MiR-21-5p alleviates trigeminal neuralgia in rats through down-regulation of voltage-gated potassium channel Kv1.1. / MiR-21-5p通过下调电压门控钾离子通道Kv1.1è¡¨è¾¾å‡è½»å¤§é¼ ä¸‰å‰ç¥žç»ç—›.

OBJECTIVES: Trigeminal neuralgia (TN) is a common neuropathic pain. Voltage-gated potassium channel (Kv) has been confirmed to be involved in the occurrence and development of TN, but the specific mechanism is still unclear. MicroRNA may be involved in neuropathic pain by regulating the expression of Kv channels and neuronal excitability in trigeminal ganglion (TG). This study aims to explore the relationship between Kv1.1 and miR-21-5p in TG with a TN model, evaluate whether miR-21-5p has a regulatory effect on Kv1.1, and to provide a new target and experimental basis for the treatment of TN. METHODS: A total of 48 SD rats were randomly divided into 6 groups: 1) a sham group (n=12), the rats were only sutured at the surgical incision without nerve ligation; 2) a sham+agomir NC group (n=6), the sham rats were microinjected with agomir NC through stereotactic brain injection in the surgical side of TG; 3) a sham+miR-21-5p agomir group (n=6), the sham rats were microinjected with miR-21-5p agomir via stereotactic brain injection in the surgical side of TG; 4) a TN group (n=12), a TN rat model was constructed using the chronic constriction injury of the distal infraorbital nerve (dIoN-CCI) method with chromium intestinal thread; 5) a TN+antagonist NC group (n=6), TN rats were microinjected with antagonist NC through stereotactic brain injection method in the surgical side of TG; 6) a TN+miR-21-5p antagonist group (n=6), TN rats were microinjected with miR-21-5p antagonist through stereotactic brain injection in the surgical side of TG. The change of mechanical pain threshold in rats of each group after surgery was detected. The expressions of Kv1.1 and miR-21-5p in the operative TG of rats were detected by Western blotting and real-time reverse transcription polymerase chain reaction. Dual luciferase reporter genes were used to determine whether there was a target relationship between Kv1.1 and miR-21-5p and whether miR-21-5p directly affected the 3'-UTR terminal of KCNA1. The effect of brain stereotaxic injection was evaluated by immunofluorescence assay, and then the analogue of miR-21-5p (agomir) and agomir NC were injected into the TG of rats in the sham group by brain stereotaxic apparatus to overexpress miR-21-5p. The miR-21-5p inhibitor (antagomir) and antagomir NC were injected into TG of rats in the TN group to inhibit the expression of miR-21-5p. The behavioral changes of rats before and after administration were observed, and the expression changes of miR-21-5p and Kv1.1 in TG of rats after intervention were detected. RESULTS: Compared with the baseline pain threshold, the facial mechanical pain threshold of rats in the TN group was significantly decreased from the 5th to 15th day after the surgery (P<0.05), and the facial mechanical pain threshold of rats in the sham group was stable at the normal level, which proved that the dIoN-CCI model was successfully constructed. Compared with the sham group, the expression of Kv1.1 mRNA and protein in TG of the TN group was down-regulated (both P<0.05), and the expression of miR-21-5p was up-regulated (P<0.05). The results of dual luciferase report showed that the luciferase activity of rno-miR-21-5p mimics and KCNA1 WT transfected with 6 nmol/L or 20 nmol/L were significantly decreased compared with those transfected with mimic NC and wild-type KCNA1 WT, respectively (P<0.001). Compared with low dose rno-miR-21-5p mimics (6 nmol/L) co-transfection group, the relative activity of luciferase in the high dose rno-miR-21-5p mimics (20 nmol/L) cotransfection group was significantly decreased (P<0.001). The results of immunofluorescence showed that drugs were accurately injected into TG through stereotaxic brain. After the expression of miR-21-5p in the TN group, the mechanical pain threshold and the expression of Kv1.1 mRNA and protein in TG were increased. After overexpression of miR-21-5p in the sham group, the mechanical pain threshold and the expression of Kv1.1 mRNA and protein in TG were decreased. CONCLUSIONS: Both Kv1.1 and miR-21-5p are involved in TN and miR-21-5p can regulate Kv1.1 expression by binding to the 3'-UTR of KCNA1.

