Public participation and outgoing audit of natural resources: Evidence from tripartite evolutionary game in China.

Public participation is essential to the success of ecological civilization. Whether public participation can effectively play a role in the outgoing audit of natural resources (OANR) is an important issue that remains to be explored. This paper uses the tripartite evolutionary game to explore the mechanism of the audit subjects, the leading cadres, and the public in the OANR. The research finds that there is a two-way linkage relationship between the audit subjects and the leading cadres. The audit subjects and the leading cadres affect the behavior strategies of the public in the indirect way and direct way, respectively. However, the public lacks the path to directly affect the other two subjects. The tripartite ideal audit model of "the audit subjects conduct due diligence audits, leading cadres perform duties, the public participate" cannot be realized. The external effect of the public's strategic choice is not enough to make the profit or loss of leading cadres change structurally and then change their behaviors. This paper demonstrates the reasons why the public cannot effectively participate in the OANR at the current stage from three aspects, which are the interpretation of the equations for replication dynamics, the particularity of the audit system, and the effectiveness of public participation. Three suggestions are put forward which are encouraging citizens' indirect participation in the OANR, disclosing information about the OANR, and improving citizens' awareness of the OANR. This paper has important guiding significance for other developing countries to promote public participation in natural resource auditing.

Artesunate inhibits the development of PVR by suppressing the TGF-ß/Smad signaling pathway.

Proliferative vitreoretinopathy (PVR) is the main cause of retinal detachment surgery failure. The epithelial-mesenchymal transition (EMT) induced by transforming growth factor (TGF-ß2) plays an important role in the development of PVR. Artesunate has been widely studied as a treatment for ophthalmic diseases because of its antioxidant, anti-inflammatory, antiapoptotic and antiproliferative properties. The purpose of this study was to investigate the effects of artesunate on the TGF-ß2-induced EMT in ARPE-19 cells and PVR development. We found that artesunate inhibited the proliferation and contraction of ARPE-19 cells after the EMT and the autocrine effects of TGF-ß2 on ARPE-19 cells. Additionally, the levels of Smad3 and p-Smad3 were increased in clinical samples, and artesunate decreased the levels of Smad3 and p-Smad3 in ARPE-19 cells treated with TGF-ß2. Artesunate also inhibited the occurrence and development of PVR in vivo. In summary, artesunate inhibits the occurrence and development of PVR by inhibiting the EMT in ARPE-19 cells.

Assessment of chronic disease management mode (CDMM) on participants with primary hypertension.

OBJECTIVE: Hypertension requires continuous and long-term care to prevent associated complications. Chronic disease management mode (CDMM) was developed to improve patients' self-management. We aimed to evaluate quality of care and clinical outcomes of CDMM versus routine care. METHODS: 300 patients aged >30 years with primary hypertension were randomly allocated to the CDMM intervention group (n = 162) or the usual care control group (n = 138). CDMM comprised nursing consultations, telephone contact, online WeChat link, health education, and appropriate referrals during hospitalisation and after discharge. QLICD-HY (V 2.0) scale was used to evaluate the quality of life. Care outcomes were biochemical parameters, body mass index, blood pressure levels, waist circumference, psychological indicators and quality of life assessed on admission (baseline) and one month post-care for both groups. Data were collected and analysed using SPSS 20.0. RESULTS: After one month, the intervention group had 6 mm Hg (95% CI: -5.12 to -9.08) lower SBP and 0.6 mM/L (95% CI: -0.52 to -0.68) lower LDL than the control group. In terms of improvements in BMI, UmAlb or waist circumference, there were no differences between both groups. The intervention group scored better on psychological indicators than controls (P < 0.05), and scores reflecting social and psychological function in the intervention group were significantly higher than scores at baseline, and higher than scores of controls after one month (P < 0.05). In the control group, there was no statistically significant difference between the scores at baseline and after one month. CONCLUSIONS: Under CDMM hypertension care, improvement of blood pressure and LDL was clinically significant. Intervention care further improves social and psychological function among participants with primary hypertension.

