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Nitric oxide (NO) and reactive oxygen species (ROS) embody excellent potential in cancer therapy. However, as a small molecule, their targeted delivery and precise, controllable release are urgently needed to achieve accurate cancer therapy. In this paper, a novel US-responsive bifunctional molecule (SD) and hyaluronic acid-modified MnO 2 nanocarrier was developed, and a US-responsive NO and ROS controlled released nanoplatform was constructed. US can trigger SD to release ROS and NO simultaneously at the tumor site. Thus, SD served as acoustic sensitizer for sonodynamic therapy and NO donor for gas therapy. In the tumor microenvironment, the MnO 2 nanocarrier can effectively deplete the highly expressed GSH, and the released Mn 2+ can make H 2 O 2 to produce . OH by Fenton-like reaction, which exhibited a strong chemodynamic effect. The high concentration of ROS and NO in cancer cell can induce cancer cell apoptosis ultimately. In addition, toxic ONOO - , which was generated by the reaction of NO and ROS, can effectively cause mitochondrial dysfunction, which induced the apoptosis of tumor cells. The 131 I was labeled on the nanoplatform, which exhibited internal radiation therapy for tumor therapy. In -vitro and -vivo experiments showed that the nanoplatform has enhanced biocompatibility, and efficient anti-tumor potential, and it achieves synergistic sonodynamic/NO/chemodynamic/radionuclide therapy for cancer., 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 Elsevier Inc. All rights reserved.)

Background: The APOE gene is the strongest genetic risk factor for late-onset Alzheimer's Disease (LOAD). However, the gene regulatory mechanisms at this locus remain incompletely characterized., Methods: To identify novel AD-linked functional elements within the APOE locus, we integrated SNP variants with multi-omics data from human postmortem brains including 2,179 RNA-seq samples from 3 brain regions and two ancestries (European and African), 667 DNA methylation samples, and ChIP-seq samples. Additionally, we plotted the expression trajectory of APOE transcripts in human brains during development., Results: We identified an AD-linked APOE transcript (jxn1.2.2) particularly observed in the dorsolateral prefrontal cortex (DLPFC). The APOE jxn1.2.2 transcript is associated with brain neuropathological features, cognitive impairment, and the presence of the APOE4 allele in DLPFC. We prioritized two independent functional SNPs (rs157580 and rs439401) significantly associated with jxn1.2.2 transcript abundance and DNA methylation levels. These SNPs are located within active chromatin regions and affect brain-related transcription factor-binding affinities. The two SNPs shared effects on the jxn1.2.2 transcript between European and African ethnic groups., Conclusion: The novel APOE functional elements provide potential therapeutic targets with mechanistic insight into the disease etiology., (© 2024. The Author(s).)

Alterations in zinc transporter expression in response to zinc loss protect cardiac cells from ischemia/reperfusion (I/R) injury. However, the underlying molecular mechanisms how cardiac cells sense zinc loss remains unclear. Here, we found that zinc deficiency induced ubiquitination and degradation of the protein inhibitor of activated STAT3 (PIAS3), which can alleviate myocardial I/R injury by activating STAT3 to promote the expression of ZIP family zinc transporter genes. The RING finger domain within PIAS3 is vital for PIAS3 degradation, as PIAS3-dRing (missing the RING domain) and PIAS3-Mut (zinc-binding site mutation) were resistant to degradation in the setting of zinc deficiency. Meanwhile, the RING finger domain within PIAS3 is critical for the inhibition of STAT3 activation. Moreover, PIAS3 knockdown increased cardiac Zn 2+ levels and reduced myocardial infarction in mouse hearts subjected to I/R, whereas wild-type PIAS3 overexpression, but not PIAS3-Mut, reduced cardiac Zn 2+ levels, and exacerbated myocardial infarction. These findings elucidate a unique mechanism of zinc sensing, showing that fast degradation of the zinc-binding regulatory protein PIAS3 during zinc deficiency can correct zinc dyshomeostasis and alleviate reperfusion injury., 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. Published by Elsevier Inc.)

The optimal timing of the transition from vegetative growth to reproductive growth is critical for plant reproductive success, and the underlying regulatory mechanisms have been well studied in angiosperm model species, but relatively little in gymnosperms. DAL1, a MADS domain transcription factor (TF) gene that shows a conserved age-related expression profile in conifers, may be an age timer. However, how the DAL1 mediates the onset of reproductive growth remains poorly understood. Here, we have shown that the PtDAL1 directly regulates the PtDAL10 transcription by binding to its promoter region in vitro. PtDAL1, forms ternary complexes in vitro and in N. benthamiana with PtDAL10 and PtMADS11, two potential candidate regulators of the vegetative to reproductive transition in Chinese pine (Pinus tabuliformis). The PtDAL10 was progressively induced in new shoots with age and highly accumulated in male and female cones. Overexpression of PtDAL10 rescued the flowering of ft-10 and soc1-1-2 mutants in Arabidopsis. We provide insight into the molecular components associated with the PtDAL1, which integrates the vegetative to reproductive phase transition into age-mediated progressive development of the whole plant in conifers., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Class II malocclusion, particularly class II division 1, poses a significant orthodontic challenge with implications for both aesthetics and health. This study aimed to explore the impact of twin-block (TB) combined with maxillary expansion treatment (TB-ME) on upper airway dimensions and inflammatory profiles in adolescents with skeletal Class II Division 1 malocclusion in adolescent., Methods: Ninety-two eligible patients were randomly assigned to two groups: TB-ME treatment and traditional McLaughlin Bennett Trevisi (MBT) straight-wire orthodontic treatment (Control). Cephalometric lateral X-ray scans were conducted before and after treatment to assess skeletal changes, including SNA, ANB, and SNB angles, which are essential to assess the anteroposterior relationships of the maxilla and mandible to the cranial base. We also measured the upper airway volumes and areas. Concentrations of inflammatory factors including intercellular adhesion molecule 1 (ICAM-1), matrix metallopeptidase 2 (MMP2), and interleukin 8 (IL-8) of gingival crevicular fluid analysis (GCF) were detected by enzyme-linked immunosorbent assay., Results: TB-ME treatment induced significant improvement in cephalometric parameters, including a decrease in SNA and ANB angles and an increase in SNB angle. Upper airway volumes and areas increased significantly in both groups, with TB-ME showing greater improvements. GCF analysis revealed a reduction in ICAM-1, MMP2, and IL-8 concentrations in the TB-ME group compared to the Control group., Conclusions: TB-ME treatment demonstrates multifaceted improvements in skeletal malocclusion, upper airway dimensions, and inflammatory profiles in adolescents with class II division 1 malocclusion, showing the promise of TB-ME in addressing the complexities associated with class II malocclusion., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Safflower ( Carthamus tinctorius L.) is a multipurpose minor crop consumed by developed and developing nations around the world with limited research funding and genetic resources. Genomic selection (GS) is an effective modern breeding tool that can help to fast-track the genetic diversity preserved in genebank collections to facilitate rapid and efficient germplasm improvement and variety development. In the present study, we simulated four GS strategies to compare genetic gains and inbreeding during breeding cycles in a safflower recurrent selection breeding program targeting grain yield (GY) and seed oil content (OL). We observed positive genetic gains over cycles in all four GS strategies, where the first cycle delivered the largest genetic gain. Single-trait GS strategies had the greatest gain for the target trait but had very limited genetic improvement for the other trait. Simultaneous selection for GY and OL via indices indicated higher gains for both traits than crossing between the two single-trait independent culling strategies. The multi-trait GS strategy with mating relationship control (GS_GY + OL + Rel) resulted in a lower inbreeding coefficeint but a similar gain compared to that of the GS_GY + OL (without inbreeding control) strategy after a few cycles. Our findings lay the foundation for future safflower GS breeding.