Divergent trajectories of future global gross primary productivity and evapotranspiration of terrestrial vegetation in Shared Socioeconomic Pathways.

Understanding the future trends of carbon and water fluxes between terrestrial ecosystems and the atmosphere is crucial for predicting Earth's climate dynamics. This study employs an advanced numerical approach to project global gross primary productivity (GPP) and evapotranspiration (ET) from 2001 to 2100 under various climate scenarios based on Shared Socioeconomic Pathways (SSPs). To improve predictions of vegetation dynamics, we introduce a novel model (CoLM-PVPM), an enhancement of the Common Land Model version 2014 (CoLM2014), incorporating a prognostic vegetation phenology model (PVPM). Compared to CoLM2014 that relies on satellite-based leaf area index (LAI) inputs, CoLM-PVPM predicts LAI time series using climate variables. Model validation using historical data from 2001 to 2010 demonstrates PVPM in capturing spatiotemporal variations in satellite LAI. Our modeling results indicate that annual averaged LAI and total GPP increase under SSP1-2.6 but decrease under SSP2-4.5, SSP3-7.0, and SSP5-8.5 by 2100. By comparison, annual total ET consistently increases under all SSP scenarios by 2100. Global annual averaged LAI is highly correlated with annual total GPP in all scenarios, while its correlation with annual total ET weakens in SSP2-4.5, SSP3-7.0, and SSP5-8.5. Global annual total vapor pressure deficit (VPD) and precipitation are highly correlated with annual total ET in all scenarios. As emission levels increase, the negative correlation between annual total VPD and GPP strengthens, while the correlation between annual total precipitation and GPP weakens. This research presents an improved model for predicting terrestrial vegetation processes and underscores the importance of low carbon emission scenarios in maintaining carbon-water balances in specific regions.

High-Sensitivity Detection of Changes in Local Refractive Index and Absorption by Analyzing WGM Microlaser Emission via a 2D Dispersion Spectrometer.

Microlasers have been widely used in biosensing applications because of their high sensitivity to changes in local conditions. However, in most applications, the sensitivity limit is not dictated by the microlaser line width but rather by the much worse spectral resolution of the detection system, typically a grating spectrometer. To address this issue, we built and characterized a two-dimensional (2D) dispersion spectrometer with a virtually imaged phase array etalon and a diffraction grating. The spectrometer can analyze microlaser emission with a spectral resolution of better than 0.300 pm, which enables high-precision measurements of spectral shifts in laser peak emission wavelength and sufficient resolution to detect changes in peak line width. Using commercial fluorescent microspheres as the microlasers, the 2D dispersion spectrometer demonstrated a detection limit for the refractive index change of a liquid medium of 1.37 × 10-5 RIU and a detection limit for absorption changes of less than 0.02 cm-1.

The transformation of dissolved organic matter and formation of halogenated by-products during electrochemical advanced oxidation pretreatment for shale gas produced water.

Electrochemical advanced oxidation processes (EAOPs) have shown great potential for the treatment of shale gas produced water (SGPW). In this study, we investigated the transformation of dissolved organic matter (DOM) during EAOPs of SGPW and the formation of toxic halogenated by-products at various current densities, using fluorescence spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry. We found that the priority of DOM removal was terrestrial humic-like > microbial humic-like > protein-like substances. Non-Halogenated organic compounds (non-HOCs) and HOCs were predominantly CHO, and CHOCl/CHOBr compounds in EAOP-treated SGPW, respectively. As applied current density and treatment time increased, the production of oxyhalides increased, with chlorate > bromate > perchlorate. Meanwhile, most DOM was mineralized, resulting in residual products with higher modified aromaticity index (AImod) and nominal oxidation state of carbon (NOSC). The resistants had lower mass-to-charge ratio (m/z), AImod, NOSC, and double bond equivalent minus oxygen per carbon ((DBE-O)/C). The dominant reactions were the addition of tri-oxygen and deallyl. Bromine addition dominated the reactions of halogenating addition, while chlorine addition took second place. Furthermore, the acute toxicity of SGPW was positively correlated with inorganic halogenated by-products. This study contributes to the understanding and improvement of EAOPs for the treatment of SGPW.

