Huntington's Disease: Complex Pathogenesis and Therapeutic Strategies.

Huntington's disease (HD) arises from the abnormal expansion of CAG repeats in the huntingtin gene (HTT), resulting in the production of the mutant huntingtin protein (mHTT) with a polyglutamine stretch in its N-terminus. The pathogenic mechanisms underlying HD are complex and not yet fully elucidated. However, mHTT forms aggregates and accumulates abnormally in neuronal nuclei and processes, leading to disruptions in multiple cellular functions. Although there is currently no effective curative treatment for HD, significant progress has been made in developing various therapeutic strategies to treat HD. In addition to drugs targeting the neuronal toxicity of mHTT, gene therapy approaches that aim to reduce the expression of the mutant HTT gene hold great promise for effective HD therapy. This review provides an overview of current HD treatments, discusses different therapeutic strategies, and aims to facilitate future therapeutic advancements in the field.

Metal-Organic Frameworks-Derived Nanocarbon Materials and Nanometal Oxides for Photocatalytic Applications.

Harnessing low-density solar energy and converting it into high-density chemical energy through photocatalysis has emerged as a promising avenue for the production of chemicals and remediation of environmental pollution, which contributes to alleviating the overreliance on fossil fuels. In recent years, metal-organic frameworks (MOFs) have gained widespread application in the field of photocatalysis due to their photostability, tunable structures, and responsiveness in the visible light range. However, most MOFs exhibit relatively low response to light, limiting their practical applications. MOFs-derived nanomaterials not only retain the inherent advantages of pristine MOFs but also show enhanced light adsorption and responsiveness. This review categorizes and summarizes MOFs-derived nanomaterials, including nanocarbons and nanometal oxides, providing representative examples for the synthetic strategies of each category. Subsequently, the recent research progress on MOFs-derived materials in photocatalytic applications are systematically introduced, specifically in the areas of photocatalytic water splitting to H2, photocatalytic CO2 reduction, and photocatalytic water treatment. The corresponding mechanisms involved in each photocatalytic reaction are elaborated in detail. Finally, the review discusses the challenges and further directions faced by MOFs-derived nanomaterials in the field of photocatalysis, highlighting their potential role in advancing sustainable energy production and environmental remediation.

Preparation of highly adsorptive biochar by sequential iron impregnation under refluxing and pyrolysis at low temperature for removal of tetracycline.

Iron-doping modification is a prevailing approach for improving adsorption capability of biochar with environmental friendliness, but usually requires high temperature and suffers from iron aggregation. Herein, a highly adsorptive biochar was manufactured via sequential disperse impregnation of iron by refluxing and pyrolysis at low temperature for eliminating tetracycline (TC) from aqueous solution. Iron oxides and hydroxides were impregnated and stably dispersed on the carbon matrix as pyrolyzed at 200 °C, meanwhile abundant oxygen and nitrogen functional groups were generated on surface. The iron-doped biochar exhibited up to 891.37 mg/g adsorption capacity at pH 5, and could be recycled with high adsorption capability. The adsorption of TC should be mostly contributed to the hydrogen bonding of N/O functional groups and the hydrogen bonding/coordination of iron oxides/hydroxides. This would provide a valuable guide for dispersedly doping iron and conserving functional groups on biochar, and a super iron-doped biochar was prepared with superior recyclability.

Association between normal saline infusion volume in the emergency department and acute kidney injury in heat stroke patients: a multicenter retrospective study.

BACKGROUND: Previous studies have shown that intravenous normal saline (NS) may be associated with the incidence of acute kidney injury (AKI). This study aimed to evaluate the association between the volume of NS infusion and AKI in heat stroke (HS) patients. METHODS: This multicenter retrospective cohort study included 138 patients with HS. The primary outcome was the incidence of AKI. Secondary outcomes included the need for continuous renal replacement therapy (CRRT), admission to the intensive care unit (ICU), length of stay in the ICU and hospital, and in-hospital mortality. Multivariate regression models, random forest imputation, and genetic and propensity score matching were used to explore the relationship between NS infusion and outcomes. RESULTS: The mean volume of NS infusion in the emergency department (ED) was 3.02 ± 1.45 L. During hospitalization, 33 patients (23.91%) suffered from AKI. In the multivariate model, as a continuous variable (per 1 L), the volume of NS infusion was associated with the incidence of AKI (OR, 2.51; 95% CI, 1.43-4.40; p = .001), admission to the ICU (OR, 3.46; 95% CI 1.58-7.54; p = .002), and length of stay in the ICU (ß, 1.00 days; 95% CI, 0.44-1.56; p < .001) and hospital (ß, 1.41 days; 95% CI, 0.37-2.45; p = .008). These relationships also existed in the forest imputation cohort and matching cohort. There were no differences in the use of CRRT or in-hospital mortality. CONCLUSIONS: The volume of NS infusion was associated with a significant increase in the incidence of AKI, admission to the ICU, and length of stay in the ICU and hospital among patients with HS.

