Macrophage polarization in adenomyosis: A review.

Adenomyosis (AM) is a common gynecological disorder characterized by the presence of endometrial glands and stroma within the uterine myometrium. It is associated with abnormal uterine bleeding (AUB), dysmenorrhea, and infertility. Although several mechanisms have been proposed to elucidate AM, the exact cause and development of the condition remain unclear. Recent studies have highlighted the significance of macrophage polarization in the microenvironment, which plays a crucial role in AM initiation and progression. However, a comprehensive review regarding the role and regulatory mechanism of macrophage polarization in AM is currently lacking. Therefore, this review aims to summarize the phenotype and function of macrophage polarization and the phenomenon of the polarization of adenomyosis-associated macrophages (AAMs). It also elaborates on the role and regulatory mechanism of AAM polarization in invasion/migration, fibrosis, angiogenesis, dysmenorrhea, and infertility. Furthermore, this review explores the underlying molecular mechanisms of AAM polarization and suggests future research directions. In conclusion, this review provides a new perspective on understanding the pathogenesis of AM and provides a theoretical foundation for developing targeted drugs through the regulation of AAM polarization.

Increased circulating cell-free mitochondrial DNA in plasma of first-diagnosed drug-naïve bipolar disorder patients: A case-control and 4-week follow-up study.

BACKGROUND: The study of clinical biological indicators in bipolar disorder (BD) is important. In recent years, basic experiments have associated the pathophysiological mechanism of BD is related to mitochondrial dysfunction, but few clinical studies have confirmed this finding. OBJECT: The present study aimed to evaluate whether plasma circulating cell-free mitochondrial DNA (ccf-mtDNA) levels, which can represent the degree of mitochondrial damage in vivo, are altered in patients with BD in early onset and during treatment compared with controls. METHOD: A total of 75 first-diagnosed drug-naive patients with BD and 60 HCs were recruited and followed up for 1 month. The clinical symptoms were assessed using HAMD, HAMA, and YMRS, and ccf-mtDNA levels were measured by qPCR before and after drug treatment in BD. RESULT: (1) The plasma ccf-mtDNA levels in first-diagnosed drug-naive patients with BD increased compared with those in HCs (p = 0.001). (2) Drug treatment for 1 month can decrease the expression of ccf-mtDNA in BD (p < 0.001). (3) No significant correlation was observed between the changes in ccf-mtDNA levels and the improvement of clinical symptoms in BD after drug treatment. CONCLUSION: The plasma ccf-mtDNA level was increased in BD, and decreased after pharmacological treatment. These outcomes suggested that plasma ccf-mtDNA level is likely to be sensitive to the drug response in BD, and mitochondrial pathway is a potential target for further therapy.

T2T reference genome assembly and genome-wide association study reveal the genetic basis of Chinese bayberry fruit quality.

Chinese bayberry (Myrica rubra or Morella rubra; 2n = 16) produces fruit with a distinctive flavor, high nutritional, and economic value. However, previous versions of the bayberry genome lack sequence continuity. Moreover, to date, no large-scale germplasm resource association analysis has examined the allelic and genetic variations determining fruit quality traits. Therefore, in this study, we assembled a telomere-to-telomere (T2T) gap-free reference genome for the cultivar 'Zaojia' using PacBio HiFi long reads. The resulting 292.60 Mb T2T genome, revealed 8 centromeric regions, 15 telomeres, and 28 345 genes. This represents a substantial improvement in the genome continuity and integrity of Chinese bayberry. Subsequently, we re-sequenced 173 accessions, identifying 6 649 674 single nucleotide polymorphisms (SNPs). Further, the phenotypic analyses of 29 fruit quality-related traits enabled a genome-wide association study (GWAS), which identified 1937 SNPs and 1039 genes significantly associated with 28 traits. An SNP cluster pertinent to fruit color was identified on Chr6: 3407532 to 5 153 151 bp region, harboring two MYB genes (MrChr6G07650 and MrChr6G07660), exhibiting differential expression in extreme phenotype transcriptomes, linked to anthocyanin synthesis. An adjacent, closely linked gene, MrChr6G07670 (MLP-like protein), harbored an exonic missense variant and was shown to increase anthocyanin production in tobacco leaves tenfold. This SNP cluster, potentially a quantitative trait locus (QTL), collectively regulates bayberry fruit color. In conclusion, our study presented a complete reference genome, uncovered a suite of allelic variations related to fruit-quality traits, and identified functional genes that could be harnessed to enhance fruit quality and breeding efficiency of bayberries.

