Search

Herbicide resistance in weeds and environmental pollution resulting from excessive application of chemical herbicides keeps increasing. Development of environment-friendly and effective weed management strategies are required for sustainable agricultural production. In this study we investigated the effects of duckweeds (Landoltia punctata (G. Meyer) LesD. J. Crawford and Spirodela polyrhiza (Linnaeus) Schle iden) introduction on the weed community and rice growth in paddy fields.The study was conducted in the two rice-growing seasons (2018 and 2019) with three treatments: rice grown without duckweed introduction (CK), with L. punctata introduction (LP), and with S. polyrhiza introduction (SP). On average, LP and SP significantly reduced total weed density by more than 90% and 97%, respectively. Early in the rice-growing season, both duckweed species completely prevented weed growth. Further, both species significantly promoted rice plant growth in the advanced stages. SP significantly improved grain yield of rice by 23%. Light transmittance, temperature of the floodwater and soil, floodwater pH, and dissolved oxygen content significantly decreased following introduction of the duckweeds, indicating that the duckweeds introduction might inhibit weeds growth by altering environmental factors.This study provides a possible environment-friendly way to inhibit weed biomass in the paddy field by introducing duckweeds and interpreted the possible reasons of the impacts of duckweed on environmental variables. Weed control is beneficial for rice growth. Duckweed coverage might be limited in open fields and the associated practice requires additional investigation. © 2022 Society of Chemical Industry.

Traditional Chinese Medicine (TCM) has been used to treat infectious diseases and could offer potential drug leads. This study evaluates the in vitro antimicrobial activities from commercially sourced Dryopteris crassirhizoma Nakai (Polypodiaceae) whose authenticity was confirmed by DNA barcoding based on the ribulose bisphosphate carboxylase (rbcL) gene. Powdered rhizomes were sequentially extracted using n-hexane, dichloromethane, ethyl acetate and methanol at ambient temperature. The dried extracts at different concentrations were tested for antimicrobial activities against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus (MRSA), and Mycobacterium smegmatis. D. crassirhizoma extracts exhibited significant antimicrobial activities only against MRSA (minimum inhibitory concentration: 3.125 µg/mL n-hexane extract). Activity-led fractionations of D. crassirhizoma and characterisation by Ultra performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) targeted a fraction (A3), with two anti MRSA phloroglucinol derivatives, Flavaspidic acid AB and Norflavaspidic acid AB – being greatly enriched with the latter. The impact of A3 on MRSA cells was examined using untargeted metabolomic analysis and compared to that of other established antibiotics (all treatments normalized to MIC50 at 6 h). This suggested that norflavaspidic acid AB had a distinctive effects one of which involved targeting bioenergetic transformation, metabolism, and particularly Acetyl CoA, in MRSA cells. No cytotoxicity was observed for the norflavaspidic acid AB enriched fraction against murine HepG2 cells. This study requires further experimental validation but can have indicated a naturally available compound that could help counter the threat of clinically relevant strains with antibiotic resistance. The uploaded data is the result of non-targeted metabolite profiling in both negative and positive ionisation modes&nbsp

Background. Traditional Chinese medicine (TCM) typically attributes the etiopathogenesis of perimenopausal syndrome (PMS) to kidney deficiency in the TCM stratification system for diagnosis. However, the molecular basis of this classical attribution remains to be investigated. Aim of the Study. By unraveling the responses to TCM treatment for kidney deficiency, the metabolomic link between PMS and kidney deficiency can be evaluated for in-depth understanding of the mechanism of TCM treatment and development of better treatment protocols. Materials and Methods. With naturally aged rats as a model for PMS, the metabolomic response to TCM treatment for kidney deficiency was investigated by 1H NMR. Results. 1H NMR metabolomic evidence of plasma samples demonstrates that treatments with two classical TCM prescriptions for kidney deficiency, decoctions of Yougui and Zuogui, result in modulating the metabolic state of the disease model towards that of rats of younger age. Conclusion. The data support the notion that kidney deficiency is responsible, in part at least, for PMS, and the relevant prescriptions are helpful in dampening the changes in the body’s metabolic states to alleviate symptoms of the disorder.

