Retrotransposon-mediated evolutionary rewiring of a pathogen response orchestrates a resistance phenotype in an insect host.

Ongoing host-pathogen interactions can trigger a coevolutionary arms race, while genetic diversity within the host can facilitate its adaptation to pathogens. Here, we used the diamondback moth (Plutella xylostella) and its pathogen Bacillus thuringiensis (Bt) as a model for exploring an adaptive evolutionary mechanism. We found that insect host adaptation to the primary Bt virulence factors was tightly associated with a short interspersed nuclear element (SINE - named SE2) insertion into the promoter of the transcriptionally activated MAP4K4 gene. This retrotransposon insertion coopts and potentiates the effect of the transcription factor forkhead box O (FOXO) in inducing a hormone-modulated Mitogen-activated protein kinase (MAPK) signaling cascade, leading to an enhancement of a host defense mechanism against the pathogen. This work demonstrates that reconstructing a cis-trans interaction can escalate a host response mechanism into a more stringent resistance phenotype to resist pathogen infection, providing a new insight into the coevolutionary mechanism of host organisms and their microbial pathogens.

Deep learning-based automatic segmentation of meningioma from T1-weighted contrast-enhanced MRI for preoperative meningioma differentiation using radiomic features.

BACKGROUND: This study aimed to establish a dedicated deep-learning model (DLM) on routine magnetic resonance imaging (MRI) data to investigate DLM performance in automated detection and segmentation of meningiomas in comparison to manual segmentations. Another purpose of our work was to develop a radiomics model based on the radiomics features extracted from automatic segmentation to differentiate low- and high-grade meningiomas before surgery. MATERIALS: A total of 326 patients with pathologically confirmed meningiomas were enrolled. Samples were randomly split with a 6:2:2 ratio to the training set, validation set, and test set. Volumetric regions of interest (VOIs) were manually drawn on each slice using the ITK-SNAP software. An automatic segmentation model based on SegResNet was developed for the meningioma segmentation. Segmentation performance was evaluated by dice coefficient and 95% Hausdorff distance. Intra class correlation (ICC) analysis was applied to assess the agreement between radiomic features from manual and automatic segmentations. Radiomics features derived from automatic segmentation were extracted by pyradiomics. After feature selection, a model for meningiomas grading was built. RESULTS: The DLM detected meningiomas in all cases. For automatic segmentation, the mean dice coefficient and 95% Hausdorff distance were 0.881 (95% CI: 0.851-0.981) and 2.016 (95% CI:1.439-3.158) in the test set, respectively. Features extracted on manual and automatic segmentation are comparable: the average ICC value was 0.804 (range, 0.636-0.933). Features extracted on manual and automatic segmentation are comparable: the average ICC value was 0.804 (range, 0.636-0.933). For meningioma classification, the radiomics model based on automatic segmentation performed well in grading meningiomas, yielding a sensitivity, specificity, accuracy, and area under the curve (AUC) of 0.778 (95% CI: 0.701-0.856), 0.860 (95% CI: 0.722-0.908), 0.848 (95% CI: 0.715-0.903) and 0.842 (95% CI: 0.807-0.895) in the test set, respectively. CONCLUSIONS: The DLM yielded favorable automated detection and segmentation of meningioma and can help deploy radiomics for preoperative meningioma differentiation in clinical practice.

Reduced microbial stability in the active layer is associated with carbon loss under alpine permafrost degradation.

Permafrost degradation may induce soil carbon (C) loss, critical for global C cycling, and be mediated by microbes. Despite larger C stored within the active layer of permafrost regions, which are more affected by warming, and the critical roles of Qinghai-Tibet Plateau in C cycling, most previous studies focused on the permafrost layer and in high-latitude areas. We demonstrate in situ that permafrost degradation alters the diversity and potentially decreases the stability of active layer microbial communities. These changes are associated with soil C loss and potentially a positive C feedback. This study provides insights into microbial-mediated mechanisms responsible for C loss within the active layer in degraded permafrost, aiding in the modeling of C emission under future scenarios.

