Repetitive transcranial magnetic stimulation promotes motor function recovery in mice after spinal cord injury via regulation of the Cx43-autophagy loop.

Spinal cord injury (SCI) is a severe condition with an extremely high disability rate. It is mainly manifested as the loss of motor, sensory and autonomic nerve functions below the injury site. High-frequency transcranial magnetic stimulation, a recently developed neuromodulation method, can increase motor function in mice with spinal cord injury. This study aimed to explore the possible mechanism by which transcranial magnetic stimulation (TMS) restores motor function after SCI. A complete T8 transection model of the spinal cord was established in mice, and the mice were treated daily with 15 Hz high-frequency transcranial magnetic stimulation. The BMS was used to evaluate the motor function of the mice after SCI. Western blotting and immunofluorescence were used to detect the expression of Connexin43 (CX43) and autophagy-related proteins in vivo and in vitro, and correlation analysis was performed to study the relationships among autophagy, CX43 and motor function recovery after SCI in mice. Western blotting was used to observe the effect of magnetic stimulation on the expression of mTOR pathway members. In the control group, the expression of CX43 was significantly decreased, and the expression of microtubule-associated protein 1 A/1b light chain 3 (LC3II) and P62 was significantly increased after 4 weeks of spinal cord transection. After high-frequency magnetic stimulation, the level of CX43 decreased, and the levels of LC3II and P62 increased in primary astrocytes. The BMS of the magnetic stimulation group was greater than that of the control group. High-frequency magnetic stimulation can inhibit the expression of CX43, which negatively regulates autophagic flux. HF-rTMS increased the expression levels of mTOR, p-mTOR and p-S6. Our experiments showed that rTMS can restore hindlimb motor function in mice after spinal cord injury via regulation of the Cx43-autophagy loop and activation of the mTOR signalling pathway.

Degradation and mechanism of PAHs by Fe-based activated persulfate: Effect of temperature and noble metal.

The accumulation of contaminants like PAHs in soil due to industrialization, urbanization, and intensified agriculture poses environmental challenges, owing to their persistence, hydrophobic nature, and toxicity. Thus, the degradation of PAHs has attracted worldwide attention in soil remediation. This study explored the effect of noble metal and temperature on the degradation of various polycyclic aromatic hydrocarbons (PAHs) in soil, as well as the types of reactive radicals generated and mechanism. The Fe-Pd/AC and Fe-Pt/AC activated persulfate exhibited high removal efficiency of 19 kinds of PAHs, about 79.95 % and 83.36 %, respectively. Fe-Pt/AC-activated persulfate exhibits superior degradation efficiency than that on Fe-Pd/AC-activated persulfate, due to the higher specific surface area and dispersity of Pt particles, thereby resulting in increased reactive radicals (·OH, SO4-· and ·OOH). Additionally, thermal activation enhances the degradation of PAHs, with initial efficiencies of 64.20 % and 55.49 % on Fe-Pd/AC- and Fe-Pt/AC-activated persulfate systems respectively, increasing to 76.05 % and 73.14 % with elevated temperatures from 21.5 to 50 °C. Metal and thermal activation facilitate S2O82- activation, generating reactive radicals, crucial for the degradation of PAHs via ring opening and oxygen hydrogenation reactions, yielding low-ring oxygen-containing derivatives such as organic acids, keto compounds, ethers, and esters. Furthermore, understanding the impact of parameters such as activation temperature and the types of noble metals on the degradation of PAHs within the activated persulfate system provides a theoretical foundation for the remediation of PAH-contaminated soil.

Disruptions of Gut Microbiota are Associated with Cognitive Deficit of Preclinical Alzheimer's Disease: A Cross-Sectional Study.

BACKGROUND: Alzheimer's Disease (AD) is the most prevalent type of dementia. The early change of gut microbiota is a potential biomarker for preclinical AD patients. OBJECTIVE: The study aimed to explore changes in gut microbiota characteristics in preclinical AD patients, including those with Subjective Cognitive Decline (SCD) and Mild Cognitive Impairment (MCI), and detect the correlation between gut microbiota characteristics and cognitive performances. METHODS: This study included 117 participants [33 MCI, 54 SCD, and 30 Healthy Controls (HC)]. We collected fresh fecal samples and blood samples from all participants and evaluated their cognitive performance. We analyzed the diversity and structure of gut microbiota in all participants through qPCR, screened characteristic microbial species through machine learning models, and explored the correlations between these species and cognitive performances and serum indicators. RESULTS: Compared to the healthy controls, the structure of gut microbiota in MCI and SCD patients was significantly different. The three characteristic microorganisms, including Bacteroides ovatus, Bifidobacterium adolescentis, and Roseburia inulinivorans, were screened based on the best classification model (HC and MCI) having intergroup differences. Bifidobacterium adolescentis is associated with better performance in multiple cognitive scores and several serum indicators. Roseburia inulinivorans showed negative correlations with the scores of the Functional Activities Questionnaire (FAQ). CONCLUSION: The gut microbiota in patients with preclinical AD has significantly changed in terms of composition and richness. Correlations have been discovered between changes in characteristic species and cognitive performances. Gut microbiota alterations have shown promise in affecting AD pathology and cognitive deficit.