Signal-off photoelectrochemical determination of miRNA-21 using aptamer-modified In2O3@Cu2MoS4 nanocomposite.

In2O3@Cu2MoS4 nanocomposite with superior photoelectrochemical (PEC) performance is used for the first time as a photoactivity material, and a signal-off PEC biosensing platform for miRNA detection has been successfully constructed. Firstly, the Cu2MoS4 nanosheets are synthesized by a hydrothermal method, and then, the homogeneous In2O3 nanoparticles (In2O3 NPs) are synthesized by calcination in the air. The In2O3@Cu2MoS4 nanocomposite is constructed with the Cu2MoS4 nanosheets as matrix and In2O3 NPs as sensitizer through a layer-by-layer assembly strategy. The nanocomposite with a tight interface and the matched band structure restrains the electron-hole pair recombination. Under visible light (400-700 nm), the nanocomposite exhibits a strong initial signal. With the catalyzed hairpin assembly, dozens of PbS quantum dots (QDs) are introduced on the surface of an electrode, significantly reducing the photocurrent of n-type In2O3@Cu2MoS4. Since PbS QDs can compete with the nanocomposite for light energy and electron donors, the signal decreased. Under optimal conditions, the biosensor manifests a broad linear range (1 fM-1 nM) and a low detection limit of about 0.57 fM, at a working potential of 0 V (vs. Ag/AgCl). The recovery of spiked human serum is between 94.0 and 102%, and the relative standard deviation (RSD) is between 1.3 and 2.7%. Therefore, the as-fabricated biosensor exhibits a potential for the determination of miRNA-21 in practical applications.Graphical abstract The In2O3@Cu2MoS4 nanocomposite owns a strong anode photocurrent signal, which can be used as a photoactive material to construct a "signal-off" biosensor for the detection of miRNA in non-enzymatically catalyzed hairpin assembly (CHA) reaction.

GluA2 trafficking is involved in apoptosis of retinal ganglion cells induced by activation of EphB/EphrinB reverse signaling in a rat chronic ocular hypertension model.

EphB1, expressed in Müller cells, and ephrinB2, expressed in both Müller cells and retinal ganglion cells (RGCs), constitute an EphB/ephrinB reverse signaling in RGCs. Whether and how this reverse signaling is involved in RGC apoptosis in a rat chronic ocular hypertension (COH) model was investigated. In the COH model, both EphB1 and ephrinB2 were significantly increased and the reverse signaling was activated, which was accompanied by increased protein levels of phosphorylated (p) src, GluA2, and p-GluA2. Intravitreal injection of EphB2-Fc, an activator of ephrinB2, induced an increase in TUNEL-positive signals in normal retinae. A coimmunoprecipitation assay demonstrated direct interactions among ephrinB2, p-src, and GluA2. Moreover, in COH rats the expression of GluA2 proteins on the surface of retinal cells was decreased. Such GluA2 endocytosis could be prevented by preoperational intravitreal injection of 4-amino-3-(4-chlorophenyl)-1-(t-butyl)-1H-pyrazolo [3,4-d] pyrimidine (PP2), an inhibitor of src family tyrosine kinases, and possibly involved the protein interacting with C kinase 1 and phosphorylation of GluA2. In normal rats, intravitreal injection of EphB2-Fc caused changes in these protein levels similar to those observed in COH rats, which all could be avoided by preinjection of PP2. Patch-clamp experiments further showed that the current-voltage relationship of AMPA receptor-mediated EPSCs of RGCs exhibited stronger inward rectification in EphB2-Fc-injected rats. Furthermore, preinjection of PP2 or N-[3-[[4-[(3-aminopropyl)amino]butyl]amino]propyl]-1-naphthaleneacetamide trihydrochloride) (Naspm), a Ca(2+)-permeable GluA2-lacking AMPA receptor inhibitor, remarkably inhibited RGC apoptosis in either EphB2-Fc-injected or COH rats. Together, elevated GluA2 trafficking induced by activated EphB2/ephrinB2 reverse signaling likely contributes to RGC apoptosis in COH rats.

