Perilla frutescens (L.) Britt. is a characteristic oil crop rich in polyunsaturated fatty acids, particularly α-linolenic acid, which has important development and utilization value. The Dof transcription factor is one of the plant-specific transcription factor families, which is widely involved in important biological processes such as plant growth, development, and metabolic regulation. In order to explore the key Dof transcription factors involved in the oil biosynthesis and systematically analyze their regulatory mechanisms of P. frutescens seeds, a total of 56 PfDof gene family members were identified from the genome and transcriptome data of P. frutescens and classified into four subfamilies according to sequence characteristics. All PfDofs contained highly conserved C₂-C₂ zinc finger domains, with gene duplication being the primary mechanism driving their evolution and expansion. Genes within the same subgroup exhibited similar gene structures and conserved motifs. The 56 PfDofs were predicted as unstable hydrophilic proteins, with α-helixes and random coils as their predominant structural components. The RNA-seq results revealed that 11 PfDofs exhibited differential expression during different developmental stages of P. frutescens seeds. RT-qPCR was performed to further validate the expression patterns of these 11 members across various tissue samples (root, stem, leaf, and flower) of P. frutescens and at different developmental stages of its seeds. The results showed that PfDof29 exhibited the highest expression level in seeds, which was consistent with the transcriptome data. Subcellular localization studies demonstrated that PfDof29 was localized to the nucleus and had a transcriptional activation activity. Overexpression of PfDof29 in Nicotiana tabacum resulted in a significant increase in total oil content of tobacco leaves, accompanied by reductions in starch and soluble sugar content, while the protein content remained unchanged. Additionally, the metabolic balance between saturated and unsaturated fatty acids in the transgenic tobacco leaves was altered, with a significant increase in α-linolenic acid content. The expression levels of the fatty acid desaturase genes NtFAD2, NtFAD3, and NtFAD8 were significantly upregulated. A yeast one-hybrid assay revealed that PfDof29 could directly bind to the promoter region of PfFAD8, thereby regulating its expression. This study provides an initial understanding of the regulatory mechanisms of PfDof transcription factors in the synthesis and accumulation of oil in P. frutescens. These findings offer new insights into the enhancement of oil content and quality of P. frutescens seeds.
Transcription Factors/physiology* ; Perilla frutescens/metabolism* ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant ; alpha-Linolenic Acid/biosynthesis* ; Lipids/biosynthesis* ; Seeds/genetics*

Liver diseases have become a major challenge threating the global health, posing a heavy burden on both social and personal well-being. In recent years, the development of the gut-liver axis theory has provided new research perspectives and intervention strategies for the prevention and treatment of liver diseases. Natural products, recognized as biological molecules with diverse sources, rich activities, and minimal side effects, demonstrate great potential in regulating intestinal flora and improving liver health. Studies have shown that natural products such as saponins, polyphenols, polysaccharides, and alkaloids can regulate the composition and metabolites of intestinal flora, thereby intervening in liver diseases. In this paper, we systematically review the role of natural products in the regulation of the intestinal flora-gut-liver axis and summarize recent research progress in the prevention and treatment of liver diseases. Furthermore, we outline the challenges and limitations currently facing the study in this field. Finally, this paper makes an outlook on the clinical application of natural products in treating liver diseases and discusses future research directions, aiming to give new insights into the mechanisms by which natural products regulate the intestinal flora-gut-liver axis and the applications of these products in the prevention and treatment of liver diseases.
Humans ; Gastrointestinal Microbiome/drug effects* ; Liver Diseases/prevention & control* ; Biological Products/pharmacology* ; Polyphenols/pharmacology* ; Saponins/pharmacology* ; Intestines/microbiology* ; Alkaloids/pharmacology* ; Polysaccharides/pharmacology* ; Liver

Sperm motility, a crucial function of sperm, refers to the ability of sperm to move progressively forward. Only sperm with adequate motility can reach the fertilization site and successfully recognize and fuse with an egg during natural reproduction. Asthenozoospermia, defined by a percentage of progressive sperm below the reference value's lower limit, is one of the most prevalent causes of male infertility. Sperm motility maintenance relies on both a normal flagellar structure and signal transduction pathways. However, extracellular environmental factors related to motility are also of significant importance. This review addresses factors influencing sperm motility, encompassing lifestyles, environmental elements, and commonly used drugs. It offers valuable insights for the prevention and diagnosis of asthenozoospermia and supports the strategies for preventing male infertility.

Sperm motility, a crucial function of sperm, refers to the ability of sperm to move progressively forward. Only sperm with adequate motility can reach the fertilization site and successfully recognize and fuse with an egg during natural reproduction. Asthenozoospermia, defined by a percentage of progressive sperm below the reference value's lower limit, is one of the most prevalent causes of male infertility. Sperm motility maintenance relies on both a normal flagellar structure and signal transduction pathways. However, extracellular environmental factors related to motility are also of significant importance. This review addresses factors influencing sperm motility, encompassing lifestyles, environmental elements, and commonly used drugs. It offers valuable insights for the prevention and diagnosis of asthenozoospermia and supports the strategies for preventing male infertility.

Kleine-Levin Syndrome (KLS), also known as "sleeping Beauty Syndrome", is characterized by a typical triad of recurrent episodes of hypersomnia, bulimia, and hypersexuality, which may be accompanied by behavioral or cognitive dysfunction and affective disorders. During the intermittent period, patient′s all functions remain intact. At present, the pathogenesis of the disease, auxiliary examination that are beneficial for diagnosis and effective treatment plans are not clear. Due to the possible genetic differences in different regions and populations, the clinical manifestations of the disease are various, which can easily lead to misdiagnosis. According to previous studies, about 66% of the abnormal eating in KLS patients are bulimia, however, anorexia is more common in China. In this case, an 11-year-old Chinese male patient with KLS presented anorexia behaviors in the first 10 months since diagnosis, and changed to bulimia in the subsequent 6 months follow-up. We carefully investigated his medical history, diagnosis, treatment process and differential diagnosis, in order to provide better insights of the clinical characteristics and diagnosis of KLS.