FGD1-related Aarskog-Scott syndrome: Identification of four novel variations and a literature review of clinical and molecular aspects.

Patients with Aarskog-Scott syndrome (AAS) have short stature, facial anomalies, skeletal deformities, and genitourinary malformations. FYVE, RhoGEF, and PH domain-containing 1 (FGD1) is the only known causative gene of AAS. However, the diagnosis of AAS remains difficult, and specific treatments are still absent. Patients suspected with AAS were recruited, and clinical information was collected. Genetic testing and functional analysis were carried out for the diagnosis. By literature review, we summarized the clinical and genetic characteristics of FGD1-related AAS and analyzed the genotype-phenotype correlation. Five patients were recruited, and four novel FGD1 variants were identified. The diagnosis of AAS was confirmed by genetic analysis and functional study. Three patients treated with growth hormone showed improved heights during the follow-up period. By literature review, clinical features of AAS patients with FGD1 variants were summarized. Regarding FGD1 variations, substitutions were the most common form, and among them, missense variants were the most frequent. Moreover, we found patients with drastic variants showed higher incidences of foot and genitourinary malformations. Missense variants in DH domain were related to a lower incidence of cryptorchidism.   Conclusion: We reported four novel pathogenic FGD1 variations in AAS patients and confirmed the efficacy and safety of growth hormone treatment in FGD1-related AAS patients with growth hormone deficiency. Additionally, our literature review suggested the crucial role of DH domain in FGD1 function. What is Known: • Aarskog-Scott syndrome is a rare genetic disease, and the only known cause is the variant in FGD1 gene. The typical clinical manifestations of AAS include facial, skeletal, and urogenital deformities and short stature. What is New: • We reported four novel FGD1 variants and reported the treatment of growth hormone in FGD1-related AAS patients. Our genotype-phenotype correlation analysis suggested the crucial role of DH domain in FGD1 function.

Cucurbitacin IIa promotes the immunogenic cell death­inducing effect of doxorubicin and modulates immune microenvironment in liver cancer.

The immunogenic cell death (ICD) has aroused great interest in cancer immunotherapy. Doxorubicin (DOX), which can induce ICD, is a widely used chemotherapeutic drug in liver cancer. However, DOX­induced ICD is not potent enough to initiate a satisfactory immune response. Cucurbitacin IIa (CUIIa), a tetracyclic triterpene, is a biologically active compound present in the Cucurbitaceae family. The present study assessed the effects of the combination of DOX and CUIIa on the viability, colony formation, apoptosis and cell cycle of HepG2 cells. In vivo anticancer effect was performed in mice bearing H22 tumor xenografts. The hallmark expression of ICD was tested using immunofluorescence and an ATP assay kit. The immune microenvironment was analyzed using flow cytometry. The combination of CUIIa and DOX displayed potent apoptosis inducing, cell cycle arresting and in vivo anticancer effects, along with attenuated cardiotoxicity in H22 mice. The combination of DOX and CUIIa also facilitated ICD as manifested by elevated high­mobility group box 1, calreticulin and ATP secretion. This combination provoked a stronger immune response in H22 mice, including dendritic cell activation, increment of cytotoxic T cells and T helper 1 cells. Moreover, the proportion of immunosuppressive cells including myeloid­derived suppressor cells, T regulatory cells and M2­polarized macrophages, decreased. These data suggested that CUIIa is a promising combination partner with DOX for liver cancer treatment, probably via triggering ICD and remolding the immune microenvironment.

Rapid detection of mexX in Pseudomonas aeruginosa based on CRISPR-Cas13a coupled with recombinase polymerase amplification.