Synergistic Enhancement of Photocatalytic H2 Evolution over NH2-MIL-125 Modified with Dual Cocatalyst.

The construction of efficient photocatalysts for water splitting to enable H2 evolution is pivotal to alleviate energy issues and environmental concerns. In this work, carbon dots (CDs) were prepared by employing "green solvent" ionic liquids as carbon sources and then combined with Pt/NH2-MIL-125, resulting in the emergence of a high-efficiency photocatalyst termed CDs-Pt/NH2-MIL-125 for the first time. This composite photocatalyst exhibited outstanding photocatalytic activity in H2 production under visible light irradiation. Notably, the H2 production rate of CDs100-Pt/NH2-MIL-125 reaches up to 951.4 µmol/g/h, which was 3.1 times that of Pt/NH2-MIL-125. The characterization results indicate that CDs and Pt uniformly dispersed on the surface of NH2-MIL-125 and fabricated a synergistic compact structure, providing a high BET surface area (985 m2 g-1) and a suitable band gap. Furthermore, the distinctive embeddable-dispersed CDs and Pt, as dual cocatalyst, can harvest light and facilitate the transfer of photogenerated electrons, thereby significantly augmenting the exploitation of visible light. The plausible mechanism of photocatalytic H2 evolution over the CDs-Pt/NH2-MIL-125 catalyst was also discussed. This work introduces a promising strategy for designing high-performance CDs-MOFs-based photocatalysts, an innovative step toward achieving efficient photocatalytic water splitting for H2 production.

Prevalence and bidirectional association between rhinitis and urticaria: A systematic review and meta-analysis.

Background: Rhinitis, allergic rhinitis in particular, and urticaria are both common diseases globally. However, there is controversy with regard to the correlation between rhinitis and urticaria. Objective: To examine the accurate association between rhinitis and urticaria. Methods: Three medical literature data bases were searched from data base inception until January 11, 2022. The prevalence and association between rhinitis and urticaria were estimated by meta-analysis. Quality assessment was performed by using the Newcastle-Ottawa Scale. Pooled odds ratios (OR) with 95% confidence intervals (CI) and pooled prevalence were calculated by using random-effects models. Results: Urticaria prevalence in patients with rhinitis was 17.6% (95% CI, 13.2%-21.9%). The pooled prevalence of rhinitis was 31.3% (95% CI, 24.2%-38.4%) in patients with urticaria, and rhinitis prevalence in patients with acute urticaria and chronic urticaria was 31.6% (95% CI, 7.4%-55.8%) and 28.7% (95% CI, 20.4%-36.9%), respectively. Rhinitis occurrence was significantly associated with urticaria (OR 2.67 [95% CI, 2.625-2.715]). Urticaria and rhinitis were diagnosed based on different criteria, possibly resulting in a potential error of misclassification. Conclusion: Rhinitis and urticaria were significantly correlated. Physicians should be cognizant with regard to this relationship and address nasal or skin symptoms in patients.

[Efficacy of electroacupuncture on acute intracerebral hemorrhage and its effect on serum AQP4 in patients].

