Discrimination of opium from Afghanistan and Myanmar by infrared spectroscopy coupled with machine learning methods.

Afghanistan and Myanmar are two overwhelming opium production places. In this study, rapid and efficient methods for distinguishing opium from Afghanistan and Myanmar were developed using infrared spectroscopy (IR) coupled with multiple machine learning (ML) methods for the first time. A total of 146 authentic opium samples were analyzed by mid-IR (MIR) and near-IR (NIR), within them 116 were used for model training and 30 were used for model validation. Six ML methods, including partial least squares discriminant analysis (PLS-DA), orthogonal PLS-DA (OPLS-DA), k-nearest neighbour (KNN), support vector machine (SVM), random forest (RF), and artificial neural networks (ANNs) were constructed and compared to get the best classification effect. For MIR data, the average of precision, recall and f1-score for all classification models were 1.0. For NIR data, the average of precision, recall and f1-score for different classification models ranged from 0.90 to 0.94. The comparison results of six ML models for MIR and NIR data showed that MIR was more suitable for opium geography classification. Compared with traditional chromatography and mass spectrometry profiling methods, the advantages of MIR are simple, rapid, cost-effective, and environmentally friendly. The developed IR chemical profiling methodology may find wide application in classification of opium from Afghanistan and Myanmar, and also to differentiate them from opium originating from other opium producing countries. This study presented new insights into the application of IR and ML to rapid drug profiling analysis.

Secondary somatosensory cortex glutamatergic innervation of the thalamus facilitates pain.

ABSTRACT: Although the secondary somatosensory cortex (SII) is known to be involved in pain perception, its role in pain modulation and neuropathic pain is yet unknown. In this study, we found that glutamatergic neurons in deep layers of the SII (SII Glu ) responded to bilateral sensory inputs by changing their firing with most being inhibited by contralateral noxious stimulation. Optical inhibition and activation of unilateral SII Glu reduced and enhanced bilateral nociceptive sensitivity, respectively, without affecting mood status. Tracing experiments revealed that SII Glu sent dense monosynaptic projections to the posterolateral nucleus (VPL) and the posterior nucleus (Po) of the thalamus. Optical inhibition and activation of projection terminals of SII Glu in the unilateral VPL and Po inhibited and facilitated pain on the contralateral side, respectively. After partial sciatic nerve ligation, SII Glu became hyperactive as evidenced by higher frequency of spontaneous firing, but the response patterns to peripheral stimulation remained. Optical inhibition of SII Glu alleviated not only bilateral mechanical allodynia and thermal hyperalgesia but also the negative affect associated with spontaneous pain. Inhibition of SII Glu terminals in the VPL and Po also relieved neuropathic pain. This study revealed that SII Glu and the circuits to the VPL and Po constitute a part of the endogenous pain modulatory network. These corticothalamic circuits became hyperactive after peripheral nerve injury, hence contributes to neuropathic pain. These results justify proper inhibition of SII Glu and associated neural circuits as a potential clinical strategy for neuropathic pain treatment.

Research progress of ginger in the treatment of gastrointestinal tumors.

Cancer seriously endangers human health. Gastrointestinal cancer is the most common and major malignant tumor, and its morbidity and mortality are gradually increasing. Although there are effective treatments such as radiotherapy and chemotherapy for gastrointestinal tumors, they are often accompanied by serious side effects. According to the traditional Chinese medicine and food homology theory, many materials are both food and medicine. Moreover, food is just as capable of preventing and treating diseases as medicine. Medicine and food homologous herbs not only have excellent pharmacological effects and activities but also have few side effects. As a typical medicinal herb with both medicinal and edible uses, some components of ginger have been shown to have good efficacy and safety against cancer. A mass of evidence has also shown that ginger has anti-tumor effects on digestive tract cancers (such as gastric cancer, colorectal cancer, liver cancer, laryngeal cancer, and pancreatic cancer) through a variety of pathways. The aim of this study is to investigate the mechanisms of action of the main components of ginger and their potential clinical applications in treating gastrointestinal tumors.

Effectiveness of acupuncture treatment for stroke and stroke complications: a protocol for meta-analysis and systematic review based on randomized, single-blind, controlled trials.