A new coumarin and a new flavonoid from Ochrocarpus longifolius.

A new coumarin (1) and a new flavonoid (2) were isolated from the air-dried flower buds of Ochrocarpus longifolius, together with ten known compounds (3-12). The structures of two new compounds were established by 1D and 2D NMR and MS data. In addition, the new compound 2 showed significant proliferation inhibitory activity on Eca-109 and MGC-803 cells. The results of this study may enrich the diversity of compounds from O. longifolius and provide a basis for further research on its natural products and pharmacological activities.

[Effect and mechanism of aqueous extract of Strychni Semen on bone destruction in rats with type â ¡ collagen-induced rheumatoid arthritis].

To investigate the mechanism of action of aqueous extract of Strychni Semen(SA) on bone destruction in rats with type Ⅱ collagen-induced arthritis(CIA), the SD rats were randomly divided into normal group, model group, low, medium, and high dose(2.85, 5.70, and 11.40 mg·kg~(-1)) groups of SA, and methotrexate group. Except for the normal group, the CIA model was prepared for the other groups. After the second immunization, different doses of SA were given to the low, medium, and high dose groups of SA once a day, and the methotrexate group was given once every three days. 0.3% sodium hydroxymethylcellulose(CMC-Na) was given once a day to the normal and model groups for 28 d. The clinical score of arthritis was evaluated every three days. Micro computed tomography(Micro-CT) method was used to evaluate the degree of bone destruction. Histopathological changes in the joint tissue and the number of osteoclasts in CIA rats were evaluated by hematoxylin-eosin(HE) staining and tartrate-resistant acid phosphatase(TRAP) staining. The expression of interleukin-1ß(IL-1ß) in the joint tissue of rats was detected by immunohistochemistry. Western blot was used to detect key protein expression in mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathways in the joint tissue of rats. The results showed that different doses of SA were able to improve the red and swollen inflammatory joint and joint deformity in CIA rats to varying degrees, reduce the clinical score, inhibit synovial inflammation, vascular opacification, cartilage erosion, and bone destruction, and reduce the number of TRAP-positive cells in bone tissue. Micro-CT results showed that the SA was able to increase bone mineral density, bone volume fraction, trabecular reduce, and trabecular number and reduce bone surface/bone volume and trabecular separation/spacing. Different doses of SA could down-regulate the protein expression of IL-1ß, p-JNK, p-ERK, p-p38, PI3K, and p-Akt to varying degrees. In conclusion, SA can improve disease severity, attenuate histopathological and imaging changes in joints, and have osteoprotective effects in CIA rats, and its mechanism of action may be related to the inhibition of the overactivation of MAPK and PI3K/Akt signaling pathways.

[Mechanism of aqueous extract of Strychni Semen in improving pain in rats with rheumatoid arthritis based on TLR4/TNF-α/MMP-9 signaling pathway].