OBJECTIVE: To observe the effects on neural function, living ability and mental state of the patients with acute intracerebral hemorrhage (ICH), as well as aquaporin 4 (AQP4) in the serum after treated with electroacupuncture (EA) on the base of routine therapy of western medicine. METHODS: Seventy-two acute ICH patients were randomized into an observation group (36 cases, 4 cases dropped off) and a control group (36 cases, 2 cases dropped off). In the control group, the conventional treatment was delivered such as stopping bleeding, preventing re-hemorrhage, controlling blood pressure, mitigating neural edema and reducing intracranial pressure. In the observation group, on the base of the treatment in the control group, EA was supplemented. Acupoints included Shuigou (GV 26), bilateral Neiguan (PC 6) and Sanyinjiao (SP 6) etc. Electric stimulation was operated at Neiguan (PC 6) and Sanyinjiao (SP 6) on the same side, with disperse-dense wave, and 2 Hz/100 Hz in frequency, tolerable current intensity. Electric stimulation was delivered for 30 min in each treatment, once daily and for 6 times per week. The duration of treatment was 2 weeks in the two groups. Before and after treatment, changes of the scores of National Institutes of Health stroke scale (NIHSS), modified Barthel index (MBI) and mini-mental state examination (MMSE), as well as AQP4 content in the serum were observed in the two groups; the efficacy and safety were compared between the two groups. RESULTS: The NIHSS scores and the serum AQP4 content decreased after treatment when compared with those before treatment in the two groups (P<0.05), while, MBI and MMSE scores increased (P<0.05). In the observation group, NIHSS score and serum AQP4 content were lower than those of the control group (P<0.05), and MBI and MMSE scores were higher (P<0.05). The total effective rate of the observation group was 93.8% (30/32), higher than that of the control group (73.5%, 25/34, P<0.05). The treatment in the two groups was safe, without adverse reactions and events occurring in the patients. CONCLUSION: Electroacupuncture, on the base of conventional treatment of western medicine, can effectively improve the neural function, living ability, mental state and serum AQP4 content of the patients with acute ICH. It is suggested that the effective treatment by electroacupuncture may be related to the regulation of the serum AQP4 content.

Role of Ferroptosis in Glial Cells after Ischemic Stroke.

Ischemic stroke (IS) is the predominant cause of morbidity and mortality worldwide. Ferroptosis, a new type of programmed cell death, has been shown to play a crucial role in IS pathogenesis. Traditionally, research focused on neurons did not uncover specific positive results for IS. However, glial cells have recently received interest as promising targets for IS treatment, not only for their structural function but also in the iron transfer between glia and neurons, which indicates a promising glia-neuron crosstalk in mediating the IS process and ischemia/reperfusion-associated neuropathology, showing their affiliation with ferroptosis. This review addresses the major phenomena of iron metabolism and the process and regulation of ferroptosis, with a particular focus on their impact on IS pathology. The review discusses iron homeostasis, the biology of reactive oxygen species, and lipid peroxidation for modulating the process of IS-induced ferroptosis in different glial cells. We then review recent therapies that leverage ferroptosis modulation for the treatment of IS. Extensive preclinical and clinical research is necessary to fully understand the roles of glia-neuron crosstalk and ferroptosis in IS.

Pore-forming activity of S. pneumoniae pneumolysin disrupts the paracellular localization of the epithelial adherens junction protein E-cadherin.

Streptococcus pneumoniae, a common cause of community-acquired bacterial pneumonia, can cross the respiratory epithelial barrier to cause lethal septicemia and meningitis. S. pneumoniae pore-forming toxin pneumolysin (PLY) triggers robust neutrophil (PMN) infiltration that promotes bacterial transepithelial migration in vitro and disseminated disease in mice. Apical infection of polarized respiratory epithelial monolayers by S. pneumoniae at a multiplicity of infection (MOI) of 20 resulted in recruitment of PMNs, loss of 50% of the monolayer, and PMN-dependent bacterial translocation. Reducing the MOI to 2 decreased PMN recruitment two-fold and preserved the monolayer, but apical-to-basolateral translocation of S. pneumoniae remained relatively efficient. At both MOI of 2 and 20, PLY was required for maximal PMN recruitment and bacterial translocation. Co-infection by wild-type S. pneumoniae restored translocation by a PLY-deficient mutant, indicating that PLY can act in trans. Investigating the contribution of S. pneumoniae infection on apical junction complexes in the absence of PMN transmigration, we found that S. pneumoniae infection triggered the cleavage and mislocalization of the adherens junction (AJ) protein E-cadherin. This disruption was PLY-dependent at MOI of 2 and was recapitulated by purified PLY, requiring its pore-forming activity. In contrast, at MOI of 20, E-cadherin disruption was independent of PLY, indicating that S. pneumoniae encodes multiple means to disrupt epithelial integrity. This disruption was insufficient to promote bacterial translocation in the absence of PMNs. Thus, S. pneumoniae triggers cleavage and mislocalization of E-cadherin through PLY-dependent and -independent mechanisms, but maximal bacterial translocation across epithelial monolayers requires PLY-dependent neutrophil transmigration.