Traditional Chinese Medicine (TCM) has been used to treat infectious diseases and could offer potential drug leads. This study evaluates the in vitro antimicrobial activities commercially sourced Dryopteris crassirhizoma Nakai whose authenticity was confirmed by DNA barcoding based on the ribulose bisphosphate carboxylase (rbcL) gene. Powdered rhizomes were sequentially extracted using n-hexane, dichloromethane, ethyl acetate and methanol at ambient temperature. The dried extracts at different concentrations were tested for antimicrobial activities against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus (MRSA), and Mycobacterium smegmatis. D. crassirhizoma extracts exhibited significant antimicrobial activities only against MRSA. Activity-led fractionations of D. crassirhizoma and characterisation by Ultra performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) identified two potent anti-MRSA phloroglucinol derivatives: Norflavaspidic acid AB and flavaspidic acid AB. The impact of norflavaspidic acid AB on MRSA cells was examined using untargeted metabolomic analysis and compared to that of other established antibiotics (all treatments normalized to MIC50 at 6 h). This suggested that norflavaspidic acid AB had a distinctive effect which involved targeting bioenergetic transformation, metabolism, and particularly acetyl CoA, in MRSA cells. No cytotoxicity was observed for norflavaspidic acid AB against murine HepG2 cells. This study requires further experimental validation but can have indicated a naturally available compound that could help counter the threat of clinically relevant strains with antibiotic resistance.

Ethnopharmacological relevance: Two types of traditional Chinese formulas of botanical drugs are prescribed for treating perimenopausal syndrome (PMS), a disorder in middle-aged women during their transition to menopause. One is for treating PMS as kidney deficiency (KD) due to senescence and declining reproductive functions, and the other is for treating it as liver qi stagnation (LQS) in association with stress and anxiety. Despite the time-tested prescriptions, an objective attestation to the effectiveness of the traditional Chinese treatment of PMS is still to be established and the associated molecular mechanism is still to be investigated.Materials and methods: A model for PMS was generated from perimenopausal rats with chronic restraint stress (CRS). The effectiveness of traditional Chinese formulas of botanical drugs and a combination of two of the formulas was evaluated based on 1H NMR plasma metabolomic, as well as behavioral and physiological, indicators. To investigate whether the formulas contained ligands that could compensate for the declining level of estrogen, the primary cause of PMS, the ligand-based NMR technique of saturation transfer difference (STD) was employed to detect possible interacting molecules to estrogen receptors in the decoction.Results: Each prescription of the classical Chinese formula moderately attenuated the metabolomic state of the disease model. The best treatment strategy however was to combine two traditional Chinese formulas, each for a different etiology, to adjust the metabolomic state of the disease model to that of rats at a much younger age. In addition, this attenuation of the metabolomics of the disease model was by neither upregulating the estrogen level nor supplementing an estrogenic compound.Conclusion: Treatment of PMS with a traditional Chinese formula of botanical drugs targeting one of the two causes separately could ameliorate the disorder moderately. However, the best outcome was to treat the two causes simultaneously with a decoction that combined ingredients from two traditional prescriptions. The data also implicated a new paradigm for phytotherapy of PMS as the prescribed decoctions contained no interacting compound to modulate the activity of estrogen receptors, in contrast to the treatment strategy of hormone replacement therapy.

Ethnopharmacological relevance Tougu Xiaotong capsule (TXC) is a Chinese herbal compound that belongs to a range of Chinese herbs functioning as ‘kidney invigorators and liver softeners’ commonly used to treat osteoarthritis (OA) in China. Aims of the study: The aims of the present study are to confirm the therapeutic effects of TXC in an OA cell model and to determine the mechanisms involved in such effects. Materials and methods A tunicamycin (Tm)-exposed OA cell model was employed, and the effects of TXC were confirmed by observing cell viability and apoptosis. The reduced cell viability and increased apoptosis caused by Tm were improved by TXC, confirming the cellular protection of TXC. We then investigated the expression of biomarkers related to the endoplasmic reticulum (ER) stress pathway, including microRNA-211 (miR-211), a regulator in the ER stress pathway. Results Downregulation of X-box binding protein 1 (Xbp-1) and miR-211 expression following Tm administration was reversed by TXC. Moreover, the upregulation by Tm of the expression levels of binding immunoglobulin protein, Xbp-1, activating transcription factor 4, C/EBP-homologous protein, Caspase-9 and Caspase-3 was downregulated by TXC. These results indicated that the ER stress pathway-related mechanism may play a potential role in the therapeutic effects of TXC. Conclusions The present study provides evidence of the therapeutic effects of TXC at the cell level and describes a cellular model for establishing the mechanisms of the effects of TXC used in the treatment of OA.