[High-risk factors for quality of general movements in infants].

OBJECTIVE: To investigate the high-risk factors for the quality of general movements (GMs), which has a predictive value for brain dysfunction in infants. METHODS: A total of 618 infants in the stage of writhing movements and 539 infants in the stage of fidgety movements were selected separately for the evaluation of GMs. The high-risk factors for the quality of GMs in infants were analyzed by ANOVA, chi-square test, and multivariate logistic regression. RESULTS: Multivariate logistic regression analysis showed that the factors significantly associated with the quality of GMs in the stage of writhing movements were gestational age (OR=0.762, P<0.001), birth weight (OR=0.264, P<0.001), severe asphyxia (OR=2.445, P=0.012), and intrauterine distress (OR=4.865, P<0.001); the factors significantly associated with the quality of GMs in the stage of fidget movements were gestational age (OR=0.786, P=0.003), birth weight (OR=0.217, P<0.001), severe asphyxia (OR=3.765, P=0.001), and hyperbilirubinemia (OR=2.640, P=0.028). CONCLUSIONS: Low gestational age, low birth weight, severe asphyxia, hyperbilirubinemia and intrauterine distress are high-risk factors for abnormal GMs in infants, and early screening and intervention should be performed to reduce the incidence of abnormal nervous system sequelae.

Design, Synthesis, and Herbicidal Evaluation of Pyrrolidinone-Containing 2-Phenylpyridine Derivatives as Novel Protoporphyrinogen Oxidase Inhibitors.

In this work, a series of pyrrolidinone-containing 2-phenylpyridine derivatives were synthesized and evaluated as novel protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) inhibitors for herbicide development. At 150 g ai/ha, compounds 4d, 4f, and 4l can inhibit the grassy weeds of Echinochloa crus-galli (EC), Digitaria sanguinalis (DS), and Lolium perenne (LP) with a range of 60 to 90%. Remarkably, at 9.375 g ai/ha, these compounds showed 100% inhibition effects against broadleaf weeds of Amaranthus retroflexus (AR) and Abutilon theophrasti (AT), which were comparable to the performance of the commercial herbicides flumioxazin (FLU) and saflufenacil (SAF) and better than that of acifluorfen (ACI). Molecular docking analyses revealed significant hydrogen bonding and π-π stacking interactions between compounds 4d and 4l with Arg98, Asn67, and Phe392, respectively. Additionally, representative compounds were chosen for in vivo assessment of PPO inhibitory activity, with compounds 4d, 4f, and 4l demonstrating excellent inhibitory effects. Notably, compounds 4d and 4l induced the accumulation of reactive oxygen species (ROS) and a reduction in the chlorophyll (Chl) content. Consequently, compounds 4d, 4f, and 4l are promising lead candidates for the development of novel PPO herbicides.

Twist piezoelectricity: giant electromechanical coupling in magic-angle twisted bilayer LiNbO3.

Twisted a pair of stacked two-dimensional materials exhibit many exotic electronic and photonic properties, leading to the emergence of flat-band superconductivity, moiré engineering and topological polaritons. These remarkable discoveries make twistronics the focus point of tremendous interest, but mostly limited to the concept of electrons, phonons or photons. Here, we present twist piezoelectricity as a fascinating paradigm to modulate polarization and electromechanical coupling by twisting precisely the stacked lithium niobate slabs due to the interlayer coupling effect. Particularly, the inversed and twisted bilayer lithium niobate is constructed to overcome the intrinsic mutual limitation of single crystals and giant effective electromechanical coupling coefficient k t 2 is unveiled at magic angle of 11 1 ∘ , reaching 85.5%. Theoretical analysis based on mutual energy integrals shows well agreements with numerical and experimental results. Our work opens new venues to flexibly control multi-physics with magic angle, stimulating progress in wideband acoustic-electric, and acoustic-optic components, which has great potential in wireless communication, timing, sensing, and hybrid integrated photonics.

