Maize auxin response factor ZmARF1 confers multiple abiotic stresses resistances in transgenic Arabidopsis.

Prolonged exposure to abiotic stresses causes oxidative stress, which affects plant development and survival. In this research, the overexpression of ZmARF1 improved tolerance to low Pi, drought and salinity stresses. The transgenic plants manifested tolerance to low Pi by their superior root phenotypic traits: root length, root tips, root surface area, and root volume, compared to wide-type (WT) plants. Moreover, the transgenic plants exhibited higher root and leaf Pi content and upregulated the high affinity Pi transporters PHT1;2 and phosphorus starvation inducing (PSI) genes PHO2 and PHR1 under low Pi conditions. Transgenic Arabidopsis displayed tolerance to drought and salt stress by maintaining higher chlorophyll content and chlorophyll fluorescence, lower water loss rates, and ion leakage, which contributed to the survival of overexpression lines compared to the WT. Transcriptome profiling identified a peroxidase gene, POX, whose transcript was upregulated by these abiotic stresses. Furthermore, we confirmed that ZmARF1 bound to the auxin response element (AuxRE) in the promoter of POX and enhanced its transcription to mediate tolerance to oxidative stress imposed by low Pi, drought and salt stress in the transgenic seedlings. These results demonstrate that ZmARF1 has significant potential for improving the tolerance of crops to multiple abiotic stresses.

Broad-band-enhanced plasmonic random laser in silver nanostar arrays.

As a novel optical device, the plasmonic random laser has unique working principle and emission characteristics. However, the simultaneous enhancement of absorption and emission by plasmons is still a problem. In this paper, we propose a broad-band-enhanced plasmonic random laser. Two-dimensional silver (Ag) nanostar arrays were prepared using a bottom-up method with the assistance of self-assembled nanosphere templates. The plasmon resonance of Ag nanostars contributes to the pump light absorption and photoluminescence (PL) of RhB. Coherent random lasing was achieved in RhB@PVA film based on localized surface plasmon resonance (SPR) dual enhancement and scattering feedback of Ag nanostars. Ag nanostars prepared with different nanosphere diameters affect the laser emission wavelength. In addition, the random laser device achieves wavelength tunability on a flexible substrate under mechanical external force.

A regional genomic surveillance program is implemented to monitor the occurrence and emergence of SARS-CoV-2 variants in Yubei District, China.

BACKGROUND: In December 2022, Chongqing experienced a significant surge in coronavirus disease 2019 (COVID-19) epidemic after adjusting control measures in China. Given the widespread immunization of the population with the BA.5 variant, it is crucial to actively monitor severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant evolution in Chongqing's Yubei district. METHODS: In this retrospective study based on whole genome sequencing, we collected oropharyngeal and nasal swab of native COVID-19 cases from Yubei district between January to May 2023, along with imported cases from January 2022 to January 2023. Through second-generation sequencing, we generated a total of 578 genomes. RESULTS: Phylogenetic analyses revealed these genomes belong to 47 SARS-CoV-2 Pango lineages. BA.5.2.48 was dominant from January to April 2023, rapidly replaced by XBB* variants from April to May 2023. Bayesian Skyline Plot reconstructions indicated a higher evolutionary rate (6.973 × 10-4 subs/site/year) for the XBB.1.5* lineage compared to others. The mean time to the most recent common ancestor (tMRCA) of BA.5.2.48* closely matched BA.2.75* (May 27, 2022). Using multinomial logistic regression, we estimated growth advantages, with XBB.1.9.1 showing the highest growth advantage (1.2, 95% HPI:1.1-1.2), followed by lineage FR.1 (1.1, 95% HPI:1.1-1.2). CONCLUSIONS: Our monitoring reveals the rapid replacement of the previously prevalent BA.5.2.48 variant by XBB and its sub-variants, underscoring the ineffectiveness of herd immunity and breakthrough BA.5 infections against XBB variants. Given the ongoing evolutionary pressure, sustaining a SARS-CoV-2 genomic surveillance program is imperative.

