Objective
Our study is the first meta-analysis to compare total mesorectal excision (TME) plus lateral lymph node dissection (LLND) with TME on rectal cancer patients regarding outcomes including ...overall survival, disease-free survival, local recurrence, complications, urinary dysfunction, and sexual dysfunction.
Methods
PubMed, Embase, and Cochrane library were searched for publications up to October 2019. Two investigators independently screened the studies for eligibility and extracted specific data. Relevant data were analyzed by Review Manager version 5.3.
Results
Patients in TME + LLND group suffered more complications (OR = 1.48, 95% CI 1.07, 2.03,
P
= 0.02) compared with TME group; no significant difference was observed in overall survival (HR = 1.11, 95% CI 0.77, 1.61,
P
= 0.57), disease-free survival (HR = 1.05, 95% CI 0.85, 1.30,
P
= 0.64), local recurrence (OR = 0.93, 95% CI 0.56, 1.54,
P
= 0.78), and urinary dysfunction (OR = 1.60, 95% CI 0.66, 3.87,
P
= 0.3).
Conclusion
TME + LLND may cause more complications compared with TME on rectal cancer patients. However, the definite conclusion still requires more researches.
Emerging per- and polyfluoroalkyl substances (PFAS) alternatives are increasingly used in daily life. Although legacy PFAS have been associated with miscarriage in previous studies, it remains ...unknown whether exposure to emerging and legacy PFAS has any impact on the risk of unexplained recurrent spontaneous abortion (URSA). We conducted a case-control study with 464 URSA cases who had at least 2 unexplained miscarriages and 440 normal controls who had at least one normal livebirth. Concentrations of 21 PFAS in plasma, including three emerging PFAS alternatives, eight linear and branched PFAS isomers, four short-chain PFAS, and six legacy PFAS, were measured by ultra-performance liquid chromatography coupled with a tandem mass spectrometry (UPLC-MS/MS). Multiple logistic regression was applied to evaluate the relationship between PFAS and URSA risk. Perfluorooctanoic acid (PFOA, median: 6.18 ng/mL), perfluorooctane sulfonate (PFOS, median: 4.10 ng/mL), and 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA, median: 2.27 ng/mL) were the predominant PFAS in the controls. Exposure to 6:2 Cl-PFESA adjusted odds ratio (aOR) = 1.18 (95% CI: 1.00, 1.39) and hexafluoropropylene oxide dimer acid (HFPO-DA) aOR = 1.35 (95% CI: 1.15, 1.59) were significantly associated with increased risks of URSA. Women with older age (>30 years old) had a stronger association between PFAS and URSA. Our results suggest that emerging PFAS alternatives may be an important risk factor for URSA.
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•The 6:2 Cl-PFAES concentration was relatively high in our study population, after PFOA and PFOS.•HFPO-DA and 6:2 Cl-PFESA were associated with elevated risks of URSA.•Emerging PFAS alternatives may not necessarily be safer than legacy PFAS for reproductive health.
Artemisinin, which has been isolated from
L., is the most effective antimalarial drug and has saved millions of lives. In addition, artemisinin and its derivatives have anti-tumor, anti-parasitic, ...anti-fibrosis, and anti-arrhythmic properties, which enhances the demand for these compounds. Improving the content of artemisinin in
is therefore becoming an increasing research interest, as the chemical synthesis of this metabolite is not viable. Ultraviolet B and C irradiation have been reported to improve the artemisinin content in
, but they are harmful to plant growth and development. Therefore, we screened other light sources to examine if they could promote artemisinin content without affecting plant growth and development. We found that red and blue light could enhance artemisinin accumulation by promoting the expression of the genes that were involved in artemisinin biosynthesis, such as
(ADS) and
(CYP71AV1) genes. Thus, in addition to being the main light sources for photosynthesis, red and blue light play a key role in plant secondary metabolism, and optimizing the combination of these light might allow for the productionof artemisinin-rich
.
Gasdermin D (GSDMD) participates in the activation of inflammasomes and pyroptosis. Meanwhile, ubiquitination strictly regulates inflammatory responses. However, how ubiquitination regulates ...Gasdermin D activity is not well understood. In this study, we show that pyroptosis triggered by Gasdermin D is regulated through ubiquitination. Specifically, SYVN1, an E3 ubiquitin ligase of gasdermin D, promotes GSDMD-mediated pyroptosis. SYVN1 deficiency inhibits pyroptosis and subsequent LDH release and PI uptake. SYVN1 directly interacts with GSDMD, and mediates K27-linked polyubiquitination of GSDMD on K203 and K204 residues, promoting GSDMD-induced pyroptotic cell death. Thus, our findings revealed the essential role of SYVN1 in GSDMD-mediated pyroptosis. Overall, GSDMD ubiquitination is a potential therapeutic module for inflammatory diseases.