Background::The calcineurin inhibitor (CNI)-based immune maintenance regimen that is commonly used after renal transplantation has greatly improved early graft survival after transplantation; however, the long-term prognosis of grafts has not been significantly improved. The nephrotoxicity of CNI drugs is one of the main risk factors for the poor long-term prognosis of grafts. Sirolimus (SRL) has been employed as an immunosuppressant in clinical practice for over 20 years and has been found to have no nephrotoxic effects on grafts. Presently, the regimen and timing of SRL application after renal transplantation vary, and clinical data are scarce. Multicenter prospective randomized controlled studies are particularly rare. This study aims to investigate the effects of early conversion to a low-dose CNI combined with SRL on the long-term prognosis of renal transplantation.Methods::Patients who receive four weeks of a standard regimen with CNI + mycophenolic acid (MPA) + glucocorticoid after renal transplantation in multiple transplant centers across China will be included in this study. At week 5, after the operation, patients in the experimental group will receive an additional administration of SRL, a reduction in the CNI drug doses, withdrawal of MPA medication, and maintenance of glucocorticoids. In addition, patients in the control group will receive the maintained standard of care. The patients’ vital signs, routine blood tests, routine urine tests, blood biochemistry, serum creatinine, BK virus (BKV)/cytomegalovirus (CMV), and trough concentrations of CNI drugs and SRL at the baseline and weeks 12, 24, 36, 48, 72, and 104 after conversion will be recorded. Patient survival, graft survival, and estimated glomerular filtration rate will be calculated, and concomitant medications and adverse events will also be recorded.Conclusion::The study data will be utilized to evaluate the efficacy and safety of early conversion to low-dose CNIs combined with SRL in renal transplant patients.Trial registration::Chinese Clinical Trial Registry, ChiCTR1800017277.

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.

Kleine-Levin Syndrome (KLS), also known as "sleeping Beauty Syndrome", is characterized by a typical triad of recurrent episodes of hypersomnia, bulimia, and hypersexuality, which may be accompanied by behavioral or cognitive dysfunction and affective disorders. During the intermittent period, patient′s all functions remain intact. At present, the pathogenesis of the disease, auxiliary examination that are beneficial for diagnosis and effective treatment plans are not clear. Due to the possible genetic differences in different regions and populations, the clinical manifestations of the disease are various, which can easily lead to misdiagnosis. According to previous studies, about 66% of the abnormal eating in KLS patients are bulimia, however, anorexia is more common in China. In this case, an 11-year-old Chinese male patient with KLS presented anorexia behaviors in the first 10 months since diagnosis, and changed to bulimia in the subsequent 6 months follow-up. We carefully investigated his medical history, diagnosis, treatment process and differential diagnosis, in order to provide better insights of the clinical characteristics and diagnosis of KLS.

In order to avoid the intra- and post-operative risks caused by massive blood loss, there are various clinical methods for evaluating the blood supply of the tumor and the distribution of blood vessels around the tumor before surgery, such as dynamic enhanced CT, dynamic enhanced magnetic resonance imaging, digital subtraction angiography, etc. And there are a variety of pre- and intra-operative methods to reduce tumor bleeding, such as transarterial vertebral tumor embolization, percutaneous or transpedicular injection of Onyx/NBCA, antifibrinolytic drugs, controlled deliberate hypotension, etc. This article reviews on spinal tumor blood supply assessment and the methods to reduce the amount of surgical bleeding.

Objective::This survey was designed to understand the misconceptions about labor epidurals.Methods::This voluntary and anonymous online survey on wenjuan.com was conducted from September 1 st, 2015 to January 1 st, 2016 via mainly WeChat groups dedicated to perinatal healthcare providers in China. The questionnaire included items inquiring the knowledge and opinions about labor epidural analgesia related to maternal complications, baby safety, and effect on laboring. Incomplete surveys were excluded from the data analysis. The data was presented as percentages and a Chi-square test or Fisher’s exact test, as appreciate, was used to quantitatively compare the results. Results::A total of 1412 respondents completed surveys with 42.9% (606/1412) of them being anesthesiologists, 35.1% (495/1412) being obstetricians, 11.8% (167/1412) being midwives, 3.7% (52/1412) being labor and delivery nurses, and 6.5% (92/1412) being hospital administrators and unspecified. The study revealed a lack of knowledge in labor pain control. Although 82.4% (1164/1412) of respondents were familiar with labor epidural analgesia, 8.9% (126/1412) did not know how it works, and 1.1% (15/1412) never heard it in a multiple-choice question. The three main groups (anesthesiologists, obstetricians, and midwives/labor and delivery nurses) were chosen for comparisons. Opinions among these three groups concerning five questions in the three main concerns were evaluated using a statistical significance of P<0.05. Conclusion::The results in our survey indicated an urgent need of continuing medical education to multidisciplinary specialties to improve evidence-based medical practices as these misconceptions have existed for over 10 years in the medical professionals. Lack of public awareness fueled by misconceptions related to labor epidural analgesia may be associated with a lack of professional knowledge. Correct knowledge in professionals needs to be disseminated to the public in order to dispel possible misconceptions and rumors about labor epidural analgesia. This would not only enhance patient understanding of their care but also improve maternal, fetal, and neonatal outcomes.