Introduction: The treatment and rehabilitation of stroke and its complications have become major global health issues. Acupuncture is widely used as a complementary and alternative treatment for stroke. Many clinical studies have evaluated the efficacy and safety of acupuncture, but the research results need to be more consistent. The quality of research based on previously published meta-analyzes is uneven, leading to unstable conclusions. This study aims to provide a comprehensive and systematic analysis of the efficacy of high-quality, randomized controlled trials (RCTs) based on blinded designs for treating stroke and its complications. It also aims to review the characteristics of blinded designs and the current use of sham/placebo acupuncture controls in treating stroke. Methods and analysis: This study will be conducted under the reporting guidelines for systematic reviews and meta-analyzes. Randomized controlled trials using acupuncture as the primary measure for stroke will be searched in databases such as China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), Wan-fang, PubMed, Embase, Cochrane Library, and Web of Science. To evaluate high-quality research based on a blind design, if the trial evaluates the efficacy of any acupuncture intervention by including a sham/placebo acupuncture control, it will be included. The primary outcome indicator will be the ability to perform daily activities. Secondary outcome indicators include evaluating quality of life and related functions in stroke-related sequelae. We will assess the quality of evidence, reporting quality, and risk of bias for the acupuncture intervention in the literature included in this study using the GRADE system, the STRICTA 2010 checklist, and ROB2.0, respectively. RevMan 5.4 software will be used to conduct the meta-analysis, and Stata 15.0 software will be used for sensitivity analysis and publication bias testing. Discussion: By analyzing high-quality, well-designed, randomized controlled trials of acupuncture, the results of this study may contribute to a more objective and standardized evaluation of acupuncture efficacy in treating stroke and its complications.Systematic review registration: PROSPERO, Identifier (CRD42023378930).

Jiangtang Decoction Ameliorates Diabetic Kidney Disease Through the Modulation of the Gut Microbiota.

Purpose: This study aimed to elucidate the impact of Jiangtang decoction (JTD) on diabetic kidney disease (DKD) and its association with alterations in the gut microbiota. Methods: Using a diabetic mouse model (KK-Ay mice), daily administration of JTD for eight weeks was undertaken. Weekly measurements of body weight and blood glucose were performed, while kidney function, uremic toxins, inflammation factors, and fecal microbiota composition were assessed upon sacrifice. Ultra-structural analysis of kidney tissue was conducted to observe the pathological changes. Results: The study findings demonstrated that JTD improve metabolism, kidney function, uremic toxins and inflammation, while also exerting a modulatory effect on the gut microbiota. Specifically, the genera Rikenella, Lachnoclostridium, and unclassified_c_Bacilli exhibited significantly increased abundance following JTD treatment, accompanied by reduced abundance of norank_f_Lachnospiraceae compared to the model group. Importantly, Rikenella and unclassified_c_Bacilli demonstrated negative correlations with urine protein levels. Lachnoclostridium and norank_f_Lachnospiraceae were positively associated with creatinine (Cr), indoxyl sulfate (IS) and interleukin (IL)-6. Moreover, norank_f_Lachnospiraceae exhibited positive associations with various indicators of DKD severity, including weight, blood glucose, urea nitrogen (UN), kidney injury molecule-1 (KIM-1) levels, trimethylamine-N-oxide (TMAO), p-cresyl sulfate (pCS), nucleotide-binding oligomerization domain (Nod)-like receptor family pyrin domain-containing 3 (NLRP3) and IL-17A production. Conclusion: These findings suggested that JTD possess the ability to modulate the abundance of Rikenella, Lachnoclostridium, unclassified_c_Bacilli and norank_f_Lachnospiraceae within the gut microbiota. This modulation, in turn, influenced metabolic processes, kidney function, uremic toxin accumulation, and inflammation, ultimately contributing to the amelioration of DKD.

Effect of low-level laser therapy on orthodontic dental alignment: a systematic review and meta-analysis.