Association between severity of nonalcoholic fatty liver disease and major adverse cardiovascular events in patients assessed by coronary computed tomography angiography.

BACKGROUND: The effect of nonalcoholic fatty liver disease (NAFLD) on major adverse cardiovascular events (MACEs) can be influenced by the degree of coronary artery stenosis. However, the association between the severity of NAFLD and MACEs in patients who underwent coronary computed tomography angiography (CCTA) is unclear. METHODS: A total of 341 NAFLD patients who underwent CCTA were enrolled. The severity of NAFLD was divided into mild NAFLD and moderate-severe NAFLD by abdominal CT results. The degree of coronary artery stenosis was evaluated by using Coronary Artery Disease Reporting and Data System (CAD-RADS) category. Cox regression analysis and Kaplan-Meier analysis were used to assess poor prognosis. RESULTS: During the follow-up period, 45 of 341 NAFLD patients (13.20%) who underwent CCTA occurred MACEs. The severity of NAFLD (hazard ratio [HR] = 2.95[1.54-5.66]; p = 0.001) and CAD-RADS categories 3-5 (HR = 16.31[6.34-41.92]; p < 0.001) were independent risk factors for MACEs. The Kaplan-Meier analysis showed that moderate to severe NAFLD patients had a worsen prognosis than mild NAFLD patients (log-rank p < 0.001). Moreover, the combined receiver operating characteristic curve of the severity of NAFLD and CAD-RADS category showed a good predicting performance for the risk of MACEs, with an area under the curve of 0.849 (95% CI = 0.786-0.911). CONCLUSION: The severity of NAFLD was independent risk factor for MACEs in patients with obstructive CAD, having CAD-RADS 3-5 categories on CCTA.

Reprogramming efficiency and pluripotency of mule iPSCs over its parents†.

The mule is the interspecific hybrid of horse and donkey and has hybrid vigor in muscular endurance, disease resistance, and longevity over its parents. Here, we examined adult fibroblasts of mule (MAFs) compared with the cells from their parents (donkey adult fibroblasts and horse adult fibroblasts) (each species has repeated three independent individuals) in proliferation, apoptosis, and glycolysis and found significant differences. We subsequently derived mule, donkey, and horse doxycycline (Dox)-independent induced pluripotent stem cells (miPSCs, diPSCs, and hiPSCs) from three independent individuals of each species and found that the reprogramming efficiency of MAFs was significantly higher than that of cells of donkey and horse. miPSCs, diPSCs, and hiPSCs all expressed the high levels of crucial endogenous pluripotency genes such as POU class 5 homeobox 1 (POU5F1, OCT4), SRY-box 2 (SOX2), and Nanog homeobox (NANOG) and propagated robustly in single-cell passaging. miPSCs exhibited faster proliferation and higher pluripotency and differentiation than diPSCs and hiPSCs, which were reflected in co-cultures and separate-cultures, teratoma formation, and chimera contribution. The establishment of miPSCs provides a unique research material for the investigation of "heterosis" and perhaps is more significant to study hybrid gamete formation.

Comparison of The Toronto IBD Global Endoscopic Reporting (TIGER) score, Mayo endoscopic score (MES), and ulcerative colitis endoscopic index of severity (UCEIS) in predicting the need for ileal pouch-anal anastomosis in patients with ulcerative colitis.

