Efficacy of physical exercise intervention on children with acute lymphoblastic leukemia during treatment and rehabilitation: a systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the impact of physical exercise intervention on children with acute lymphoblastic leukemia (ALL) during the treatment and rehabilitation consolidation periods. METHOD: Randomized controlled trials (RCTs) were retrieved from PubMed, Scopus, Web of Science, CNKI, and Cochrane databases, with a search time range from database establishment to September 1, 2023. The quality of the included RCTs was evaluated using the Cochrane risk assessment tool, and a systematic evaluation was conducted using RevMan 5.4. The study has been registered with INPLASY (registration number: 202390100). RESULT: A total of 12 RCTs including 423 subjects was included. The meta-analysis results showed that long-term exercise intervention can effectively improve the endurance performance (SMD = 1.37, 95% CI 0.45 to 2.29, p = 0.004), functional mobility (MD = - 1.17, 95% CI - 1.85 to - 0.49, p = 0.0008), cancer-related fatigue (CRF) (MD = - 1.25, 95% CI - 1.69 to - 0.80, p < 0.00001), and quality of life (QOL) (MD = 4.93, 95% CI 1.80 to 8.05, p = 0.002) of ALL children during the treatment and rehabilitation consolidation periods. Its promoting effect on the muscle strength (SMD = 0.53, 95% CI - 0.33 to 1.39, p = 0.23) and bone mineral density (BMD) (SMD = 0.48, 95% CI 0.20 to 0.77, p = 0.05) of the subjects was not significant. Further meta-analysis showed that exercise intervention with a duration of less than 1 year (SMD = 0.91, 95% CI 0.55 to 1.28, p < 0.00001) rather than more than 1 year (SMD = - 0.16, 95% CI - 0.61 to 0.29, p = 0.49) can effectively reduce subject BMD, while in terms of strength, exercise intervention can effectively improve strength during the treatment period (SMD = 0.97, 95% CI 0.40 to 1.54, p = 0.0008) rather than the consolidation period (SMD = - 0.27, 95% CI - 1.08 to 0.53, p = 0.51). CONCLUSION: Long-term regular exercise can effectively improve the endurance, functional mobility, CRF, and QOL of children with ALL in the rehabilitation and treatment consolidation stages. Their strength and BMD may be influenced by the timing of treatment and the intervention cycle, respectively. Considering the limited number of included literature and the instability of some outcome indicators, it is necessary to design more comprehensive and rigorous high-quality RCTs in the future to test the exercise efficacy of ALL children.

Characterizing the temporal dynamics of intrinsic brain activities in depressed adolescents with prior suicide attempts.

Converging evidence has revealed disturbances in the corticostriatolimic system are associated with suicidal behaviors in adults with major depressive disorder. However, the neurobiological mechanism that confers suicidal vulnerability in depressed adolescents is largely unknown. A total of 86 depressed adolescents with and without prior suicide attempts (SA) and 47 healthy controls underwent resting-state functional imaging (R-fMRI) scans. The dynamic amplitude of low-frequency fluctuations (dALFF) was measured using sliding window approach. We identified SA-related alterations in dALFF variability primarily in the left middle temporal gyrus, inferior frontal gyrus, middle frontal gyrus (MFG), superior frontal gyrus (SFG), right SFG, supplementary motor area (SMA) and insula in depressed adolescents. Notably, dALFF variability in the left MFG and SMA was higher in depressed adolescents with recurrent suicide attempts than in those with a single suicide attempt. Moreover, dALFF variability was capable of generating better diagnostic and prediction models for suicidality than static ALFF. Our findings suggest that alterations in brain dynamics in regions involved in emotional processing, decision-making and response inhibition are associated with an increased risk of suicidal behaviors in depressed adolescents. Furthermore, dALFF variability could serve as a sensitive biomarker for revealing the neurobiological mechanisms underlying suicidal vulnerability.

Diversity in Cell Morphology, Composition, and Function among Adipose Depots in River Buffaloes.