Introduction: The objective of the study was to compare the effects of orthodontic microimplant anchorage (MIA) and conventional extraoral arch anchorage (EAA) on tooth structure and oral inflammatory response in patients with Class II Division I malocclusion., Methods: A total of 104 patients with Class II malocclusion were enrolled and were randomly assigned to receive MIA or EAA treatments. Clinical efficacy was assessed at 6 months after treatment by measuring molar shift, convex distance, and hinge angle difference between maxillary and mandibular incisors. X-ray was performed for tissue evaluations. The levels of cell adhesion molecule-1 (CAM-1), matrix metalloproteinase-2 (MMP-2), and proinflammatory cytokines in gingival sulcus fluid were measured using enzyme-linked immunosorbent assay to assess inflammatory responses to the implants., Results: Our study demonstrated superior efficacy of MIA compared to EAA in terms of overall efficacy, molar shift, convex distance between upper and middle incisors, as well as hinge angle difference between upper and middle incisors. MIA also showed greater efficacy in reducing tissue fix-point measurements, including saddle point-nasal root point-superior alveolar seat point (SNA), alveolar seat point-nasal root point-inferior alveolar seat point (ANB), overlying (OJ), and overbite (OB)., Conclusions: MIA is a novel orthodontic treatment that showed stronger efficacy in inducing molar shift and correcting soft/hard tissue positions, whilst generating suppressed inflammatory responses. Our study could have significant implications for practice in the orthodontic treatment of Class II malocclusion., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Endogenous formaldehyde (FA) is produced in the human body via various mechanisms to preserve healthy energy metabolism and safeguard the organism. However, endogenous FA can have several negative effects on the body through epigenetic alterations, including cancer growth promotion; neuronal, hippocampal and endothelial damages; atherosclerosis acceleration; haemopoietic stem cell destruction and haemopoietic cell production reduction. Certain medications with antioxidant effects, such as glutathione, vitamin E, resveratrol, alpha lipoic acid and polyphenols, lessen the detrimental effects of endogenous FA by reducing oxidative stress, directly scavenging endogenous FA or promoting its degradation. This study offers fresh perspectives for managing illnesses associated with endogenous FA exposure., (© 2023 John Wiley & Sons Ltd.)

Two deep ultraviolet (DUV) hydroxylated-alkali-metal borates, NaRbB 10 O 14 (OH) 4 (I) and Na 3 CsB 10 O 16 (OH) 2 (II), have been successfully synthesized by a high-temperature solution and solvothermal method. Both of them feature [B 5 O m (OH) n ] units, which form chains for (I) and bilayers with nine-membered boron rings for (II). It is worth noting that both compounds exhibit very wide theoretical band gaps of 7.33 and 6.55 eV for (I) and (II), respectively, which denotes that they should have desirable DUV transmittance ability. Moreover, the title compounds have moderate birefringence owing to the π-conjugated [BO 3 ], [BO 2 (OH)] groups, corresponding to 0.070 for (I) and 0.054 for (II) at 1064 nm. The structure characteristics and optical properties were also investigated and discussed. The results make it beneficial for exploring novel DUV hydroxylated borate optical crystals.

Endometrial cancer (EC) is one of the most common malignant tumors in women, and the increasing incidence and mortality pose a serious threat to the public health. Early diagnosis of EC could prolong the survival period and optimize the survivorship, greatly alleviating patients' suffering and social medical pressure. In this study, we collected urine and serum samples from the recruited patients, analyzed the samples using LC-MS approach, and identified the differential metabolites through metabolomic analysis. Then, the differentially expressed genes were identified through the systematic transcriptomic analysis of EC-related dataset from Gene Expression Omnibus (GEO), followed by network profiling of metabolic-reaction-enzyme-gene. In this experiment, a total of 83 differential metabolites and 19 hub genes were discovered, of which 10 different metabolites and 3 hub genes were further evaluated as more potential biomarkers based on network analysis. According to the KEGG enrichment analysis, the potential biomarkers and gene-encoded proteins were found to be involved in the arginine and proline metabolism, histidine metabolism, and pyrimidine metabolism, which was of significance for the early diagnosis of EC. In particular, the combination of metabolites (histamine, 1-methylhistamine, and methylimidazole acetaldehyde) as well as the combination of RRM2, TYMS and TK1 exerted more accurate discrimination abilities between EC and healthy groups, providing more criteria for the early diagnosis of EC., Competing Interests: Declaration of competing interest The authors declare no potential conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Antioxidants and UV stabilizers have some endocrine disrupting effects and liver toxicity. Both types of additives are still widely used in food contact plastics to improve the durability of plastic products. However, efficient and rapid detection of antioxidants and UV stabilizers has been a challenge due to the complexity of the plastic matrix and the low content of antioxidants and UV stabilizers. In this study, a sodium alginate/MOF-derived magnetic multistage pore carbon material (MIL-101(Fe)/SA-CAs) was developed, having the merits of abundant multistage pore structure, large specific surface area, and good magnetic separation properties. Thus, this material was selected as the sorbent for magnetic solid-phase extraction combined with a dissolution-precipitation method for the extraction and purification of antioxidants and UV stabilizers from polylactic acid food contact plastics. The extraction parameters such as sorbent type, sorbent dosage, sample solution pH, ionic strength, sorption time, elution solution type, volume, and time were investigated. Under the optimized conditions, all the analytes determined by UPLC-MS/MS showed good linear range (r > 0.99), detection limit (0.023-3.105 ng g -1 ), accuracy (70.6-102.3 %), and reproducibility (RSD<9.8 %). Further, the developed method was applied to determine the antioxidants and UV stabilizers in polylactic acid lunch boxes and straws, showing excellent applicability. The results showed that the antioxidants and UV stabilizers were detected in some of the samples, with a maximum detection of antioxidant 1010 at 7297 ng g -1 . This study provided a sensitive, efficient, and environmentally friendly method for antioxidants and UV stabilizers in polylactic acid food contact plastics. The ideas for the design of environmentally friendly metal-organic frameworks and biomass composite multifunctional materials would promise in the sample pretreatment field for the emerging contaminants., 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 © 2023 Elsevier B.V. All rights reserved.)

Nucleic acid modifications have attracted increasing attention in recent years since they have been found to be related to a number of diseases including cancer. Previous studies have shown that the early development of endometrial cancer (EC) is often accompanied by changes in methylation levels of related genes, and the expression of related proteins that regulate reactive oxygen species (ROS) shows significant differences in EC cells and tissues. However, it has not been reported whether nucleic acid modifications related to methylation or ROS can serve as biomarkers for EC. Accurate quantification of these nucleic acid modifications still has challenges because their amounts in urine are very low and the interferences in urine are complicated. In this study, a novel dispersive solid-phase extraction (DSPE) method based on chitosan-carbon nanotube-Al 2 O 3 (CS-CNT-Al 2 O 3 ) has been established for the analysis of 5-hydroxymethyluracil (5 mU), 5-methyl-2'-deoxycytidine (5-mdC), 5-hydroxymethyl-2'-deoxycytidine (5-hmdC), 5-formyl-2'-deoxycytidine (5-fdC), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in EC patient urine samples coupled with UHPLC-QE-Orbitrap-MS/MS and HPLC-UV. Firstly, the synthesis of the CS-CNT-Al 2 O 3 nanocomposite was conducted by a sono-coprecipitation method and was characterized by scanning electron microscope (SEM), energy dispersive spectrometer (EDS), and Fourier transform infrared (FTIR). Under the optimal extraction conditions of DSPE, we successfully quantified 5 mU, 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG in urine samples from 37 EC patients and 39 healthy controls. The results showed that there were significant differences in the levels of 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG in EC patients compared to the healthy control group. The receiver operator characteristic (ROC) curve analysis was carried out to evaluate the potential of 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG to distinguish EC patients from healthy volunteers. The area under the curve (AUC) for 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG was 0.7412, 0.667, 0.8438, and 0.7981, respectively. It indicated that 5-mdC, 5-hmdC, 5-fdC, and 8-OHdG had certain potential in distinguishing between EC patients and healthy volunteers and they could act as potential non-invasive biomarkers for early diagnosis of EC. Moreover, the present study would stimulate investigations of the effects of nucleic acid modifications on the initiation and progression of EC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Close correlation between vitamin D (VitD) deficiency and Parkinson's Disease (PD) risk, VitD as an adjuvant treatment promising to improve PD progression. However, VitD excessive intake could induce hypercalcemia and renal damage. Therefore, upregulation of vitD receptor (VDR) is considered a compensatory strategy to overcome VitD insufficiency and alleviate PD symptoms. In this study, we discovered that VDR played antioxidative roles in dopaminergic neurons by decreasing reactive oxygen species (ROS) and maintaining mitochondrial membrane potential. Further, we newly identified VDR downstream events in C. elegans, including glutathione S-transferase (gst) and forkhead box transcription factor class O (daf-16) mediated oxidative stress resistance. VDR upregulation also mitigated microglial activation through inhibition of NLRP3/caspase-1-mediated inflammation and membrane permeabilization. These findings highlight the multifaceted protective effects of VDR in both neurons and microglia against the development of PD. Importantly, we discovered a novel deubiquitinase DUB3, whose N-terminal catalytic domain interacted with the C-terminal ligand-binding domain of VDR to reduce VDR ubiquitination. Identification of DUB3 as an essential player in the deubiquitinating mechanism of VDR provides valuable insights into VDR regulation and its potential as a therapeutic target for PD., (© 2024. The Author(s).)