This study aims to explore the mechanism of aqueous extract of Strychni Semen(SA) in relieving pain in the rat model of rheumatoid arthritis(RA) via Toll-like receptor 4(TLR4)/tumor necrosis factor-α(TNF-α)/matrix metalloproteinase-9(MMP-9) signaling pathway. Firstly, the main chemical components of Strychni Semen were searched against TCMSP, TCMID, ETCM, and related literature, and the main targets of the chemical components were retrieved from TargetNet and SwissTargetPrediction. The main targets of RA and pain were searched against GeneCards, Online Mendelian Inheritance in Man(OMIM), and Therapeutic Target Database(TTD). Venny 2.1.0 was used to obtain the common targets shared by Strychni Semen, RA, and pain, and STRING and Cytoscape 3.6.1 were used to build the protein-protein interaction network. Then, molecular docking was carried out in AutoDock Vina. Finally, the rat model of type Ⅱ collagen-induced arthritis(CIA) was established. The up-down method and acetone method were employed to examine the mechanical pain threshold and cold pain threshold of rats, and the pain-relieving effect of SA on CIA rats was evaluated comprehensively. Hematoxylin-eosin(HE) staining was employed to evaluate the histopathological changes of joints in CIA rats. The expression levels of key target proteins was determined by immunohistochemistry and Western blot, and the mRNA levels of key targets were determined by real-time fluorescence quantitative polymerase chain reaction(real-time PCR). The results of network prediction showed that Strychni Semen may act on the TLR4/TNF-α/MMP-9 signaling pathway to exert the pain-relieving effect. The results of molecular docking showed that brucine, the main active component of SA, had strong binding ability to TLR4, TNF-α, and MMP-9. The results of animal experiments showed that SA improved the mechanical and cold pain sensitivity(P<0.05, P<0.01) and reduced the joint histopathological score of CIA rats(P<0.01). In addition, medium and high doses of SA down-regulated the protein and mRNA levels of TNF-α, TLR4, and MMP-9(P<0.05,P<0.01). In conclusion, SA alleviated the mechanical pain sensitivity, cold pain sensitivity, and joint histopathological changes in CIA rats by inhibiting the over activation of TLR4/TNF-α/MMP-9 signaling pathway.

The regulation landscape of MAPK signaling cascade for thwarting Bacillus thuringiensis infection in an insect host.

Host-pathogen interactions are central components of ecological networks where the MAPK signaling pathways act as central hubs of these complex interactions. We have previously shown that an insect hormone modulated MAPK signaling cascade participates as a general switch to trans-regulate differential expression of diverse midgut genes in the diamondback moth, Plutella xylostella (L.) to cope with the insecticidal action of Cry1Ac toxin, produced by the entomopathogenic bacterium Bacillus thuringiensis (Bt). The relationship between topology and functions of this four-tiered phosphorylation signaling cascade, however, is an uncharted territory. Here, we carried out a genome-wide characterization of all the MAPK orthologs in P. xylostella to define their phylogenetic relationships and to confirm their evolutionary conserved modules. Results from quantitative phosphoproteomic analyses, combined with functional validations studies using specific inhibitors and dsRNAs lead us to establish a MAPK "road map", where p38 and ERK MAPK signaling pathways, in large part, mount a resistance response against Bt toxins through regulating the differential expression of multiple Cry toxin receptors and their non-receptor paralogs in P. xylostella midgut. These data not only advance our understanding of host-pathogen interactions in agricultural pests, but also inform the future development of biopesticides that could suppress Cry resistance phenotypes.

Design, Synthesis and Characterization of Palladium-Functionalized Covalent Organic Framework and Its Application as Heterogeneous Catalysis for C-H Arylation of Azoles.

A novel triazine-based covalent organic framework (TFPT-Bz COF) has been constructed by the condensation of 2,4,6-tris(5-formyl-2-pyridinoxy)-1,3,5-triazine (TFPT) and benzidine (BZ) with deep eutectic solvent (DES) as the reaction medium. After the introduction of Pd ions through strong coordination to TFPT-Bz COF matrix, the constructed TFPT-Bz COF/Pd composite exhibited excellent catalytic activity for C-H arylation of azoles with aryl halides in 2-methyltetrahydrofuran. The protocol allows the arylation of a variety of substituted azoles with diverse aryl halides in high to excellent yield. Moreover, the TFPT-Bz COF/Pd catalyst can be recycled several times without significantly reducing its activity.

Comparison of response evaluation criteria in solid tumors and tumor regression grade in evaluating the effect of preoperative systemic therapy of gastric cancer.