Persulfate-Based Advanced Oxidation Process for Chlorpyrifos Degradation: Mechanism, Kinetics, and Toxicity Assessment.

Persulfate-based advanced oxidation process has been proven to be a promising method for the toxic pesticide chlorpyrifos (CPY) degradation in wastewater treatment. However, due to the limitation for the short-lived intermediates detection, a comprehensive understanding for the degradation pathway remains unclear. To address this issue, density functional theory was used to analyze the degradation mechanism of CPY at the M06-2X/6-311++G(3df,3pd)//M06-2X/6-31+G(d,p) level, and computational toxicology methods were employed to explore the toxicity of CPY and its degradation products. Results show that hydroxyl radicals (·OH) and sulfate radicals (SO4•-) initiate the degradation reactions by adding to the P=S bond and abstracting the H atom on the ethyl group, rather than undergoing α-elimination of the pyridine ring in the persulfate oxidation process. Moreover, the addition products were attracted and degraded by breaking the P-O bond, while the abstraction products were degraded through dealkylation reactions. The transformation products, including 3,5,6-trichloro-2-pyridynol, O,O-diethyl phosphorothioate, chlorpyrifos oxon, and acetaldehyde, obtained through theoretical calculations have been detected in previous experimental studies. The reaction rate constants of CPY with ·OH and SO4•- were 6.32 × 108 and 9.14 × 108 M-1·s-1 at room temperature, respectively, which was consistent with the experimental values of 4.42 × 109 and 4.5 × 109 M-1 s-1. Toxicity evaluation results indicated that the acute and chronic toxicity to aquatic organisms gradually decreased during the degradation process. However, some products still possess toxic or highly toxic levels, which may pose risks to human health. These research findings contribute to understanding the transformation behavior and risk assessment of CPY in practical wastewater treatment.

Topological properties of individual gray matter morphological networks in identifying the preclinical stages of Alzheimer's disease: a preliminary study.

Background: Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are preclinical stages of Alzheimer's disease (AD). Individual biomarkers are essential for evaluating altered neurological outcomes at both SCD and MCI stages for early diagnosis and intervention of AD. In this study, we aimed to investigate the relationships between topological properties of the individual brain morphological network and clinical cognitive performances among healthy controls (HCs) and patients with SCD or MCI. Methods: The topological measurements of individual morphological networks were analyzed using graph theory, and inter-group differences of standard graph topology were correlated and regressed to scores of clinical cognitive functions. Results: Compared with HCs, the topology of the individual morphological networks in SCD and MCI patients was significantly altered. At the global level, altered topology was characterized by lower global efficiency, shorter characteristics path length, and normalized characteristics path length [all P<0.05, false discovery rate (FDR) corrected]. In addition, at the regional level, SCD and MCI patients exhibited abnormal degree centrality in the caudate nucleus and nodal efficiency in the caudate nucleus, right insula, lenticular nucleus, and putamen (all P<0.05, FDR corrected). Conclusions: The topological features of individual gray matter morphological networks may serve as biomarkers to improve disease prognosis and intervention in the early stages of AD, namely SCD and MCI. Moreover, these findings may further elucidate the relationships between brain morphological alterations and cognitive dysfunctions in SCD and MCI.

Stability and biomineralization of cadmium sulfide nanoparticles biosynthesized by the bacterium Rhodopseudomonas palustris under light.