The aim of this study is to systematically summarize the available evidence regarding low-level laser therapy (LLLT) speed-up effect on dental alignment in comprehensive orthodontic treatment. An extensive electronic search was conducted in PubMed, ScienceDirect, Cochrane, Web of Science, and Scopus up to February 20, 2023. The Cochrane risk of bias tool and the Newcastle-Ottawa Quality Assessment Form were used by two authors independently to assess the risk of bias (RoB). Statistical analysis was performed by Review Manager 5.3. The eight eligible trials were reviewed and included in qualitative synthesis. Four studies reported the overall time of leveling and alignment (OLAT, days), enabling a synthesizing of the data. The meta-analysis results showed that LLLT significantly reduced the overall time of leveling and alignment compared to control group (MD=-30.36, 95% CI range -41.50 to -19.22, P<0.0001), with moderate heterogeneity (χ2=4.10, P=0.25, I2=27%). Based on the data available, statistically significant evidence with moderate risk of bias suggests that LLLT may have a positive effect on accelerating dental alignment. However, due to the differences in intervention strategy and evaluating method, the conclusions should be interpreted with caution.

AR/PCC herb pair inhibits osteoblast pyroptosis to alleviate diabetes-related osteoporosis by activating Nrf2/Keap1 pathway.

Osteoporosis is a prevalent complication of diabetes, characterized by systemic metabolic impairment of bone mass and microarchitecture, particularly in the spine. Anemarrhenae Rhizoma/Phellodendri Chinensis Cortex (AR/PCC) herb pair has been extensively employed in Traditional Chinese Medicine to manage diabetes; however, its potential to ameliorate diabetic osteoporosis (DOP) has remained obscure. Herein, we explored the protective efficacy of AR/PCC herb pair against DOP using a streptozotocin (STZ)-induced rat diabetic model. Our data showed that AR/PCC could effectively reduce the elevated fasting blood glucose and reverse the osteoporotic phenotype of diabetic rats, resulting in significant improvements in vertebral trabecular area percentage, trabecular thickness and trabecular number, while reducing trabecular separation. Specifically, AR/PCC herb pair improved impaired osteogenesis, nerve ingrowth and angiogenesis. More importantly, it could mitigate the aberrant activation of osteoblast pyroptosis in the vertebral bodies of diabetic rats by reducing increased expressions of Nlrp3, Asc, Caspase1, Gsdmd and IL-1ß. Mechanistically, AR/PCC activated antioxidant pathway through the upregulation of the antioxidant response protein Nrf2, while concurrently decreasing its negative feedback regulator Keap1. Collectively, our in vivo findings demonstrate that AR/PCC can inhibit osteoblast pyroptosis and alleviate STZ-induced rat DOP, suggesting its potential as a therapeutic agent for mitigating DOP.

[LC-MS analysis of 2-(2-phenylethyl) chromones in sodium chloride-treated suspension cells of Aquilaria sinensis].

Qualitative and quantitative analysis of 2-(2-phenylethyl) chromones in sodium chloride(NaCl)-treated suspension cells of Aquilaria sinensis was conducted by UPLC-Q-Exactive-MS and UPLC-QQQ-MS/MS. Both analyses were performed on a Waters T3 column(2.1 mm×50 mm, 1.8 µm) with 0.1% formic acid aqueous solution(A)-acetonitrile(B) as mobile phases at gradient elution. MS data were collected by electrospray ionization in positive ion mode. Forty-seven phenylethylchromones was identified from NaCl-treated suspension cell samples of A. sinensis using UPLC-Q-Exactive-MS, including 22 flindersia-type 2-(2-phenylethyl) chromones and their glycosides, 10 5,6,7,8-tetrahydro-2-(2-phenylethyl) chromones and 15 mono-epoxy or diepoxy-5,6,7,8-tetrahydro-2-(2-phenylethyl) chromones. Additionally, 25 phenylethylchromones were quantitated by UPLC-QQQ-MS/MS. Overall, the rapid and efficient qualitative and quantitative analysis of phenylethylchromones in NaCl-treated suspension cells of A. sinensis by two LC-MS techniques, provides an important reference for the yield of phenylethylchromones in Aquilariae Lignum Resinatum using in vitro culture and other biotechnologies.

Glutamatergic and GABAergic neurons in the vLGN mediate the nociceptive effects of green and red light on neuropathic pain.