Arsenic trioxide (ATO, Trisenox) is an ancient Chinese medicine which have good clinical effects for acute promyelocytic leukemia (APL). However, ATO has serious cardiotoxicity which has restricted its widely applied in clinic. Saposhnikovia divaricata (Trucz.) Schischk was an antidote to ATO in Chinese medical book. Sec-O-Glucosylhamaudol (SOG) is one of its four main active ingredients. So we explore if SOG can detoxify the ATO’s cardiotoxicity through the Nuclear factor erythroid 2-related factor 2(Nrf2) signal pathway and apoptosis pathway. We added 10 μM ATO and 10, 50, 100 μM SOG in Rat cardiac myocyte-like H9c2 cells. The results indicate SOG can active Nrf2 signal pathway, improve Nrf2 phosphorylation levels, promote the expression of Nrf2, HO-1, NQO1 gene and protein, increase the contents of antioxidant enzyme SOD, CAT and GSH-PX, reduce the ROS levels, increase cell activity. By testing the apoptosis-related protein Bax, Bcl-2 and caspase-3, also proved that 10 μM SOG can improve ATO-induced cell apoptosis. So SOG can plays a role in detoxifying ATO cardiac toxicity.

This paper combines echocardiographic signal processing and artificial intelligence technology to propose a deep neural network model adapted to echocardiographic signals to achieve left atrial volume measurement and automatic assessment of pulmonary veins efficiently and quickly. Based on the echocardiographic signal generation mechanism and detection method, an experimental scheme for the echocardiographic signal acquisition was designed. The echocardiographic signal data of healthy subjects were measured in four different experimental states, and a database of left atrial volume measurements and pulmonary veins was constructed. Combining the correspondence between ECG signals and echocardiographic signals in the time domain, a series of preprocessing such as denoising, feature point localization, and segmentation of the cardiac cycle was realized by wavelet transform and threshold method to complete the data collection. This paper proposes a comparative model based on artificial intelligence, adapts to the characteristics of one-dimensional time-series echocardiographic signals, automatically extracts the deep features of echocardiographic signals, effectively reduces the subjective influence of manual feature selection, and realizes the automatic classification and evaluation of human left atrial volume measurement and pulmonary veins under different states. The experimental results show that the proposed BP neural network model has good adaptability and classification performance in the tasks of LV volume measurement and pulmonary vein automatic classification evaluation and achieves an average test accuracy of over 96.58%. The average root-mean-square error percentage of signal compression is only 0.65% by extracting the coding features of the original echocardiographic signal through the convolutional autoencoder, which completes the signal compression with low loss. Comparing the training time and classification accuracy of the LSTM network with the original signal and encoded features, the experimental results show that the AI model can greatly reduce the model training time cost and achieve an average accuracy of 97.97% in the test set and increase the real-time performance of the left atrial volume measurement and pulmonary vein evaluation as well as the security of the data transmission process, which is very important for the comparison of left atrial volume measurement and pulmonary vein. It is of great practical importance to compare left atrial volume measurements with pulmonary veins.

The discovery of antimalarial artemisinin from Artemisia annua L. is an example of how Traditional Chinese Medicine (TCM) may be exploited to meet a recognized need. In this study, we systemically investigated A. annua L. for its antimicrobial activity and assessed it as a source of bioactive natural products for anti-mycobacterial activity.We used a silica gel column to perform antimicrobial activity-guided purification of the A. annua leaf, whose identity was confirmed by rbcL DNA barcoding, and used UHPLC-HRMS and NMR to elucidate the structure of purified active compounds. The antimicrobial activity of crude extracts, isolated compounds and the control artemisinin (Apollo Scientific Ltd) was assessed against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium smegmatis strains by serial micro dilution method (31.25-1000 μg/mL). The isolated compounds were tested for synergistic effects against mycobacterium.Bioactive compounds were purified and identified as deoxyartemisinin and artemisinic acid. Artemisinic acid (MIC 250 μg/mL) was more effective in comparison to deoxyartemisinin (MIC 500 μg/mL) and artemisinin (MIC 1000 μg/mL) against M. smegmatis. We used a molecular docking approach to investigate the interactions between selected anti-mycobacterial compounds and proteins involved in vital physiological functions in M. tuberculosis, namely MtPks13, MtPknB, MtPanK, MtKasA, MtInhA and MtDprE1 and found artemisinic acid showed docking scores superior to the control inhibiters for MtKasA, suggesting it to be a potential nick for further in vitro biological evaluation and anti-TB drug design.