The principal pathogen responsible for chronic urinary tract infections, immunocompromised hosts, and cystic fibrosis patients is Pseudomonas aeruginosa, which is difficult to eradicate. Due to the extensive use of antibiotics, multidrug-resistant P. aeruginosa has evolved, complicating clinical therapy. Therefore, a rapid and efficient approach for detecting P. aeruginosa strains and their resistance genes is necessary for early clinical diagnosis and appropriate treatment. This study combines recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats-association protein 13a (CRISPR-Cas13a) to establish a one-tube and two-step reaction systems for detecting the mexX gene in P. aeruginosa. The test times for one-tube and two-step RPA-Cas13a methods were 5 and 40 min (including a 30 min RPA amplification reaction), respectively. Both methods outperform Quantitative Real-time Polymerase Chain Reactions (qRT-PCR) and traditional PCR. The limit of detection (LoD) of P. aeruginosa genome in one-tube and two-step RPA-Cas13a is 10 aM and 1 aM, respectively. Meanwhile, the designed primers have a high specificity for P. aeruginosa mexX gene. These two methods were also verified with actual samples isolated from industrial settings and demonstrated great accuracy. Furthermore, the results of the two-step RPA-Cas13a assay could also be visualized using a commercial lateral flow dipstick with a LoD of 10 fM, which is a useful adjunt to the gold-standard qRT-PCR assay in field detection. Taken together, the procedure developed in this study using RPA and CRISPR-Cas13a provides a simple and fast way for detecting resistance genes.

Molecular Genetic Analysis and Growth Hormone Treatment in a Three-Generation Chinese Family with Tricho-Rhino-Phalangeal Syndrome I.

INTRODUCTION: Tricho-rhino-phalangeal syndrome (TRPS) is a rare genetic disorder characterized by craniofacial and skeletal abnormalities, which is caused by variants in the TRPS1 gene. METHODS: Clinical information and follow-up data were collected. Whole-exome sequencing (WES) was performed for variants and validated by Sanger sequencing. Bioinformatic analysis was performed to predict the pathogenicity of the identified variant. Moreover, wild-type and mutated TRPS1 vectors were constructed and transfected into human embryonic kidney (HEK) 293T cells. Immunofluorescence experiments were performed to assess the localization and expression of the mutated protein. Western blot analysis and RT-qPCR were used to detect the expression of downstream genes. RESULTS: The affected family members had typical craniofacial phenotype including sparse lateral eyebrows, pear-shaped nasal tip, and large prominent ears, plus skeletal abnormalities including short stature and brachydactyly. WES and Sanger sequencing identified the TRPS1 c.880_882delAAG variant in affected family members. In vitro functional studies showed that the TRPS1 variant did not affect the cellular localization and the expression of TRPS1, but the transcriptional repression effect of the TRPS1 on the RUNX2 and STAT3 was disturbed. The proband and his brother have been treated with growth hormone (GH) for 2 years until now, and we have observed the improvement of the linear growth in both. CONCLUSIONS: The variant of c.880_882delAAG in TRPS1 was responsible for the pathogenesis of the Chinese family with TRPS I. The treatment of GH could be beneficial for the height outcome in TRPS I patients, and earlier initiation and longer duration of the therapy in prepubertal or early pubertal stage could be associated with better height outcomes.

A key mutation in magnesium chelatase I subunit leads to a chlorophyll-deficient mutant of tea (Camellia sinensis).

Tea (Camellia sinensis) is a highly important beverage crop renowned for its unique flavour and health benefits. Chlorotic mutants of tea, known worldwide for their umami taste and economic value, have gained global popularity. However, the genetic basis of this chlorosis trait remains unclear. In this study, we identified a major-effect quantitative trait locus (QTL), qChl-3, responsible for the chlorosis trait in tea leaves, linked to a non-synonymous polymorphism (G1199A) in the magnesium chelatase I subunit (CsCHLI). Homozygous CsCHLIA plants exhibited an albino phenotype due to defects in magnesium protoporphyrin IX and chlorophylls in the leaves. Biochemical assays revealed that CsCHLI mutations did not affect subcellular localization or interactions with CsCHLIG and CsCHLD. However, combining CsCHLIA with CsCHLIG significantly reduced ATPase activity. RNA-seq analysis tentatively indicated that CsCHLI inhibited photosynthesis and enhanced photoinhibition, which in turn promoted protein degradation and increased the amino acid levels in chlorotic leaves. RT-qPCR and enzyme activity assays confirmed the crucial role of asparagine synthetase and arginase in asparagine and arginine accumulation, with levels increasing over 90-fold in chlorotic leaves. Therefore, this study provides insights into the genetic mechanism underlying tea chlorosis and the relationship between chlorophyll biosynthesis and amino acid metabolism.