Phototherapy is an emerging non-pharmacological treatment for depression, circadian rhythm disruptions, and neurodegeneration, as well as pain conditions including migraine and fibromyalgia. However, the mechanism of phototherapy-induced antinociception is not well understood. Here, using fiber photometry recordings of population-level neural activity combined with chemogenetics, we found that phototherapy elicits antinociception via regulation of the ventral lateral geniculate body (vLGN) located in the visual system. Specifically, both green and red lights caused an increase of c-fos in vLGN, with red light increased more. In vLGN, green light causes a large increase in glutamatergic neurons, whereas red light causes a large increase in GABAergic neurons. Green light preconditioning increases the sensitivity of glutamatergic neurons to noxious stimuli in vLGN of PSL mice. Green light produces antinociception by activating glutamatergic neurons in vLGN, and red light promotes nociception by activating GABAergic neurons in vLGN. Together, these results demonstrate that different colors of light exert different pain modulation effects by regulating glutamatergic and GABAergic subpopulations in the vLGN. This may provide potential new therapeutic strategies and new therapeutic targets for the precise clinical treatment of neuropathic pain.

[Network visual data mining and analysis of literature on electroacupuncture treatment of post-stroke sequelae].

OBJECTIVE: To analyze the optimum stimulating parameters and acupoint combination law of electroacupuncture (EA) treatment of post-stroke sequelae (PSS) through the network visual data mining and analysis of the literature，so as to provide reference for clinical application. METHODS: The related articles of acupuncture treatment of PSS patients published from January 1, 2005 to December 31, 2021 were collected from databases of CNKI, Wanfang, Weipu（VIP), SinoMed, CHAOXING, DUXIU, PubMed, Ovid, Embase and Cochrane Library. After the articles were screened according to our formulated inclusion and exclusion criteria, a "Clinical Literature Database of EA Treatment of PSS" was established. The SPSS Modeler14.1 software was used for modeling (by using the parameters of EA, types of apoplexy sequelae, names of acupoints, methods of acupoint matching, acupoint-attributed meridians, etc.) and association rule analysis, and the Cytoscape 3.6.0 software was used for data network visualization analysis. RESULTS: A total of 354 articles were collected, including 13 types of PSS, among which the hemi-plegia accounts for the highest proportion (51.13%), followed by depression (17.51%) and dysphagia (14.97%). A total of 228 acupoints are used, with a total frequency-time of 1 690. Among the 8 PSS (hemiplegia, depression, dysphagia, cognitive impairment, urinary incontinence, urinary retention, speech disorders, constipation) with the frequency of application of acupoints greater than or equal to 3, 275 articles are involved, with the frequency of dense wave being the highest (123 times), followed by continuous waves (95 times). The stimulation frequency of EA appears 275 times, with the low frequency being the highest (188 times). For hemiplegia type of PSS, low frequency and continuous waves or dense waves are mostly used, and the high correlation acupoint groups are Zusanli(ST36)/Hegu(LI4), LI4/Quchi(LI11) and ST36/LI11. For depression, low frequency and dense waves are mostly used, and the high correlation acupoint groups are Baihui(GV20)/Yintang(EX-HN3), GV20/Shenting(GV24) and GV20/Neiguan(PC6). For swallowing disorder, the mostly used stimulation parameter is low frequency, and the high correlation acupoint groups are Lianquan(CV23)/ST36/Fenglong(ST40), Tongli(HT5)/Yifeng(TE17)/PC6/ST40, and TE17/HT5/PC6/LI4. CONCLUSION: EA therapy is frequently used in the treatment of PSS, for which ST36, LI4 and LI11 are most frequently used in the treatment of hemiplegia, with the stimulation parameters being low-frequency and continuous waves or dense waves. For depression, GV20, EX-HN3, GV24 and PC6 are used, with the stimulation parameters being low frequency and dense waves. For dysphagia, CV23, HT5, TE17, PC6, ST36, ST40 and LI4 are employed, with low frequency electrical stimulation.

[Impounding Impacts of the Three Gorges Reservoir on Phytoplankton Function Groups and Its Relationship with Resource Use Efficiency].