Effective treatment of deep-seated tumors relies on enhanced drug penetration in transdermal drug delivery systems. While microneedles (MNs) and iontophoresis techniques have shown improved transdermal drug delivery efficiency, challenges such as skin elasticity, high electrical resistance of the stratum corneum, and external power supply requirements hinder their efficacy in treating deep-seated tumors. In this study, a wearable, self-powered MN patch that integrates a flexible triboelectric nanogenerator (F-TENG) is presented, aimed at advancing deep-seated tumor therapy. MNs are composed of water-soluble materials mixed with negatively charged pH-responsive nanoparticles (NPs) loaded with therapeutic drugs. The F-TENG harnesses personal mechanical movements generate electrical energy. Leveraging the advantages of both MNs and F-TENG, therapeutic NPs can penetrate deep skin locations upon MN patch insertion, releasing drugs rapidly in acidic tumor tissues. Owing to these features, a single administration of the integrated MN-patch in a mouse model with deep-seated melanoma exhibits superior therapeutic efficacy in inhibiting deep-located tumor compared to using the MN-patch alone, indicating promising potential for treating tumors at deep sites., (© 2023 Wiley-VCH GmbH.)

Objective: The current models of estimating vascular age (VA) primarily rely on the regression label expressed with chronological age (CA), which does not account individual differences in vascular aging (IDVA) that are difficult to describe by CA. This may lead to inaccuracies in assessing the risk of cardiovascular disease based on VA. To address this limitation, this work aims to develop a new method for estimating VA by considering IDVA. This method will provide a more accurate assessment of cardiovascular disease risk., Methods: Relative risk difference in vascular aging (RRDVA) is proposed to replace IDVA, which is represented as the numerical difference between individual predicted age (PA) and the corresponding mean PA of healthy population. RRDVA and CA are regard as the influence factors to acquire VA. In order to acquire PA of all samples, this work takes CA as the dependent variable, and mines the two most representative indicators from arteriosclerosis data as the independent variables, to establish a regression model for obtaining PA., Results: The proposed VA based on RRDVA is significantly correlated with 27 indirect indicators for vascular aging evaluation. Moreover, VA is better than CA by comparing the correlation coefficients between VA, CA and 27 indirect indicators, and RRDVA greater than zero presents a higher risk of disease., Conclusion: The proposed VA overcomes the limitation of CA in characterizing IDVA, which may help young groups with high disease risk to promote healthy behaviors., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A magnetic fluorescent molecularly imprinted sensor was successfully prepared and implemented to determine catechol (CT). Fe 3 O 4 nanoparticles were synthesized by the solvothermal technique and mesoporous Fe 3 O 4 @SiO 2 @mSiO 2 imprinted carriers were prepared by coating nonporous and mesoporous SiO 2 shells on the surface of the Fe 3 O 4 subsequently. The magnetic surface molecularly imprinted fluorescent sensor was created after the magnetic mesoporous carriers were modified with γ-methacryloxyl propyl trimethoxy silane to introduce double bonds on the surface of the carries and the polymerization was carried out in the presence of CT and fluorescent monomers. The magnetic mesoporous carriers were modified with γ-methacryloxyl propyl trimethoxy silane and double bonds were introduced on the surface of the carriers. After CT binding with the molecularly imprinted polymers (MIPs), the fluorescent intensity of the molecularly imprinted polymers (E x  = 400 nm, E m  = 523 nm) increased significantly. The fluorescent intensity ratio (F/F 0 ) of the sensor demonstrated a favorable linear correlation with the concentration of CT between 5 and 50 μM with a detection limit of 0.025 μM. Furthermore, the sensor was successfully applied to determine CT in actual samples with recoveries of 96.4-105% and relative standard deviations were lower than 3.5%. The results indicated that the research of our present work provided an efficient approach for swiftly and accurately determining organic pollutant in water., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Lentivirus containing simian virus 40 large T antigen (SV40T) is routinely used to induce cell immortalization. However, the roles of viral integration itself in this progress is still controversial. Here, we transformed primary mouse embryonic fibroblasts (MEFs) with SV40T lentivirus and studied the roles of viral integration in the immortalization using RNA sequencing (RNA-seq) and whole genome sequencing (WGS). During the immortalization, differentially expressed genes (DGEs) are enriched in viral infection and several diverse activities. However, DEGs between immortalized and aging cells are significantly enriched in DNA/chromosome- and extracellular matrix (ECM)-associated activities. Gene regulatory network (GRN) analysis shows that although p53 is a key regulatory factor, many other transcription factors also play critical roles in the process, like STAT1. Of these DEGs, 32 genes have viral integration in their coding and/or regulatory regions. Our findings suggest that viral integration may promote SV40T-mediated immortalization by disturbing the expression of DNA/chromosome- and ECM-associated genes., 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 © 2023 Elsevier B.V. All rights reserved.)

Yield and quality are two crucial breeding objects of wheat therein grain weight and grain protein content (GPC) are two key relevant factors correspondingly. Investigations of their genetic mechanisms represent special significance for breeding. In this study, 199 F 2 plants and corresponding F 2:3 families derived from Nongda3753 (ND3753) and its EMS-generated mutant 564 (M564) were used to investigate the genetic basis of larger grain and higher GPC of M564. QTL analysis identified a total of 33 environmentally stable QTLs related to thousand grain weight (TGW), grain area (GA), grain circle (GC), grain length (GL), grain width (GW), and GPC on chromosomes 1B, 2A, 2B, 4D, 6B, and 7D, respectively, among which QGw.cau-6B.1 , QTgw.cau-6B.1 , QGa.cau-6B.1 , and QGc.cau-6B.1 shared overlap confidence interval on chromosome 6B. This interval contained the TaGW2 gene playing the same role as the QTLs, so TaGW2-6B was cloned and sequenced. Sequence alignment revealed two G/A SNPs between two parents, among which the SNP in the seventh exon led to a premature termination in M564. A KASP marker was developed based on the SNP, and single-marker analysis on biparental populations showed that the mutant allele could significantly increase GW and TGW, but had no effect on GPC. Distribution detection of the mutant allele through KASP marker genotyping and sequence alignment against databases ascertained that no materials harbored this allele within natural populations. This allele was subsequently introduced into three different varieties through molecular marker-assisted backcrossing, and it was revealed that the allele had a significant effect on simultaneously increasing GW, TGW, and even GPC in all of three backgrounds. Summing up the above, it could be concluded that a novel elite allele of TaGW2-6B was artificially created and might play an important role in wheat breeding for high yield and quality., Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01455-y., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s), under exclusive licence to Springer Nature B.V. 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Currently, cancer poses a significant health challenge in the medical community. Traditional chemotherapeutic agents are often accompanied by toxic side effects and limited therapeutic efficacy, restricting their application and advancement in cancer treatment. Therefore, there is an urgent need for developing intelligent drug release systems. Mesoporous silica nanoparticles (MSNs) have many advantages, such as a large specific surface area, substantial pore volume and size, adjustable mesoporous material pore size, excellent biocompatibility, and thermodynamic stability, making them ideal carriers for drug delivery and release. Additionally, they have been widely used to develop novel anticancer drug carriers. Recently, MSNs have been employed to design responsive systems that react to the tumor microenvironment and external stimuli for controlled release of anticancer drugs. This includes factors within the intratumor environment, such as pH, temperature, enzymes, and glutathione as well as external tumor stimuli, such as light, magnetic field, and ultrasound, among others. In this review, we discuss the research progress on environmental stimulus-responsive MSNs in anticancer drug delivery systems, including internal and external environment single stimulus-responsive release and combined stimulus-responsive release. We also summarize the current challenges associated with environmental stimulus-responsive MSNs and elucidate future directions, providing a reference for the functionalization modification and practical application of these MSNs., 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 Elsevier B.V. All rights reserved.)