Cadmium (Cd) pollution is regarded as a potent problem due to its hazard risks to the environment, making it crucial to be removed. Compared to the physicochemical techniques (e.g., adsorption, ion exchange, etc.), bioremediation is a promising alternative technology for Cd removal, due to its cost-effectiveness, and eco-friendliness. Among them, microbial-induced cadmium sulfide mineralization (Bio-CdS NPs) is a process of great significance for environmental protection. In this study, microbial cysteine desulfhydrase coupled with cysteine acted as a strategy for Bio-CdS NPs by Rhodopseudomonas palustris. The synthesis, activity, and stability of Bio-CdS NPs-R. palustris hybrid was explored under different light conditions. Results show that low light (LL) intensity could promote cysteine desulfhydrase activities to accelerate hybrid synthesis, and facilitated bacterial growth by the photo-induced electrons of Bio-CdS NPs. Additionally, the enhanced cysteine desulfhydrase activity effectively alleviated high Cd-stress. However, the hybrid rapidly dissolved under changed environmental factors, including light intensity and oxygen. The factors affecting the dissolution were ranked as follows: darkness/microaerobic ≈ darkness/aerobic < LL/microaerobic < high light (HL)/microaerobic < LL/aerobic < HL/aerobic. The research provides a deeper understanding of Bio-CdS NPs-bacteria hybird synthesis and its stability in Cd-polluted water, allowing advanced bioremediation treatment of heavy metal pollution in water.

HDGF promotes gefitinib resistance by activating the PI3K/AKT and MEK/ERK signaling pathways in non-small cell lung cancer.

Hepatoma-derived growth factor (HDGF) expression is associated with poor prognosis in non-small cell lung cancer (NSCLC); however, whether HDGF affects gefitinib resistance in NSCLC remains unknown. This study aimed to explore the role of HDGF in gefitinib resistance in NSCLC and to discover the underlying mechanisms. Stable HDGF knockout or overexpression cell lines were generated to perform experiments in vitro and in vivo. HDGF concentrations were determined using an ELISA kit. HDGF overexpression exacerbated the malignant phenotype of NSCLC cells, while HDGF knockdown exerted the opposite effects. Furthermore, PC-9 cells, which were initially gefitinib-sensitive, became resistant to gefitinib treatment after HDGF overexpression, whereas HDGF knockdown enhanced gefitinib sensitivity in H1975 cells, which were initially gefitinib-resistant. Higher levels of HDGF in plasma or tumor tissue also indicated gefitinib resistance. The effects of HDGF on promoting the gefitinib resistance were largely attenuated by MK2206 (Akt inhibitor) or U0126 (ERK inhibitor). Mechanistically, gefitinib treatment provoked HDGF expression and activated the Akt and ERK pathways, which were independent of EGFR phosphorylation. In summary, HDGF contributes to gefitinib resistance by activating the Akt and ERK signaling pathways. The higher HDGF levels may predict poor efficacy for TKI treatment, thus it has the potential to serve as a new target for overcoming tyrosine kinase inhibitor resistance in combating NSCLC.

Degradation of PAHs in soil by activated persulfate system with activated carbon supported iron-based bimetal.

We developed a material of activated carbon (AC)-supported highly active iron-based bimetal (iron-copper bimetal/AC, Fe-Cu/AC) with high efficiency for polycyclic aromatic hydrocarbons (PAHs) degradation in soil by activating persulfate, benefiting from the synergistic effect that the characteristics of AC with porous carbon backbone, multiple active functional groups, high loading capacity and the characteristics of FeCu bimetal with high activity. The addition of Cu to the Fe-based/AC activator not only improved the dispersibility of Fe particles but also maintained the stability of the metal in the Fe-Cu/AC. The thermal activation (50 °C) promoted the degradation of PAHs by the Fe-Cu/AC-activated S2O82- system. Of the various systems tested, the Fe-Cu/AC-activated S2O82- system had the best degradation efficiency for 19 PAHs, with the overall efficiency following the order of Fe-Cu/AC + S2O82- > Fe-Cu + S2O82- > Fe-Cu/AC > S2O82-. The degradation mechanism of the Fe-Cu/AC-activated S2O82- system on soil PAHs showed that OH, OOH, and SO4- were the main active groups involved in the degradation of target PAHs. The target pollutants and their degradation products in the Fe-Cu/AC-activated S2O82- system indicated specific exposure pathways, providing a theoretical basis for the remediation of PAH-contaminated soil.

Limited Role of Rhamnolipids on Cadmium Resistance for an Endogenous-Secretion Bacterium.