BACKGROUND: Both Response Evaluation Criteria in Solid Tumors (RECIST) and tumor regression grade (TRG) play key roles in evaluating tumor response. We analyzed the consistency of TRG and RECIST 1.1 for gastric cancer (GC) patients and compared their prognostic values. METHODS: Patients with GC who received preoperative chemotherapy or chemoimmunotherapy and had records of TRG from December 2013 to October 2021 were enrolled retrospectively. TRG 0-1 and 2-3 are considered as corresponding to complete response (CR)/partial response (PR) and stable disease (SD)/progress disease (PD) in RECIST 1.1, respectively. The primary endpoints were disease-free survival (DFS) and overall survival (OS). The consistency of RECIST and TRG was examined by kappa statistics. Survival analysis was performed using the Kaplan Meier method. RESULT: One hundred fifty seven GC patients were enrolled, including 125 with preoperative chemotherapy and 32 with chemoimmunotherapy. Among them, 56 patients had measurable lesions. Only 19.6% (11/56) of the patients had consistent results between RECIST 1.1 and TRG. TRG was correlated with both OS and DFS (P = 0.02 and 0.03, respectively) while response according to RECIST1.1 was not (P = 0.86 and 0.23, respectively). The median DFS had not reached in the TRG 0-1 group and was 16.13 months in TRG 2-3 group. TRG 2-3 was associated with young age and peritoneal or liver metastasis. Besides, preoperative chemoimmunotherapy had a significantly higher pCR rate than chemotherapy alone (34.4% vs 8.0%, P < 0.001). CONCLUSION: TRG was in poor agreement with RECIST 1.1. TRG was better than RECIST 1.1 in predicting DFS and OS for GC patients who received preoperative therapy.

Longitudinal symptom network structure in first-episode psychosis: a possible marker for remission.

BACKGROUND: Network approach has been applied to a wide variety of psychiatric disorders. The aim of the present study was to identify network structures of remitters and non-remitters in patients with first-episode psychosis (FEP) at baseline and the 6-month follow-up. METHODS: Participants (n = 252) from the Korean Early Psychosis Study (KEPS) were enrolled. They were classified as remitters or non-remitters using Andreasen's criteria. We estimated network structure with 10 symptoms (three symptoms from the Positive and Negative Syndrome Scale, one depressive symptom, and six symptoms related to schema and rumination) as nodes using a Gaussian graphical model. Global and local network metrics were compared within and between the networks over time. RESULTS: Global network metrics did not differ between the remitters and non-remitters at baseline or 6 months. However, the network structure and nodal strengths associated with positive-self and positive-others scores changed significantly in the remitters over time. Unique central symptoms for remitters and non-remitters were cognitive brooding and negative-self, respectively. The correlation stability coefficients for nodal strength were within the acceptable range. CONCLUSION: Our findings indicate that network structure and some nodal strengths were more flexible in remitters. Negative-self could be an important target for therapeutic intervention.

Aluminum sheet induced flower-like carbon nitride anchored with silver nanowires for highly efficient SERS detection of trace malachite green.

The sensitive detection of malachite green (MG) in aquaculture wastewater is necessary for its residual poses a great threat to the living systems. Herein, the flower-like C3N4 (f-C3N4) nanostructure induced by Al sheet in the hydrothermal process is constructed. Subsequently, Ag nanowires (AgNWs) supported on Al/f-C3N4 and the strong interaction between AgNWs and Al/f-C3N4 are confirmed by XPS, Raman spectroscopy, UV-vis diffuse reflectance and fluorescence spectroscopy. Importantly, the portable Al/f-C3N4/AgNWs substrate shows the outstanding SERS response for MG, which is attributed to enhanced electromagnetic effect of AgNWs on large amount of corrugated and creviced regions in the flower-like Al/f-C3N4 and the charge transfer among the components. Also, the prepared Al/f-C3N4 nanostructure provides large specific surface area and abundant "N" active sites for AgNWs, and the high enrichment ability of Al/f-C3N4 towards MG molecules by the strong π-π stacking interaction. The detection limit of Al/f-C3N4/AgNWs for MG is as low as 8.38 × 10-12 mol L-1. The substrate can be reproduced and reused for at least 7 cycles, and the activity can still be kept after laid up for 49 days. Importantly, it unfolds a good sensitivity and selectivity for MG in actual water sample. Results indicate that the Al/f-C3N4/AgNWs substrate has a promising potential in practical application for trace detection of MG.