Background: Connective tissue diseases (CTD), including systemic lupus erythematosus and rheumatoid arthritis (RA), have long been treated with hydroxychloroquine (HCQ). However, prolonged HCQ use poses a risk of adverse effects, particularly retinopathy., Objective: To detect early retinal changes assessed by optical coherence tomography angiography (OCTA) in CTD patients with long-term HCQ treatment and to explore the relationship between OCTA parameters and the concentrations of HCQ and its metabolites., Design: A cross-sectional study conducted from March 2020 to October 2021 at the First Affiliated Hospital of Anhui Medical University., Methods: The area and perimeter of the foveal avascular zone (FAZ), the thickness of the fovea and parafovea, and the vascular density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in each area of the macula were measured by OCTA in 43 CTD patients treated with HCQ for over 6 months. Meantime, blood concentrations of HCQ and its metabolites were determined by high-performance liquid chromatography-tandem mass spectrometry, and the clinical documents of all 43 involved patients were collected., Results: There is no significant correlation between OCTA outcomes and the patient's age, disease duration, and weight-dependent dose. HCQ cumulative duration positively correlated with FAZ area and perimeter ( r  = 0.419, p  = 0.005 and r  = 0.407, p  = 0.007, respectively) and negatively correlated with the foveal vessel density in DCP ( r  = -0.378, p  = 0.012). HCQ cumulative dose had a positive correlation with FAZ area and perimeter ( r  = 0.445, p  = 0.003 and r  = 0.434, p  = 0.004, respectively) and had a negative correlation with foveal vessel density in SCP and DCP ( r  = -0.383, p  = 0.011 and r  = -0.424, p  = 0.005, respectively). OCTA outcomes did not correlate with HCQ and its metabolite concentrations., Conclusion: OCTA could be used to detect microvascular changes in the macula of CTD patients with long-term HCQ therapy. It was not found the concentrations of HCQ and its metabolites were associated with retinal vascular changes., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

The capability of embryogenic callus induction is a prerequisite for in vitro plant regeneration. However, embryogenic callus induction is strongly genotype-dependent, thus hindering the development of in vitro plant genetic engineering technology. In this study, to examine the genetic variation in embryogenic callus induction rate (CIR) in peanut ( Arachis hypogaea L.) at the seventh, eighth, and ninth subcultures (T7, T8, and T9, respectively), we performed genome-wide association studies (GWAS) for CIR in a population of 353 peanut accessions. The coefficient of variation of CIR among the genotypes was high in the T7, T8, and T9 subcultures (33.06%, 34.18%, and 35.54%, respectively), and the average CIR ranged from 1.58 to 1.66. A total of 53 significant single-nucleotide polymorphisms (SNPs) were detected (based on the threshold value -log 10 ( p ) = 4.5). Among these SNPs, SNPB03-83801701 showed high phenotypic variance and neared a gene that encodes a peroxisomal ABC transporter 1. SNPA05-94095749, representing a nonsynonymous mutation, was located in the Arahy.MIX90M locus (encoding an auxin response factor 19 protein) at T8, which was associated with callus formation. These results provide guidance for future elucidation of the regulatory mechanism of embryogenic callus induction in peanut.

Tumor is a serious threat to human health, with extremely high morbidity and mortality rates. However, tumor treatment is challenging, and the development of antitumor drugs has always been a significant research focus. Plant polysaccharides are known to possess various biological activities. They have many pharmacological properties such as immunomodulation, antitumor, antiviral, antioxidative, antithrombotic, and antiradiation effects, reduction of blood pressure and blood sugar levels, and protection from liver injury. Among these effects, the antitumor effect of plant polysaccharides has been widely studied. Plant polysaccharides can inhibit tumor proliferation and growth by inhibiting tumor cell invasion and metastasis, inducing cell apoptosis, affecting the cell cycle, and regulating the tumor microenvironment. They also have the characteristics of safety, high efficiency, and low toxicity, which can alleviate, to a certain extent, the adverse reactions caused by traditional tumor treatment methods such as surgery, radiotherapy, and chemotherapy. Therefore, this paper systematically summarizes the direct antitumor effects of plant polysaccharides, their regulatory effects on the tumor microenvironment, and intervening many common high-incidence tumors in other ways. It also provides data support for the administration of plant polysaccharides in modern tumor drug therapy, enabling the identification of new targets and development of new drugs for tumor therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Glutamate stimuli and hyperactivation of its receptor are predominant determinants of ischemia-induced cytotoxic cerebral edema, which is closely associated with protein nanoparticle (PN)-induced increases in osmotic pressure. Herein, we investigated the electrochemical and mechanical mechanisms underlying the neuron swelling induced by PNs via the co-activation of N-methyl-D-aspartate receptor subunit (NMDAR) and excitatory metabotropic glutamate receptors (mGluRs)., Results: We observed that co-activation of ionic glutamate receptor NMDAR and Group I metabotropic mGluRs promoted alteration of PN-induced membrane potential and increased intracellular osmosis, which was closely associated with calcium and voltage-dependent ion channels. In addition, activation of NMDAR-induced calmodulin (CaM) and mGluR downstream diacylglycerol (DAG)/protein kinase C α (PKCα) were observed to play crucial roles in cytotoxic hyperosmosis. The crosstalk between CaM and PKCα could upregulate the sensitivity and sustained opening of sulfonylurea receptor 1 (SUR1)-transient receptor potential cation channel subfamily M member 4 (TRPM4) and transmembrane protein 16 A (TMEM16A) channels, respectively, maintaining the massive Na + /Cl - influx, and the resultant neuron hyperosmosis and swelling. Intracellular PNs and Na + /Cl - influx were found to be as potential targets for cerebral edema treatment, using the neurocyte osmosis system and a cerebral ischemic rat model., Conclusions: This study highlights PNs as a key factor in "electrochemistry-tension" signal transduction controlling Na + /Cl - ion channels and increased osmotic pressure in ischemia-induced cytotoxic edema. Moreover, enhanced sensitivity in both Na + and Cl - ion channels also has a crucial role in cerebral edema., 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 © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Extracellular protein nanoparticles (PNs) and ions perform synergistical functions in the control of transmembrane osmotic pressure (OP) under isotonic conditions. Intravenous injection may disrupt the ion balance and alter PN levels in blood plasma, changing transmembrane OP and damaging vascular endothelial cells., Methods: Na ions were injected into AngII-induced HUVECs to simulate cell injury in vitro, and tail vein infusion of Na ions into hypertensive rats was performed to assess vascular damage. Optical measurements using an intermediate filament (IF) tension probe were conducted to detect indicators related to transmembrane OP. Immunofluorescence, Western blotting and small interfering RNA (siRNA) transfection were employed to investigate inflammasomes and the relationship between Abl2 and inflammation., Results: Electrolyte injections with sodium ions (but not glucose and hydroxyethyl starch) induced the production of ASC and NLRP3 inflammasomes in Ang II-induced HUVECs; this in turn resulted in the disorder of calcium signals, and changes in transmembrane OP and cell permeability. Moreover, injection of Na ions into Ang II-induced HUVECs activated the mechanosensitive protein Abl2, involved in inflammation-induced transmembrane OP changes. A drug combination was identified that could induce OP recovery and block hyperpermeability induced by cytoplasmic inflammatory corpuscles in vivo and in vitro., Conclusion: Changes in extracellular PNs and ions following chemical stimuli (Ang II) participate in the regulation of transmembrane OP. Furthermore, injection of Na ions causes vascular endothelial injury in Ang II-induced cells in vitro and hypertension rats in vivo , suggesting it is not safe for hypertensive patients, and we propose a new drug combination as a solution., Competing Interests: The authors declare that they have no competing interests in this work., (© 2023 Song et al.)

Mitochondrial viscosity is a critical factor affecting numerous physiological processes, including phagocytosis. Abnormal viscosity in mitochondria is related to some pathological activities and diseases. Evaluating and detecting the changes in mitochondrial viscosity in vivo is crucial. Thus, a mitochondria-targeted red-emitting fluorescent probe (VP) was prepared, and can be used to detect viscosity with high selectivity and sensitivity. The synthesis of probe VP was as simple as two steps and the cost was low. In addition, the fluorescence intensity (log I 615 ) exhibited an excellent relationship with viscosity (log η) in the range of 0.5 - 2.5 (R 2  = 0.9985) in water/glycerol mixture. It is noteworthy that the probe VP displayed the highest signal-to-noise ratio (about 50-fold) for viscosity in water and glycerol system. The probe VP can visualize the mitochondrial viscosity change in living cells. More importantly, phagocytic test for BV2 cells further demonstrated that phagocytosis decreased with increased viscosity. Furthermore, VP was successfully used for monitoring the mitophagy process induced by starvation, and mitochondrial viscosity exhibited enhancement during mitophagy. The probe was a potential tool for studying viscosity and phagocytosis., 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 © 2023 Elsevier B.V. All rights reserved.)