Biogeochemical niche conservatism relates to plant species diversification and life form evolution in a subtropical montane evergreen broad-leaved forest.

The evolutionary mechanisms underlying the biogeochemical niche conservatism in forests remain incompletely understood. Here we aimed to determine how the strengths of biogeochemical niche conservatism vary among elements and between life forms. We measured leaf concentrations of basal elements (C, N, P, K, Ca, and Mg) in a wide range of life forms in a subtropical montane evergreen broad-leaved forest. We found that differences in life forms such as evergreen/deciduous woody species and herbaceous/woody species significantly affected leaf elemental composition. The significant phylogenetic signal was present in leaf C, N, K, and Mg concentrations but absent in leaf P and Ca concentrations in all species. These contrasting strengths of biogeochemical niche conservatism were best generated by Ornstein-Uhlenbeck processes toward optima. Woody species were evolutionarily selected to show lower optimal leaf N, P, and K concentrations and higher optimal leaf C, Ca, and Mg concentrations than herbaceous species. The number of optima varied from the least in leaf C concentration to the most in leaf Ca concentration, suggesting the stronger convergent evolution of leaf Ca concentration. The positions of optima toward the tips were more selected in woody species, suggesting the more frequency of species-specific adaptations in woody species. The positions of optima were also selected at the nodes towards the species groupings from certain life forms (e.g., the group of 12 Polypodiales ferns in leaf Ca evolution and the group of three evergreen Theaceae species in leaf P evolution) that were converged to present similar leaf elemental composition. During the evolution of biogeochemical niche, strong correlations were found among leaf C, N, P, and K concentrations and between leaf Ca and Mg concentrations. In conclusion, the strengths of biogeochemical niche conservatism can vary among elements and between life forms due to the different tempo and mode of Ornstein-Uhlenbeck processes.

Preliminary evidence of safety and effectiveness of Loxoprofen Sodium Cataplasm combined with physiotherapy for myofascial pain syndrome treatment: A randomized controlled pilot clinical trial.

Background: Myofascial pain syndrome (MPS) is one of the most common causes of chronic skeletal muscle pain, which is closely related to skeletal muscle myofascial trigger point (MTRP). Since there is no first-line treatment for MPS, we investigated Loxoprofen Sodium Cataplasm combined with physiotherapy as a non-invasive therapy in patients at different levels to a protocol with superior efficacy that is safe and easy to promote. Moreover, this treatment could represent an alternative therapeutic strategy for low-income patients to a safer, more convenient, and more economical treatment scheme. Methods: A randomized clinical study was aimed at evaluating the safety and efficacy of Loxoprofen Sodium Cataplasm combined with physiotherapy in patients diagnosed with MPS in the pain clinic. We screened 100 patients with MPS, and using a computer-generated random allocation sequence, we stratified patients in a ratio of 2:1:1:1 (A: B: C: D) to one of the four treatment groups. Group A received Loxoprofen Sodium Cataplasm combined with extracorporeal shock wave therapy (ESWT) and transcutaneous electrical nerve stimulation (TENS). Group B received Loxoprofen Sodium Cataplasm alone. Group C received physiotherapy alone. Group D received Flurbiprofen Cataplasm combined with physiotherapy. After 2 weeks of treatment, the overall efficiency and secondary assessment indicators, including visual analog scale (VAS) scores, chronic soft tissue injury (CSTI) scores, Oswestry Disability Index (ODI) scores, or Northwick Park Neck Pain Questionnaire (NPQ) scores, were evaluated before and after treatment to analyze the difference in efficacy of each group. Results: All groups were well tolerated with no reported adverse events. Significant treatment differences in the change from baseline in overall efficiency (primary efficacy endpoint) (P = 0.0078) were observed in subjects of groups A and C. Conclusion: Showing valuable data of efficacy in primary and secondary endpoints, Loxoprofen Sodium Cataplasm combined with physiotherapy is superior in the treatment of MPS. Trial registration number: https://www.chictr.org.cn/ (ChiCTR2100054756).

Patient-Generated Subjective Global Assessment (PG-SGA) predicts length of hospital stay in lung adenocarcinoma patients.