Oxidative magnetization of biochar at relatively low pyrolysis temperature for efficient removal of different types of pollutants.

A novel oxidative magnetization, involving phosphomolybdic acid and Fe(NO3)3 co-promoted pyrolysis, was established to manufacture highly adsorptive magnetic biochars for adsorbing aqueous tetracycline, methylene blue, and Cr6+. The modification of phosphomolybdic acid greatly boosted the formation of γ-Fe2O3 and oxygen containing groups with enhancement of specific surface area and pore volume at 400 °C. Importantly, γ-Fe2O3 was stably fixed on surface in quasi-nanoscale. The oxidized magnetic biochar displayed 631.53, 158.45, 155.13 mg/g adsorption capabilities for tetracycline, methylene blue, and Cr6+ with 22.79 emu/g saturation magnetization, respectively. Oxygen containing groups and quasi-nanoscale γ-Fe2O3 served as key adsorption sites for these pollutants. A general oxidative magnetization was established for manufacturing high-performance magnetic biochar through phosphomolybdic acid/Fe(NO3)3 co-promoted pyrolysis at relatively low temperature.

The association of standard base excess upon emergency admission with outcomes in patients with heat stroke.

OBJECTIVES: Standard base excess (SBE) is a quick and effective tool to identify acid-base disorders in critically ill patients, independent of respiratory factors. The predictive value of SBE for adverse outcomes in patients with heat stroke (HS) is still unclear. This study aimed to explore the prognostic significance of SBE for in-hospital mortality and other adverse outcomes in patients with HS. METHODS: A retrospective, observational multicenter cohort study with consecutive patients between 2021 and 2022 was conducted. The SBE was performed upon emergency department (ED) admission. The primary outcome was in-hospital mortality. Secondary outcomes included the use of vasoactive drugs in the ED, admission to the ICU, acute kidney failure, acute heart failure, acute respiratory failure, sepsis, and coagulation impairment. Logistic regression models and receiver operating characteristic (ROC) curves were used to estimate the association of SBE with outcomes in HS patients. Interaction and stratified analyses were also conducted. RESULTS: The median level of SBE was -4.70 (-8.05- -1.55) mmol/L. Overall hospital mortality in these 151 HS patients was 12.58%. SBE was independently associated with hospital mortality (OR 0.81, 95% CI 0.70-0.95, P = 0.011). Age and HS type played interactive roles in the relationship between SBE and in-hospital mortality. The OR between SBE and hospital mortality was 0.5 (95% CI, 0.3-0.9; p < 0.018) in classic HS participants and 0.62 (95% CI, 0.45-0.87; p = 0.005) in participants aged >65 years. The AUC of SBE to predict in-hospital mortality was 0.868 (95% CI: 0.704-0.962) and 0.883 (95% CI: 0.750-0.951) in these two groups, respectively. SBE was significantly associated with admission to the ICU, acute kidney failure, acute respiratory failure, sepsis, and coagulation impairment. CONCLUSION: SBE upon emergency admission was significantly associated with adverse outcomes in patients with HS.

Copper and In Situ-Generated Triflic Acid Relay-Promoted Four-Component Cascade Reaction for the Construction of Polysubstituted Cycloguanidines.

An unprecedented copper and in situ-generated triflic acid relay-promoted four-component cascade reaction of cyanamides, diaryliodonium triflates, propargylic amines, and H2O was established for rapid and concise construction of diverse five-membered cycloguanidines. Copper-catalyzed guanidination/intramolecular hydroamination and in situ-generated HOTf-accelerated hydration proceeded sequentially with high level of chemoselectivity and regioselectivity, and six new bonds were simultaneously built in high yields. Thus, diaryliodonium triflates served not only as an arylation reagent but also as an internal acid promoter, establishing an alternative strategy for highly efficient utilization of diaryliodonium trifates.