Effect of Tirofiban Injection on vascular endothelial function, cardiac function and inflammatory cytokines in patients with acute myocardial infarction after emergency Percutaneous Coronary Intervention.

OBJECTIVES: To evaluate the effect of tirofiban injection on vascular endothelial function, cardiac function, inflammatory cytokines and other indicators in patients with acute myocardial infarction after emergency PCI and its clinical significance. METHODS: Eighty patients with acute myocardial infarction admitted to Affiliated Hospital of Hebei University from March 18, 2020 to October 18, 2020 were enrolled and randomly divided into two groups: the experimental group and the control group, with 40 cases in each group. Patients in both groups underwent PCI. Patients in the control group were given oxygen inhalation, monitoring, and basic medications for myocardial infarction, such as nutritional myocardial drugs, statins, aspirin, nitrates, clopidogrel, and ß-blockers. In contrast, patients in the experimental group received tirofiban 10 ug/kg intravenously over 5min immediately before PCI in addition to basic treatment, and then tirofiban 0.1 ug/(kg/min) was pumped via intravenous pump postoperatively for 48 hour. The changes of vascular endothelial function, cardiac function and adverse drug reactions (ADRs) in the two groups before treatment, one week and one month after treatment, as well as changes of inflammatory cytokines such as CRP and IL-6 in the two groups before and after treatment were compared and analyzed. RESULTS: Compared with the control group, FMD, NO, ET-1 and other indexes in the experimental group were significantly improved one week and one month after treatment, with statistically significant differences (p<0.05). BNP, LVEDD, LVEF and additional indexes in the experimental group were significantly lower than those in the control group at one week and one month after treatment, with statistically significant differences (p=0.00). Moreover, the incidence of ST-segment fallback > 70% in the experimental group was 72.5% after treatment, which was significantly better than that of 47.5% in the control group, with a statistically significant difference (p=0.03). CRP and IL-6 in the experimental group were significantly lower than those in the control group after treatment, with a statistically significant difference (p=0.00). There was no statistical significance in the incidence of ADRs between the two groups after treatment (p=0.42). CONCLUSION: Tirofiban injection after emergency PCI is a beneficial treatment regime for patients with STEMI. With such a treatment regime, cardiac function and vascular endothelial function of patients can be dramatically improved, coronary blood supply will be ameliorated, inflammatory cytokines can be reduced, and no significant increase can be seen in the incidence of adverse reactions.

Clinical significance of N-terminal natriuretic peptide combined with inflammatory factors, oxidative stress factors and blood lipid detection in elderly patients with Type-2 diabetes complicated with coronary heart disease.

Objectives: To observe the clinical significance of N-terminal natriuretic peptide combined with inflammatory factors, oxidative stress factors and blood lipid detection in elderly patients with Type-2 diabetes complicated with CHD (CHD), and provide a theoretical basis for the diagnosis and treatment of elderly patients with Type-2 diabetes complicated with CHD. Methods: A total of 40 patients with Type-2 diabetes complicated with CHD admitted to Affiliated Hospital of Hebei University from July 2019 and July 2020 were selected as the experimental group, and 40 patients with CHD who were hospitalized in our hospital during the same period without diabetes were selected as the control group. Venous blood was taken from all patients on morning and fasting basis, and their serum inflammatory factors as well as antioxidant molecules were examined respectively. Serum inflammatory factors include serum tumor necrosis factor α (TNF-A), interleukin-6 (IL-6), and C-reactive protein. Antioxidant molecules include antioxidant molecules superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (TAC), catalase (CAT), glutathione reductase (GR), N-terminal natriuretic peptide (NT-proBNP), white blood cells (WBC), hemoglobin (HBG), albumin (ALB) and blood lipid levels. The differences of the above indexes between experimental group and control group were compared and analyzed. Results: The serum levels of TNF-a, CRP, and IL-6 in the experimental group were apparently higher than those in the control group, with a statistically significant difference (P=0.00); The levels of SOD, TAC and CAT in the experimental group were significantly lower than those in the control group, with a statistically significant difference (P=0.00); The level of NT-proBNP and WBC count in the experimental group were significantly higher than those in the control group, with a statistically significant difference (NT-proBNP, P=0.01; WBC, P=0.00). However, no statistically significant difference was observed in the levels of HBG and ALB between the two groups (P>0.05). The experimental group had significantly higher TC and TG levels than the control group, with statistically significant differences (TC, P=0.01; TG, P=0.02), but had a significantly lower HDL level than the control group, with a statistically significant difference (P=0.00). Conclusion: Elderly patients with Type-2 diabetes complicated with CHD showed systemic microinflammation, decreased antioxidant molecule content, as well as myocardial damage and abnormal lipid metabolism compared with patients with CHD alone. For this reason, attention should be paid to the above risk factors in clinical practice, and proactive prevention and treatment should be taken to reduce the probability of related complications.