Objectives: To determine the levels of estrogen and estrogen metabolites in the urine of premenopausal women with obesity and their correlation with glucose and lipid metabolism., Methords: 135 premenopausal women were selected from the same area. According to the body mass index (BMI), they were divided into four different groups. High performance liquid chromatography-mass spectrometry (HPLC/MS) was adopted to detect the concentrations of estrogen and estrogen metabolites in the urine. The influencing factors of BMI were analyzed, the correlation between the urinary degrees of estrogen and estrogen metabolites and glucose and lipid metabolism levels was assessed., Results: (1) The concentrations of 17β-estradiol (E2), estrone (E1), 16α-hydroxyestrone (16α-OHE1) and 2-hydroxyestrone (2-OHE1) gradually increased with increasing BMI (p < 0.05). (2) Stepwise regression analysis displayed that the concentrations of E2, 16α-OHE1 and 2-OHE1 in urine were significantly positively correlated with BMI (p < 0.05). (3) The concentrations of E2, E1, 16α-OHE1, 2-OHE1 and 16α-OHE1/2-OHE1 in urine were greatly positively related to fasting insulin (FIN), Triglyceride (TG), Total Cholesterol (TC) and Low-density lipoprotein (LDL) (p < 0.05). And they were greatly negatively related to High-density lipoprotein (HDL) (p < 0.05)., Conclusions: Early screening can reflect the degree of obesity and glucose and lipid metabolism disorders in premenopausal middle-aged women, thereby providing guidance for improving the prognosis of obese women., 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 Published by Elsevier Ltd.)

Background: Oral cancer is associated with high risk of morbidity and mortality. However, effective treatment for oral cancer is urgently required in clinics. In this study, we aimed to determine whether F-box/WD repeat-containing protein 7 (FBXW7), an essential tumor suppressor gene, can regulate autophagy and improve the prognosis in oral squamous cell carcinoma (OSCC)., Methods: mRNA levels of FBXW7 and myeloid cell leukemia 1 (MCL-1) in OSCC tissues and adjacent normal tissues were measured by qRT-PCR. FBXW7 and MCL-1 were overexpressed in OSCC cell line using lentivirus containing FBXW7 and MCL-1, respectively. Protein expression was determined by Western blot., Results: The mRNA and protein levels of FBXW7 were decreased in patients with OSCC, whereas the mRNA and protein levels of MCL-1 were increased. Moreover, the mRNA coding for autophagy proteins was reduced in patients with OSCC. Additionally, it was found that overexpression of FBXW7 significantly reduced MCL-1 expression and upregulated autophagy-related proteins, including Beclin1, autophagy related 7, and microtubule-associated protein light chain 3., Conclusion: Our results suggest that FBXW7 affects autophagy through MCL1 in OSCC., (© 2022 Wiley Periodicals LLC.)

Background: About one-third of patients with oral squamous cell carcinoma (OSCC) have a risk of occurrence and chemoresistance, making survival rates abysmal. We aim to evaluate the role of F-box/WD repeat-containing protein 7 (FBXW7) to further develop efficient treatment of chemoresistant OSCC., Methods: FBXW7 overexpression was induced in human OSCC cell lines including SCC9 and CAL27 by a lentiviral vector, Lv-FBXW7 or lv-NC (noncoding control), and overexpression efficiency was assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot of FBXW7. Cell viability was measured using MTT assay. The effects of FBXW7 overexpression on cell migration and invasion was evaluated by the colony formation assay and Matrigel assay. Apoptosis of cells with lv-FBXW7 transfection was measured by qRT-PCR and western blot analyses of BAX, BAK, MCL1, and BCL2 expression. Growth rate and cisplatin sensitivity of CAL27 xenografts with or without FBXW7 overexpression was monitored. Ki-67 and PCMA levels-which are biomarkers of intratumoural apoptosis-BAX, MCL1, Beclin1, and LC3I&II-which are autophagy biomarkers-were assessed., Results: Transfection of lv-FBXW7 in SCC9 and CAL27 cells resulted in increased sensitivity to cisplatin treatment, as evidenced by slower cell proliferation, lower colony formation and invasion, higher apoptosis, and autophagy compared to those transfected with lv-NC. Mice with CAL27 xenografts overexpressing FBXW7 also demonstrated slower tumour growth and upregulation in Ki067 and PCNA. Tumours also showed higher apoptosis and autophagy activities., Conclusions: FBXW7 overexpression was herein shown to effectively sensitise OSCC cells to cisplatin treatment in vitro and in vivo., Competing Interests: Conflict of interest None disclosed., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The human gastrointestinal tract houses an enormous microbial ecosystem. Recent studies have shown that the gut microbiota plays significant physiological roles and maintains immune homeostasis in the human body. Dysbiosis, an imbalanced gut microbiome, can be associated with various disease states, as observed in infectious diseases, inflammatory diseases, autoimmune diseases, and cancer. Modulation of the gut microbiome has become a therapeutic target in treating these disorders. Fecal microbiota transplantation (FMT) from a healthy donor restores the normal gut microbiota homeostasis in the diseased host. Ample evidence has demonstrated the efficacy of FMT in recurrent Clostridioides difficile infection (rCDI). The application of FMT in other human diseases is gaining attention. This review aims to increase our understanding of the mechanisms of FMT and its efficacies in human diseases. We discuss the application, route of administration, limitations, safety, efficacies, and suggested mechanisms of FMT in rCDI, autoimmune diseases, and cancer. Finally, we address the future perspectives of FMT in human medicine., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Endometrial cancer is known to be an estrogen-dependent cancer, and it is believed that exposure to estrogens increases the risk of developing endometrial cancer in the absence of progesterone. Estrogens and estrogen metabolites may help to predict the risk of endometrial hyperplasia (EH) with atypia. Estrogens and estrogen metabolites were measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) in the first morning urine sample collected from 150 patients with EH and 50 healthy premenopausal women in the study. In healthy premenopausal women, the level of 16α-hydroxyestrone (16α-OHE1) in the overweight group was significantly higher than that in the lean group (p < 0.05). The levels of 4-hydroxyestradiol (4-OHE2) and 16α-OHE1 were elevated in the AEH group as compared to that in the control group (p < 0.05). Overweight is related to EH incidence as it causes an imbalance of estrogen metabolites. This study provides identifies potential biomarkers for estrogen-induced AEH., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Background: Hypertension is the most prevalent chronic condition and a significant risk factor for cardiovascular and kidney diseases. The efficacy of health behavioral interventions in blood pressure (BP) control has been demonstrated by a large and expanding body of literature, with "adherence" playing a crucial role. WeChat is the most common social communication mobile app in China, and it has been shown to be an acceptable delivery platform for delivering health interventions. The WeChat-based health behavioral digital intervention program (WHBDIP) showed high feasibility and efficacy. However, the results regarding BP improvement between the WHBDIP and control groups were inconsistent., Objective: The objective of this study is to develop a WHBDIP and assess its efficacy in controlling BP and improving adherence among patients with hypertension., Methods: A 2-arm, parallel-group, and randomized trial design was used. Patients older than 60 years and with hypertension were randomly assigned to either the control group or the experimental group, which received a 12-week intervention. The program, primarily developed based on the Behavior Change Wheel (BCW) theory, offers health education on exercise, diet, BP monitoring, and medicine adherence (MA). It also includes other behavior interventions guided by an intervention manual, incorporating behavior change techniques (BCTs). The primary outcomes encompass BP and adherence indicators, while the secondary outcomes encompass cardiovascular function indicators, body composition indicators, learning performance, satisfaction, and acceptability. The exercise and blood pressure monitoring adherence (BPMA) indicators for the WHBDIP group were assessed weekly via WeChat during the initial 3 months, while other outcome data for both groups will be collected at the baseline assessment phase, 3 months after the intervention, and 1 year after the program., Results: The trial will assess the efficacy of WHBDIP for patients with hypertension (N=68). The WHBDIP seeks to enhance participants' knowledge of healthy behaviors and assist patients in developing positive health behaviors to improve their health outcomes. Patient recruitment for individuals with hypertension commenced on September 5, 2022, and concluded on September 19, 2022. The 3-month intervention and phased data collection were finalized in January 2023. Data analysis will commence in August 2023, and the final 1-year health outcome results will be collected in September 2023., Conclusions: A successful WHBDIP will establish the management mode as a feasible approach for hypertension management in the community. Additionally, it will pave the way for the development of related mobile health programs., Trial Registration: Chinese Clinical Trial Registry ChiCTR2200062643; https://tinyurl.com/mwyv67wk., International Registered Report Identifier (irrid): PRR1-10.2196/46883., (©Ting Sun, Huanhuan Zhao, Zenghui Ding, Hui Xie, Linlin Ma, Yu Zhang, Yingying Wang, Yinju Yang, Chunyi Xu, Yining Sun, Xuejie Xu, Zuchang Ma. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 12.09.2023.)