BACKGROUND: Total proctocolectomy (TPC) with ileal pouch-anal anastomosis (IPAA) has been accepted as a radical surgery for refractory ulcerative colitis (UC). We aimed to assess the predictive value of several novel and widely used endoscopic core systems, The Toronto IBD Global Endoscopic Reporting (TIGER) score, Mayo endoscopic score (MES), and ulcerative colitis endoscopic index of severity (UCEIS) in guiding the need for IPAA. METHODS: Data on patients with UC from June 1986 and June 2022 at our institute were collected. The endoscopic evaluation was recorded according to the first colonoscopy after hospitalization. Primary outcome was the need for IPAA during admission and follow-up. RESULTS: A total of 313 patients with a median follow-up time and a median TIGER score of 12.0 years (interquartile range (IQR): 6.0-17.0) and 212.0 (IQR: 7.0-327.0) were enrolled. IPAA was conducted in 110 (35.1%) patients, which significantly improved the long-term quality of life. TIGER score had the biggest area under the receiver-operating characteristic curve of 0.810 with a sensitivity of 75.0% and specificity of 87.1% at the cut-off value of 315 (p < 0.001). TIGER score ≥ 315 was an independent risk factor with the highest odds ratio for the need for IPAA and associated with the shortest IPAA-free survival time compared with UCEIS and MES. CONCLUSION: TIGER score was superior to UCEIS and MES in predicting the need for IPAA. For colorectal surgeons, three or more segments with moderate-to-severe endoscopic activity should be considered as a threshold value for decision-making for IPAA.

Chirality detection of biological molecule through spin selectivity effect.

The ability to accurately monitor chiral biological molecules is of great significance for their potential applications in disease diagnosis and virus detection. As the existing chiral detection technologies are mainly relying on an optical method by using left/right circularly polarized light, the universality is low and the operation is complicated. Moreover, large quantity of chiral molecules is required, causing low detection efficiency. Here, a self-assembled monolayer of polypeptides has been fabricated to realize trace detection of chirality based on spin selectivity of photon-electron interaction. We have utilized Kerr technique to detect the rotation angle by the molecular monolayer, which indicates the chirality of polypeptides. The chiral structure of a biological molecule could result in spin-selectivity of electrons and thus influence the interaction between electron spin and light polarization. A Kerr rotation angle of ∼3° has been obviously observed, equivalent to the magneto-optic Kerr effect without magnetic material or magnetic field. Furthermore, we have provided a novel solution to achieve chirality discrimination and amplification simultaneously through an optical fiber. The proposed design is applicable for chiral detection via increasing their differential output signal, which clearly demonstrates a useful strategy toward chirality characterization of biological molecules.

Interactive effect of increased high sensitive C-reactive protein and dyslipidemia on cardiovascular diseases: a 12-year prospective cohort study.

BACKGROUND: Dyslipidemia and inflammation are significant factors for the onset of cardiovascular diseases (CVD); however, studies regarding their interactions on the risk of CVD are scarce. This study aimed to assess the interaction of dyslipidemia and high-sensitivity C-reactive protein (hs-CRP) on CVD. METHODS: This prospective cohort enrolled 4,128 adults at baseline in 2009 and followed them up until May 2022 for collecting CVD events. Cox-proportional hazard regression analysis estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) of the associations of increased hs-CRP (≥ 1 mg/L) and dyslipidemia with CVD. The additive interactions were explored using the relative excess risk of interaction (RERI) and the multiplicative interactions were assessed with HRs (95% CI) while the multiplicative interactions were assessed by the HRs (95% CI) of interaction terms. RESULTS: The HRs of the association between increased hs-CRP and CVD were 1.42 (95% CI: 1.14-1.79) and 1.17 (95% CI: 0.89-1.53) among subjects with normal lipid levels and subjects with dyslipidemia, respectively. Stratified analyses by hs-CRP levels showed that among participants with normal hs-CRP (< 1 mg/L), TC ≥ 240 mg/dL, LDL-C ≥ 160 mg/dL, non-HDL-C ≥ 190 mg/dL, ApoB < 0.7 g/L, and LDL/HDL-C ≥ 2.02 were associated with CVD [HRs (95%CIs): 1.75 (1.21-2.54), 2.16 (1.37-3.41), 1.95 (1.29-2.97), 1.37 (1.01-1.67), and 1.30 (1.00-1.69), all P < 0.05, respectively]. While in the population with increased hs-CRP, only ApoAI > 2.10 g/L had a significant association with CVD [HR (95% CI): 1.69 (1.14-2.51)]. Interaction analyses showed that increased hs-CRP had multiplicative and additive interactions with LDL-C ≥ 160 mg/dL and non-HDL-C ≥ 190 mg/dL on the risk of CVD [HRs (95%CIs): 0.309 (0.153-0.621), and 0.505 (0.295-0.866); RERIs (95%CIs): -1.704 (-3.430-0.021 and - 0.694 (-1.476-0.089), respectively, all P < 0.05]. CONCLUSION: Overall our findings indicate negative interactions between abnormal blood lipid levels and hs-CRP on the risk of CVD. Further large-scale cohort studies with trajectories measurement of lipids and hs-CRP might verify our results as well explore the biological mechanism behind that interaction.