Discovery of Pyridyl-Benzothiazol Hybrids as Novel Protoporphyrinogen Oxidase Inhibitors via Scaffold Hopping.

In order to discover novel protoporphyrinogen oxidase (PPO) inhibitors with excellent herbicidal activity, a series of structurally novel 6-(pyridin-2-yl) benzothiazole derivatives were designed based on the scaffold hopping strategy. The in vitro experiments demonstrated that the newly synthesized compounds exhibited noteworthy inhibitory activity against Arabidopsis thaliana PPO (AtPPO), with IC50 values ranging from 0.06 to 1.36 µM. Preliminary postemergence herbicidal activity tests and crop safety studies indicated that some of our compounds exhibited excellent herbicidal activity and crop safety. For instance, compound (rac)-7as exhibited superior herbicidal activities to commercially available flumioxazin (FLU) and saflufenacil (SAF) at all the tested concentrations and showed effective herbicidal activities even at a dosage as low as 18.75 g ai/ha. Meanwhile, compound (rac)-7as showed good crop safety for wheat at a dosage as high as 150 g of ai/ha. Although the absolute configuration of compound 7as has no obvious effect on its herbicidal activity, compound (R)-7as showed a slightly higher crop safety than compound (S)-7as. Molecular simulation studies of Nicotiana tabacum PPO (NtPPO) and our candidate compounds showed that the benzothiazole moiety of compounds (R)-7as or (S)-7as formed multiple π-π stacking interactions with FAD, and the pyridine ring generated π-π stacking with Phe-392. Our finding proved that the pyridyl-benzothiazol hybrids are promising scaffolds for the development of PPO-inhibiting herbicides.

Armillariella tabescens-derived polysaccharides alleviated â±°-Gal-induced neuroinflammation and cognitive injury through enterocerebral axis and activation of keap-1/Nrf2 pathway.

The early symptoms of neurodegenerative diseases include oxidative stress disorder and accelerated inflammation levels. Edible fungi polysaccharides play essential roles in anti-neuroinflammation. We analyzed the regulatory mechanisms of polysaccharides from extracellular Armillariella tabescens (ATEP) in alleviating neuroinflammation in mice. Mice were induced with d-galactose and aluminum chloride to establish an animal model of Alzheimer's disease, then intragastrically treated with ATEP, which had been previously analyzed for its physicochemical properties. We assessed the critical characteristics of mice treated for neuroinflammation, including cognitive behavior, the anti-inflammatory potential of ATEP in hippocampal pathology and critical protein expression, and changes in fecal microbial composition and metabolites. ATEP intervened in oxidative stress by enhancing antioxidant enzyme activities and suppressing the Keap-1/Nrf2 signaling pathway. Changing the Nrf2 content in the nucleus led to changes in the downstream oxidation-related enzymes, HO-1, NQO-1, iNOS, and COX-2, and the neuronal morphology in CA3 region of the hippocampus. Microbiome analysis revealed that ATEP remodeled the gut microbiotas and regulated the short-chain fatty acids-producing bacteria. Early intervention with ATEP via active dietary supplementation may promote neuroprotection.

Nanoengineered Red Blood Cells Loaded with TMPRSS2 and Cathepsin L Inhibitors Block SARS-CoV-2 Pseudovirus Entry into Lung ACE2+ Cells.