In order to investigate the relationship between phytoplankton community functional group compositions and resource use efficiency in important tributaries of the Three Gorges Reservoir, phytoplankton and environment parameters were sampled from five tributaries, the Xiangxi River, Daning River, Meixi River, Pengxi River, and Huangjin River, in August and November, 2020. There were 119 species (variants) belonging to 62 genera and 7 phyla identified in summer, whereas 118 species (variants) belonging to 7 divisions of 58 genera were found in winter. According to Padisak's theory, all phytoplankton were divided into 25 functional groups, of which there were six important functional groups in both summer and winter:L0, H1, D, Y, MP, and P in summer and L0, H1, A, M, MP, and Y in winter. The α-diversity of the phytoplankton functional group in summer was higher than that in winter. Moreover, a higher α-diversity was also found in downstream samples relative to that in upstream samples, indicating that the community structure was more complex, and the community stability was relatively better in downstream regions of the rivers. Redundancy analysis (RDA) showed that the environment factors, i.e., ν, pH, permanganate index, WT, and RUETN, significantly affected phytoplankton functional groups (P<0.05). Variance partitioning analysis (VPA) indicated that environmental factors had a higher explanatory degree for the change in functional group composition in summer (45.23%); on the contrary, resource use efficiency had a higher explanatory degree in winter (42.33%). The linear fitted model showed that functional groups L0, H1, D, and Y showed a significant positive correlation relationship with RUETN and RUETP in summer, whereas only four functional groups (M, MP, Y, and A) had a linear relationship with RUETP, and all function groups had a good linear relationship with RUETN in winter. These results indicated that the functional groups belonging to cyanobacteria, dinoflagellates, and cryptophyta were more efficient at using limited resources in summer, whereas the diatoms had a good linear relationship with resource use efficiency and formed a dominant group in the low temperature environment of winter. These results suggest that the impounding of the Three Gorges Reservoir area can significantly change the resource use efficiency of phytoplankton, resulting in changes in the phytoplankton functional group composition and community structure.

The potato StMKK5-StSIPK module enhances resistance to Phytophthora pathogens through activating the salicylic acid and ethylene signalling pathways.

Mitogen-activated protein kinase (MAPK) cascades play pivotal roles in plant responses to both biotic and abiotic stress. A screen of a Nicotiana benthamiana cDNA virus-induced gene silencing (VIGS) library for altered plant responses to inoculation with Phytophthora infestans previously identified an NbMKK gene, encoding a clade D MAPKK that we renamed as NbMKK5, which is involved in immunity to P. infestans. To study the role of the potato orthologous gene, referred to as StMKK5, in the response to P. infestans, we transiently overexpressed StMKK5 in N. benthamiana and observed that cell death occurred at 2 days postinfiltration. Silencing of the highly conserved eukaryotic protein SGT1 delayed the StMKK5-induced cell death, whereas silencing of the MAPK-encoding gene NbSIPK completely abolished the cell death response. Further investigations showed that StMKK5 interacts with, and directly phosphorylates, StSIPK. Furthermore, both StMKK5 and StSIPK trigger salicylic acid (SA)- and ethylene (Eth)-related gene expression, and co-expression of the salicylate hydroxylase NahG with the negative regulator of Eth signalling CTR1 hampers StSIPK-triggered cell death. This observation indicates that the cell death triggered by StMKK5-StSIPK is dependent on the combination of SA- and Eth-signalling. By introducing point mutations, we showed that the kinase activity of both StMKK5 and StSIPK is required for triggering cell death. Genetic analysis showed that StMKK5 depends on StSIPK to trigger plant resistance. Thus, our results define a potato StMKK5-SIPK module that positively regulates immunity to P. infestans via activation of both the SA and Eth signalling pathways.

A Phytophthora infestans RXLR effector targets a potato ubiquitin-like domain-containing protein to inhibit the proteasome activity and hamper plant immunity.

