis atnac055 mutant rescued its drought-sensitive phenotype by decreasing stomatal aperture. Under drought stress, overexpression of RtNAC055 in poplar promoted ROS (H 2 O 2 ) accumulation in stomata, which accelerated stomatal closure and maintained a high photosynthetic rate. Drought upregulated the expression of PtRbohD/F , PtP5CS2 , and PtDREB1 . 1 , as well as antioxidant enzyme activities in heterologous expression poplars. RtNAC055 promoted H 2 O 2 production in guard cells by directly binding to the promoter of RtRbohE , thus regulating stomatal closure. The stress-related genes RtDREB1 . 1/P5CS1 were directly regulated by RtNAC055. These results indicate that RtNAC055 regulates stomatal closure by maintaining the balance between the antioxidant system and H 2 O 2 level, reducing the transpiration rate and water loss, and improving photosynthetic efficiency and drought resistance., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Aims: We aim to explore new potential therapeutic targets and markers in human glioma., Background: Gliomas are the most common malignant primary tumor in the brain., Objective: In the present research, we evaluated the effect of CAI2, a long non-coding RNA, on the biological behaviors of glioma and explored the related molecular mechanism., Methods: The expression of CAI2 was analyzed using qRT-PCR in 65 cases of glioma patients. The cell proliferation was determined with MTT and colony formation assays, and the PI3K-AKt signaling pathway was analyzed using western blot., Results: CAI2 was upregulated in human glioma tissue compared with the matched, adjacent nontumor tissue and was correlated with WHO grade. Survival analyses proved that the overall survival of patients with high CAI2 expression was poor compared to that of patients with low CAI2 expression. High CAI2 expression was an independent prognostic factor in glioma. The absorbance values in the MTT assay after 96 h were .712 ± .031 for the si-control and .465 ± .018 for the si- CAI2-transfected cells, and si-CAI2 inhibited colony formation in U251 cells by approximately 80%. The levels of PI3K, p-AKt, and AKt in si-CAI2-treated cells were decreased., Conclusion: CAI2 may promote glioma growth through the PI3K-AKt signaling pathway. This research provided a novel potential diagnostic marker for human glioma., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: IgG4-related disease with multiorgan involvement predicts higher disease activity, thus, it is necessary to identify whether IgG4-related disease involves multiple organs at the early stage. To further clarify the clinical characteristics and risk factors for IgG4-related disease with multiorgan involvement, we conducted an observational study., Methods: We retrospectively analysed the clinical data of 160 patients who were primarily diagnosed with IgG4-related disease at the First Affiliated Hospital of Zhengzhou University from January 2015 to January 2021. According to the number of involved organs, patients were divided into two groups: multiorgan involvement and nonmultiorgan involvement. Patients were divided into a multiorgan group and a nonmultiorgan group according to multiple organ involvement., Results: There were 82 cases identified with multiorgan involvement and 78 cases diagnosed with no multiorgan involvement in this series. Most cases were elderly and male (p > 0.05). The most frequently affected organs in IgG4-RD were the lymph nodes (50.6 %), pancreas (38.7 %) and salivary glands (35.6 %). Multivariate analysis showed that eosinophilia, IgG4>2*ULN, lymph node involvement, salivary gland involvement and lung involvement were independent risk factors for multiorgan involvement (p < 0.05)., Conclusions: The main issues in clinical practice are how to accurately diagnose the disease and screen the more vulnerable organs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

The cabbage white butterfly (Pieris rapae), a major agricultural pest, has become one of the most abundant and destructive butterflies in the world. It is widely distributed in a large variety of climates and terrains of China due to its strong adaptability. To gain insight into the population genetic characteristics of P. rapae in China, we resequenced the genome of 51 individuals from 19 areas throughout China. Using population genomics approaches, a dense variant map of P. rapae was observed, indicating a high level of polymorphism that could result in adaptation to a changing environment. The feature of the genetic structure suggested considerable genetic admixture in different geographical groups. Additionally, our analyses suggest that physical barriers may have played a more important role than geographic distance in driving genetic differentiation. Population history showed the effective population size of P. rapae was greatly affected by global temperature changes, with mild periods (i.e., temperatures warmer than those during glaciation but not excessively hot) leading to an increase in population size. Furthermore, by comparing populations from south and north China, we have identified selected genes related to sensing temperature, growth, neuromodulation and immune response, which may reveal the genetic basis of adaptation to different environments. Our study is the first to illustrate the genetic signatures of P. rapae in China at the population genomic level, providing fundamental knowledge of the genetic diversity and adaptation of P. rapae., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The mechanisms of ovarian cancer generate chemotherapy resistance are still unclear. This study aimed to explore the role of microRNA (miR)-590-5p in regulating hMSH2 expression and cisplatin resistance in ovarian cancer., Methods: MiR-590-5p was identified as a regulator of hMSH2 with miRDB database and Target Scan database. Then cisplatin sensitive cell line (SKOV3) and resistant cell line (SKOV3-DDP) of ovarian cancer were cultured for cell functional assay and molecular biology assay. The expression levels of MiR-590-5p and hMSH2 were compared between the two cell lines. Dual luciferase reporter assay was used to verify the targeted regulatory relationship between miR-590-5p and hMSH2. CCK-8 assay and cell apoptosis assay were utilized to assess the role of MiR-590-5p and hMSH2 in cell viability under cisplatin., Results: The expression of hMSH2 was significantly decreased, and miR-590-5p was significantly up-regulated in SKOV3-DDP. Up-regulation