Fat deposition is a significant economic trait in livestock animals. Adipose tissues (ATs) developed in subcutaneous and visceral depots are considered waste whereas those within muscle are highly valued. In river buffaloes, lipogenesis is highly active in subcutaneous (especially in the sternum subcutaneous) and visceral depots but not in muscle tissue. Revealing the features and functions of ATs in different depots is significant for the regulation of their development. Here, we characterize the cell size, composition, and function of six AT depots in river buffaloes. Our data support that the subcutaneous AT depots have a larger cell size than visceral AT depots, and the subcutaneous AT depots, especially the sternum subcutaneous AT, are mainly associated with the extracellular matrix whereas the visceral AT depots are mainly associated with immunity. We found that sternum subcutaneous AT is significantly different from ATs in other depots, due to the high unsaturated fatty acid content and the significant association with metabolic protection. The perirenal AT is more active in FA oxidation for energy supply. In addition, the expression of HOX paralogs supports the variable origins of ATs in different depots, indicating that the development of ATs in different depots is mediated by their progenitor cells. The present study enhances our understanding of the cellular and molecular features, metabolism, and origin of AT depots in buffaloes, which is significant for the regulation of fat deposition and provides new insights into the features of AT depots in multiple discrete locations.

WRKY Transcriptional Factor IlWRKY70 from Iris laevigata Enhances Drought and Salinity Tolerances in Nicotiana tabacum.

Drought and high salinity greatly affect plant growth and development. WRKY transcription factors play a key role in plant tolerance to abiotic stress, but the functions of WRKYs in the ornamental monocotyledon Iris laevigata remain largely unexplored. In this study, we cloned IlWRKY70 and found that it is a Group III WRKY localized in the nucleus. The expression of IlWRKY70 was induced by NaCl and PEG-6000, which reached peaks (4.38 and 5.65 times) after 3 h and 1 h, respectively. The exogenous overexpression of IlWRKY70 in N. tabacum significantly improved the resistance under NaCl and drought treatments, as evidenced by higher germination rates, longer root lengths, and increased fresh weights compared to those of control plants. In addition, transgenic seedlings showed significantly reduced wilting, higher photosynthetic performance, higher Fv/Fm and chlorophyll content, and lower stomatal conductance. Moreover, transgenic lines showed higher antioxidant enzymatic activities, lower reactive oxygen species (ROS), and lower malondialdehyde contents. Accordingly, we also found higher expressions of antioxidant defense genes, including SOD, CAT, and POD, in transgenic lines compared to controls under salt and drought stresses. Thus, IlWRKY70 enhances the abilities of salt and drought tolerances in plants, at least partially, via ROS regulation and can be used for breeding I. laevigata possessing enhanced salt and drought resistances.

Effects of Dietary Inclusion of ß-Hydroxy-ß-Methylbutyrate on Growth Performance, Fat Deposition, Bile Acid Metabolism, and Gut Microbiota Function in High-Fat and High-Cholesterol Diet-Challenged Layer Chickens.

Excessive lipid deposition in layer chickens due to inappropriate feeding adversely affects egg production; however, nutritional manipulation methods to deal with this issue are still limited. ß-hydroxy-ß-methylbutyrate (HMB), a metabolite of L-leucine, was recently reported as a lipid-lowering nutrient in mice and pigs, although its role in layers had not been investigated. Here, we employed high-fat and high-cholesterol diet (HFHCD)-challenged growing layers as an obese model to explore HMB function in the regulation of lipid metabolism and the potential mechanisms involved. We found that dietary supplementation with (0.05% or 0.10%) HMB significantly reduced HFHCD-induced bodyweight growth in layers, mainly due to reduction in abdominal fat deposition. Mechanistically, HMB supplementation enhanced hepatic bile acid synthesis from cholesterol through elevating expression of Cyp7a1, a gene coding a key enzyme in bile acid synthesis. Furthermore, 16S rRNA gene sequencing revealed that HMB supplementation remodeled the diversity and composition of the layers' cecal microbiota, and the abundance of Bacteroidetes at the phylum level were especially affected. Correlation analysis further indicated a strong negative association between Bacteroidetes abundance and lipid metabolism-related parameters. Taken together, these data suggest that dietary HMB supplementation could improve abdominal fat deposition in layers, probably through modulating hepatic bile acid synthesis and gut microbiota function.

Physiological and metabolomics responses of Hydrangea macrophylla (Thunb.) Ser. and Hydrangea strigosa Rehd. to lead exposure.