Rhamnolipids, a type of biosurfactant, represent a potential strategy for both enhancing organismic resistance and in situ remediation of heavy metals contaminations. In-depth study of the mechanism of rhamnolipids synthesis in response to heavy metals stress, is indispensable for a wide use of biosurfactant-secreting microbes in bioremediation. In this study, we employed the wild-type and the rhlAB deficient strain (ΔrhlAB) of Pseudomonas aeruginosa, a prototypal rhamnolipids-producing soil microorganism, to investigate its responses to cadmium resistance based on its physicochemical, and physiological properties. Compared with the wild-type strain, the ΔrhlAB were more sensitive to Cd-stress at low Cd concentration (<50 mg/L), whereas there was little difference in sensitivity at higher Cd concentrations, as shown by spot titers and cell viability assays. Secreted rhamnolipids reduced intracellular Cd2+ accumulation to alleviate Cd2+ stress, whereas endogenous rhamnolipids played a limited role in alleviating Cd2+ stress. Synthesized rhamnolipids exhibited a higher critical micelle concentration (CMC) (674.1 mg/L) and lower emulsification index (4.7%) under high Cd-stress, while these parameters showed no obvious changes. High Cd-stress resulted in high hydrophilic wild-type bacterial surface and lower bioremediation ability. This study could advance a deeper understanding of the mechanism of cadmium resistance and provide a theoretical foundation for the application of biosurfactant and biosurfactant-secreted bacterium in contaminant bioremediation.

Predictive value of proteomic markers for advanced rectal cancer with neoadjuvant chemoradiotherapy.

BACKGROUND: Preoperative neoadjuvant chemoradiation (nCRT) has been the standard treatment for locally advanced rectal cancer. Serum biomarkers to stratify patients with respect to prognosis and response to nCRT are needed due to the diverse response to the therapy. METHODS: Thirteen paired pre- and post-nCRT sera from rectal cancer patients were analyzed by isobaric tags for relative and absolute quantitation (iTRAQ) method. Twenty-five proteins were selected for validation by parallel reaction monitoring (PRM) in ninety-one patients. RESULTS: Totally, 310 proteins were identified and quantified in sera samples. Reactome pathway analysis showed that the immune activation-related pathways were enriched in response to nCRT. Twenty-five proteins were selected for further validation. PRM result showed that the level of PZP was higher in pathological complete response (pCR) patients than non-pCR patients. The Random Forest algorithm identified a prediction model composed of 10 protein markers, which allowed discrimination between pCR patients and non-pCR patients (area under the curve (AUC) = 0.886 on testing set). Higher HEP2 and GELS or lower S10A8 in baseline sera were associated with better prognosis. Higher APOA1 in post nCRT sera was associated with better disease-free survival (DFS). CONCLUSIONS: We identified and confirmed a 10-protein panel for nCRT response prediction and four potential biomarkers HEP2, GELS, S10A8 and APOA1 for prognosis of rectal cancer based on iTRAQ-based comparative proteomics screening and PRM-based targeted proteomic validation.

A novel dual-task paradigm with story recall shows significant differences in the gait kinematics in older adults with cognitive impairment: A cross-sectional study.

Objective: Cognitive and motor dysfunctions in older people become more evident while dual-tasking. Several dual-task paradigms have been used to identify older individuals at the risk of developing Alzheimer's disease and dementia. This study evaluated gait kinematic parameters for dual-task (DT) conditions in older adults with mild cognitive impairment (MCI), subjective cognitive decline (SCD), and normal cognition (NC). Method: This is a cross-sectional, clinical-based study carried out at the Zhongshan Rehabilitation Branch of First Affiliated Hospital of Nanjing Medical University, China. Participants: We recruited 83 community-dwelling participants and sorted them into MCI (n = 24), SCD (n = 33), and NC (n = 26) groups based on neuropsychological tests. Their mean age was 72.0 (5.55) years, and male-female ratio was 42/41 (p = 0.112). Each participant performed one single-task walk and four DT walks: DT calculation with subtracting serial sevens; DT naming animals; DT story recall; and DT words recall. Outcome and measures: Kinematic gait parameters of speed, knee peak extension angle, and dual-task cost (DTC) were obtained using the Vicon Nexus motion capture system and calculated by Visual 3D software. A mixed-effect linear regression model was used to analyze the data. Results: The difference in gait speed under DT story recall and DT calculation was -0.099 m/s and - 0.119 m/s (p = 0.04, p = 0.013) between MCI and SCD, respectively. Knee peak extension angle under DT story recall, words recall, and single task was bigger in the MCI group compared to the NC group, respectively (p = 0.001, p = 0.001, p = 0.004). DTC was higher in the DT story recall test than all other DT conditions (p < 0.001). Conclusion: Kinematic gait parameters of knee peak extension angle for the DT story recall were found to be sensitive enough to discriminate MCI individuals from NC group. DTC under DT story recall was higher than the other DT conditions.