Women are vulnerable to adverse stress events, especially during perimenopause. Substantial evidence has associated the impaired neuronal plasticity with abnormal behaviors under stressful conditions in animals. The Notch signaling pathway is critical for neuronal plasticity in the structure and function of brain areas. In this study, the mid-aged female rats were subjected to chronic restraint stress(CRS) in combination with isolated rearing for 6 weeks. The behavior tests and HPA activity were conducted to evaluate the model. The mRNA and protein levels of Notch1 signaling related genes in the hippocampus(HIP) and prefrontal cortex(PFC) were analyzed by RT-qPCR and western blotting. The promoter methylation levels were measured by bisulfite sequencing PCR analysis. CRS induced depression-like and anxiety-like behaviors in mid-aged stressed females, as shown by decreased locomotor activity, sucrose consumption and increased HPA activity. Moreover, after CRS, the rats exhibited decreased mRNA and protein levels in Jagged1, Notch1 and Hes5 in the HIP and Notch1, Hes1 and Hes5 in the PFC. However, there were no significant promotor methylation changes between the stressed and control female rats. These findings suggest that Notch1 signaling pathway may contribute to the behavioral changes following CRS in mid-aged female rats and the upstream cause of the gene expression changes needs to be further investigated.

Using an enzyme-linked immunosorbent assay (ELISA) and limited dilution methods to screen and clone antigen-specific hybridoma cells is extremely time-consuming and labor-intensive. This work features a simple and rapid cell surface fluorescence immunosorbent assay (CSFIA), designed for the detection and isolation of antigen-specific hybridoma clones. In this assay, antigens are first anchored to the hybridoma cell surface through a dual-functioning molecular Oleyl-PEG4000-NHS. Specific antibodies secreted from hybridoma cells are then captured by the antigens on the cell surface. Positive hybridoma cells are stained using a fluorescently labeled anti-mouse IgG-Fc antibody. After the addition of a methylcellulose semisolid medium, positive clones are easily picked using a pipet. These positive cell clones can be used to produce monoclonal antibodies after direct expansion. Using this method, positive hybridoma clones against both malachite green and porcine epidemic diarrhea virus are selected with high efficiency. Compared to the ELISA-based method, the CSFIA-based method achieved the capability of isolating2-fold more hybridoma clones in25% of the corresponding processing time. In brief, the CSFIA-based method is highly efficient and inexpensive with a simple and direct operation, which is an excellent candidate method for antigen-specific positive clone isolation in a monoclonal antibody preparation.

Expanded hexanucleotide GGGGCC repeat in a noncoding region of C9ORF72 is the most common cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). However, its molecular pathogenesis remains unclear. In our previous study, the expanded GGGGCC repeats have been shown to be sufficient to cause neurodegeneration. In order to investigate the further role of expanded GGGGCC repeats in the neuron, the normal r(GGGGCC)3 and mutant-type expanded r(GGGGCC)30 expression vectors were transfected into Neuro-2a cells. Cell proliferation, dendrite development, and the proteins’ levels of microtubule-associated protein-2 (MAP2) and cyclin-dependent kinase-5 (CDK5) were used to evaluate the cell toxicity of GGGGCC repeats on Neuro-2a cells. The results were shown that expression of expanded GGGGCC repeats caused neuronal cell toxicity in Neuro-2a cells, enhanced the expression of pMAP2 and pCDK5. Moreover, overexpression of Purα repaired expanded GGGGCC repeat-inducing neuronal toxicity in Neuro-2a cells and reduced the expression of pMAP2 and pCDK5. In all, our findings suggested that the expanded GGGGCC repeats might cause neurodegeneration through destroyed neuron cells. And the GGGGCC repeat-induced neuronal cell toxicity was inhibited by upregulation of Purα. We inferred that Purα inhibits expanded GGGGCC repeat-inducing neurodegeneration, which might reveal a novel mechanism of neurodegenerative diseases ALS and FTD.