How to achieve carbon neutrality and low-carbon economic development-evidence from provincial data in China.

"Carbon Peaking and Carbon Neutrality" is a major strategy for China to cope with climate change at present. We define the carbon neutrality capability (CNC) to reflect the current situation of regional carbon neutrality, and propose a new coupling model to explore the coupling relationship between regional economic development and carbon neutrality capability (CNC). Finally, the influence mechanism of the energy consumption structure on CNC was further discussed by using STRIPAT model. The results show that: during we study period, the national average carbon sink was about 77.89 Mt, and the carbon sinks in Inner Mongolia, Heilongjiang, Sichuan and Yunnan were as high as 164 Mt, mainly concentrated in the western region. The national average carbon source is 222.12 Mt, which is about three times that of carbon sink. The carbon source in Shandong, Hebei and Jiangsu are as high as 400 Mt or more, mainly concentrated in the eastern region. In addition, the growth rate of carbon source is much faster than that of carbon sink, especially the carbon emission caused by energy consumption, which leads to a general decline in CNC, and the development of CNC in various provinces is not optimistic. CNC and economic development level of most provinces are in a state of recession decoupling, and the coupling state of the provinces studied in certain years is significantly different. The spatial distribution of CNC and GDP has shown a northeast-southwest pattern. In addition, the influence of coal consumption structure on CNC is significantly negative, so we should optimize the energy consumption structure and increase the proportion of clean energy consumption. This study can make clear the current carbon neutrality capability of provinces in China, facilitate the formulation and adjustment of emission reduction strategies of provinces and cities, and help China to achieve carbon neutrality as soon as possible.

Osteoporosis and low bone mass among schizophrenia and bipolar disorder: A cross-sectional study with newly diagnosed, drug-naïve subjects.

BACKGROUND: A growing body of data shows that schizophrenia (SCZ) and bipolar disorder (BD) have substantial metabolic risks; however, few studies have focused on bone metabolism. This study aimed to assess the prevalence and associated influencing factors of low bone mass and osteoporosis in SCZ and BD before pharmacological effects occur. METHODS: 108 healthy controls (HCs) and drug-naïve individuals with SCZ (n = 56) and BD (n = 130) had their lumbar spine (L1-L4) and left femur (Neck/Trochanter/Ward's triangle) bone mineral density (BMD) determined using dual-energy X-ray absorptiometry. Besides, we measured bone turnover markers (BTMs) levels, including procollagen I N-terminal propeptide, osteocalcin, and C-terminal cross-linking telopeptide of type I collagen in different groups. RESULTS: Individuals with SCZ and BD had significantly lower BMD and significantly higher prevalence of low bone mass and osteoporosis compared with HCs. In the main observation regions of the total lumbar (F = 18.368, p < 0.001) and left femur (F = 14.790, p < 0.001), BMD was lower in individuals with SCZ and BD than HCs, with SCZ showing lower BMD than BD. The osteocalcin (H = 11.421, p = 0.003) levels were significantly higher in SCZ and BD than HCs. Binary regression analysis showed that SCZ or BD was an independent risk factor for low bone mass and osteoporosis. In addition, sex, age, and BTMs also influenced the occurrence of low bone mass and osteoporosis. LIMITATIONS: Cross-sectional study. CONCLUSION: The results findings of the study might contribute to our understanding of the increased risk of bone metabolism in SCZ and BD. CLINICAL TRIAL REGISTRATION: www.chictr.org.cn, identifier ChiCTR1900021379.

Development and validation of functional kompetitive allele-specific PCR markers for herbicide resistance in Brassica napus.