The prevalence of malnutrition is high among oncology patients in Northern China. Malnutrition is related to the longer hospital stay, and it can be used to predict the prognostic outcome of patients. This work focused on investigating the relationship of nutritional condition with the length of hospital stay (LOS) in Northern Chinese patients with lung adenocarcinoma (LUAD). The Patient-Generated Subjective Global Assessment (PG-SGA), Nutritional Risk Screening 2002 (NRS 2002) score, recent weight loss and BMI were assessed in a probabilistic sample of 389 LUAD patients without epidermal growth factor receptor (EGFR) mutations. This study collected the demographic and clinical features of patients in a prospective manner. Then, we examined the association of nutritional status with LOS among the population developing LUAD. According to the PG-SGA, 63 (16·3 %), 174 (44·7 %) and 78 (20·1 %) patients were at risk for undernutrition, moderate undernutrition and severe undernutrition, respectively. Nutritional risk was found in 141 (36·2 %) patients based on the NRS 2002. The average LOS for tumour patients in Northern China was 12·5 d. At admission, a risk of undernutrition or undernutrition according to the PG-SGA (P < 0·001), NRS 2002 (P < 0·001) and latest weight loss (P < 0·001) predicted the longer LOS. LOS was related to nutritional status and hospitalisation expenses (P < 0·001). LUAD patients who stayed in the ICU had a poorer nutritional status and a longer LOS (P < 0·001). In Northern Chinese patients with LUAD, a risk for undernutrition evaluated by the PG-SGA, the NRS 2002 and recent weight loss, but not BMI, could predict a longer LOS.

Predictive value of small dense low-density lipoprotein cholesterol for cardiovascular events in Chinese elder diabetes mellitus patients.

BACKGROUND: As a subcomponent of low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C) has been suggested to be a better predictor of cardiovascular diseases (CVD). The aim of this research was to evaluate the predictive value of the sdLDL-C in cardiovascular events (CVs) in Chinese elderly patients with type 2 diabetes mellitus (DM). METHODS: A total of 386 consecutive type 2 DM patients were included into this study during December 2014 to December 2016. The serum sdLDL-C level of each subject was measured by homogeneous method. During a period of 48-month's follow-up, the occurrence of CVs and associated clinical information were recorded. Receiver operating characteristic (ROC) curves were used to assess the predictive value of serum sdLDL-C to occurrence of major CVs. RESULTS: A total of 92 CVs occurred during the study period. The ROC curve analysis manifested that sdLDL-C in the study population had a matchable discriminatory power (AUC for sdLDL-C was 0.7366, P = 0.003). In addition, Kaplan-Meier event-free survival curves displayed an obvious increase of CVs risk for sdLDL-C ≧ 26 mg/dL (log-rank = 9.10, P = 0.003). This phenomenon had analogous results in patients who received statins at baseline (log rank = 7.336, P = 0.007). Cox regression analysis revealed that the increase in HbA1c, glucose, LDL-C, sdLDL-C, non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (ApoB) and the decrease in apolipoprotein AI (ApoAI) were obviously interrelated with heightened CVs risk. Multiple Cox regression demonstrated that the increase of sdLDL-C and hemoglobin A1c (HbA1c) was significantly correlated with CVs. The results of the study indicated that high sdLDL-C level (> 10 mg/dL) was a risk factor for CVs in the multivariate model (HR 1.281, 95% CI 1.225-16.032; P < 0.01). CONCLUSION: sdLDL-C level could be an effective predictor in predicting the future CVs for Chinese elderly patients with type 2 DM and dyslipidemia.

Discovery of new fluorescent thiazole-pyrazoline derivatives as autophagy inducers by inhibiting mTOR activity in A549 human lung cancer cells.