MicroRNA-148a-3p in pericyte-derived extracellular vesicles improves erectile function in diabetic mice by promoting cavernous neurovascular regeneration.

BACKGROUND: To investigate the regulatory role of microRNA (miR)-148a-3p in mouse corpus cavernous pericyte (MCPs)-derived extracellular vesicles (EVs) in the treatment of diabetes-induced erectile dysfunction (ED). METHODS: Mouse corpus cavernous tissue was used for MCP primary culture and EV isolation. Small-RNA sequencing analysis was performed to assess the type and content of miRs in MCPs-EVs. Four groups of mice were used: control nondiabetic mice and streptozotocin-induced diabetic mice receiving two intracavernous injections (days - 3 and 0) of phosphate buffered saline, MCPs-EVs transfected with reagent control, or MCPs-EVs transfected with a miR-148a-3p inhibitor. miR-148a-3p function in MCPs-EVs was evaluated by tube-formation assay, migration assay, TUNEL assay, intracavernous pressure, immunofluorescence staining, and Western blotting. RESULTS: We extracted EVs from MCPs, and small-RNA sequencing analysis showed miR-148a-3p enrichment in MCPs-EVs. Exogenous MCPs-EV administration effectively promoted mouse cavernous endothelial cell (MCECs) tube formation, migration, and proliferation, and reduced MCECs apoptosis under high-glucose conditions. These effects were significantly attenuated in miR-148a-3p-depleted MCPs-EVs, which were extracted after inhibiting miR-148a-3p expression in MCPs. Repetitive intracavernous injections of MCPs-EVs improved erectile function by inducing cavernous neurovascular regeneration in diabetic mice. Using online bioinformatics databases and luciferase report assays, we predicted that pyruvate dehydrogenase kinase-4 (PDK4) is a potential target gene of miR-148a-3p. CONCLUSIONS: Our findings provide new and reliable evidence that miR-148a-3p in MCPs-EVs significantly enhances cavernous neurovascular regeneration by inhibiting PDK4 expression in diabetic mice.

MRI-based radiomics nomogram for differentiation of solitary metastasis and solitary primary tumor in the spine.

BACKGROUND: Differentiating between solitary spinal metastasis (SSM) and solitary primary spinal tumor (SPST) is essential for treatment decisions and prognosis. The aim of this study was to develop and validate an MRI-based radiomics nomogram for discriminating SSM from SPST. METHODS: One hundred and thirty-five patients with solitary spinal tumors were retrospectively studied and the data set was divided into two groups: a training set (n = 98) and a validation set (n = 37). Demographics and MRI characteristic features were evaluated to build a clinical factors model. Radiomics features were extracted from sagittal T1-weighted and fat-saturated T2-weighted images, and a radiomics signature model was constructed. A radiomics nomogram was established by combining radiomics features and significant clinical factors. The diagnostic performance of the three models was evaluated using receiver operator characteristic (ROC) curves on the training and validation sets. The Hosmer-Lemeshow test was performed to assess the calibration capability of radiomics nomogram, and we used decision curve analysis (DCA) to estimate the clinical usefulness. RESULTS: The age, signal, and boundaries were used to construct the clinical factors model. Twenty-six features from MR images were used to build the radiomics signature. The radiomics nomogram achieved good performance for differentiating SSM from SPST with an area under the curve (AUC) of 0.980 in the training set and an AUC of 0.924 in the validation set. The Hosmer-Lemeshow test and decision curve analysis demonstrated the radiomics nomogram outperformed the clinical factors model. CONCLUSIONS: A radiomics nomogram as a noninvasive diagnostic method, which combines radiomics features and clinical factors, is helpful in distinguishing between SSM and SPST.