Effective weed control in the field is essential for maintaining favorable growing conditions and rapeseed yields. Sulfonylurea herbicides are one kind of most widely used herbicides worldwide, which control weeds by inhibiting acetolactate synthase (ALS). Molecular markers have been designed from polymorphic sites within the sequences of ALS genes, aiding marker-assisted selection in breeding herbicide-resistant rapeseed cultivars. However, most of them are not breeder friendly and have relatively limited application due to higher costs and lower throughput in the breeding projects. The aims of this study were to develop high throughput kompetitive allele-specific PCR (KASP) assays for herbicide resistance. We first cloned and sequenced BnALS1 and BnALS3 genes from susceptible cultivars and resistant 5N (als1als1/als3als3 double mutant). Sequence alignments of BnALS1 and BnALS3 genes for cultivars and 5N showed single nucleotide polymorphisms (SNPs) at positions 1676 and 1667 respectively. These two SNPs for BnALS1 and BnALS3 resulted in amino acid substitutions and were used to develop a KASP assay. These functional markers were validated in three distinct BC1F2 populations. The KASP assay developed in this study will be valuable for the high-throughput selection of elite materials with high herbicide resistance in rapeseed breeding programs.

Single-cell immune profiling reveals broad anti-inflammation response in bipolar disorder patients with quetiapine and valproate treatment.

Bipolar disorder (BD) is a common mental disorder characterized by manic and depressive episodes. Mood disorders have been associated with immune dysfunction. The combination of quetiapine and valproate has shown positive effects in treating BD, but the impact on immune dynamics remains less understood. Using single-cell RNA sequencing, we observed that B cells exhibited downregulation of inflammation-related genes, while pro-inflammatory mast and eosinophil cells decreased following treatment. Ribosomal peptide production genes were found to be reduced in both B and T cells after treatment. Additionally, our findings suggest that the combined therapy effectively alleviates inflammation by reducing myloid-mediated immune signaling pathways. This study provides valuable insights into the immune atlas and uncovers a potential mechanism for immune disorder alleviation in patients with BD treated with quetiapine and valproate.

FGL2 deficiency alleviates maternal inflammation-induced blood-brain barrier damage by blocking PI3K/NF-κB mediated endothelial oxidative stress.

Introduction: The impairment of blood-brain barrier (BBB) is one of the key contributors to maternal inflammation induced brain damage in offspring. Our previous studies showed Fibrinogen-like protein 2 (FGL2) deficiency alleviated maternal inflammation induced perinatal brain damage. However, its role in BBB remains undefined. Methods: Lipopolysaccharide (LPS) was intraperitoneally injected to dams at Embryonic day 17 to establish maternal inflammation model. FGL2 knockout mice and primary brain microvascular endothelial cells (BMECs) were used for the in-vivo and in-vitro experiments. BBB integrity was assessed by sodium fluorescein extravasation and tight junction (TJ) protein expression. Oxidative stress and the activation of PI3K/NF-κB pathway were evaluated to explore the mechanisms underlying. Results: Upon maternal inflammation, BBB integrity was remarkedly reduced in neonatal mice. Meanwhile, FGL2 expression was consistently increased in BBB-impaired brain as well as in LPS-treated BMECs. Moreover, FGL2 deficiency attenuated the hyperpermeability of BBB, prevented the decline of TJ proteins, and reduced the cytokine expressions in LPS-exposed pups. Mechanistically, the indicators of oxidative stress, as well as the activation of PI3K/NF-κB pathway, were upregulated after LPS exposure in vivo and in vitro. FGL2 deletion decreased the generation of ROS and NO, reduced the endothelial iNOS and NOX2 expressions, and suppressed the PI3K/NF-κB pathway activation. Besides, inhibition of PI3K by LY294002 decreased the oxidative stress in LPS-treated wild-type BMECs. While, overexpression of PI3K by lentivirus reemerged the induction of NOX2 and iNOS as well as NF-κB activation in FGL2-deleted BMECs. Conclusion: Our findings indicate that FGL2 deficiency alleviates the maternal inflammation-induced BBB disruption by inhibiting PI3K/NF-κB mediated oxidative stress in BMECs. Targeting FGL2 may provide a new therapy for prenatal brain damage of offspring.

Metabolomic Analysis Reveals Domestication-Driven Reshaping of Polyphenolic Antioxidants in Soybean Seeds.