A series of fluorescent thiazole-pyrazoline derivatives was synthesized and their structures were characterized by 1H NMR, 13C NMR, and HRMS. Biological evaluation demonstrated that these compounds could effectively inhibit the growth of human non-small cell lung cancer (NSCLC) A549 cells in a dose- and time-dependent manner in vitro and inhibit tumor growth in vivo. The structure-activity relationship (SAR) of the compounds was analyzed. Further mechanism research revealed they could induce autophagy and cell cycle arrest while had no influence on cell necrosis. Compound 5e inhibited the activity of mTOR via FKBP12, which could be reversed by 3BDO, an mTOR activator and autophagy inhibitor. Compound 5e inhibited growth, promoted autophagy of A549 cells in vivo. Moreover, compound 5e showed good selectivity with no influence on normal vascular endothelial cell growth and the normal chick embryo chorioallantoic membrane (CAM) capillary formation. Therefore, our research provides potential lead compounds for the development of new anticancer drugs against human lung cancer.

Evaluation of Fluence Correction Algorithms in Multispectral Photoacoustic Imaging.

Multispectral photoacoustic imaging (MPAI) is a promising emerging diagnostic technology, but fluence artifacts can degrade device performance. Our goal was to develop well-validated phantom-based test methods for evaluating and comparing MPAI fluence correction algorithms, including a heuristic diffusion approximation, Monte Carlo simulations, and an algorithm we developed based on novel application of the diffusion dipole model (DDM). Phantoms simulated a range of breast-mimicking optical properties and contained channels filled with chromophore solutions (ink, hemoglobin, or copper sulfate) or connected to a previously developed blood flow circuit providing tunable oxygen saturation (SO2). The DDM algorithm achieved similar spectral recovery and SO2 measurement accuracy to Monte Carlo-based corrections with lower computational cost, potentially providing an accurate, real-time correction approach. Algorithms were sensitive to optical property uncertainty, but error was minimized by matching phantom albedo. The developed test methods may provide a foundation for standardized assessment of MPAI fluence correction algorithm performance.

Photoacoustic oximetry imaging performance evaluation using dynamic blood flow phantoms with tunable oxygen saturation.

Multispectral photoacoustic oximetry imaging (MPOI) is an emerging hybrid modality that enables the spatial mapping of blood oxygen saturation (SO2) to depths of several centimeters. To facilitate MPOI device development and clinical translation, well-validated performance test methods and improved quantitative understanding of physical processes and best practices are needed. We developed a breast-mimicking blood flow phantom with tunable SO2 and used this phantom to evaluate a custom MPOI system. Results provide quantitative evaluation of the impact of phantom medium properties (Intralipid versus polyvinyl chloride plastisol) and device design parameters (different transducers) on SO2 measurement accuracy, especially depth-dependent performance degradation due to fluence artifacts. This approach may guide development of standardized test methods for evaluating MPOI devices.

Electrokinetically controlled fluid injection into unicellular microalgae.

Electrokinetically controlled microinjection is reported as an effective transport mechanism for microinjection into the wild-type strain of the widely studied model microalga Chlamydomonas reinhardtii. A microinjection system using glass capillary pipettes was developed to capture and impale the motile cells. To apply an electric field and induce electrokinetic flow (e.g., electrophoresis and electroosmosis), an electrode was inserted directly into the solution inside the impaling injection pipette and another electrode was inserted into the external cell media. The viability of the impaled cells was confirmed for more than an hour under 0.01 V using the fluorescein diacetate/propidium iodide dual fluorescent dye based assay. The viability was also found to increase almost logarithmically with decreasing voltage and to depend strongly on the solution within the injection pipette. Successful electrokinetic microinjection into cells was confirmed by both an increase in cell volume under an applied voltage and electric field dependent delivery of fluorescent fluorescein molecules into an impaled cell. Our study offers novel opportunities for quantitative delivery of biomolecules into microalgae and advancing the research and development of these organisms as biosynthetic factories.

[IHA detection results of outpatients in schistosomiasis clinic, 2005-2014].

OBJECTIVE: To understand the changes of positive rates of IHA detections of outpatients in schistosomiasis clinic. RESULTS: The data of IHA detections of outpatients in schistosomiasis clinic in Hubei Provincial Center for Disease Control and Prevention were collected and analyzed statistically from 2005 to 2014. RESULTS: A total of 7 113 outpatients were detected by IHA test, and 547 of them were positives with a positive rate of 7.69%. The positive rate of IHA test was on an upward slope before 2008, and the rate reached 14.85% in 2008, which was significantly higher than that in 2005 (5.81%) (χ² = 47.40, P < 0.01), then it was on a declined stage after 2008, and the positive rate decreased to 3.76 in 2014, which was significantly lower than that in 2008 (χ² = 12.29, P < 0.01). The positive rate of outpatients in the 10 ~ < 30 years age group was higher than those in other age groups (all P < 0.012 5), and the male positives were more than the female ones. CONCLUSIONS: The schistosomiasis endemic situation has been significantly decreased in Hubei Province. The male and people in 10 ~ < 30 age group are the high risk groups, so the targeted health education should be strengthened.