Many species of the genus
Kalanchoe
are important horticultural plants. They have evolved the Crassulacean acid metabolism (CAM) photosynthetic pathway to allow them to be better adapted to dry ...environments. Despite their importance, it is still debating whether
Kalanchoe
is monophyletic, and understanding the past diversification of this genus requires a tremendous amount of effort and work being devoted to the studies of morphological and molecular characters of this genus. However, molecular information, plastic sequence data, in particular, reported on
Kalanchoe
species is scarce, and this has posed a great challenge in trying to interpret the evolutionary history of this genus. In this study, plastomes of the five
Kalanchoe
species, including
Kalanchoe daigremontiana, Kalanchoe delagoensis, Kalanchoe fedtschenkoi, Kalanchoe longiflora
, and
Kalanchoe pinnata
, were sequenced and analyzed. The results indicate that the five plastomes are comparable in size, guanine-cytosine (GC) contents and the number of genes, which also demonstrate an insignificant difference in comparison with other species from the family Crassulaceae. About 224 simple sequence repeats (SSRs) and 144 long repeats were identified in the five plastomes, and most of these are distributed in the inverted repeat regions. In addition, highly divergent regions containing either single nucleotide polymorphism (SNP) or insertion or deletion (InDel) mutations are discovered, which could be potentially used for establishing phylogenetic relationships among members of the
Kalanchoe
genus in future studies. Furthermore, phylogenetic analyses suggest that
Bryophyllum
should be placed into one single genus as
Kalanchoe
. Further genomic analyses also reveal that several genes are undergone positive selection. Among them, 11 genes are involved in important cellular processes, such as cell survival, electron transfer, and may have played indispensable roles in the adaptive evolution of
Kalanchoe
to dry environments.
Polycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders. Evidence of familial aggregation analysis and different clinical traits among different regions and ...ethnicities indicated that the pathogenesis of PCOS is associated with multiple genetic and environmental factors. Our previous research had identified three susceptibility loci (rs2479106, DENND1A; rs13405728, LHCGR; rs13429458, THADA) for PCOS in Han Chinese women. The overall aim of this study was to investigate the relationship between three susceptibility gene polymorphisms and PCOS in Hui ethnic women.
151 patients with PCOS (case group) and 99 healthy women (control group) were recruited from the Reproductive Medicine Center of the General Hospital of Ningxia Medical University. Clinical data and serum hormone characteristics of case and control groups were collected and analyzed. The three susceptibility single-nucleotide polymorphisms have been replicated in both case and control groups. Gene polymorphisms were detected by direct sequencing after polymerase chain reaction.
The Body Mass Index, LH, LH/FSH ratio and total testosterone were significantly elevated in PCOS patients compared to control group (P<0.05). The frequencies of genotype and allele in rs13405728 were significantly different between the PCOS and the control groups (P<0.05). Of the SNP rs13405728, the PCOS cases with TT genotype stayed at a higher level of total testosterone, TG and LDL than those with the CC and CT genotypes. In contrary, there was no statistical difference between the two groups for SNP rs13429458 and rs2479106 (P>0.05).
The present study suggested that the SNP rs13405728 in the LHCGR gene was associated with PCOS in Hui ethnic women, and its TT genotype characterized with higher level of TT, TG and LDL.
The difficulty of feature extraction and the small sample size are two challenges in the field of mechanical fault diagnosis for a long time. Here we propose an intelligent mechanical fault diagnosis ...method for scenario with small sample datasets. This method can not only diagnose bearing faults but also gear faults, and has strong generalization performance. We use convolutional neural network to realize automatic feature extraction. Through sliding window scanning, one sample set is expanded to three sub-sample sets with different scales to meet the needs of deep learning training. Three convolutional networks are used to extract the features of the subsets respectively to ensure that their useful features are fully extracted. After feature extraction, the feature is reconstructed through feature splicing. Because of the unique advantages of SVM in dealing with small sample sets, we use SVM to classify the reconstructed features. We use the bearing data set collected by Case Western Reserve University in the United States, the bearing fault data set collected by Xi'an Jiaotong University in China, and the gearbox fault data collected by the University of Connecticut in the United States to conduct experiments. The experimental results show that the accuracy of training, validation and testing of the proposed method on the three data sets all reach 100%. This proves that our method can not only tackle the two challenges, but also has high fault diagnosis accuracy and strong generalization performance. It is hoped that our proposed method can contribute to the development of mechanical fault diagnosis.