MAPK-Activated Transcription Factor PxJun Suppresses PxABCB1 Expression and Confers Resistance to Bacillus thuringiensis Cry1Ac Toxin in Plutella xylostella (L.).

Deciphering the molecular mechanisms underlying insect resistance to Cry toxins produced by Bacillus thuringiensis (Bt) is pivotal for the sustainable utilization of Bt biopesticides and transgenic Bt crops. Previously, we identified that mitogen-activated protein kinase (MAPK)-mediated reduced expression of the PxABCB1 gene is associated with Bt Cry1Ac resistance in the diamondback moth, Plutella xylostella (L.). However, the underlying transcriptional regulation mechanism remains enigmatic. Here, the PxABCB1 promoter in Cry1Ac-susceptible and Cry1Ac-resistant P. xylostella strains was cloned and analyzed and found to contain a putative Jun binding site (JBS). A dual-luciferase reporter assay and yeast one-hybrid assay demonstrated that the transcription factor PxJun repressed PxABCB1 expression by interacting with this JBS. The expression levels of PxJun were increased in the midguts of all resistant strains compared to the susceptible strain. Silencing of PxJun expression significantly elevated PxABCB1 expression and Cry1Ac susceptibility in the resistant NIL-R strain, and silencing of PxMAP4K4 expression decreased PxJun expression and also increased PxABCB1 expression. These results indicate that MAPK-activated PxJun suppresses PxABCB1 expression to confer Cry1Ac resistance in P. xylostella, deepening our understanding of the transcriptional regulation of midgut Cry receptor genes and the molecular basis of insect resistance to Bt Cry toxins. IMPORTANCE The transcriptional regulation mechanisms underlying reduced expression of Bt toxin receptor genes in Bt-resistant insects remain elusive. This study unveils that a transcription factor PxJun activated by the MAPK signaling pathway represses PxABCB1 expression and confers Cry1Ac resistance in P. xylostella. Our results provide new insights into the transcriptional regulation mechanisms of midgut Cry receptor genes and deepen our understanding of the molecular basis of insect resistance to Bt Cry toxins. To our knowledge, this study identified the first transcription factor that can be involved in the transcriptional regulation mechanisms of midgut Cry receptor genes in Bt-resistant insects.

[Knowledge map analysis of research progress of Strychni Semen based on CiteSpace].

To analyze the study advance of Strychni Semen, a kind of traditional Chinese medicine, this study systematically retrieved the related Chinese literatures about Strychni Semen from CNKI database platforms and the core database of Web of Science, and used bibliometrics and CiteSpace 5.6.R5 software to visually display the authors, research institutions, keywords and other contents. A total of 1 895 Chinese literatures and 1 599 English literatures were included in the study. The analysis of Chinese and English literature authors showed that CAI Bao-chang and CHEN Jun had the most publications on Strychni Semen, and CAI Bao-chang's team was the core research team. According to the analysis of publishing institutions, Nanjing University of Traditional Chinese Medicine and Chinese Academy of Science were the research institutions with the largest number of Chinese and English literatures, respectively. But there was less cooperation between Chinese and English study institutions. The analysis of keywords in Chinese and English literatures showed that the research contents of Strychni Semen mainly focused on component analysis, research methods, receptor targets, clinical application, synergistic and attenuation measures. Break analysis showed that the apoptosis induced by Strychni Semen was a hot research topic, and research on components, toxicity and pharmacokinetics will be the research hotspot in future. The research on Strychni Semen is still in the developing period. This study has provided reference for the rapid grasp of the research contents and the judgment of research hotspots.