Electroacupuncture Inhibits Ferroptosis Induced by Cerebral Ischemiareperfusion.

BACKGROUND: Electroacupuncture (EA) treatment has been recommended by World Health Organization (WHO) for years on cerebral ischemia treatment, but the specific mechanism is still elusive. Studies have shown that EA can relieve brain damage after ischemic stroke by inhibiting programmed cell death (PCD), such as apoptosis, necroptosis, and autophagy. Ferroptosis, a unique form of cell death, has been highlighted recently and found to occur in I/R injury. We, therefore, investigated whether EA plays an essential role in relieving cerebral I/R injury via ferroptosis. METHODS: The modified MCAO/R rats model was established and then divided into four groups with or without EA treatment. Neurological deficit score and TTC staining were used to evaluate the neurological deficit and infarct volume of each group. Transmission electron microscope (TEM) and immunofluorescence staining were applied for mitochondrial ultrastructure and ROS accumulation observation, respectively. The proteins and mRNA expression of ACSL4, TFR1, and GPX4 were assessed by western blot and qPCR to detect the progress of ferroptosis. RESULTS: EA treatment improved neurological deficits and reduced infarct volume. Moreover, EA significantly relieved the mitochondrial morphological changes and inhibited ROS Production in MCAO rats. In terms of its mechanism, EA obviously decreased the ACSL4 and TFR1 expressions and promoted GPX4 levels in MCAO/R model rats. CONCLUSION: These findings indicate that EA might play an essential role in relieving cerebral I/R injury via ferroptosis.

Association between cooling temperature and outcomes of patients with heat stroke.

This study explored the relationship between body temperature and adverse outcomes in patients with heat stroke to identify the optimal target body temperature within the first 24 h. This retrospective, multicentre study enrolled 143 patients admitted to the emergency department and diagnosed with heat stroke. The primary outcome was the in-hospital mortality rate, while secondary outcomes included the presence and number of damaged organs and neurological sequelae at discharge. A body temperature curve was built using a generalized additive mixed model, and the association between body temperatures and outcomes was established by logistic regression. The threshold and saturation effects were used to explore the targeted body temperature management. Cases were divided into the surviving and non-surviving groups. The cooling rate within the first 2 h was significantly higher in the survival group than the non-survival group (ß: 0.47; 95% confidence interval [CI]: 0.09-0.84; P = 0.014), while the non-survival group exhibited a lower body temperature within 24 h (ß: - 0.06; 95% CI: - 0.08 to - 0.03; P ≤ 0.001). Body temperature after 2 h (odds ratio [OR]: 2.27; 95% CI: 1.14-4.50; P = 0.019) and lowest temperature within 24 h (OR: 0.18; 95% CI: 0.06-0.55; P = 0.003) were significantly related to in-hospital mortality rate. When the body temperature at 0.5 h was 38.5-40.0 °C, the number of damaged organs was at its lowest. In patients with heat stroke, both hyperthermia and hypothermia were associated with adverse outcomes. Hence, an accurate body temperature management is required during the early stages of care.

The functional connectivity between left insula and left medial superior frontal gyrus underlying the relationship between rumination and procrastination.

Procrastination is regarded as a prevalent problematic behavior that impairs people's physical and mental health. Although previous studies have indicated that trait rumination is robustly positively correlated with procrastination, it remains unknown about the neural substrates underlying the relationship between trait rumination and procrastination. To address this issue, we used voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) approaches to explore the neural basis of the relationship between trait rumination and procrastination. Our behavior results found that trait rumination was significantly positively correlated to procrastination, while the VBM analysis showed that trait rumination was negatively correlated with gray matter volume of the insula. Furthermore, the RSFC results revealed a negative association of the left insula-lmSFG (left medial superior frontal gyrus) functional connectivity with trait rumination. More importantly, the mediation analysis showed that trait rumination could completely mediate the relationship between left insula-lmSFG functional connectivity and procrastination. These results suggest that the left insula-lmSFG functional connectivity involved in emotion regulation modulates the association between trait rumination and procrastination, which provides neural evidence for the relationship between trait rumination and procrastination.