The upregulation of ELTD1 ([epidermal growth factor (EGF), latrophilin and seven transmembrane domain-containing 1] on chromosome 1) in tumor cells has been reported in several types of cancer and correlates with poor cancer prognosis. However, the role of ELTD1 in glioma progression remains unknown. In this study, we examined ELTD1 expression levels in human glioma cell lines and in sixteen human gliomas of different grades. The molecular effects of ELTD1 in glioma cells were measured using quantitative polymerase chain reaction (qRT-PCR), Western blotting, Cell proliferation assays, Matrigel migration and invasion assays and brain orthotopic xenografts. We found that high expression levels of ELTD1 were positively associated with cancer progression and poor prognosis in human glioma. Mechanistically, ELTD1 activated the JAK/STAT3/HIF-1α signaling axis and p-STAT3 bound with HIF-1α. Taken together, our data provide a plausible mechanism for ELTD1-modulated glioma progression and suggest that ELTD1 may represent a potential therapeutic target in the prevention and therapy of glioma.

Receptor tyrosine kinases are believed to be activated through ligand-induced dimerization. We now demonstrate that in cultured neurons, a substantial amount of endogenous TrkB, the receptor for brain-derived neurotrophic factor (BDNF), exists as an inactive preformed dimer, and the application of BDNF activates the pre-existing dimer. Deletion of the extracellular juxtamembrane motif (EJM) of TrkB increased the amount of preformed dimer, suggesting an inhibitory role of EJM on dimer formation. Further, binding of an agonistic antibody (MM12) specific to human TrkB-EJM activated the full-length TrkB and unexpectedly also truncated TrkB lacking ECD (TrkBdelECD365), suggesting that TrkB is activated by attenuating the inhibitory effect of EJM through MM12 binding-induced conformational changes. Finally, in cells co-expressing rat and human TrkB, MM12 could only activate TrkB human-human dimer but not TrkB human-rat TrkB dimer, indicating that MM12 binding to two TrkB monomers is required for activation. Our results support a model that TrkB preforms as an inactive dimer and BDNF induces TrkB conformation changes leading to its activation.

The temporomandibular joint (TMJ), a unique synovial joint whose development differs from that of other synovial joints, develops from two distinct mesenchymal condensations that grow toward each other and ossify through different mechanisms. The short stature homeobox 2 (Shox2) gene serves an important role in TMJ development and previous studies have demonstrated that Shox2SHOX KI/KI mice display a TMJ defective phenotype, congenital dysplasia and premature eroding of the articular disc, which is clinically defined as a TMJ disorder. In the present study, Shox2SHOX KI/KI mouse models were used to investigate the mechanisms of congenital osteoarthritis (OA)‑like disease during postnatal TMJ growth. Shox2SHOX KI/KI mice were observed to develop a severe muscle wasting syndrome from day 7 postnatal. Histological examination indicated that the condyle and glenoid fossa of Shox2SHOX KI/KI mice was reduced in size in the second week after birth. The condyles of Shox2SHOX KI/KI mice exhibited reduced expression levels of collagen type II and Indian hedgehog, and increased expression of collagen type I. A marked increase in matrix metalloproteinase 9 (MMP9) and MMP13 in the condyles was also observed. These cellular and molecular defects may contribute to the observed (OA)‑like phenotype of Shox2SHOX KI/KI mouse TMJs.

Recovery of common agricultural weeds after burial by soil was studied in four greenhouse and three field experiments. Species studied included velvetleaf, Powell amaranth, common lambsquarters, barnyardgrass, and giant foxtail. Seedlings were bent over before burial to simulate the effect of the impact of soil thrown by a cultivator. Altogether, more than 35,000 seedlings were marked and observed for recovery. No seedlings recovered from 4 cm of burial. Recovery from complete burial under 2 cm of soil ranged from 0 to 24% depending on the experiment, species, and watering treatment, but recovery greater than 5% was rare. Large-seeded species tended to recover from complete burial under 2 cm of soil better than small-seeded species. The study did not reveal a difference in recovery of grasses relative to broadleaf weeds. Overall, seedlings tended to recover best when water was applied daily after burial, worst when water was applied once on the day of burial, and to an intermediate extent when no water was applied. However, difference in recovery between the no-water and watering-once treatments were usually small. Also, many experiment by species combinations showed no significant differences among watering treatments. When even a small portion of the seedling was left exposed, recovery generally exceeded 50%. Organic weed management systems commonly use burial of weed seedlings with tine weeders and soil thrown by sweeps and hilling disks to control weeds in crop rows. Recovery from burial could pose a substantial weed management problem in some circumstances, particularly for large-seeded weed species. Maximizing burial depth is important for limiting recovery. Recovery from burial can be minimized by withholding irrigation for several days after hilling-up operations.