[Visual analysis of research progress of Sophorae Tonkinensis Radix et Rhizoma based on CiteSpace].

To analyze the study advance of Sophorae Tonkinensis Radix et Rhizoma, this study utilized CiteSpace 5.6.R5 software to conduct bibliometrics analysis on the Chinese literatures of Sophorae Tonkinensis Radix et Rhizoma from 1990 to 2020 included in the CNKI database retrieval platform. The analysis contents involved the number of published papers, co-authors, cooperative institutions, emergence, co-occurrence and clustering of keywords. A total of 808 Chinese literatures were included in the study, of which 17 were published by SUN Rong, the author with the most published papers, and formed a research team centered on SUN Rong; the analysis of the cooperation of publishing institutions showed that the Drug Safety Evaluation Research Center, Shanghai University of Traditional Chinese Medicine was the organization with the largest number of publications, with a total of 29 articles. It also formed a scientific research coorperation institution with Shandong Academy of Traditional Chinese Medicine as the core, and formed a relatively close cooperative network relationship. The analysis of literature keywords showed that the research direction was concentrated on the traditional Chinese medicine of Sophorae Tonkinensis Radix et Rhizoma, pharmacological mechanism, and side effects, active ingredients, etc. Among them, the research on the efficacy and toxicity of the active ingredients of Sophorae Tonkinensis Radix et Rhizoma has become a hot trend.

Photocatalytic activity and the electron transport mechanism of titanium dioxide microsphere/porphyrin implanted with small size copper.

To obtain efficient photocatalysts by coupling architectures, developing novel materials and elucidating the charge transport mechanism at the semiconductor interface are vital. Herein, a special nanocomposite (TiO2 microsphere/CuNPs/THPP) for photocatalytic hydrogen production was facilely fabricated with copper nanoparticles (CuNPs) as the interfacial linker of the TiO2 microspheres and meso-tetra(p-hydroxypheny)porphyrin (THPP). The assembly mode of the nanocomposite was studied in detail. It was found that the CuNPs implanted at the interface of the TiO2 microspheres and THPP can dramatically strengthen the interaction between the TiO2 microspheres and THPP, and improve the separation and transfer of photo-produced charges. Therefore, the nanocomposite displayed excellent performance for photocatalytic hydrogen production. Moreover, by recycling hydrogen production, it is demonstrated that the nanocomposite was a highly efficient and long-term stable photocatalyst. By investigating the energy band location and the charge transfer, the photocatalytic mechanism over the special nanocomposite was explored and proposed to explain the better activity of the TiO2 microsphere/CuNPs/THPP photocatalytic system. It will be helpful to provide deep insights into the construction of efficient photocatalytic systems.

Comprehensive analysis of Cry1Ac protoxin activation mediated by midgut proteases in susceptible and resistant Plutella xylostella (L.).