Development of alveolar-capillary-exchange (ACE) chip and its application for assessment of PM2.5-induced toxicity.

Although standard two-dimensional (2D) cell culture is an effective tool for cell studies, monolayer cultivation can yield imperfect or misleading information about numerous biological functions. In this study, we developed an alveolar-capillary exchange (ACE) chip aiming to simulate the cellular microenvironment at the alveolar-capillary interface. The ACE chip was designed with two chambers for culturing alveolar epithelial cells and vascular endothelial cells separately, which are separated by a microporous polycarbonate film that allows for the exchange of soluble biomolecules. Using this model, we further tested the toxic effects of fine particulate matter (PM2.5), a form of airborne pollutant known to induce adverse effects on human respiratory system. These effects are largely associated with the ability of PM2.5 to penetrate the alveoli, where it negatively affects the pulmonary function. Our results indicate that alveolar epithelial cells cultured in the ACE chip in solo and coculture with vascular endothelial cells underwent oxidative injury-induced apoptosis mediated via the PEAK-eIF2α signaling pathway of endoplasmic reticulum stress. The use of ACE chip in an alveolar epithelial cell-vascular endothelial cell coculture model revealed cellular vulnerability to PM2.5. Therefore, this chip provides a feasible surrogate approach in vitro for investigating and simulating the cellular microenvironment responses associated with ACE in vivo.

Genotoxicity of chloroacetamide herbicides and their metabolites in vitro and in vivo.

The toxicity of chloroacetamide herbicide in embryo development remains unclear. Acetochlor (AC) is a chloroacetamide that metabolizes into 2­ethyl­6­methyl-2-chloroacetanilide (CMEPA) and 6­ethyl­o­toluidine (MEA). The present study determined the potential effect of AC and its metabolites on embryo development. Both HepG2 cells and zebrafish embryos were exposed to AC, CMEPA and MEA in the presence or absence of co­treatment with anti­reactive oxygen species (ROS) reagent N­acetylcysteine. The generation of ROS, levels of superoxide dismutase (SOD) and glutathione (GSH) in HepG2 cells and lactate dehydrogenase (LDH) leakage from HepG2 cells were investigated. The effects of AC, CMEPA and MEA on DNA breakage, MAPK/ERK pathway activity, viability and apoptosis of HepG2 cells were examined by comet assay, western blotting, MTT assay and flow cytometry, respectively. Levels of LDH, SOD and GSH in zebrafish embryos exposed to AC, CMEPA and MEA were measured. The hatching and survival rates of zebrafish embryos exposed to AC, CMEPA and MEA, were determined, and apoptosis of hatched fish was investigated using acridine orange staining. The present data showed AC, CMEPA and MEA induced generation of ROS and decreased levels of SOD and GSH in HepG2 cells, which in turn promoted DNA breakage and LDH leakage from cells, ultimately inhibiting cell viability and inducing apoptosis, as well as phosphorylation of JNK and P38. However, co­treatment with N­acetylcysteine alleviated the pro­apoptosis effect of AC and its metabolites. Moreover, exposure to AC, CMEPA and MEA lead to toxicity of zebrafish embryos with decreased SOD and GSH and increased LDH levels and cell apoptosis, ultimately decreasing the hatching and survival rates of zebrafish, all of which was attenuated by treatment with N­acetylcysteine. Therefore, AC and its metabolites (CMEPA and MEA) showed cytotoxicity and embryo development toxicity.

Enhanced hepatic cytotoxicity of chemically transformed polystyrene microplastics by simulated gastric fluid.

Microplastics pollution has emerged as one of the top-ranked global environmental issues, receiving worldwide attention in recent years. However, knowledge about the detrimental effects of microplastics on human health is still limited. In real-world settings, the physicochemical characteristics of microplastics were modified by environmental and biological transformation, largely changing their ultimate toxicity. Nonetheless, the toxicity change related to transformation of microplastics has not been considered in most published studies thus far. In the current study, we investigated the cytotoxicity of transformed polystyrene microplastics in hepatocytes. Our results revealed that 500 nm polystyrene microplastics, which were chemically transformed by simulated gastricfluid, exacerbated their adverse effects on SMMC-7721 cells at 20 µg/mL for 24 h treatment, including morphological alteration, membrane damage and increased cell apoptosis via oxidative stress. This exacerbated cytotoxicity could be at least partially explained by the degradation, changed surface charge and altered surface chemistry of these polystyrene microplastics after transformation. In conclusion, our study demonstrates that the hepatic cytotoxicity of polystyrene microplastics is enhanced after transformation.