Coronaviruses (CoVs) are a family of RNA viruses that typically cause respiratory, enteric, and hepatic diseases in animals and humans. Here, we use porcine epidemic diarrhea virus (PEDV) as a model ...of CoVs to illustrate the reciprocal regulation between CoV infection and pyroptosis. For the first time, we elucidate the molecular mechanism of porcine gasdermin D (pGSDMD)-mediated pyroptosis and demonstrate that amino acids R238, T239, and F240 within pGSDMD-p30 are critical for pyroptosis. Furthermore, 3C-like protease Nsp5 from SARS-CoV-2, MERS-CoV, PDCoV, and PEDV can cleave pGSDMD at the Q193-G194 junction to produce two fragments unable to trigger pyroptosis. The two cleaved fragments could not inhibit PEDV replication. In addition, Nsp5 from SARS-CoV-2 and MERS-CoV also cleave human GSDMD (hGSDMD). Therefore, we provide clear evidence that PEDV may utilize the Nsp5-GSDMD pathway to inhibit pyroptosis and, thus, facilitate viral replication during the initial period, suggesting an important strategy for the coronaviruses to sustain their infection.
Recently, GSDMD has been reported as a key executioner for pyroptosis. This study first demonstrates the molecular mechanism of pGSDMD-mediated pyroptosis and that the pGSDMD-mediated pyroptosis protects host cells against PEDV infection. Notably, PEDV employs its Nsp5 to directly cleave pGSDMD in favor of its replication. We found that Nsp5 proteins from other coronaviruses, such as porcine deltacoronavirus, severe acute respiratory syndrome coronavirus 2, and Middle East respiratory syndrome coronavirus, also had the protease activity to cleave human and porcine GSDMD. Thus, we provide clear evidence that the coronaviruses might utilize Nsp5 to inhibit the host pyroptotic cell death and facilitate their replication during the initial period, an important strategy for their sustaining infection. We suppose that GSDMD is an appealing target for the design of anticoronavirus therapies.
The clustered regularly interspaced short palindromic repeat/CRISPR-associated protein 9 (CRISPR/Cas9) technology is an efficient genome editing tool used in multiple plant species. However, it has ...not been applied to Tartary buckwheat (
), which is an important edible and medicinal crop rich in rutin and other flavonoids.
is an R2R3-type MYB transcription factor that negatively regulates flavonoid biosynthesis in Tartary buckwheat. Here, the CRISPR/Cas9 system polycistronic tRNA-sgRNA (PTG)/Cas9 was employed to knock out the
gene in Tartary buckwheat. Two single-guide RNAs (sgRNAs) were designed to target the second exon of the
gene. Twelve transgenic hairy roots were obtained using
mediated transformation. Sequencing data revealed that six lines containing six types of mutations at the predicted double-stranded break site were generated using sgRNA1. The mutation frequency reached 50%. A liquid chromatography coupled with triple quadrupole mass spectrometry (LC-QqQ-MS) based metabolomic analysis revealed that the content of rutin, catechin, and other flavonoids was increased in hairy root mutants compared with that of lines transformed with the empty vector. Thus, CRISPR/Cas9-mediated targeted mutagenesis of
effectively increased the flavonoids content of Tartary buckwheat. This finding demonstrated that the CRISPR/Cas9 system is an efficient tool for precise genome editing in Tartary buckwheat and lays the foundation for gene function research and quality improvement in Tartary buckwheat.
Se-biofortified agricultural products receive considerable interest due to the worldwide severity of selenium (Se) deficiency. Alfalfa (
L.), the king of forage, has a large biomass, a high protein ...content, and a high level of adaptability, making it a good resource for Se biofortification. Analyses of agronomic, quality, physiological, and microstructure results indicated the mechanism of biomass increase and quality development in alfalfa during Se treatment. Se treatment effectively increased Se content, biomass accumulation, and protein levels in alfalfa. The enhancement of antioxidant capacity contributes to the maintenance of low levels of reactive oxygen species (ROS), which, in turn, serves to increase alfalfa's stress resistance and the stability of its intracellular environment. An increase in the rate of photosynthesis contributes to the accumulation of biomass in alfalfa. To conduct a more comprehensive investigation of the regulatory networks induced by Se treatment, the transcriptome sequencing of non-coding RNA (ncRNA) was employed to compare 100 mg/kg Se treatment and control groups. The analysis identified 1,414, 62, and 5 genes as DE-long non-coding RNAs (DE-lncRNA), DE-microRNAs (DE-miRNA), and DE-circular RNA (DE-circRNA), respectively. The function of miRNA-related regulatory networks during Se biofortification in alfalfa was investigated. Subsequent enrichment analysis revealed significant involvement of transcription factors, DNA replication and repair mechanisms, photosynthesis, carbohydrate metabolism, and protein processing. The antioxidant capacity and protein accumulation of alfalfa were regulated by the modulation of signal transduction, the glyoxalase pathway, proteostasis, and circRNA/lncRNA-related regulatory networks. The findings offer new perspectives on the regulatory mechanisms of Se in plant growth, biomass accumulation, and stress responses, and propose potential strategies for enhancing its utilization in the agricultural sector.