The enzymatic activities of Furin, Transmembrane serine proteinase 2 (TMPRSS2), Cathepsin L (CTSL), and Angiotensin-converting enzyme 2 (ACE2) receptor binding are necessary for the entry of coronaviruses into host cells. Precise inhibition of these key proteases in ACE2+ lung cells during a viral infection cycle shall prevent viral Spike (S) protein activation and its fusion with a host cell membrane, consequently averting virus entry to the cells. In this study, dual-drug-combined (TMPRSS2 inhibitor Camostat and CTSL inhibitor E-64d) nanocarriers (NCs) are constructed conjugated with an anti-human ACE2 (hACE2) antibody and employ Red Blood Cell (RBC)-hitchhiking, termed "Nanoengineered RBCs," for targeting lung cells. The significant therapeutic efficacy of the dual-drug-loaded nanoengineered RBCs in pseudovirus-infected K18-hACE2 transgenic mice is reported. Notably, the modular nanoengineered RBCs (anti-receptor antibody+NCs+RBCs) precisely target key proteases of host cells in the lungs to block the entry of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), regardless of virus variations. These findings are anticipated to benefit the development of a series of novel and safe host-cell-protecting antiviral therapies.

Group I mGluR-mediated inhibition of Kir channels contributes to retinal Müller cell gliosis in a rat chronic ocular hypertension model.

Müller cell gliosis, which is characterized by upregulated expression of glial fibrillary acidic protein (GFAP), is a universal response in many retinal pathological conditions. Whether down-regulation of inward rectifying K+ (Kir) channels, which commonly accompanies the enhanced GFAP expression, could contribute to Müller cell gliosis is poorly understood. We investigated changes of Kir currents, GFAP and Kir4.1 protein expression in Müller cells in a rat chronic ocular hypertension (COH) model, and explored the mechanisms underlying Müller cell gliosis. We show that Kir currents and Kir4.1 protein expression in Müller cells were reduced significantly, while GFAP expression was increased in COH rats, and these changes were eliminated by MPEP, a group I metabotropic glutamate receptors (mGluR I) subtype mGluR5 antagonist. In normal isolated Müller cells, the mGluR I agonist (S)-3,5-dihydroxyphenylglycine (DHPG) suppressed the Kir currents and the suppression was blocked by MPEP. The DHPG effect was mediated by the intracellular Ca2+ -dependent PLC/IP3-ryanodine/PKC signaling pathway, but the cAMP-PKA pathway was not involved. Moreover, intravitreal injection of DHPG in normal rats induced changes in Müller cells, similar to those observed in COH rats. The DHPG-induced increase of GFAP expression in Müller cells was obstructed by Ba2+, suggesting the involvement of Kir channels. We conclude that overactivation of mGluR5 by excessive extracellular glutamate in COH rats could contribute to Müller cell gliosis by suppressing Kir channels.

Enhanced expression of NR2B subunits of NMDA receptors in the inherited glaucomatous DBA/2J mouse retina.

DBA/2J mouse has been used as a model for spontaneous secondary glaucoma. Here, we investigated changes in expression of NMDA receptor (NMDAR) subunits and Cdk5/p35/NMDAR signaling in retinas of DBA/2J mice using Western blot technique. The protein levels of NR1 and NR2A subunits in retinas of DBA/2J mice at all ages (6-12 months) were not different from those in age-matched C57BL/6 mice. In contrast, the protein levels of NR2B subunits, in addition to age-dependent change, significantly increased with elevated intraocular pressure (IOP) in DBA/2J mice at 6 and 9 months as compared with age-matched controls. Moreover, expression of Cdk5, p35 and ratio of p-NR2A(S1232)/NR2A progressively increased with time in both strains, suggestive of activated Cdk5/p35 signaling pathway. However, the changes in these proteins were in the same levels in both strain mice, except a significant increase of p35 proteins at 6 months in DBA/2J mice. Meanwhile, the protein levels of Brn-3a, a retinal ganglion cell (RGC) maker, remarkably decreased at 9-12 months in DBA/2J mice, which was in parallel with the changes of NR2B expression. Our results suggest that elevated IOP-induced increase in expression of NR2B subunits of NMDARs may be involved in RGC degeneration of DBA/2J mice.

Application of apical negative pressure irrigation in the nonsurgical treatment of radicular cysts: A case report.