Absorption behavior of polycarboxylate superplasticizer with different molecular structures on montmorillonite.

Polycarboxylate (PCE) is a high performance superplasticizer for modern concrete. With the high quality sand becoming precious, more and more low quality sands are used in concrete. However, low quality sands generally contain a relatively high content of montmorillonite (MMT), which could seriously reduce the efficiency of PCE. In order to develop PCE suitable for concrete with low quality sands, the absorption behavior on MMT of PCE with different side chains and acid/ether ratio was investigated. In order to explore the effect of MMT on PCE, two macromonomers were selected, isoprene glycol ether 400(TPEG400) and isoprene glycol ether 2400 (TPEG2400), to synthesize six long and short side chain comb-type PCEs with acid-ether ratios of 1.5:1, 2.5:1 and 3.5:1, respectively. The MMT tolerance mechanism of comb-type PCE in MMT-containing cement slurry was examined by FT-IR, DLS, TOC and other analysis. The PCE with long side chain is much easier to be inserted into the layered structure of MMT, resulting in intercalation absorption. The absorption amount of two kinds of side chain PCE on the MMT particles decreased as the acid ether ratio increases. PCE with long side chains showed shear-thickening properties in MMT-containing cement slurry, on the contrary, short side chains showed shear-thinning properties.

Electro-acupuncture Promotes Angiogenesis via Exosomal miR-210 in the Hypoxia-induced HUVECs Mediated HIF-1α/VEGF/Notch 1 Signal Pathway.

BACKGROUND: Acupuncture has been wildly applied for cerebral ischemia treatment in China for thousands of years, while the specific mechanism remains uncertain. Recently, many studies have shown that acupuncture promotes angiogenesis after ischemia occurs. Here, we examined the effect of electro-acupuncture (EA) exosomes on angiogenesis in hypoxia-induced human umbilical vein endothelial cells (HUVECs). OBJECTIVE: To investigate whether EA exosomal miR-210 promotes angiogenesis in the hypoxiainduced HUVECs via the HIF-1α/VEGF/Notch 1 signal pathway. METHODS: The middle cerebral artery occlusion (MCAO) model was established and treated with EA therapy. Then, exosomes were identified and isolated from rats' plasma in the MCAO+EA group by transmission electron microscopy (TEM), surface markers expressions, and PKH26 reagent. MiR- 210 mimic, miR-210 inhibitor, and HIF-1α were transfected. Flow cytometry, CCK-8 assay, and Transwell assay were conducted to assess the migration, apoptosis, and proliferation of each group of cells. Western blot and quantitative PCR were performed to detect the CD34, HIF-1α, VEGF, Notch 1, and miR-210 expression levels in each group. RESULTS: MiR-210 was significantly upregulated in exosomes of the MCAO plasma, and further enhanced by EA therapy. EA-EXOs and miR-210 mimic inhibited cell apoptosis, promoted cell proliferation and cell migration in hypoxia-induced HUVECs. However, the miR-210 inhibitor reversed the proliferation and migration number induced by EA-EXOs. Besides, EA-EXOs and miR- 210 mimic further enhanced those HIF-1α, VEGF, and Notch 1 levels compared to the hypoxia treatment only. Silencing HIF-1α or miR-210 reversed the high expressions of those three angiogenic factors induced by hypoxia and EA-EXO. qPCR showed similar trends with their relative mRNAs. To analyze these associations quantificationally, Spearman's rank correlation coefficient was calculated. As revealed by results, the expression of proteins and mRNA were highly correlative with each other. CONCLUSION: These results indicated that EA-EXO miR-210 promotes angiogenesis in hypoxia conditions via HIF-1α/VEGF/Notch 1 signal pathway.

[Electroacupuncture for acute ischemic stroke and its effect on plasma levels of IL-17 and IL-10].