Ubiquitin-like domain-containing proteins (UDPs) are involved in the ubiquitin-proteasome system because of their ability to interact with the 26S proteasome. Here, we identified potato StUDP as a target of the Phytophthora infestans RXLR effector Pi06432 (PITG_06432), which supresses the salicylic acid (SA)-related immune pathway. By overexpressing and silencing of StUDP in potato, we show that StUDP negatively regulates plant immunity against P. infestans. StUDP interacts with, and destabilizes, the 26S proteasome subunit that is referred to as REGULATORY PARTICLE TRIPLE-A ATP-ASE (RPT) subunit StRPT3b. This destabilization represses the proteasome activity. Proteomic analysis and Western blotting show that StUDP decreases the stability of the master transcription factor SYSTEMIC ACQUIRED RESISTANCE DEFICIENT 1 (SARD1) in SA biosynthesis. StUDP negatively regulates the SA signalling pathway by repressing the proteasome activity and destabilizing StSARD1, leading to a decreased expression of the SARD1-targeted gene ISOCHORISMATE SYNTHASE 1 and thereby a decrease in SA content. Pi06432 stabilizes StUDP, and it depends on StUDP to destabilize StRPT3b and thereby supress the proteasome activity. Our study reveals that the P. infestans effector Pi06432 targets StUDP to hamper the homeostasis of the proteasome by the degradation of the proteasome subunit StRPT3b and thereby suppresses SA-related immunity.

Tilianin improves lipid profile and alleviates atherosclerosis in ApoE-/- mice through up-regulation of SREBP2-mediated LDLR expression.

BACKGROUND: The huge global burden of atherosclerotic cardiovascular diseases (CVDs) represents an urgent unmet need for the development of novel therapeutics. Dracocephalum moldavica L. has been used as a traditional Uygur medicine to treat various CVDs for centuries. Tilianin is a major flavonoid component of D. moldavica L. and has potential for preventing atherosclerosis. However, the molecular mechanisms that tilianin attenuate atherosclerosis are far from fully understood. PURPOSES: The purpose of this study is to investigate the efficiency and underlying mechanisms of tilianin in controlling lipid profile and preventing atherogenesis. METHODS: The lipid-lowering effect of tilianin was evaluated in C57BL/6 and ApoE-/- mice by systematically determining serum biochemical parameters. The effects of tilianin on the atherosclerotic lesion were observed in aortic roots and whole aortas of ApoE-/- mice with oil red O staining. Caecal content from ApoE-/- mice were collected for 16S rRNA gene sequence analysis to assess the structure of the gut microbiota. The inhibition of hepatosteatosis was verified by histological examination, and a liver transcriptome analysis was performed to elucidate the tilianin-induced hepatic transcriptional alterations. Effects of tilianin on the expression and function of LDLR were examined in HepG2 cells and ApoE-/- mice. Further mechanisms underlying the efficacy of tilianin were investigated in HepG2 cells. RESULTS: Tilianin treatment improved lipid profiles in C57BL/6 and dyslipidemic ApoE-/- mice, especially reducing the serum LDL-cholesterol (LDL-C) level. Significant reductions of atherosclerotic lesion area and hepatosteatosis were observed in tilianin-treated ApoE-/- mice. The altered gut microbial composition in tilianin groups was associated with lipid metabolism and atherosclerosis. The liver transcriptome revealed that tilianin regulated the transcription of lipid metabolism-related genes. Then both in vitro and in vivo analyses revealed the potent effect of tilianin to enhance hepatic LDLR expression and its mediated LDL-C uptake. Further studies confirmed a critical role of SREBP2 in hepatic LDLR up-regulation by tilianin via increasing precursor and thus mature nuclear SREBP2 level. CONCLUSION: This study demonstrated the lipid-lowering effect of tilianin through SREBP2-mediated transcriptional activation of LDLR. Our findings reveal a novel anti-atherosclerotic mechanism of tilianin and underlie its potential clinical use in modulating CVDs with good availability and affordability.

Ultrasensitive deafness gene DNA hybridization detection employing a fiber optic Mach-Zehnder interferometer: Enabled by a black phosphorus nanointerface.

The rapid and efficient detection of deafness gene DNA plays an important role in the clinical diagnosis of deafness diseases. This study demonstrates the ultrasensitive detection of complementary DNA (cDNA) by employing a nanointerface-sensitized fiber optic biosensor. The sensor consists of SMF-TNCF-MMF-SMF (abbreviated as STMS) structure with lateral offset. Besides, it is functionalized with a nanointerface of black phosphorus (BP) to enhance the light-matter interaction and eventually improve the sensing performances. Relying on this nanointerface-sensitized sensor, we successfully realize the in-situ detection of cDNA at concentrations ranging from 1 pM to 1 µM, with a sensitivity of 0.719 nm/lgM. The limit of detection (LOD) is as low as 0.24 pM, which is at least two orders of magnitude lower than those of existing methods. The sensor exhibits the advantages of simple operation, fast response, label-free measurement, excellent repeatability, and high selectivity. Our contribution suggests a convenient approach for deafness gene DNA detection and can be extended for general ultra-low concentration DNA detection applications.