Objective: We constructed 3D-model of ONFH in computer according to three-dimensional computerized tomography (3D-CT) data. We determined the location and volume of necrosis to investigate its clinical efficacy. Method: Totally 92 hips (59 cases) with ONFH (44 males, 15 females) were included, with mean age of 37.5 years (range from 26 to 58). Totally 20 cases (35 hips) were induced by corticosteroid (CTSs), 31 (49 hips) induced by alcohol, 4 (4 hips) induced by trauma and 4 (4 hips) idiopathic. All the hips were categorized into stage ARCO II. Finally diagnosed by MRI, all hips were scanned by CT to acquire data in DICOM format. The images were imported into software to extract 3D-shape of femoral heads, necrotic foci, their volumes and distribution in each quadrant. Deviation of volumes between digital image and biopsy specimen was analyzed by SAS9.1 package. Correlativity between collapse and volume of necrosis under specific pathogeneses was also analyzed. Among the cases necessitating total hip arthroplasty (THA) due to advancing to ARCO III, we randomly selected 8 of them to perform 3D-CT scanning thrice prior to surgical operation. Total femoral heads harvested were torn asunder. Cubic capacity of femoral heads and necrotic foci were hereby measured and compared with those acquired from digital models. Result: Through the digital model, necrotic foci were found mainly locating within the super lateral portion of femoral head, coinciding with those observed in biopsy specimen. Average volumetric ratio of digitally acquired necrosis focus/femoral head in 58 collapsed hips was 36.8%. The ratio of the 34 hips without collapse was 17.3%. In collapsed femoral heads, the distribution of necrosis focus was 23.4% in quadrant 1 (q1), 23.6% in q2, 12.1% in q3, 14.4% in q4, 9.0% in q5, 11.8% in q6, 1.6% in q7 and 3.9% in q8. In femoral heads without collapse, the distribution was 34.2% in q1, 29.6% in q2, 11.8% in q3, 11.3% in q4, 6.0% in q5, 6.0% in q6, 0.5% in q7 and 0.4% in q8. As for the average cubic capacities of femoral heads and necrotic foci, those acquired from the digital model and biopsy specimen had no significant difference in matched-pairs test (t = -1.49, P = 0.179 for femoral heads and t = -1.52, P = 0.172 for necrotic foci). There was significant difference (F = 2.720, P = 0.035 < 0.05) among volumetric ratios of necrotic focus/total femoral head under different pathogeneses, which were 33.55% in alcohol-induced cases, 26.74% in the CTSs-induced, 40.41% in the trauma-induced, and 18.39% in idiopathic cases. Shapes of necrotic foci could be subdivided into 5 types: vault, sublobe, dumbbell, ball and petal. The distribution of these 5 types of shape was different among necroses caused by CTSs, alcohol, trauma and idiopathic pathogeneses. The distribution in 58 collapsed femoral heads was also distinct from that in 34 femoral heads without collapse. Through multinomial logistic regression, we analyzed the correlativity among volumetric ratios of necrotic tissue, its distribution in q2(superioanteriomedial portion of femoral head) and collapse. The result showed statistical significance (P was respectively 0.0001 and 0.0005). Decision tree model showed that 94.6% (53/56) hips would progress into collapse if the volumetric ratio of necrotic tissue was over 23.48%. Otherwise, if distribution in q2 was over 45.13%, 83.3% (5/6) hips would progress into collapse. No collapse (0/30) would occur if the distribution of necrotic tissue in q2 was under 45.13%. Conclusion: Digital 3D-model reconstructed from CT scanning can precisely incarnate spatial orientation of necrotic foci in femoral head. Multinomial logistic regression and decision-making tree shows that volumetric ratio of necrotic tissues plays an important role in anticipating collapse of femoral head.

Women are vulnerable to adverse stress events, especially during perimenopause. Substantial evidence has associated the impaired neuronal plasticity with abnormal behaviors under stressful conditions in animals. The Notch signaling pathway is critical for neuronal plasticity in the structure and function of brain areas. In this study, the mid-aged female rats were subjected to chronic restraint stress(CRS) in combination with isolated rearing for 6 weeks. The behavior tests and HPA activity were conducted to evaluate the model. The mRNA and protein levels of Notch1 signaling related genes in the hippocampus(HIP) and prefrontal cortex(PFC) were analyzed by RT-qPCR and western blotting. The promoter methylation levels were measured by bisulfite sequencing PCR analysis. CRS induced depression-like and anxiety-like behaviors in mid-aged stressed females, as shown by decreased locomotor activity, sucrose consumption and increased HPA activity. Moreover, after CRS, the rats exhibited decreased mRNA and protein levels in Jagged1, Notch1 and Hes5 in the HIP and Notch1, Hes1 and Hes5 in the PFC. However, there were no significant promotor methylation changes between the stressed and control female rats. These findings suggest that Notch1 signaling pathway may contribute to the behavioral changes following CRS in mid-aged female rats and the upstream cause of the gene expression changes needs to be further investigated.