Hydrangea is a potential remediation plant for lead (Pb) pollution. Plant roots communicate with soil through the release of root exudates. It is crucial to study rhizoremediation mechanisms to understand the response of root exudates to contamination stress. Here, we investigated the physiological responses and metabolomic profiling of two Hydrangea species, a horticultural cultivar (Hydrangea macrophylla (Thunb.) Ser.) and a wild type (Hydrangea strigosa Rehd.), under Pb-free and Pb-stressed conditions for 50 days. The results showed that Pb treatment adversely affected the biomass and root growth of the two species. H. strigosa was a Pb-tolerant species with higher superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) activities and more ascorbic acid (AsA) content in roots. Metabolomic profiling showed that 181 and 169 compounds were identified in H. macrophylla and H. strigosa root exudates, respectively, among which 18 showed significant differences between H. macrophylla and H. strigosa under Pb exposure. H. strigosa showed significantly (P < 0.05) higher secretion of sucrose, glycolic acid, and nonanoic acid than H. macrophylla after Pb treatment. Pb stress promoted fatty acid metabolism in H. strigosa, suppressed amino acid metabolism in H. macrophylla, and promoted a higher carbohydrate metabolism in H. strigosa compared with H. macrophylla. This study provides a possible mechanism for the high Pb absorption potential of Hydrangea.

The optimal time for the initiation of in vitro fertilization and embryo transfer among women with atypical endometrial hyperplasia and endometrial carcinoma receiving fertility-sparing treatment.

OBJECTIVE: To explore the optimal time for initiating in vitro fertilization and embryo transfer (IVF-ET) in women with complete remission after fertility-sparing treatment for grade I endometrial cancer (EC) or atypical endometrial hyperplasia (AEH). PATIENTS AND METHODS: Young women who demonstrated complete remission after fertility-sparing treatment for grade I EC or AEH and underwent IVF-ET treatment were included. A generalized estimating equation (GEE) was used to compare the outcomes of controlled ovarian hyperstimulation (COH) and embryo transfer at different times after discontinuing high-dose progesterone therapy, and patients were divided into three groups: ≤ 3 months (time 1), 3-9 months (time 2) and > 9 months (time 3). RESULTS: Thirty-seven women with complete remission after fertility-sparing treatment for grade I EC or AEH underwent 75 IVF-ET cycles. Regarding initiation of COH, 10 cycles for time 1, 31 cycles for time 2 and 34 cycles for time 3 were included. The odds ratios (95% confidence intervals) for the number of available embryos at time 2 and time 3 were 1.82 (1.08-3.08) and 2.45 (1.39-4.33), and those for the number of high-quality embryos at time 2 and time 3 were, respectively, 3.64 (1.34-9.87) and 3.62 (1.10-11.91), compared with that at time 1. Nineteen (51.4%) women had at least one clinical pregnancy and 13 (35.1%) women had live births. During a median follow-up period of 51 months (range 5-168 months), 10 (27.0%) women had disease relapse, with a median interval of 15.5 months (range 5-104 months). CONCLUSION: Initiating IVF-ET 3 months after ceasing high-dose progesterone therapy can lead to better outcomes of controlled ovarian hyperstimulation for women with endometrial cancer or atypical endometrial hyperplasia.

Discovery of New Inhibitors of eEF2K from Traditional Chinese Medicine Based on In Silico Screening and In Vitro Experimental Validation.

Eukaryotic elongation factor 2 kinase (eEF2K) is a highly conserved α kinase and is increasingly considered as an attractive therapeutic target for cancer as well as other diseases. However, so far, no selective and potent inhibitors of eEF2K have been identified. In this study, pharmacophore screening, homology modeling, and molecular docking methods were adopted to screen novel inhibitor hits of eEF2K from the traditional Chinese medicine database (TCMD), and then cytotoxicity assay and western blotting were performed to verify the validity of the screen. Resultantly, after two steps of screening, a total of 1077 chemicals were obtained as inhibitor hits for eEF2K from all 23,034 compounds in TCMD. Then, to verify the validity, the top 10 purchasable chemicals were further analyzed. Afterward, Oleuropein and Rhoifolin, two reported antitumor chemicals, were found to have low cytotoxicity but potent inhibitory effects on eEF2K activity. Finally, molecular dynamics simulation, pharmacokinetic and toxicological analyses were conducted to evaluate the property and potential of Oleuropein and Rhoifolin to be drugs. Together, by integrating in silico screening and in vitro biochemical studies, Oleuropein and Rhoifolin were revealed as novel eEF2K inhibitors, which will shed new lights for eEF2K-targeting drug development and anticancer therapy.