Molecular-targeted therapy has shown its effectiveness in pancreatic cancer, while single-targeted drug often cannot provide long-term benefit because of drug resistance. Fortunately, multitarget combination therapy can reverse drug resistance and achieve better efficacy. The typical treatment characteristics of traditional Chinese medicine monomer on tumor are multiple targets, with small side effects, low toxicity, and so forth. Agrimoniin has been reported to be effective on some cancers, while the mechanism still needs to be clarified. In this study, we used 5-ethynyl-2'-deoxyuridine, cell counting kit-8, flow cytometry, and western blot experiments to confirm that agrimoniin can significantly inhibit the proliferation of pancreatic cancer cell PANC-1 by inducing apoptosis and cell cycle arrest. In addition, by using SC79, LY294002 (the agonist or inhibitor of AKT pathway), and U0126 (the inhibitor of ERK pathway), we found that agrimoniin inhibited cell proliferation by simultaneously inhibiting AKT and ERK pathways. Moreover, agrimoniin could significantly increase the inhibitory effect of LY294002 and U0126 on pancreatic cancer cells. Meanwhile, in vivo experiments also supported the above results. In general, agrimoniin is a double-target inhibitor of AKT and ERK pathways in pancreatic cancer cells; it is expected to be used as a resistance reversal agent of targeted drugs or a synergistic drug of the inhibitor of AKT pathway or ERK pathway., (© 2023 John Wiley & Sons Ltd.)

Discovery of target-binding molecules, such as aptamers and peptides, is usually performed with the use of high-throughput experimental screening methods. These methods typically generate large datasets of sequences of target-binding molecules, which can be enriched with high affinity binders. However, the identification of the highest affinity binders from these large datasets often requires additional low-throughput experiments or other approaches. Bioinformatics-based analyses could be helpful to better understand these large datasets and identify the parts of the sequence space enriched with high affinity binders. BinderSpace is an open-source Python package that performs motif analysis, sequence space visualization, clustering analyses, and sequence extraction from clusters of interest. The motif analysis, resulting in text-based and visual output of motifs, can also provide heat maps of previously measured user-defined functional properties for all the motif-containing molecules. Users can also run principal component analysis (PCA) and t-distributed stochastic neighbor embedding (t-SNE) analyses on whole datasets and on motif-related subsets of the data. Functionally important sequences can also be highlighted in the resulting PCA and t-SNE maps. If points (sequences) in two-dimensional maps in PCA or t-SNE space form clusters, users can perform clustering analyses on their data, and extract sequences from clusters of interest. We demonstrate the use of BinderSpace on a dataset of oligonucleotides binding to single-wall carbon nanotubes in the presence and absence of a bioanalyte, and on a dataset of cyclic peptidomimetics binding to bovine carbonic anhydrase protein. BinderSpace is openly accessible to the public via the GitHub website: https://github.com/vukoviclab/BinderSpace., (© 2023 Wiley Periodicals LLC.)

The proper response to various abiotic stresses is essential for plants' survival to overcome their sessile nature, especially for perennial trees with very long-life cycles. However, in conifers, the molecular mechanisms that coordinate multiple abiotic stress responses remain elusive. Here, the transcriptome response to various abiotic stresses like salt, cold, drought, heat shock and osmotic were systematically detected in Pinus tabuliformis ( P. tabuliformis ) seedlings. We found that four transcription factors were commonly induced by all tested stress treatments, while PtNAC3 and PtZFP30 were highly up-regulated and co-expressed. Unexpectedly, the exogenous hormone treatment assays and the content of the endogenous hormone indicates that the upregulation of PtNAC3 and PtZFP30 are mediated by ethylene. Time-course assay showed that the treatment by ethylene immediate precursor, 1-aminocyclopropane-1-carboxylic acid (ACC), activated the expression of PtNAC3 and PtZFP30 within 8 hours. We further confirm that the PtNAC3 can directly bind to the PtZFP30 promoter region and form a cascade. Overexpression of PtNAC3 enhanced unified abiotic stress tolerance without growth penalty in transgenic Arabidopsis and promoted reproductive success under abiotic stress by shortening the lifespan, suggesting it has great potential as a biological tool applied to plant breeding for abiotic stress tolerance. This study provides novel insights into the hub nodes of the abiotic stresses response network as well as the environmental adaptation mechanism in conifers, and provides a potential biofortification tool to enhance plant unified abiotic stress tolerance., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Introduction: Psychological security is the outcome of interaction between individuals and society, and it is an important indicator reflecting adolescent mental health and self-growth. Previous studies have paid more attention to external security, but less attention to individual's internal psychological security. In addition, few previous studies have examined the changes of psychological security over time and the influence of socio-cultural environmental factors on psychological security., Methods: A cross-temporal meta-analysis was performed using papers that measured the psychological security level of Chinese adolescent college students between 2004 and 2020. Moreover, a time-lag analysis was conducted to define whether the macro-social indicators can explain the changes in Chinese adolescent college students' psychological security., Results: (1) A total of 85 papers was included in the final sample (included 48,817 Chinese adolescent college students); (2) the scores of psychological security and its two sub-dimensions were significantly negatively correlated with the year, indicating that Chinese college students' psychological security declined significantly over time; (3) seven macro social indicators from the socioeconomic environmental, social connectedness and overall social threats can predict the changes in college students' psychological security; (4) the psychological security of male and female college students decreased over time, but the gender difference was insignificant., Conclusions: Evidently, social changes play an important role in predicting changes in Chinese college students' psychological security. The results can provide a research basis for the mental health education of adolescent college students, and also provide an explanation perspective for the increasingly serious "involution" phenomenon among Chinese college students., (© 2023 The Foundation for Professionals in Services for Adolescents.)

Bulk nanobubbles fascinate scientists because of their stability over long periods of time and their ability to carry gases, leading to numerous potential applications. Considering the hypoxic tumor microenvironment and the advantages of bulk nanobubbles, lipid-encapsulated oxygen nanobubbles are prepared from free bulk oxygen nanobubbles in this study. The obtained carrier is then modified with a protein fused with the single-chain antibody of human epidermal growth factor receptor 2 (anti-HER2 scFv) and tandem-repeat cytochrome c (anti-HER2 scFv-nCytc) to enhance tumor targeting and induce tumor apoptosis. Copper phthalocyanine is used as the photosensitizer to demonstrate how the oxygen in the nanobubbles affects the efficiency of photodynamic therapy (PDT). The combination of anti-HER2 scFv-nCytc and PDT synergistically improves the therapeutic effect and alleviates hypoxia in tumors in vivo while causing little inflammatory response. Based on the findings, bulk nanobubble water shows promise in the targeted delivery of oxygen and can be combined with antibody therapy to enhance the efficiency of PDT., (© 2023 Wiley-VCH GmbH.)