Potato protein tyrosine phosphatase StPTP1a is activated by StMKK1 to negatively regulate plant immunity.

Phytophthora infestans causes severe losses in potato production. The MAPK kinase StMKK1 was previously found to negatively regulate potato immunity to P. infestans. Our results showed that StMKK1 interacts with a protein tyrosine phosphatase, referred to as StPTP1a, and StMKK1 directly phosphorylates StPTP1a at residues Ser-99, Tyr-223 and Thr-290. StPTP1a is a functional phosphatase and the phosphorylation of StPTP1a at these three residues enhances its stability and catalytic activity. StPTP1a negatively regulates potato immunity and represses SA-related gene expression. Furthermore, StPTP1a interacts with, and dephosphorylates, the StMKK1 downstream signalling targets StMPK4 and -7 at their Tyr-203 residue resulting in the repression of salicylic acid (SA)-related immunity. Silencing of NbPTP1a + NbMPK4 or NbPTP1a + NbMPK7 abolished the plant immunity to P. infestans caused by NbPTP1a silencing, indicating that PTP1a functions upstream of NbMPK4 and NbMPK7. StMKK1 requires StPTP1a to negatively regulate SA-related immunity and StPTP1a is phosphorylated and stabilized during immune activation to promote the de-phosphorylation of StMPK4 and -7. Our results reveal that potato StMKK1 activates and stabilizes the tyrosine phosphatase StPTP1a that in its turn de-phosphorylates StMPK4 and -7, thereby repressing plant SA-related immunity.

Applicability of Zipf's Law in Traditional Chinese Medicine Prescriptions.

Objective Traditional Chinese medicine (TCM) prescriptions have been used to cure diseases in China for thousands of years, in which many TCM herbs have no definite common quantity. Some key TCM herbs are commonly used and thus deserve in-depth investigations based on a more acceptable classification method. This study analyzes whether TCM prescriptions follow Zipf's law and attempts to obtain the thresholds of key TCM herbs based on the application of Zipf's law. Methods A total of 84,418 TCM prescriptions were collected and standardized. We tested whether Zipf's law and Zipf's distribution fit the Chinese herb distributions. A linear fitting experiment was performed to verify the relationship between the frequency distribution and frequency of TCM herbs. Results The distribution of TCM herbs in TCM prescriptions conformed to Zipf's law. Accordingly, the thresholds were obtained for the key TCM herbs. Conclusion The distribution of TCM herbs in TCM prescriptions follows Zipf's law.

Arginine-modified black phosphorus quantum dots with dual excited states for enhanced electrochemiluminescence in bioanalysis.

The electrochemiluminescence (ECL) is generally emitted via radiative transition of singlet or triplet excited state (S1 or T1). Herein, an ECL mechanism with the transitions of both S1 and T1 of black phosphorus quantum dots (BPQDs) is found, and an arginine (Arg) modification strategy is proposed to passivate the surface oxidation defects of BPQDs, which could modulate the excited states for enhancing the ECL efficiency of BPQDs. The Arg modification leads to greater spatial overlap of highest and lowest occupied molecular orbitals, and spectral shift of radiative transitions, and improves the stability of anion radical of BPQDs. To verify the application of the proposed mechanism, it is used to construct a sensitive method for conveniently evaluating the inhibiting efficiency of cyclo-arginine-glycine-aspartic acid-d-tyrosine-lysine to cell surface integrin by using Arg containing peptide modified BPQDs as signal tag. The dual excited states mediated ECL emitters provide a paradigm for adjustable ECL generation and extend the application of ECL analysis.

LC-MS/MS combined with blood-brain dual channel microdialysis for simultaneous determination of active components of astragali radix-safflower combination and neurotransmitters in rats with cerebral ischemia reperfusion injury: Application in pharmacokinetic and pharmacodynamic study.