Translatome analysis reveals the regulatory role of betaine in high fat diet (HFD)-induced hepatic steatosis.

Non-alcoholic fatty liver disease (NAFLD) is a common disease with a multitude of complications. Increasing evidence shows that the dietary supplement with betaine, a natural chemical molecule, can effectively reduce the fat accumulation in the liver. Translational regulation is considered to play a vital role in gene expression, but whether betaine functions through the regulation of gene translational level is still unclear. To this end, RNC-seq (mRNAs bound to ribosome-nascent chain complex sequencing) and RNA-seq co-analyses were performed to identify betaine target genes by using the liver samples from high-fat diet adding betaine treated and high-fat diet treated mice. The results showed that betaine does play a lipid-lowering role by regulating the expression of gene translation levels; some NAFLD- and lipid metabolism-associated genes were differentially expressed at translational level, for example. And the translation ratio (TR) of gene significantly increased after betaine treatment. Finally, we identified a novel function gene, Gpc1, which may mediate the lipid-lowering effect of betaine in the liver. To sum up, this study depicted the molecular portrait of mice liver with or without betaine treatment from the angel of translatome and transcriptome, giving insights into the molecular mechanism of betaine-mediated lipid-lowering effect and also providing new clues for understanding and prevention of NAFLD.

Lipogenic SREBP-1a/c transcription factors activate expression of the iron regulator hepcidin, revealing cross-talk between lipid and iron metabolisms.

The sterol regulatory element-binding proteins (SREBPs) are a family of transcription factors best known for stimulating the expression of genes encoding key lipogenic enzymes. However, SREBP functions beyond lipid metabolism are less understood. Here, we show that hepcidin antimicrobial peptide (Hamp), encoding the hormone hepcidin essential for iron homeostasis and regulated by dietary iron and inflammation, is a target gene of the two SREBP isoforms SREBP-1a/c. We found that in tissue culture, mature, active, and nuclear forms of the SREBP-1a/c proteins induce endogenous Hamp gene expression and increase the Hamp promoter activity primarily via three regulatory sequences, including an E-box. Moreover, ChIP experiments revealed that SREBP-1a binds to the Hamp gene promoter. Overexpression of nuclear SREBP-1a under the control of the phosphoenolpyruvate carboxylase-1 (Pck1) promoter in mice increased hepatic Hamp mRNA and blood hepcidin levels, and as expected, caused fatty liver. Consistent with the known effects of Hamp up-regulation, SREBP-1a-overexpressing mice displayed signs of dysregulation in iron metabolism, including reduced serum iron and increased hepatic and splenic iron storage. Conversely, liver-specific depletion of the nuclear forms of SREBPs, as in SREBP cleavage-activating protein knockout mice, impaired lipopolysaccharide-induced up-regulation of hepatic Hamp Together, these results indicate that the SREBP-1a/c transcription regulators activate hepcidin expression and thereby contribute to the control of mammalian iron metabolism.

Genomic analysis of worldwide sheep breeds reveals PDGFD as a major target of fat-tail selection in sheep.