Purpose: Intravitreal injection of conbercept (IVC) is a novel anti-vascular endothelial growth factor (anti-VEGF) treatment for retinopathy of prematurity (ROP). This study aimed to assess the intraocular pressure (IOP) effect of IVC. Methods: All IVC surgeries were performed in the Department of Ophthalmology, Guangdong Women and Children Hospital, from January 2021 to May 2021. In this study, 30 eyes of 15 infants who received intravitreal injections of conbercept at a dose of 0.25 mg/0.025 mL were included. The IOP of all participants was measured prior to administering the injection and subsequently at 2 min, 1 h, 1 day, and 1 week thereafter. Results: We included 30 eyes (10 boys and 5 girls) with ROP. For the male group, the mean birth weight, mean gestational age at birth, and the mean time of postmenstrual age (PMA) at IVC treatment were 1,174.0 ± 446.0 g, 28.4 ± 3.0 weeks, and 37.1 ± 1.6 weeks, respectively; for the female group, they were 1,108 ± 285.5 g, 28.2 ± 2.5 weeks, and 36.8 ± 2.1 weeks, respectively. For the male group, the IOP at baseline, 2 min, 1 h, 1 day, and 1 week after IVC were 12.4 ± 1.5 mmHg, 49.0 ± 3.1 mmHg, 26.3 ± 2.5 mmHg, 13.4 ± 2.2 mmHg, and 11.6 ± 1.7 mmHg, respectively; for the female group, they were 10.7 ± 2.0 mmHg, 47.3 ± 3.2 mmHg, 26.4 ± 3.2 mmHg, 10.7 ± 1.8 mmHg, and 10.2 ± 1.8 mmHg, respectively. In both groups, the IOP immediately (2 min) after the operation was significantly higher than that at any other time point ( p < 0.01). IOP values returned to the preoperative baseline level on the first day after surgery, with no significant difference compared with that before injection ( p > 0.05). IOP continued to be maintained at the preoperative baseline level on the first week after surgery, with no significant difference compared with that before surgery ( p > 0.05). Conclusion: Infants with ROP who received IVC experienced a sharp increase in the IOP immediately after injection, which decreased to below 30 mmHg after 1 h and maintain that level for 1 week or longer., 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 Gao, Mu, Zhao, Zheng, Feng, Wu, Li, Huang and Sun.)

Based on the self-regulation theory, this study aims to examine the relationship between youths' future orientation and judgment of their own immoral behaviors. A moderated mediation model was constructed to investigate the mediating role of moral disengagement and moderating role of self-control. Six hundred and twenty-eight Chinese youths, with an age range from 16 to 34 years ( M  = 23.08, SD  = 2.65), were recruited to take part in an anonymous survey about future orientation, moral disengagement, self-control, and moral judgment. Results revealed that youths with high future orientation judged their own moral transgressions more harshly and that moral disengagement partially mediated the relationship between the two. Moderated mediation analysis further demonstrated that self-control moderated the relationship between future orientation and moral disengagement and the indirect effect between future orientation and youths' judgment of their own immoral behaviors. To be specific, the indirect effect was much stronger for youths with high levels of self-control. These findings not only enrich the research about how future orientation affects youths' judgment of their own immoral behaviors, but also reveal the underlying mechanisms between future orientation and moral judgment, which can provide practical guidance for implementing measures that effectively enhance youths' moral character and cultivate their ability to think positively about the future., Competing Interests: Conflict of interestThe authors have no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The aim of this study was to examine how positive meta-stereotypes impacted cognitive performance among disadvantaged groups and the mediating effect of negative emotions. In Experiments 1 and 2, Chinese migrant children and rural college students were randomly allocated to the positive meta-stereotype, negative meta-stereotype, or a non-meta-stereotype activation group to examine positive meta-stereotypes' effect on creativity and working memory performance. Both experiments revealed that positive meta-stereotypes had a choking under-pressure effect on cognitive performance, and negative emotions may act as significant mediators between meta-stereotypes and cognitive performance. The choking under pressure effect may occur under positive meta-stereotypes, necessitating more clarification on meta-stereotypes' negative effects.

Background: The GINS complex is related to cancer development, invasion, and poor prognosis in multiple tumors. In the study, we attempted to investigate the prognostic value of GINS1 in sarcoma patients., Methods: We analyzed GINS1 expression using Tumor IMmune Estimation Resource (TIMER) 2.0, Gene Expression Omnibus (GEO; GSE21122, GSE39262, and GSE21050), and The Cancer Genome Atlas (TCGA) databases. The prognostic value of GINS1 was explored using the survival and survminer packages of R. Genetic alteration analysis was investigated using cBioPortal. The Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) R script was used for the immunocyte infiltration analysis. MicroRNAs (miRNAs) targeting GINS1 were predicted using GEO (GSE69470) and MicroRNA Target Prediction Database (miRDB)., Results: We found that GINS1 was overexpressed in sarcoma, especially in metastatic samples, and was associated with a worse prognosis. High GINS1 expression was a poor prognostic indicator for sarcoma patients. Moreover, GINS1 alteration was associated with worse survival of sarcoma patients. Immune infiltration analysis indicated that GINS1 expression was correlated with the infiltration of M0 and M2 macrophages in sarcoma. Finally, the miRNA hsa-miR-376a-3p was identified to potentially regulate GINS1 in sarcoma., Conclusions: These results indicate that GINS1 may be a promising prognostic biomarker and therapeutic target for sarcoma., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-524/coif). The authors have no conflicts of interest to declare., (2023 Translational Cancer Research. All rights reserved.)

Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) is a necrotizing vasculitis mainly involving small blood vessels. It is demonstrated that T cells are important in the pathogenesis of AAV, including regulatory T cells (Treg) and helper T cells (Th), especially Th2, Th17, and follicular Th cells (Tfh). In addition, the exhaustion of T cells predicted the favorable prognosis of AAV. The immune checkpoints (ICs) consist of a group of co-stimulatory and co-inhibitory molecules expressed on the surface of T cells, which maintains a balance between the activation and exhaustion of T cells. CD28, inducible T-cell co-stimulator (ICOS), OX40, CD40L, glucocorticoid induced tumor necrosis factor receptor (GITR), and CD137 are the common co-stimulatory molecules, while the programmed cell death 1 (PD-1), cytotoxic T lymphocyte-associated molecule 4 (CTLA-4), T cell immunoglobulin (Ig) and mucin domain-containing protein 3 (TIM-3), B and T lymphocyte attenuator (BTLA), V-domain Ig suppressor of T cell activation (VISTA), T-cell Ig and ITIM domain (TIGIT), CD200, and lymphocyte activation gene 3 (LAG-3) belong to co-inhibitory molecules. If this balance was disrupted and the activation of T cells was increased, autoimmune diseases (AIDs) might be induced. Even in the treatment of malignant tumors, activation of T cells by immune checkpoint inhibitors (ICIs) may result in AIDs known as rheumatic immune-related adverse events (Rh-irAEs), suggesting the importance of ICs in AIDs. In this review, we summarized the features of AAV induced by immunotherapy using ICIs in patients with malignant tumors, and then reviewed the biological characteristics of different ICs. Our aim was to explore potential targets in ICs for future treatment of AAV., 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 Pan, Zhao, Jin, Leung and Shuai.)

Rating of perceived exertion (RPE) can serve as a more convenient and economical alternative to heart rate (HR) for exercise intensity control. This study aims to explore the influence of factors, such as indicators of demographic, anthropometric, body composition, cardiovascular function and basic exercise ability on the relationship between HR and RPE, and to develop the model predicting RPE from HR. 48 healthy participants were recruited to perform an incrementally 6-stage pedaling test. HR and RPE were collected during each stage. The influencing factors were identified with the forward selection method to train Gaussian Process regression (GPR), support vector machine (SVM) and linear regression models. Metrics of R2, adjusted R2 and RMSE were calculated to evaluate the performance of the models. The GPR model outperformed the SVM and linear regression models, and achieved an R2 of 0.95, adjusted R2 of 0.89 and RMSE of 0.52. Indicators of age, resting heart rate (RHR), Central arterial pressure (CAP), body fat rate (BFR) and body mass index (BMI) were identified as factors that best predicted the relationship between RPE and HR. It is possible to use GPR model to estimate RPE from HR accurately, after adjusting for age, RHR, CAP, BFR and BMI.

Background: Macrosomia has increased rapidly worldwide in the past few decades, with a huge impact on health. However, the effect of PM 2.5 and extreme high-temperature (EHT) on macrosomia has been ignored., Objective: This study aimed to explore the association between maternal exposure to EHT, PM 2.5 and macrosomia based on the Seventh Demographic and Health Survey (DHS) in 14 countries of Africa., Methods: The study included detailed demographic information on 106 382 births and maternal. Satellite inversion models estimated monthly mean PM 2.5 and mean surface temperature of 2 m (SMT 2m ). Macrosomia was defined as the birth weight ≥ 4000 g. We used a Cox proportional risk regression model to estimate the association between PM 2.5 , EHT and macrosomia. We further explored the susceptibility of exposure to EHT and PM 2.5 at different pregnancy periods to macrosomia, and plotted the expose-response curve between PM 2.5 and macrosomia risk using a restricted cubic spline function. In addition, the Interplot model was used to investigate the interaction between EHT and PM 2.5 on macrosomia. Finally, some potential confounding factors were analysed by stratification., Results: There was the positive association between EHT, PM 2.5 and macrosomia, and the risk of macrosomia with the increase in concentrations of PM 2.5 without clear threshold. Meanwhile, EHT and PM 2.5 had a higher effect on macrosomia in middle/later and early/middle stages of pregnancy, respectively. There was a significant interaction between EHT and PM 2.5 on macrosomia., Conclusions: Maternal exposure to EHT, PM 2.5 during pregnancy was associated with an increased risk of macrosomia in Africa., (© 2023 World Obesity Federation.)