BACKGROUND: Astragali Radix-Safflower combination (ARSC) is widely utilized in clinic to treat cerebral ischemia/reperfusion injury (CI/RI). Whereas, there is no in-depth research of the pharmacokinetics (PK) and pharmacodynamics (PD) analysis of ARSC after intragastric administration in rats with CI/RI. PURPOSE: The purpose of this research is to investigate the PK characteristics of eight active ingredients (astragaloside IV, calycosin, calycosin-7-O-ß-glucoside, formononetin, ononin, hydroxysafflor yellow A, syringin and vernine) of ARSC, and the regulation of neurotransmitters disorders, revealing the pharmacodynamic substance basis and the mechanism of ARSC in treating CI/RI from the molecular level. METHODS: We established a new method which based on blood-brain dual channel microdialysis (MD) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to continuously gather, and determine the components of ARSC and neurotransmitters related to CI/RI in vivo. The collected data were analyzed by sigmoid-Emax function. The neurotransmitters primarily regulated in CI/RI rat were discussed by principal component analysis and the compound most associated with total pharmacodynamics was chosen by partial least squares regression. RESULTS: The validated LC-MS/MS method had specificity and selectivity to simultaneously analyze the concentration of eight active components of ARSC extract and five neurotransmitters of CI/RI rats. The recovery rates of brain MD probe and blood MD probe were stable within six hours. The MD probes recovery rates decreased with the increase of flow rates, but the solution concentration had little effect on the probes recovery rates. It was feasible to correct the recovery rates of probes in vivo by using reverse dialysis method. All eight active ingredients of ARSC could pass across the blood brain barrier after CI/RI. ARSC regulated the release of glutamate (Glu), γ-aminobutyric acid (GABA), dopamine (DA), 5-hydroxytryptamine (5-HT) and aspartic acid (Asp). Notably, astragaloside IV and hydroxysafflor yellow A might have better regulatory effect on neurotransmitters in comparison with other six measured components of ARSC, and Glu was the neurotransmitter mainly regulated in CI/RI rats. CONCLUSION: The ARSC was able to treat CI/RI through ameliorating neurotransmitters disorders. There was a hysteresis between the peaked drug concentration and maximum therapeutic effect of ARSC. The drug effective concentrations range of ASIV, calycosin, calycosin-7-O-ß-glucoside, syringin and vernine in blood microdialysate and calycosin, syringin, vernine in brain microdialysate were narrow, which need be paid attention in clinical use.

Transcriptome Analysis Reveals an Essential Role of Exogenous Brassinolide on the Alkaloid Biosynthesis Pathway in Pinellia Ternata.

Pinellia ternata (Thunb.) Druce is a traditional medicinal plant containing a variety of alkaloids, which are important active ingredients. Brassinolide (BR) is a plant hormone that regulates plant response to environmental stress and promotes the accumulation of secondary metabolites in plants. However, the regulatory mechanism of BR-induced alkaloid accumulation in P. ternata is not clear. In this study, we investigated the effects of BR and BR biosynthesis inhibitor (propiconazole, Pcz) treatments on alkaloid biosynthesis in the bulbil of P. ternata. The results showed that total alkaloid content and bulbil yield was enhanced by 90.87% and 29.67% under BR treatment, respectively, compared to the control. We identified 818 (476 up-regulated and 342 down-regulated) and 697 (389 up-regulated and 308 down-regulated) DEGs in the BR-treated and Pcz-treated groups, respectively. Through this annotated data and the Kyoto encyclopedia of genes and genomes (KEGG), the expression patterns of unigenes involved in the ephedrine alkaloid, tropane, piperidine, pyridine alkaloid, indole alkaloid, and isoquinoline alkaloid biosynthesis were observed under BR and Pcz treatments. We identified 11, 8, 2, and 13 unigenes in the ephedrine alkaloid, tropane, piperidine, and pyridine alkaloid, indole alkaloid, and isoquinoline alkaloid biosynthesis, respectively. The expression levels of these unigenes were increased by BR treatment and were decreased by Pcz treatment, compared to the control. The results provided molecular insight into the study of the molecular mechanism of BR-promoted alkaloid biosynthesis.