BACKGROUND: Fat tail is a unique trait in sheep acquired during domestication. Several genomic analyses have been conducted in sheep breeds from limited geographic origins to identify the genetic factors underlying this trait. Nevertheless, these studies obtained different candidates. The results of these regional studies were easily biased by the breed structures. RESULTS: To minimize the bias and distinguish the true candidates, we used an extended data set of 968 sheep representing 18 fat-tailed breeds and 14 thin-tailed breeds from around the world, and integrated two statistical tests to detect selection signatures, including Genetic Fixation Index (FST) and difference of derived allele frequency (ΔDAF). The results showed that platelet derived growth factor D (PDGFD) exhibited the highest genetic differentiation between fat- and thin-tailed sheep breeds. Analysis of sequence variation identified that a 6.8-kb region within the first intron of PDGFD is likely the target of positive selection and contains regulatory mutation(s) in fat-tailed sheep. Histological and gene expression analyses demonstrated that PDGFD expression is associated with maturation and hemostasis of adipocytes. Further retrospective analysis of public transcriptomic datasets revealed that PDGFD expression is down-regulated during adipogenesis in both human and mouse, and is higher in fat tissues of obese individuals than that in lean individuals. CONCLUSIONS: These results reveal that PDGFD is the predominant factor for the fat tail phenotype in sheep by contributing to adiopogenesis and maintaining the hemostasis of mature adipocytes. This study provides insights into the selection of fat-tailed sheep and has important application to animal breeding, as well as obesity-related human diseases.

Annual variations of black carbon over the Yangtze River Delta from 2015 to 2018.

In this study, the black carbon (BC) measurements in the atmosphere of Nanjing, China were continuously conducted from 2015 to 2018 using a Model AE-33 aethalometer. By combining dataset of PM2.5, PM10, CO, NO2, SO2, O3 and meteorological parameters, the temporal variations and the source apportionment of BC were given in this study. The results showed that the PM2.5 mass concentrations decreased in Nanjing, with an average annual rate of variation of 6.50 µg/(m3⋅year). Differently, the annual average concentrations of BC increased with an average annual variation rate of 214.71 ng/(m3⋅year). The seasonal variations showed the pattern of BC mass concentrations in winter > autumn > spring > summer. The diurnal variations of BC mass concentrations showed a double-peak in all four seasons. The first peak occurred at approximately 7:00 in spring, summer and autumn and around 8:00 in winter. The second peak took place after 18:00. The average AAE (absorption Ångström exponent) was 1.26 with a maximum of 1.35 during wintertime and the lowest (1.12) during summertime. In addition, the AAE was smaller in the daytime than that at night, with a minimum occurring between 13:00 and 14:00. BC and visibility show a good power-function relationship at different humidity levels. The average values of the visibility thresholds of the BC mass concentrations in spring, summer, autumn and winter were 1.326, 5.522, 1.340 and 0.708 µg/m3, respectively. The greater the relative humidity, the smaller the visibility threshold for the BC mass concentrations was.

Glucose-Sensing Transcription Factor MondoA/ChREBP as Targets for Type 2 Diabetes: Opportunities and Challenges.

The worldwide increase in type 2 diabetes (T2D) is becoming a major health concern, thus searching for novel preventive and therapeutic strategies has become urgent. In last decade, the paralogous transcription factors MondoA and carbohydrate response element-binding protein (ChREBP) have been revealed to be central mediators of glucose sensing in multiple metabolic organs. Under normal nutrient conditions, MondoA/ChREBP plays vital roles in maintaining glucose homeostasis. However, under chronic nutrient overload, the dysregulation of MondoA/ChREBP contributes to metabolic disorders, such as insulin resistance (IR) and T2D. In this review, we aim to provide an overview of recent advances in the understanding of MondoA/ChREBP and its roles in T2D development. Specifically, we will briefly summarize the functional similarities and differences between MondoA and ChREBP. Then, we will update the roles of MondoA/ChREBP in four T2D-associated metabolic organs (i.e., the skeletal muscle, liver, adipose tissue, and pancreas) in physiological and pathological conditions. Finally, we will discuss the opportunities and challenges of MondoA/ChREBP as drug targets for anti-diabetes. By doing so, we highlight the potential use of therapies targeting MondoA/ChREBP to counteract T2D and its complications.

Cyclin C regulates adipogenesis by stimulating transcriptional activity of CCAAT/enhancer-binding protein α.