While Brain-derived Neurotrophic Factor (BDNF) has long been implicated in treating neurological diseases, recombinant BDNF protein has failed in multiple clinical trials. In addition to its unstable and adhesive nature, BDNF can activate p75NTR, a receptor mediating cellular functions opposite to those of TrkB. We have now identified TrkB agonistic antibodies (TrkB-agoAbs) with several properties superior to BDNF: They exhibit blood half-life of days instead of hours, diffuse centimeters in neural tissues instead millimeters, and bind and activate TrkB, but not p75NTR. In addition, TrkB-agoAbs elicit much longer TrkB activation, reduced TrkB internalization and less intracellular degradation, compared with BDNF. More importantly, some of these TrkB-agoAbs bind TrkB epitopes distinct from that by BDNF, and work cooperatively with endogenous BDNF. Unlike BDNF, the TrkB-agoAbs exhibit a half-life of days/weeks and diffused readily in nerve tissues. We tested one of TrkB-agoAbs further and showed that it enhanced motoneuron survival in the spinal-root avulsion model for motoneuron degeneration in vivo. Thus, TrkB-agoAbs are promising drug candidates for the treatment of neural injury.

Plasma membrane (PM) and mitochondrial membrane (MM) proteins of rat hippocampal neurons were identified and comparatively characterized on the basis of a sequential digestion-centered combinative strategy for sample treatment. A total of 478 membrane proteins were identified, of which 240 had PM localization, 170 had MM localization, and 33 had both of the two subcellular localizations. Compared with the PM proteome, the MM proteome not only was smaller, more basic, and more hydrophobic, but also had a narrower protein molecular mass distribution range and a higher proportion of transmembrane proteins. By functional enrichment analysis, 287 molecular function terms for the PM proteome and 173 for the MM proteome were obtained. The MM proteome had a lower percentage of binding function terms and a higher percentage of catalysis function terms than the PM proteome, suggesting that mitochondrial proteins were more inclined to affect the physiological and biochemical processes by binding various molecules and as enzymes. Biological process enrichment showed that the genes of the PM and MM proteomes were mapped to 1104 and 460 biological processes, respectively. The biological processes with the most mapped genes of the PM proteome included those involved in vesicle recycling, transmitter release, neuronal development, protein and ion transport, etc., whereas those involved in electron transport, ATP synthesis, mitochondrial transport, mitochondrial apoptosis, etc., were the most gene-mapped biological processes for the MM proteome. The present work has deepened our understanding of the structure and function of hippocampal neurons and provided reference methods for research in the related field. Graphical abstract Functional comparison of the plasma membrane and mitochondrial membrane proteomes.

Background Contrast-induced nephropathy (CIN) after coronary angiography is frequently observed in patients with chronic renal insufficiency and no effective measures have been developed for prevention of CIN. There is evidence showing that trimetazidine (TMZ) has renoprotective effect on CIN. This study was to evaluate the role of TMZ in the prevention of CIN in renal dysfunction patients undergoing coronary angiography. Methods A total of 132 patients with renal dysfunction who underwent coronary angiography were enrolled in our study and divided into control group (n = 70) and TMZ group (n = 62). Standard hydration was administered in all the patients. In TMZ group, patients were administered TMZ orally for 48 hours before and 24 hours after coronary angiography. Serum creatinine (SCr) and cystatin (CysC) were detected before and after contrast media injection, and the incidence of CIN was evaluated according to the elevation of SCr. Adverse events were observed in 12 months. Results In both groups, CysC and SCr increased significantly after coronary angiography and peaked at 24 and 48 hours, respectively. CysC and SCr were significantly lower in TMZ group than in control group after coronary angiography. The incidence of CIN and adverse events was reduced in TMZ group when compared with control group ( P = 0.034 and P = 0.043, respectively). Conclusions TMZ in combination with standard hydration is more effective than isotonic saline alone in protecting renal function in patients with renal dysfunction who undergo coronary angiography and can reduce the adverse events within 12 months.