Salidroside ameliorates pathological cardiac hypertrophy via TLR4-TAK1-dependent signaling.

Salidroside, a prominent active ingredient in traditional Chinese medicines, is garnering increased attention because of its unique pharmacological effects against ischemic heart disease via MAPK signaling, which plays a critical role in regulating the evolution of ventricular hypertrophy. However, the function of Salidroside on myocardial hypertrophy has not yet been elucidated. C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with Salidroside (100 mg kg-1  day-1 ) by oral gavage for 3 weeks starting 1 week after surgery. Four weeks after TAC surgery, the mice were subjected to echocardiography and then sacrificed to harvest the hearts for analysis. For in vitro study, neonatal rat cardiomyocytes were used to validate the protective effects of Salidroside in response to Angiotensin II (Ang II, 1 µM) stimulation. Here, we proved that Salidroside dramatically inhibited hypertrophic reactions generated by pressure overload and isoproterenol (ISO) injection. Salidroside prevented the activation of the TAK1-JNK/p38 axis. Salidroside pretreatment of TAK1-inhibited cardiomyocytes shows no additional attenuation of Ang II-induced cardiomyocytes hypertrophy and signaling pathway activation. The overexpression of constitutively active TAK1 removed the protective effects of Salidroside on myocardial hypertrophy. TAC-induced increase of TLR4 protein expression was reduced considerably in the Salidroside treated mice. Transient transfection of small interfering RNA targeting TLR4 (siTLR4) in cardiomyocytes did not further decrease the activation of the TAK1/JNK-p38 axis. In conclusion, Salidroside functioned as a TLR4 inhibitor and displayed anti-hypertrophic action via the TAK1/JNK-p38 pathway.

Abundance of Transgene Transcript Variants Associated with Somatically Active Transgenic Helitrons from Multiple T-DNA Integration Sites in Maize.

Helitrons, a novel type of mysterious DNA transposons discovered computationally prior to bench work confirmation, are components ubiquitous in most sequenced genomes of various eukaryotes, including plants, animals, and fungi. There is a paucity of empirical evidence to elucidate the mechanism of Helitrons transposition in plants. Here, by constructing several artificial defective Helitron (dHel) reporter systems, we aim to identify the autonomous Helitrons (aHel) in maize genetically and to demonstrate the transposition and repair mechanisms of Helitrons upon the dHel-GFP excision in maize. When crossing with various inbred lines, several transgenic lines produced progeny of segregated, purple-blotched kernels, resulting from a leaky expression of the C1 gene driven by the dHel-interrupted promoter. Transcription analysis indicated that the insertion of different dHels into the C1 promoter or exon would lead to multiple distinct mRNA transcripts corresponding to transgenes in the host genome. Simple excision products and circular intermediates of dHel-GFP transposition have been detected from the leaf tissue of the seedlings in F1 hybrids of transgenic lines with corresponding c1 tester, although they failed to be detected in all primary transgenic lines. These results revealed the transposition and repair mechanism of Helitrons in maize. It is strongly suggested that this reporter system can detect the genetic activity of autonomic Helitron at the molecular level. Sequence features of dHel itself, together with the flanking regions, impact the excision activity of dHel and the regulation of the dHel on the transcription level of the host gene.

Argonaute 2 Restores Erectile Function by Enhancing Angiogenesis and Reducing Reactive Oxygen Species Production in Streptozotocin (STZ)-Induced Type-1 Diabetic Mice.