BACKGROUND: Radicular cysts are one of the most common odontogenic cystic lesions found in the jaw. Nonsurgical treatment of large radicular cysts is a topic of ongoing debate, and there is still no clear consensus on the most effective therapies. The apical negative pressure irrigation system aspirates the cystic fluid and releases the static pressure in the radicular cyst, representing a minimally invasive approach for decompression. In this case, the radicular cyst was in close proximity to the mandibular nerve canal. We used nonsurgical endodontic treatment with a homemade apical negative pressure irrigation system and the prognosis was good. CASE SUMMARY: A 27-year-old male presented to our Department of General Dentistry with complaints of pain in the mandibular right molar when chewing. The patient had no history of drug allergies or systemic disease. A multidisciplinary management approach was designed and included root canal retreatment with a homemade apical negative pressure irrigation system, deep margin elevation and prosthodontic treatment. According to a 1-year follow-up period, the patient showed a favorable outcome. CONCLUSION: This report reveals that nonsurgical treatment with an apical negative pressure irrigation system may provide new insights into the treatment of radicular cysts.

A survival prediction model based on PCA-HSIDA-LSSVM for patients with esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a type of cancer and has some of the highest rates of both incidence and mortality globally. Developing accurate models for survival prediction provides a basis clinical judgment and decision making, improving the survival status of ESCC patients. Although many predictive models have been developed, there is still lack of highly accurate survival prediction models for ESCC patients. This study proposes a novel survival prediction model for ESCC patients based on principal component analysis (PCA) and least-squares support vector machine (LSSVM) optimized by an improved dragonfly algorithm with hybrid strategy (HSIDA). The original 17 blood indicators are condensed into five new variables by PCA, reducing data dimensionality and redundancy. An improved dragonfly algorithm based on hybrid strategy is proposed, which addresses the limitations of dragonfly algorithm, such as slow convergence, low search accuracy and insufficient vitality of late search. The proposed HSIDA is used to optimize the regularization parameter and kernel parameter of LSSVM, improving the prediction accuracy of the model. The proposed model is validated on the dataset of 400 patients with ESCC in the clinical database of First Affiliated Hospital of Zhengzhou University and the State Key Laboratory of Esophageal Cancer Prevention and Control of Henan Province. The experiment results demonstrate that the proposed HSIDA-LSSVM has the best prediction performance than LSSVM, HSIDA-BP, IPSO-LSSVM, COA-LSSVM and IBA-LSSVM. The proposed model achieves the accuracy of 96.25%, sensitivity of 95.12%, specificity of 97.44%, precision of 97.50%, and F1 score of 96.30%.

Herbicidal Activity of Beflubutamid Analogues as PDS Inhibitors and SAR Analysis and Degradation Dynamics in Wheat.

In this work, a series of beflubutamid (BF) analogues' postemergent herbicidal activity was evaluated, and the structure-activity relationship (SAR) was discussed. At a dosage of 300 g ai/ha, compounds (Rac)-6h and (Rac)-6q showed excellent herbicidal activity against Amaranthus retroflexus, Abutilon theophrasti, and Medicago sativa, with inhibition rates of 90, 100, and 80% and 100, 100, and 100%, respectively, comparable to that of commercial herbicide BF, which showed inhibition rates of 90, 100, and 100%, respectively. Notably, at dosages of 150 and 300 g ai/ha, the chiral compounds (S)-6h and (S)-6q exhibited higher herbicidal activities than their racemates. Molecular docking results indicated that compounds (S)-BF and (S)-6h have stronger binding affinities with Oryza sativa phytoene desaturase (OsPDS), resulting in a higher herbicidal activity. Additionally, the degradation dynamics half-life of (S)-BF in wheat was determined to be 77.02 h. Consequently, compounds (S)-6h and (S)-6q are promising lead candidates for the development of highly effective herbicides.

Integration of IDPC Clustering Analysis and Interpretable Machine Learning for Survival Risk Prediction of Patients with ESCC.