Crop domestication has resulted in nutrient losses, so evaluating the reshaping of phytonutrients is crucial for improving nutrition. Soybean is an ideal model due to its abundant phytonutrients and wild relatives. In order to unravel the domestication consequence of phytonutrients, comparative and association analyses of metabolomes and antioxidant activities were performed on seeds of six wild (Glycine soja (Sieb. and Zucc.)) and six cultivated soybeans (Glycine max (L.) Merr.). Through ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), we observed a greater metabolic diversity in wild soybeans, which also displayed higher antioxidant activities. (-)-Epicatechin, a potent antioxidant, displayed a 1750-fold greater abundance in wild soybeans than in cultivated soybeans. Multiple polyphenols in the catechin biosynthesis pathway were significantly higher in wild soybeans, including phlorizin, taxifolin, quercetin 3-O-galactoside, cyanidin 3-O-glucoside, (+)-catechin, (-)-epiafzelechin, catechin-glucoside, and three proanthocyanidins. They showed significant positive correlations with each other and antioxidant activities, indicating their cooperative contribution to the high antioxidant activities of wild soybeans. Additionally, natural acylation related to functional properties was characterized in a diverse range of polyphenols. Our study reveals the comprehensive reprogramming of polyphenolic antioxidants during domestication, providing valuable insights for metabolism-assisted fortification of crop nutrition.

Approaches for Modes of Action Study of Long Non-Coding RNAs: From Single Verification to Genome-Wide Determination.

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides (nt) that are not translated into known functional proteins. This broad definition covers a large collection of transcripts with diverse genomic origins, biogenesis, and modes of action. Thus, it is very important to choose appropriate research methodologies when investigating lncRNAs with biological significance. Multiple reviews to date have summarized the mechanisms of lncRNA biogenesis, their localization, their functions in gene regulation at multiple levels, and also their potential applications. However, little has been reviewed on the leading strategies for lncRNA research. Here, we generalize a basic and systemic mind map for lncRNA research and discuss the mechanisms and the application scenarios of 'up-to-date' techniques as applied to molecular function studies of lncRNAs. Taking advantage of documented lncRNA research paradigms as examples, we aim to provide an overview of the developing techniques for elucidating lncRNA interactions with genomic DNA, proteins, and other RNAs. In the end, we propose the future direction and potential technological challenges of lncRNA studies, focusing on techniques and applications.

Association between uric acid and cognitive dysfunction: A cross-sectional study with newly diagnosed, drug-naïve with bipolar disorder.

BACKGROUND: Cognitive impairment is one of the major symptoms of individuals with bipolar disorder (BD). Purine system disorders may play an important role in cognitive dysfunction. So far, the relationship between cognitive deficits and purinergic metabolism in BD has been seldom discussed in previous studies. This study aims to explore its relevance and potential biological mechanisms. METHODS: In this cross-sectional study, 205 first time diagnosed drug-naive individuals with BD and 97 healthy volunteers were recruited. The uric acid(UA) level was measured using automatic biochemical analyzer, and cognitive function was assessed by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Stroop color-word test. In addition, general information and clinical symptoms were collected and evaluated. RESULTS: In this study, the UA level of BD group (U = 8475.000, p = 0.038) was found to be significantly higher than that of the healthy controls, but the scores of RBANS (t = -11.302, p < 0.001) and Stroop color-word test (t = -6.962, p < 0.001) were significantly lower than that of the healthy controls. In gender subgroup analysis, females had lower UA level and higher RBANS scores. In correlation analysis, the cognitive function of individuals with BD was found to present a significant negative correlation with UA level in attention (r = -0.23, p = 0.001) and delayed memory(r = -0.16, p = 0.022). LIMITATIONS: This is a cross-sectional design. CONCLUSION: Elevated UA levels may be a potential mechanism of cognitive impairment in BD. This provides a new possible strategy for the prevention and treatment of cognitive impairment in BD.

Emerging role of hypothalamus in the metabolic regulation in the offspring of maternal obesity.

Maternal obesity has a significant impact on the metabolism of offspring both in childhood and adulthood. The metabolic regulation of offspring is influenced by the intrauterine metabolic programming induced by maternal obesity. Nevertheless, the precise mechanisms remain unclear. The hypothalamus is the primary target of metabolic programming and the principal regulatory center of energy metabolism. Accumulating evidence has indicated the crucial role of hypothalamic regulation in the metabolism of offspring exposed to maternal obesity. This article reviews the development of hypothalamus, the role of the hypothalamic regulations in energy homeostasis, possible mechanisms underlying the developmental programming of energy metabolism in offspring, and the potential therapeutic approaches for preventing metabolic diseases later in life. Lastly, we discuss the challenges and future directions of hypothalamic regulation in the metabolism of children born to obese mothers.