Severe vascular and nerve damage from diabetes is a leading cause of erectile dysfunction (ED) and poor response to oral phosphodiesterase 5 inhibitors. Argonaute 2 (Ago2), a catalytic engine in mammalian RNA interference, is involved in neurovascular regeneration under inflammatory conditions. In the present study, we report that Ago2 administration can effectively improve penile erection by enhancing cavernous endothelial cell angiogenesis and survival under diabetic conditions. We found that although Ago2 is highly expressed around blood vessels and nerves, it is significantly reduced in the penis tissue of diabetic mice. Exogenous administration of the Ago2 protein restored erectile function in diabetic mice by reducing reactive oxygen species production-signaling pathways (inducing eNOS Ser1177/NF-κB Ser536 signaling) and improving cavernous endothelial angiogenesis, migration, and cell survival. Our study provides new evidence that Ago2 mediation may be a promising therapeutic strategy and a new approach for diabetic ED treatment.

Identification and pathogenicity of multidrug-resistant Elizabethkingia miricola isolated from farmed American bullfrogs Rana catesbeiana in China with in vitro screening of herbal antimicrobial agents.

OBJECTIVE: In 2021, an outbreak of an infectious disease characterized by torticollis, cataracts, and neurological disorders caused massive mortality in farmed American bullfrogs Rana catesbeiana in Hubei province, China. We identified the causal agent in this outbreak, characterized its pathogenicity, and screened candidate antimicrobial agents for future disease control. METHODS: Bacterium was isolated from the diseased American bullfrogs and identified based on biochemical tests, sequence analyses (16S ribosomal RNA; DNA gyrase subunit B), and experimental challenge. Furthermore, antibiotic sensitivity of the isolated strain was detected with Kirby-Bauer paper diffusion method, and the antibacterial activity of 60 traditional Chinese herbal extracts against the isolated strain was evaluated by agar disc diffusion and broth dilution assays. RESULT: We identified Elizabathkingia miricola strain FB210601 as the causative agent of this disease. The isolated E. miricola strain FB210601 exhibited extensive antibiotic resistance to all tested quinolones, ß-lactam antibiotics, and aminoglycosides. Eight herbal extracts exhibited excellent antimicrobial activity against E. miricola FB210601, especially Caesalpinia sappan and Rhus chinensis, with minimal inhibitory concentrations less than 0.2 mg/mL. Additionally, the combined effects of two-component herbal mixtures containing C. sappan or R. chinensis were greater than those of the individual extracts. CONCLUSION: Our results provide a reference for understanding the pathogenesis of Elizabethkingia infection in frogs. Furthermore, this study will aid in the application of herbal extracts for protection against infections caused by multidrug-resistant Elizabathkingia in the future.

[Advances in mechanism of traditional Chinese medicine in inhibiting angiogenesis in ovarian cancer].

Ovarian cancer is one of the three major cancers in gynecology. Ovarian cancer has insidious symptoms in its early stages and mostly has progressed to advanced stages when detected. Surgical treatment combined with chemotherapy is currently the main treatment, but the 5-year survival rate is still less than 45%. Angiogenesis is a key step in the growth and metastasis of ovarian cancer. The inhibition of ovarian cancer angiogenesis has become a new hotspot in anti-tumor targeted therapy, which has many advantages such as less drug resistance, high specificity, few side effects, and broad anti-tumor spectrum. Modern research has confirmed that traditional Chinese medicine(TCM) can inhibit tumor angiogenesis by inhibiting the expression of pro-angiogenic factors, up-regulating the expression of anti-angiogenic factors, inhibiting the proliferation of vascular endothelial cells, reducing the density of tumor microvessels, and regulating related signaling pathways, with unique advantages in the treatment of ovarian cancer. This paper presented a review of the role of TCM in inhibiting ovarian cancer angiogenesis in order to provide references for the optimization of clinical ovarian cancer treatment strategies.

Transcriptomics and metagenomics of common cutworm (Spodoptera litura) and fall armyworm (Spodoptera frugiperda) demonstrate differences in detoxification and development.