of hMSH2 weakened the viability of SKOV3 and SKOV3-DDP cell under cisplatin. Transfection with miR‑590-5p mimics reduced the expression of hMSH2 and enhanced the viability of ovarian cancer cells under cisplatin, whereas inhibition of miR‑590-5p increased the expression of hMSH2, and decreased ovarian cancer cells' viability under cisplatin. Furthermore, luciferase reporter assay showed that hMSH2 was a direct target of miR-590-5p., Conclusion: The present study demonstrates that miR‑590-5p promotes cisplatin resistance of ovarian cancer via negatively regulating hMSH2 expression. Inhibition of miR‑590-5p decreases ovarian cancer cells' viability under cisplatin. Thus miR‑590-5p and hMSH2 may serve as therapeutic targets for cisplatin resistant ovarian cancer., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Immunotherapy resistance has become a difficult point in treating kidney renal clear cell carcinoma (KIRC) patients, mainly because of immune evasion. Currently, there is no effective signature to predict immunotherapy. Therefore, we use machine learning algorithms to construct a signature based on cytotoxic T lymphocyte evasion genes (CTLEGs) to predict the immunotherapy responses of patients, so as to screen patients effective for immunotherapy., Methods: In public data sets and our in-house cohort, we used 10 machine learning algorithms to screen the optimal model with 89 combinations under the cross-validation framework, and 101 published signatures were collected. The relationship between the CTLEG signature (CTLEGS) and clinical variables was analyzed. We analyzed the role of CTLES in other types of cancer by pan-cancer analysis. The immune cell infiltration and biological characteristics were evaluated. Moreover, the response to immunotherapy and drug sensitivity of different risk groups were investigated. The key gene closely related to the signature was identified by WGCNA. We also conducted cell functional experiments and clinical tissue validation of key gene., Results: In public data sets and our in-house cohort, the CTLEGS shows good prediction performance. The CTLEGS can be regard as an independent risk factor for KIRC. Compared with 101 published models, our signature shows considerable superiority. The high-risk group has abundant infiltration of immunosuppressive cells and high expression of T cell depletion markers, which are characterized by immunosuppressive phenotype, minimal benefit from immunotherapy, and resistance to sunitinib and sorafenib. The CTLEGS was also strongly correlated with immunity in pan-cancer. Immunohistochemistry verified that T cell depletion marker LAG3 is highly expressed in high-risk groups in the clinical in-house cohort. The key CTLEG STAT2 can promote the proliferation, migration and invasion of KIRC cell., Conclusions: CTLEGS can accurately predict the prognosis of patients and their response to immunotherapy. It can provide guidance for the precise treatment of KIRC and help clinicians identify patients who may benefit from immunotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Nie, Huang, Gao, Cao, Zheng and Zhang.)

As sorafenib is a first-line drug for treating advanced hepatocellular carcinoma, sorafenib resistance has historically attracted attention. However, most of this attention has been focused on a series of mechanisms related to drug resistance arising after sorafenib treatment. In this study, we used proteomic techniques to explore the potential mechanisms by which pretreatment factors affect sorafenib resistance. The degree of redundant pathway PI3K/AKT activation, biotransformation capacity, and autophagy level in hepatocellular carcinoma patients prior to sorafenib treatment might affect their sensitivity to sorafenib, in which ADH1A and STING1 are key molecules. These three factors could interact mechanistically to promote tumor cell survival, might be malignant features of tumor cells, and are associated with hepatocellular carcinoma prognosis. Our study suggests possible avenues of therapeutic intervention for patients with sorafenib-resistance and the potential application of immunotherapy with the aim of improving the survival of such patients., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Objective: Although surgical resection is one of the most effective way to treat liver cancer, its efficacy and safety in treatment of centrally located hepatocellular carcinoma (HCC) remains elusive. Therefore, it is very important to find a comprehensive treatment mode, such as radical resection combined with neoadjuvant radiotherapy (neoRT)., Methods: The centrally located HCC patients who underwent radical resection from July 2015 to April 2021 were enrolled. According to whether the neoRT was implemented or not, these patients were allocated into neoadjuvant radiotherapy combined with liver resection (neoRT+LR) and liver resection alone (LR) group. The research method used propensity-score analysis and Cox proportional-hazards regression models. We generated an E-value to assess the sensitivity to unmeasured confounding. This study is a real-world, retrospective study based on phase II clinical trial., Results: A total of 168 patients were enrolled, including 38 patients treating with neoRT+LR and 130 patients with LR. The 1-, 3-, 5-year disease free survival (DFS) rates were 74%, 55% and 39% in the neoRT+LR group, and 44%, 28%, and 24% in the LR group, respectively. Neoadjuvant radiotherapy was an independent prognostic factor for postoperative recurrence ([HR]0.42, 95% CI [0.25, 0.69]). There was significant association between neoRT+LR and longer disease-free survival (Match, [HR] 0.43, 95% CI [0.24, 0.76]; GenMatch, [HR] 0.32, 95% CI [0.23, 0.43]; Adjusted for propensity score, [HR] 0.41, 95% CI [0.23, 0.73]; Inverse probability weighting, [HR] 0.38, 95% CI [0.22, 0.65], respectively). DFS before and after matching analysis was statistically different in two groups ( p -value=0.005, p -value=0.0024, respectively). Neoadjuvant radiotherapy can significantly reduce the postoperative early recurrence ( p -value <0.05). E-value analysis suggested robustness to unmeasured confounding., Conclusion: Liver resection combined with neoadjuvant radiotherapy was effective and safe for treatment of centrally located HCC patients, which improved the prognosis of patients and reduced the incidence of early recurrence., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article., (© 2023 Tao et al.)