Insecticidal Cry toxins produced by Bacillus thuringiensis (Bt) have been widely used to control agricultural pests in both foliage sprays and transgenic crops. Nevertheless, rapid evolution of insect resistance to Cry toxins requires elucidation of the molecular mechanisms involved in Cry resistance. Two proposed models have been described to explain the toxicity of Cry proteins, the classic model states that Cry protoxin is activated by midgut proteases resulting in activated toxin that binds to receptors and forms a pore in the midgut cells triggering larval death, and the newly proposed dual model of the mode of action of Bt Cry toxins states that protoxin and activated toxins may have different mechanisms of action since several resistant strains to activated Cry toxins are still susceptible to the same Cry-protoxin. Protoxin activation by midgut proteases is a key step in both models. Herein, we evaluated Cry1Ac protoxin activation in a susceptible Plutella xylostella (L.) strain (DBM1Ac-S) and in the near-isogenic strain (NIL-R) with high field-evolved Cry1Ac resistance. Previous work showed that Cry1Ac resistance in NIL-R correlates with reduced binding to midgut receptors due to enhanced MAPK signaling pathway and down regulation of ABCC2 receptor. However, reduced midgut trypsin levels and altered midgut protease gene transcription were also observed in the Cry1Ac-resistant field isolated strain that is parent of the NIL-R strain. Therefore, we analyzed the midgut protease activities in both DBM1Ac-S and NIL-R strains. Detection of enzymatic activities showed that caseinolytic protease, trypsin and chymotrypsin activities were not significantly different between the susceptible and resistant strains. Furthermore, treatment with different trypsin or chymotrypsin inhibitors, such as Nα-tosyl-l-lysine chloromethyl ketone (TLCK) or Np-tosyl-L-phenylalanine chloromethyl ketone (TPCK) did not affect the susceptibility to Cry1Ac protoxin of the DBM1Ac-S and NIL-R larvae. Bioassay results indicated that the NIL-R larvae showed similar resistant levels to both Cry1Ac protoxin and trypsin-activated toxin. Taken together, our results demonstrated that high-level field-evolved Cry1Ac resistance in the NIL-R strain is independent of Cry1Ac protoxin activation and the specific protoxin mechanism of action. This discovery will strengthen our comprehensive understanding of the complex mechanistic basis of Bt resistance in different insects.

Total Synthesis of Spirotryprostatins through Organomediated Intramolecular Umpolung Cyclization.

Cyclodipeptide 2,5-diketopiperazines (DKP) are privileged structural units present in drugs and natural alkaloids. This work reports a new method for the synthesis of biologically important DKP scaffolds based on an intramolecular nucleophilic α-addition of general amides towards an alkynamide system. The utility of this umpolung cyclization mediated by trimethyl phosphine and l-glutamic acid is highlighted by its application to the concise total syntheses of 6-methoxyspirotryprostatin B (the first total synthesis), spirotryprostatin A, and spirotryprostatin B.

Tissue-specific Proteogenomic Analysis of Plutella xylostella Larval Midgut Using a Multialgorithm Pipeline.

The diamondback moth, Plutella xylostella (L.), is the major cosmopolitan pest of brassica and other cruciferous crops. Its larval midgut is a dynamic tissue that interfaces with a wide variety of toxicological and physiological processes. The draft sequence of the P. xylostella genome was recently released, but its annotation remains challenging because of the low sequence coverage of this branch of life and the poor description of exon/intron splicing rules for these insects. Peptide sequencing by computational assignment of tandem mass spectra to genome sequence information provides an experimental independent approach for confirming or refuting protein predictions, a concept that has been termed proteogenomics. In this study, we carried out an in-depth proteogenomic analysis to complement genome annotation of P. xylostella larval midgut based on shotgun HPLC-ESI-MS/MS data by means of a multialgorithm pipeline. A total of 876,341 tandem mass spectra were searched against the predicted P. xylostella protein sequences and a whole-genome six-frame translation database. Based on a data set comprising 2694 novel genome search specific peptides, we discovered 439 novel protein-coding genes and corrected 128 existing gene models. To get the most accurate data to seed further insect genome annotation, more than half of the novel protein-coding genes, i.e. 235 over 439, were further validated after RT-PCR amplification and sequencing of the corresponding transcripts. Furthermore, we validated 53 novel alternative splicings. Finally, a total of 6764 proteins were identified, resulting in one of the most comprehensive proteogenomic study of a nonmodel animal. As the first tissue-specific proteogenomics analysis of P. xylostella, this study provides the fundamental basis for high-throughput proteomics and functional genomics approaches aimed at deciphering the molecular mechanisms of resistance and controlling this pest.