BACKGROUND: Spodoptera litura is an important polyphagous pest that causes significant damage to the agricultural sector. We performed RNA-seq of 15 S. litura individuals from larval (fifth and sixth instar larvae), chrysalis, and adult developmental stages. We also compared the S. litura transcriptome data with Spodoptera frugiperda across the same developmental stages, which was sequenced in our previous study. RESULTS: A total of 101,885 differentially expressed transcripts (DETs) were identified in S. litura. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that S. litura may undergo active xenobiotic and detoxifying metabolism during its larval and adult stages, which may explain difficulties with current population control measures. We also found that DETs of single-copy orthologous genes between S. litura and S. frugiperda were involved in basic metabolism and development. However, energy and metabolic processes genes had a higher expression in S. litura, whereas nervous and olfactory function genes had a higher expression in S. frugiperda. Metagenomics analysis in larval S. litura and S. frugiperda revealed that microbiota participate in the detoxification and metabolism processes, but the relative abundance of detoxification-related microbiota was more abundant in S. frugiperda. Transcriptome results also confirmed the detoxification-related pathway of S. frugiperda was more abundant than in S. litura. CONCLUSIONS: Significant changes at transcriptional level were identified during the different development stages of S. litura. Importantly, we also identified detoxification associated genes and gut microbiota between S. litura and S. frugiperda at different developmental stages, which will be valuable in revealing possible mechanisms of detoxification and development in these two lepidopterans.

The role of vaginal microecology in the cervical cancer.

AIM: To explore the role of vaginal microecology in cervical cancer, so as to increase the understanding of cervical cancer and lay a foundation for future large-sample clinical trials. METHODS: We reviewed and summarized the literature comprehensively, and discussed the relationship between vaginal microecology and HPV infection, CIN progression and cervical cancer, as well as the potential molecular mechanism and the prospects of probiotics and prebiotics in future cancer treatments. RESULTS: With the popularization of high-throughput sequencing technology and the development of bioinformatics analysis technology, many evidences show that the increase in the diversity of the bacterial community in the vaginal microecological environment and the decrease in the number of Lactobacilli are associated with the continuous infection of HPV and the further development of CIN, cervical cancer-related. CONCLUSIONS: Vaginal microecological imbalance has an important impact on the occurrence and development of cervical cancer. However, the pathogenesis is not completely clear, and more high-level basic research and longitudinal clinical studies are needed to verify.

Cloning of Maize TED Transposon into Escherichia coli Reveals the Polychromatic Sequence Landscape of Refractorily Propagated Plasmids.

MuDR, the founder member of the Mutator superfamily and its MURA transcripts, has been identified as toxic sequences to Escherichia coli (E. coli), which heavily hindered the elucidation of the biochemical features of MURA transposase and confined the broader application of the Mutator system in other organisms. To harness less constrained systems as alternatives, we attempted to clone TED and Jittery, two recently isolated autonomous Mutator-like elements (MULEs) from maize, respectively. Their full-length transcripts and genomic copies are successfully cloned when the incubation time for bacteria to recover from heat shock is extended appropriately prior to plating. However, during their proliferation in E. coli, TED transformed plasmids are unstable, as evidenced by derivatives from which frameshift, deletion mutations, or IS transposon insertions are readily detected. Our results suggest that neither leaky expression of the transposase nor the presence of terminal inverse repeats (TIRs) are responsible for the cloning barriers, which were once ascribed to the presence of the Shine-Dalgarno-like sequence. Instead, the internal sequence of TED (from 1250 to 2845 bp), especially the exons in this region, was the most likely causer. The findings provide novel insights into the property and function of the Mutator superfamily and shed light on the dissection of toxic effects on cloning from MULEs.

[Activity of Codonopsis canescens against rheumatoid arthritis based on TLRs/MAPKs/NF-κB signaling pathways and its mechanism].