Brown adipose tissue is important for maintaining energy homeostasis and adaptive thermogenesis in rodents and humans. As disorders arising from dysregulated energy metabolism, such as obesity and metabolic diseases, have increased, so has interest in the molecular mechanisms of adipocyte biology. Using a functional screen, we identified cyclin C (CycC), a conserved subunit of the Mediator complex, as a novel regulator for brown adipocyte formation. siRNA-mediated CycC knockdown (KD) in brown preadipocytes impaired the early transcriptional program of differentiation, and genetic KO of CycC completely blocked the differentiation process. RNA sequencing analyses of CycC-KD revealed a critical role of CycC in activating genes co-regulated by peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα). Overexpression of PPARγ2 or addition of the PPARγ ligand rosiglitazone rescued the defects in CycC-KO brown preadipocytes and efficiently activated the PPARγ-responsive promoters in both WT and CycC-KO cells, suggesting that CycC is not essential for PPARγ transcriptional activity. In contrast, CycC-KO significantly reduced C/EBPα-dependent gene expression. Unlike for PPARγ, overexpression of C/EBPα could not induce C/EBPα target gene expression in CycC-KO cells or rescue the CycC-KO defects in brown adipogenesis, suggesting that CycC is essential for C/EBPα-mediated gene activation. CycC physically interacted with C/EBPα, and this interaction was required for C/EBPα transactivation domain activity. Consistent with the role of C/EBPα in white adipogenesis, CycC-KD also inhibited differentiation of 3T3-L1 cells into white adipocytes. Together, these data indicate that CycC activates adipogenesis in part by stimulating the transcriptional activity of C/EBPα.

Differentiation of 3T3-L1 preadipocytes is inhibited under a modified ceiling culture.

Ceiling culture is an inverted and closed cell culture system which represents a novel method for exploring adipocyte characteristics and function. Although the role of ceiling culture in mature adipocyte dedifferentiation has been extensively studied, its potential effects on preadipocyte differentiation remain unclear. In this study, we established a simplified dish ceiling culture method for 3T3-L1 preadipocytes and showed that our novel ceiling culture method could reproduce the function of the traditional flask ceiling culture. Then, we investigated the effects of ceiling culture on 3T3-L1 preadipocyte differentiation by Oil red O staining and RT-qPCR. The results showed that ceiling culture significantly impaired triglyceride accumulation and adipogenic marker genes expression in 3T3-L1 preadipocytes. These findings suggest that ceiling culture inhibited 3T3-L1 preadipocyte differentiation while inducing mature adipocytes dedifferentiation. Taken together, our data facilitate the understanding of the property of ceiling culture and promote the study of revealing the underlying mechanisms of mature adipocytes dedifferenatiation.

MicroRNA-199a-5p affects porcine preadipocyte proliferation and differentiation.

MicroRNAs (miRNAs), a class of small non-coding RNAs, have emerged as novel and potent regulators of adipogenesis. However, few miRNAs have been fully investigated in porcine adipogenesis, given the fact that pig is not only an apropos model of human obesity research, but also a staple meat source of human diet. In this study, we showed that miRNA-199a-5p is highly expressed in porcine subcutaneous fat deposits compared to several other tissue types and organs measured alongside. Overexpression of miR-199a-5p in porcine preadipocytes significantly promoted cell proliferation while attenuating the lipid deposition in porcine adipocytes. By target gene prediction and experimental validation, we demonstrated that caveolin-1 (Cav-1) may be a bona fide target of miR-199a-5p in porcine adipocytes, accounting for some of miR-199a-5p's functions. Taken together, our data established a role of miR-199a-5p in porcine preadipocyte proliferation and differentiation, which is at least partially played by downregulating Cav-1.

Functionally conserved PPARG exonic circRNAs enhance intramuscular fat deposition by regulating PPARG and HSL.

Circular RNAs (circRNA) are a kind of endogenous biological macromolecules that play significant roles in many biological processes, including adipogenesis, a precisely orchestrated process that is mediated by a large number of factors. Among them, peroxisome proliferator-activated receptor gamma (PPARG), is undoubtedly the most important regulator of adipocyte development in all types of adipose tissue. The formation of intramuscular fat (IMF), is a key factor that influences the meat quality in livestock animals. PPARG has been demonstrated to show a positive correlation with IMF deposition although the regulatory mechanism involved is not known. This study demonstrates that PPARG mediates IMF deposition by producing multiple exonic circRNAs (circPPARGs). Three circPPARGs promote adipogenic differentiation and inhibit the proliferation of intramuscular preadipocytes and these effects are conserved across several species including buffaloes, cattle and mice. Notably, circPPARG1 interacts with PPARG protein to inhibit the transcription of hormone sensitive lipase (HSL) involved in lipolysis. In addition, the positive effects of circPPARG1 on IMF deposition were identified in mice in vivo. Thus, PPARG drives IMF deposition, not only through the common transcription factor pathway, but also by producing circRNAs. This study provides new insights into our understanding of the regulatory mechanisms of PPARG in IMF deposition.