Mitochondrial dysfunction in cardiovascular disease: Towards exercise regulation of mitochondrial function.

The morbidity and mortality of cardiovascular diseases are exceedingly high worldwide. Pathological heart remodeling, which is developed as a result of mitochondrial dysfunction, could ultimately drive heart failure. More recent research target exercise modulation of mitochondrial dysfunction to improve heart failure. Therefore, finding practical treatment goals and exercise programs to improve cardiovascular disease is instrumental. Better treatment options are available with the recent development of exercise and drug therapy. This paper summarizes pathological states of abnormal mitochondrial function and intervention strategies for exercise therapy.

Biotinylated Tn5 transposase-mediated CUT&Tag efficiently profiles transcription factor-DNA interactions in plants.

In contrast to CUT&Tag approaches for profiling bulk histone modifications, current CUT&Tag methods for analysing specific transcription factor (TF)-DNA interactions remain technically challenging due to TFs having relatively low abundance. Moreover, an efficient CUT&Tag strategy for plant TFs is not yet available. Here, we first applied biotinylated Tn5 transposase-mediated CUT&Tag (B-CUT&Tag) to produce high-quality libraries for interrogating TF-DNA interactions. B-CUT&Tag combines streptavidin-biotin-based DNA purification with routine CUT&Tag, optimizing the removal of large amounts of intact chromatin not targeted by specific TFs. The biotinylated chromatin fragments are then purified for construction of deep sequencing libraries or qPCR analysis. We applied B-CUT&Tag to probe genome-wide DNA targets of Squamosa promoter-binding-like protein 9 (SPL9), a well-established TF in Arabidopsis; the resulting profiles were efficient and consistent in demonstrating its well-established target genes in juvenile-adult transition/flowering, trichome development, flavonoid biosynthesis, wax synthesis and branching. Interestingly, our results indicate functions of AtSPL9 in modulating growth-defence trade-offs. In addition, we established a method for applying qPCR after CUT&Tag (B-CUT&Tag-qPCR) and successfully validated the binding of SPL9 in Arabidopsis and PHR2 in rice. Our study thus provides a convenient and highly efficient CUT&Tag strategy for profiling TF-chromatin interactions that is widely applicable to the annotation of cis-regulatory elements for crop improvement.

Physiological and transcriptomic evidence of antioxidative system and ion transport in chromium detoxification in germinating seedlings of soybean.

Chromium (Cr) toxicity impairs the productivity of crops and is a major threat to food security worldwide. However, the effect of Cr toxicity on seed germination and transcriptome of germinating seedlings of soybean crop has not been fully explored. In this study, two Cr-tolerant lines (J82, S125) and two Cr-sensitive ones (LD1, RL) were screened out of twenty-one soybean (Glycine max L.) genotypes based on seed germination rate, seed germinative energy, seed germination index, and growth of germinating seedlings under 50 mg L-1 Cr treatment. We found that Cr stress inhibits the growth of soybean seed germinating seedlings due to the Cr-induced overaccumulation of reactive oxygen species (ROS). Significantly different levels of element contents, antioxidant enzyme activities, malondialdehyde content were observed in the four soybean genotypes with contrasting Cr tolerance. Further, a total of 13,777 differentially expressed genes (DEGs) were identified in transcriptomic sequencing and 1298 DEGs in six gene modules were found highly correlated with the physiological traits by weighted correlation network analysis (WGCNA) analysis. The DEGs encoding antioxidant enzymes, transcription factors, and ion transporters are proposed to confer Cr tolerance in soybean germinating seedlings by reducing the uptake and translocation of Cr, decreasing the level of ROS, and keeping the osmotic balance in soybean germinating seedings. In conclusion, our study provided a molecular regulation network on soybean Cr tolerance at seed germinating stage and identified candidate genes for molecular breeding of low Cr accumulation soybean cultivars.