A novel acetolactate synthase (ALS) gene was cloned from Anabaena azotica , which was isolated from China and is regarded as a vital and beneficial photosynthetic microorganism that can contribute to soil fertility and maintain ecosystem stability. The full-length gene consists of an open reading frame (ORF) of 1644 bp and encodes a 59.2 kDa 547 amino acid protein. Sequence alignment using the BLAST similarity search in the GenBank database revealed that the amino acid sequence was similar to ALS derived from Anabaena sp. PCC 7120. The ALS gene was subcloned into the plasmid pET28a (+) and expressed in Escherichia coli BL21 (DE3) by IPTG induction. The recombinant protein was purified and subsequently characterized. The properties of ALS from the E. coli transformant are similar to that of an enzyme from the original A. azotica . Conserved amino acid sequence and the predicted structure of the active site were consistent with those observed for the bacterial enzyme Klebsiella pneumoniae ALS in similar experiments. Our results represent a significant functional demonstration of the existence of an algae ALS subunit and provide a solid basis for further studies on the structure, function and properties of ALS, as well as its response mechanism to inhibitors.

Background: Appropriate expression and regulation of the transcriptome, which mainly comprise of mRNAs and lncRNAs, are important for all biological and cellular processes including the physiological activities of bone microvascular endothelial cells (BMECs). Through an intricate intracellular signaling systems, the transcriptome regulates the pharmacological response of the cells. Although studies have elucidated the impact of glucocorticoids (GCs) cell-specific gene expression signatures, it remains necessary to comprehensively characterize the impact of lncRNAs to transcriptional changes. Methods: BMECs were divided into two groups. One was treated with GCs and the other left untreated as a paired control. Differential expression was analyzed with GeneSpring software V12.0 (Agilent, Santa Clara, CA, USA) and hierarchical clustering was conducted using Cluster 3.0 software. The Gene Ontology (GO) analysis was performed with Molecular Annotation System provided by CapitalBio Corporation. Results: Our results highlight the involvement of genes implicated in development, differentiation and apoptosis following GC stimulation. Elucidation of differential gene expression emphasizes the importance of regulatory gene networks induced by GCs. We identified 73 up-regulated and 166 down-regulated long noncoding RNAs, the expression of 107 of which significantly correlated with 172 mRNAs induced by hydrocortisone. Conclusions: Transcriptome analysis of BMECs from human samples was performed to identify specific gene networks induced by GCs. Our results identified complex RNA crosstalk underlying the pathogenesis of steroid-induced necrosis of femoral head.

Magnetic manipulation of cell activity offers advantages over optical manipulation but an ideal tool remains elusive. The MagR protein was found through its interaction with cryptochrome (Cry) and the protein in solution appeared to respond to magnetic stimulation (MS). After we initiated an investigation on the specific role of MagR in cellular response to MS, a subsequent study claimed that MagR expression alone could achieve cellular activation by MS. Here we report that despite systematically testing different ways of measuring intracellular calcium and different magnetic stimulation protocols, it was not possible to detect any cellular or neuronal responses to magnetic stimulation in MagR-expressing HEK cells or primary neurons from the dorsal root ganglion and the hippocampus. By contrast, in neurons co-expressing MagR and channelrhodopin, optical but not magnetic stimulation increased calcium influx in hippocampal neurons. Our results indicate that MagR alone is not sufficient to confer cellular magnetic responses.

Amyloid β-peptide (Aβ) has been implicated as a key molecule in the neurodegenerative cascades of Alzheimer's disease (AD). Humanin (HN) is a secretory peptide that inhibits the neurotoxicity of Aβ. However, the mechanism(s) by which HN exerts its neuroprotection against Aβ-induced AD-like pathological changes and memory deficits are yet to be completely defined. In the present study, we provided evidence that treatment of rats with HN increases the number of dendritic branches and the density of dendritic spines, and upregulates pre- and post-synaptic protein levels; these effects lead to enhanced long-term potentiation and amelioration of the memory deficits induced by Aβ(1-42). HN also attenuated Aβ(1-42)-induced tau hyperphosphorylation, apparently by inhibiting the phosphorylation of Tyr307 on the inhibitory protein phosphatase-2A (PP2A) catalytic subunit and thereby activating PP2A. HN also inhibited apoptosis and reduced the oxidative stress induced by Aβ(1-42). These findings provide novel mechanisms of action for the ability of HN to protect against Aβ(1-42)-induced AD-like pathological changes and memory deficits.