Novel Virophages Discovered in a Freshwater Lake in China.

Virophages are small double-stranded DNA viruses that are parasites of giant DNA viruses that infect unicellular eukaryotes. Here we identify a novel group of virophages, named Dishui Lake virophages (DSLVs) that were discovered in Dishui Lake (DSL): an artificial freshwater lake in Shanghai, China. Based on PCR and metagenomic analysis, the complete genome of DSLV1 was found to be circular and 28,788 base pairs in length, with a G+C content 43.2%, and 28 predicted open reading frames (ORFs). Fifteen of the DSLV1 ORFs have sequence similarity to known virophages. Two DSLV1 ORFs exhibited sequence similarity to that of prasinoviruses (Phycodnaviridae) and chloroviruses (Phycodnaviridae), respectively, suggesting horizontal gene transfer occurred between these large algal DNA viruses and DSLV1. 46 other virophages-related contigs were also obtained, including six homologous major capsid protein (MCP) gene. Phylogenetic analysis of these MCPs showed that DSLVs are closely related to OLV (Organic Lake virophage) and YSLVs (Yellowstone Lake virophages), especially to YSLV3, except for YSLV7. These results indicate that freshwater ecotopes are the hotbed for discovering novel virophages as well as understanding their diversity and properties.

[Prediction of Promoter Motifs in Virophages].

Virophages have crucial roles in ecosystems and are the transport vectors of genetic materials. To shed light on regulation and control mechanisms in virophage--host systems as well as evolution between virophages and their hosts, the promoter motifs of virophages were predicted on the upstream regions of start codons using an analytical tool for prediction of promoter motifs: Multiple EM for Motif Elicitation. Seventeen potential promoter motifs were identified based on the E-value, location, number and length of promoters in genomes. Sputnik and zamilon motif 2 with AT-rich regions were distributed widely on genomes, suggesting that these motifs may be associated with regulation of the expression of various genes. Motifs containing the TCTA box were predicted to be late promoter motif in mavirus; motifs containing the ATCT box were the potential late promoter motif in the Ace Lake mavirus . AT-rich regions were identified on motif 2 in the Organic Lake virophage, motif 3 in Yellowstone Lake virophage (YSLV)1 and 2, motif 1 in YSLV3, and motif 1 and 2 in YSLV4, respectively. AT-rich regions were distributed widely on the genomes of virophages. All of these motifs may be promoter motifs of virophages. Our results provide insights into further exploration of temporal expression of genes in virophages as well as associations between virophages and giant viruses.

[Establishment of archives of Schistosoma japonicum antibody indirect hemagglutination tests].

OBJECTIVE: To establish written and electronic archives of Schistosoma japonicum antibody indirect hemagglutination (IHA) tests. METHODS: In the process of schistosomiasis screening by IHA, the written records, electronic records, and serum sample bank were combined to make comprehensive archives. RESULTS: The S. japonicum antibody IHA test archives can preserve the schistosomiasis screening data in the long term and even can trace the source of experiments, and the operation was simple. CONCLUSION: The archives of S. japonicum antibody IHA tests are simple and useful, and worth of popularization.

Synthesis of 6-cinnamoyl-2H-benzo[b][1,4]oxazin-3(4H)-ones and their effects on A549 lung cancer cell growth.

A series of novel 6-cinnamoyl-2H-benzo[b][1,4]oxazin-3(4H)-one derivatives was synthesized. The structures of compounds were characterized by (1)H NMR, IR, and MS. Moreover, representative crystal structure was determined by X-ray diffraction analysis. The preliminary biological evaluation of all these compounds showed that compounds 3a-3d would suppress the growth of A549 lung cells effectively by inducing autophagy and cell cycle arrest.