WRKY22 Transcription Factor from Iris laevigata Regulates Flowering Time and Resistance to Salt and Drought.

Iris laevigata Fisch. is an excellent ornamental plant in cold regions due to its unique ornamental ability and strong cold resistance. However, the flowering period of the population is only about 20 days, greatly limiting its potential uses in landscaping and the cutting flower industry. In addition, I. laevigata is often challenged with various abiotic stresses including high salinity and drought in its native habitats. Thus, breeding novel cultivars with delayed flowering time and higher resistance to abiotic stress is of high importance. In this study, we utilized sequencing data from the I. laevigata transcriptome to identify WRKYs and characterized IlWRKY22, a key transcription factor that modulates flowering time and abiotic stress responses. IlWRKY22 is induced by salt and drought stress. We cloned IlWRKY22 and found that it is a Group IIe WRKY localized in the nucleus. Overexpressing IlWRKY22 in Arabidopsis thaliana (L.) Heynh. and Nicotiana tabacum L. resulted in a delayed flowering time in the transgenic plants. We created transgenic N. tabacum overexpressing IlWRKY22, which showed significantly improved resistance to both salt and drought compared to the control plants. Thus, our study revealed a unique dual function of IlWRKY22, an excellent candidate gene for breeding novel Iris cultivars of desirable traits.

Recent autumn sea ice loss in the eastern Arctic enhanced by summer Asian-Pacific Oscillation.

Recent rapid Arctic sea ice loss was documented as combined results from anthropogenic forcing and climate system internal variability. However, the role of internal variability is not well understood. Here, we propose that the Asian-Pacific Oscillation (APO), an intrinsic atmospheric mode featuring out-of-phase variations in upper-tropospheric temperatures between Asia and the North Pacific, is one driver for autumn sea ice variability in the eastern Arctic. The positive summer APO favors warming of the mid-latitude North Atlantic sea surface temperatures. This warming persists to autumn and in turn triggers strong anticyclonic anomalies over the Barents-Kara-Laptev Seas and weak lower-tropospheric cyclonic anomalies over the East Siberian Sea, enhancing moisture transport into the eastern Arctic. Such changes consequently increase lower-tropospheric humidity, downwelling longwave radiation, and surface air temperature in the eastern Arctic, thereby melting sea ice. Hence, a recent tendency of the summer APO towards the positive phase accelerates autumn sea ice loss in the eastern Arctic.

Self-assembly of maltose-albumin nanoparticles for efficient targeting delivery and therapy in liver cancer.

The effective delivery and targeted release of drugs within tumor cells are critical factors in determining the therapeutic efficacy of nanomedicine. To achieve this objective, a conjugate of maltose (Mal) and bovine serum albumin (BSA) was synthesized by the Maillard reaction and self-assembled into nanoparticles with active-targeting capabilities upon pH/heating induction. This nanoparticle could be effectively loaded with doxorubicin (DOX) to form stable nanodrugs (Mal-BSA/DOX) that were sensitive to low pH or high glutathione (GSH), thereby achieving a rapid drug release (96.82 % within 24 h). In vitro cell experiments indicated that maltose-modified BSA particles efficiently enhance cellular internalization via glucose transporters (GLUT)-mediated endocytosis, resulting in increased intracellular DOX levels and heightened expression of γ-H2AX. Consequently, these results ultimately lead to selective tumor cells death, as evidenced by an IC50 value of 3.83 µg/mL in HepG2 cells compared to 5.87 µg/mL in 293t cells. The efficacy of Mal-BSA/DOX in tumor targeting therapy has been further confirmed by in vivo studies, as it effectively delivered a higher concentration of DOX to tumor tissue. This targeted delivery approach not only reduces the systemic toxicity of DOX but also effectively inhibits tumor growth (TGI, 75.95 %). These findings contribute valuable insights into the advancement of targeting-albumin nanomedicine and further support its potential in tumor treatment.