This paper aims to explore the activity of Codonopsis canescens extract against rheumatoid arthritis(RA) based on the Toll-like receptors(TLRs)/mitogen-activated protein kinases(MAPKs)/nuclear factor kappa B(NF-κB) signaling pathways and its mechanism. The ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) was used to identify the components of C. canescens extract. Forty-eight male SD rats were randomly divided into six groups, namely the normal group, the model group, the methotrexate(MTX) tablet group, and the low, medium, and high-dose C. canescens extract(ZDS-L, ZDS-M, and ZDS-H) groups, with 8 rats in each group. The model of collagen-induced arthritis in rats was induced by injection of bovine type Ⅱ collagen emulsion. MTX(2.5 mg·kg~(-1)), ZDS-L, ZDS-M, and ZDS-H(0.3 g·kg~(-1), 0.6 g·kg~(-1), and 1.2 g·kg~(-1)) were administrated by gavage. Rats in the normal group and the model group received distilled water. MTX was given once every three days for 28 days, and the rest medicines were given once daily for 28 days. Body weight, degree of foot swelling, arthritis index, immune organ index, synovial histopathological changes, and serum levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), and interleukin-6(IL-6) were observed. Protein expressions of TLR2, TLR4, NF-κB p65, p38 MAPK, and p-p38 MAPK in rats were determined by Western blot. Thirty-four main components were identified by UPLC-Q-TOF-MS, including 15 flavonoids, 7 phenylpropanoids, 4 terpenoids, 4 organic acids, 2 esters, and 2 polyalkynes. As compared with the normal group, the body weight of the model group was significantly decreased(P<0.01), and foot swelling(P<0.05, P<0.01), arthritis index(P<0.01), and the immune organ index(P<0.01) were significantly increased. The synovial histopathological injury was obviously observed in the model group. The serum levels of inflammatory factors TNF-α, IL-1ß, and IL-6 were significantly increased(P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK in the synovial tissue were significantly increased(P<0.01) in the model group. As compared with the model group, the body weights of the ZDS dose groups were increased(P<0.01), and the degree of foot swelling(P<0.01) and the arthritis index were decreased(P<0.05, P<0.01). The immune organ index was decreased(P<0.01) in the ZDS dose groups, and the synovial tissue hyperplasia and inflammatory cell infiltration were alleviated. The serum levels of TNF-α, IL-1ß, and IL-6 were significantly decreased(P<0.05, P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK were decreased(P<0.05, P<0.01) in the ZDS dose groups. C. canescens extract containing apigenin, tricin, chlorogenic acid, aesculin, ferulic acid, caffeic acid, and oleanolic acid has a good anti-RA effect, and the mechanism may be related to the inhibition of TLRs/MAPKs/NF-κB signaling pathways.

6-Gingerol protects against cardiac remodeling by inhibiting the p38 mitogen-activated protein kinase pathway.

6-Gingerol, a pungent ingredient of ginger, has been reported to possess anti-inflammatory and antioxidant activities, but the effect of 6-gingerol on pressure overload-induced cardiac remodeling remains inconclusive. In this study, we investigated the effect of 6-gingerol on cardiac remodeling in in vivo and in vitro models, and to clarify the underlying mechanisms. C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with 6-gingerol (20 mg/kg, ig) three times a week (1 week in advance and continued until the end of the experiment). Four weeks after TAC surgery, the mice were subjected to echocardiography, and then sacrificed to harvest the hearts for analysis. For in vitro study, neonatal rat cardiomyocytes and cardiac fibroblasts were used to validate the protective effects of 6-gingerol in response to phenylephrine (PE) and transforming growth factor-ß (TGF-ß) challenge. We showed that 6-gingerol administration protected against pressure overload-induced cardiac hypertrophy, fibrosis, inflammation, and dysfunction in TAC mice. In the in vitro study, we showed that treatment with 6-gingerol (20 µM) blocked PE-induced-cardiomyocyte hypertrophy and TGF-ß-induced cardiac fibroblast activation. Furthermore, 6-gingerol treatment significantly decreased mitogen-activated protein kinase p38 (p38) phosphorylation in response to pressure overload in vivo and extracellular stimuli in vitro, which was upregulated in the absence of 6-gingerol treatment. Moreover, transfection with mitogen-activated protein kinase kinase 6 expressing adenoviruses (Ad-MKK6), which specifically activated p38, abolished the protective effects of 6-gingerol in both in vitro and in vivo models. In conclusion, 6-gingerol improves cardiac function and alleviates cardiac remodeling induced by pressure overload in a p38-dependent manner. The present study demonstrates that 6-gingerol is a promising agent for the intervention of pathological cardiac remodeling.