Precise forecasting of survival risk plays a pivotal role in comprehending and predicting the prognosis of patients afflicted with esophageal squamous cell carcinoma (ESCC). The existing methods have the problems of insufficient fitting ability and poor interpretability. To address this issue, this work proposes a novel interpretable survival risk prediction method for ESCC patients based on extreme gradient boosting improved by whale optimization algorithm (WOA-XGBoost) and shapley additive explanations (SHAP). Given the imbalanced nature of the data set, the adaptive synthetic sampling (ADASYN) is first used to generate the samples with high survival risk. Then, an improved clustering by fast search and find of density peaks (IDPC) algorithm based on cosine distance and K nearest neighbors is used to cluster the patients. Next, the prediction model for each cluster is obtained by WOA-XGBoost and the constructed model is visualized with SHAP to uncover the factors hidden in the structured model and improve the interpretability of the black-box model. Finally, the effectiveness of the proposed scheme is demonstrated by analyzing the data collected from the First Affiliated Hospital of Zhengzhou University. The results of the analysis reveal that the proposed methodology exhibits superior performance, as indicated by the area under the receiver operating characteristic curve (AUROC) of 0.918 and accuracy of 0.881.

Ovariectomy induces hyperalgesia accompanied by upregulated estrogen receptor α and protein kinase B in the rat spinal cord.

Hormone supplementation is one of the common therapies for menopause-related disorders. Among different tools, the ovariectomy (OVX) rodents are widely accepted as an appropriate menopausal pain model. Our previous study has showed that OVX produces a significant pain facilitation in both acute pain and tonic pain, however, the underlying mechanisms remain unclear. In this study, we examined the effects of OVX treatment and estradiol (E2) supplementation on formalin-induced nociceptive responses, and explored the associated spinal mechanisms. Female Sprague-Dawley rats underwent bilateral OVX, and E2 supplementation was given subcutaneously from the 5th week after surgery (30 µg/day for 7 days). Our results showed that formalin-induced nociceptive behaviors did not differ between diestrus and proestrus stages of the estrous in intact rats. However, OVX exacerbated formalin-evoked inflammatory pain, especially in the late phase at 4-5 weeks but not 2 weeks post-surgery. E2 supplementation significantly reversed the OVX-triggered hyperalgesia. Double immunofluorescence staining revealed that both ERα and ERß in the spinal dorsal horn were co-labeled with the neuronal markers, but not with markers of astrocytes or microglia. The spinal ERα (but not ERß) expression significantly increased in the OVX group, which was reversed by E2 supplementation. Moreover, the OVX individuals showed an increased protein kinase B (AKT) level in lumbar spinal cord, and E2 supplementation diminished the AKT expression in OVX rats. Finally, intrathecal injection Wortmannin, an inhibitor for AKT signaling, effectively reduced the nociceptive behaviors in the late phase and the number of c-fos positive cells. Together, our findings indicate that E2 supplementation alleviates the OVX-induced hyperalgesia, which might be involved in spinal ERα and AKT mechanisms.

Giardia intestinalis: effects of Pulsatilla chinensis extracts on trophozoites.

Pulsatilla chinensis is a medicinal root plant that has been used to treat a wide range of disease conditions. Our study determined the antiprotozoal activity of various P. chinensis extracts and fractions against Giardia intestinalis including their effects on parasite growth, cell viability, adherence, and morphology. Ethyl acetate extracts (IC50 = 257.081 µg/ml) were the most active to inhibit the growth of G. intestinalis followed by aqueous extract (PWE), saponins, and n-butanol extract. The PWE and ethyl acetate extract inhibited G. intestinalis trophozoites adherence after 3 h of incubation and killed almost 50 % of the parasite population in a time-dependent manner. Changes in morphology, presence of precipitates in the cytoplasm, dissolved cytoplasm with large vacuole, break of flagella and ventral disk, membrane blebs, and intracellular and nuclear clearance of the treated trophozoites were observed by scanning and transmission electron microscopy. We demonstrated that P. chinensis induced these changes in G. intestinalis morphology and consequently has potential therapeutic use against giardiasis.