OBJECTIVE: To compare the clinical efficacy on acute ischemic stroke (AIS) between electroacupuncture combined with conventional western medicine therapy and simple conventional western medicine therapy and its effect on plasma levels of interleukin (IL)-17 and IL-10. METHODS: A total of 60 patients with AIS were randomized into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 4 cases dropped off). The control group was treated with conventional western medicine therapy i.e neuroprotection and cerebral circulation improvement. On the basis of the treatment in the control group, in the observation group, acupuncture was applied at Baihui (GV 20), Yintang (GV 24+) and Quchi (LI 11), Zusanli (ST 36), Sanyinjiao (SP 6), etc. on the affected side, Baihui (GV 20)-Yintang (GV 24+), Quchi (LI 11)-Hegu (LI 4) and Zusanli (ST 36)-Sanyinjiao (SP 6) were connected with electroacupuncture, with disperse-dense wave, 2 Hz/15 Hz in frequency, once a day for consecutive 10 days. Before and after treatment, the scores of National Institution of Health stroke scale (NIHSS) and modified Barthel index (MBI) were observed, plasma levels of IL-17 and IL-10 were detected by ELISA method. RESULTS: After treatment, NIHSS scores were decreased while MBI scores were increased compared before treatment in both groups (P<0.01); compared with the control group, NIHSS score was decreased while MBI score was increased in the observation group (P<0.05). After treatment, IL-17 levels were decreased while IL-10 levels were increased compared before treatment in both groups (P<0.01); compared with the control group, IL-17 level was decreased while IL-10 level was increased in the observation group (P<0.05). CONCLUSION: Electroacupuncture combined with conventional western medinice therapy can improve the nerve function and activity of daily living in patients with AIS, its clinical efficacy is superior to simple conventional western medicine therapy, the mechanism may relate to the regulation on IL-17/IL-10 imbalance.

Dynamic Python-Based Method Provides Quantitative Analysis of Intercellular Junction Organization During S. pneumoniae Infection of the Respiratory Epithelium.

Many respiratory pathogens compromise epithelial barrier function during lung infection by disrupting intercellular junctions, such as adherens junctions and tight junctions, that maintain intercellular integrity. This includes Streptococcus pneumoniae, a leading cause of pneumonia, which can successfully breach the epithelial barrier and cause severe infections such as septicemia and meningitis. Fluorescence microscopy analysis on intercellular junction protein manipulation by respiratory pathogens has yielded major advances in our understanding of their pathogenesis. Unfortunately, a lack of automated image analysis tools that can tolerate variability in sample-sample staining has limited the accuracy in evaluating intercellular junction organization quantitatively. We have created an open source, automated Python computer script called "Intercellular Junction Organization Quantification" or IJOQ that can handle a high degree of sample-sample staining variability and robustly measure intercellular junction integrity. In silico validation of IJOQ was successful in analyzing computer generated images containing varying degrees of simulated intercellular junction disruption. Accurate IJOQ analysis was further confirmed using images generated from in vitro and in vivo bacterial infection models. When compared in parallel to a previously published, semi-automated script used to measure intercellular junction organization, IJOQ demonstrated superior analysis for all in vitro and in vivo experiments described herein. These data indicate that IJOQ is an unbiased, easy-to-use tool for fluorescence microscopy analysis and will serve as a valuable, automated resource to rapidly quantify intercellular junction disruption under diverse experimental conditions.

The Yin and Yang of Pneumolysin During Pneumococcal Infection.

Pneumolysin (PLY) is a pore-forming toxin produced by the human pathobiont Streptococcus pneumoniae, the major cause of pneumonia worldwide. PLY, a key pneumococcal virulence factor, can form transmembrane pores in host cells, disrupting plasma membrane integrity and deregulating cellular homeostasis. At lytic concentrations, PLY causes cell death. At sub-lytic concentrations, PLY triggers host cell survival pathways that cooperate to reseal the damaged plasma membrane and restore cell homeostasis. While PLY is generally considered a pivotal factor promoting S. pneumoniae colonization and survival, it is also a powerful trigger of the innate and adaptive host immune response against bacterial infection. The dichotomy of PLY as both a key bacterial virulence factor and a trigger for host immune modulation allows the toxin to display both "Yin" and "Yang" properties during infection, promoting disease by membrane perforation and activating inflammatory pathways, while also mitigating damage by triggering host cell repair and initiating anti-inflammatory responses. Due to its cytolytic activity and diverse immunomodulatory properties, PLY is integral to every stage of S. pneumoniae pathogenesis and may tip the balance towards either the pathogen or the host depending on the context of infection.