In plant breeding programs, multiple traits are recorded in each trial, and the traits are often correlated. Correlated traits can be incorporated into genomic selection models, especially for traits with low heritability, to improve prediction accuracy. In this study, we investigated the genetic correlation between important agronomic traits in safflower. We observed the moderate genetic correlations between grain yield (GY) and plant height (PH, 0.272-0.531), and low correlations between grain yield and days to flowering (DF, -0.157-0.201). A 4%-20% prediction accuracy improvement for grain yield was achieved when plant height was included in both training and validation sets with multivariate models. We further explored the selection responses for grain yield by selecting the top 20% of lines based on different selection indices. Selection responses for grain yield varied across sites. Simultaneous selection for grain yield and seed oil content (OL) showed positive gains across all sites with equal weights for both grain yield and oil content. Combining g×E interaction into genomic selection (GS) led to more balanced selection responses across sites. In conclusion, genomic selection is a valuable breeding tool for breeding high grain yield, oil content, and highly adaptable safflower varieties., Competing Interests: Authors HZ, ZL, MK, JT, and MH were employed by Agriculture Victoria., (Copyright © 2023 Zhao, Lin, Khansefid, Tibbits and Hayden.)

Fulvic acid (FA) can significantly alleviate cadmium (Cd) stress, but the specific metabolic response of FA to Cd toxicity is still not clarified. In the present study, we used untargeted metabolomic [gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS)] analysis to profile cucumber metabolism in response to Cd stress after spray application of FA. Our results showed that 331 differentially enriched metabolites (DEMs) were identified in leaf materials. These DEMs were enriched in 21 shared pathways in comparative groups of "Cd treatment vs. the control treatment" and "FA + Cd treatment vs. the Cd treatment." Specifically, treatment with FA significantly enhanced the organic acid content (citric acid, isocitric acid, 2-oxoglutaric acid, fumaric acid, and malic acid), which would contribute to provide sufficient substrates for the tricarboxylic acid (TCA) cycle and amino acid biosynthesis, thereby ensuring the normal production of energy and amino acid. At the same time, FA significantly increased the amino acid content (aspartate, citrulline, histidine, leucine, and phenylalanine). The accumulation of organic acid and amino acid can act as chelating agents for heavy metal ions and as scavengers of reactive oxygen species (ROS), thereby reducing intracellular oxidative damage. Furthermore, the application of FA improves antioxidant enzymes and accelerates ROS clearance. The improved contents of organic acid and amino acid, and the increased activity of antioxidant enzymes both played a central role in the reduction of malondialdehyde (MDA, 14.08%), hydrogen peroxide (H 2 O 2 , 61.70%) contents, and superoxide anion radical (O 2 - , 30.41%) production rate in plants under Cd stress. Taken together, the present study demonstrates the effects of FA on the antioxidant capacity and carbohydrate and amino acid metabolism of cucumber seedlings exposed to Cd stress, which provides comprehensive insights into the regulation of plants' response to Cd toxicity with FA was applied in cucumber., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: RNA methylation is a widely known post-transcriptional regulation which exists in many cancer and immune system diseases. However, the potential role and crosstalk of five types RNA methylation regulators in diabetic nephropathy (DN) and immune microenvironment remain unclear., Methods: The mRNA expression of 37 RNA modification regulators and RNA modification regulators related genes were identified in 112 samples from 5 Gene Expression Omnibus datasets. Nonnegative Matrix Factorization clustering method was performed to determine RNA modification patterns. The ssGSEA algorithms and the expression of human leukocyte antigen were employed to assess the immune microenvironment characteristics. Risk model based on differentially expression genes responsible for the modification regulators was constructed to evaluate its predictive capability in DN patients. Furthermore, the results were validated by using immunofluorescence co-localizations and protein experiments in vitro., Results: We found 24 RNA methylation regulators were significant differently expressed in glomeruli in DN group compared with control group. Four methylation-related genes and six RNA regulators were introduced into riskScore model using univariate Logistic regression and integrated LASSO regression, which could precisely distinguish the DN and healthy individuals. Group with high-risk score was associated with high immune infiltration. Three distinct RNA modification patterns were identified, which has significant differences in immune microenvironment, biological pathway and eGFR. Validation analyses showed the METTL3, ADAR1, DNMT1 were upregulated whereas YTHDC1 was downregulated in DN podocyte cell lines comparing with cells cultured by the normal glucose., Conclusion: Our study reveals that RNA methylation regulators and immune infiltration regulation play critical roles in the pathogenesis of DN. The bioinformatic analyses combine with verification in vitro could provide robust evidence for identification of predictive RNA methylation regulators in DN., (© 2023. The Author(s).)

In the world, chronic kidney disease (CKD) has been recognized as one of the critical public health problems, and the prevalence is higher in the elderly people. However, there are few studies on the association between exposure to multiple serum metal levels and CKD. A case-control study, we established, for elderly people in Anhui Province, China, to explore the effects of different metals and analyze the effect of mixed exposure on CKD. In this study, 287 cases of CKD and 287 controls were selected in the elderly health physical examination project in Tongling City, Anhui Province. Questionnaire survey, physical examination, and blood collection were conducted. Graphite furnace atomic absorption spectrometry (GFAAS) and inductively coupled plasma optical emission spectrometry (ICP-OES) were used to measure the concentration of serum metals. After selecting by least absolute shrinkage and selection operator (LASSO), 5 metals were brought into the multi-metal model. After adjusting all potential covariates additionally, the concentrations of lead (Pb), cadmium (Cd), cobalt (Co), and manganese (Mn) were significantly associated with CKD risk, whereas Pb, Se, and Cd had significant non-linearity with CKD. Besides, patients with highest quartiles of cobalt (Co), lead (Pb), and manganese (Mn) were 1.64, 1.39, and 0.64 times more possible to have CKD, respectively, as compared with the lowest levels. In the Bayesian kernel machine regression (BKMR) model, cadmium (Cd) had a combined effect with lead (Pb) possibly. This study suggested that the CKD risk was associated with exposure of multiple metals in elderly people. The underlying mechanisms of serum metals and CKD need more experimental and prospective studies to elucidate., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Plastid-to-nucleus retrograde signaling coordinates nuclear gene expression with chloroplast developmental status and is essential for the photoautotrophic lifestyle of plants. Previous studies have established that tetrapyrrole biosynthesis (TPB) and plastid gene expression (PGE) play essential roles in plastid retrograde signaling during early chloroplast biogenesis; however, their functional relationship remains unknown. In this study, we generated a series of rice TPB-related gun (genome uncoupled) mutants and systematically analyzed their effects on nuclear and plastid gene expression under normal conditions or when subjected to treatments with norflurazon (NF; a noncompetitive inhibitor of carotenoid biosynthesis) and/or lincomycin (Lin; a specific inhibitor of plastid translation). We show that under NF treatment, expression of plastid-encoded polymerase (PEP)-transcribed genes is significantly reduced in the wild type but is derepressed in the TPB-related gun mutants. We further demonstrate that the derepressed expression of PEP-transcribed genes may be caused by increased expression of the PEP core subunit and nuclear-encoded sigma factors and by elevated copy numbers of plastid genome per haploid genome. In addition, we show that expression of photosynthesis-associated nuclear genes (PhANGs) and PEP-transcribed genes is correlated in the rice TPB-related gun mutants, with or without NF or Lin treatment. A similar correlation between PhANGs and PGE is also observed in the Arabidopsis gun4 and gun5 mutants. Moreover, we show that increased expression of PEP-transcribed plastid genes is necessary for the gun phenotype in NF-treated TPB-related gun mutants. Further, we provide evidence that these TPB-related GUN genes act upstream of GUN1 in the regulation of retrograde signaling. Taken together, our results suggest that the TPB-related GUN genes control retrograde plastid signaling by regulating the PGE-dependent retrograde signaling pathway., (Copyright © 2022. Published by Elsevier Inc.)