Characterization and degradation mechanism of bimetallic iron-based/AC activated persulfate for PAHs-contaminated soil remediation.

In this research, a novel iron based bimetallic nanoparticles (Fe-Ni) supported on activated carbon (AC) were synthesized and employed as an activator of persulfate in polycyclic aromatic hydrocarbons (PAHs) polluted sites remediation. AC-supported Fe-Ni activator was prepared according to two-step reduction method: the liquid phase reduction and H2- reduction under high temperature (600 °C), which was defined as Fe-Ni/AC. Characterizations using micropore physisorption analyzer, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and high-resolution transmission electron microscopy (HR-TEM) showed that the synthetic material had large specific surface area, nano-size and carbon-encapsulated metal particles, moreover, the lattice fringes of metals were clearly defined. The PAH compound types and their concentrations were determined by gas chromatography mass spectrometry (GC-MS) with SIM mode, the method detection limit (MDL) was estimated to about 0.21 µg/kg for PAHs, and the average recovery of PAHs was 96.3%. Mechanisms of PAH oxidation degradation with the reaction system of Fe-Ni/AC activated persulfate were discussed, the results showed that short-life free radicals, such as SO4-·, OH·, and OOH· were generated simultaneously, which acted as strong oxidizing radicals, resulting in the oxidation and almost complete opening of the PAH rings.

Characteristics of PVP-stabilised NZVI and application to dechlorination of soil-sorbed TCE with ionic surfactant.

The characteristics of polyvinylpyrrolidone (PVP)-stabilised nano-zero-valent iron (PVP-NZVI) and its application, combined with surfactant, to trichloroethylene (TCE)-contaminated soil were investigated. Two surfactants (cetyltrimethylammonium bromide [CTAB] and sodium dodecyl sulphate [SDS]) were tested for their ability to enhance the remedial activity of PVP-NZVI in 3 h batch experiments. The prepared PVP-NZVI formed nanoparticles ∼70 nm in diameter. The isoelectric point of PVP-NZVI was about 8.51, similar to the initial pH. X-ray diffraction and X-ray photoelectron spectroscopy analyses revealed that ZVI was the main active component of PVP-NZVI, and carbonised products of the target were observed. The TCE dechlorination efficiency by PVP-NZVI was about 84.73%; the efficiency by PVP-NZVI was about 20% higher when combined with SDS than with CTAB. Therefore, application of PVP-NZVI with SDS represents a potential remediation approach for TCE-contaminated soil.

Two Coxsackievirus B3 outbreaks associated with hand, foot, and mouth disease in China and the evolutionary history worldwide.

BACKGROUND: Coxsackievirus B3 (CV-B3) is usually associated with aseptic meningitis and myocarditis; however, the association between CV-B3 and hand, foot, and mouth disease (HFMD) has not been clearly demonstrated, and the phylogenetic dynamics and transmission history of CV-B3 have not been well summarized. METHOD: Two HFMD outbreaks caused by CV-B3 were described in Hebei Province in 2012 and in Shandong Province in 2016 in China. To analyze the epidemiological features of two CV-B3 outbreaks, a retrospective analysis was conducted. All clinical specimens from CV-B3 outbreaks were collected and disposed according to the standard procedures supported by the WHO Global Poliovirus Specialized Laboratory. EV genotyping and phylogenetic analysis were performed to illustrate the genetic characteristics of CV-B3 in China and worldwide. RESULTS: Two transmissible lineages (lineage 2 and 3) were observed in Northern China, which acted as an important "reservoir" for the transmission of CV-B3. Sporadic exporting and importing of cases were observed in almost all regions. In addition, the global sequences of CV-B3 showed a tendency of geographic-specific clustering, indicating that geographic-driven adaptation plays a major role in the diversification and evolution of CV-B3. CONCLUSIONS: Overall, our study indicated that CV-B3 is a causative agent of HFMD outbreak and revealed the phylogenetic dynamics of CV-B3 worldwide, as well as provided an insight on CV-B3 outbreaks for effective intervention and countermeasures.

Interactions between human hemoglobin subunits and peroxiredoxin 2.

Red blood cells (RBCs) are exposed to exogenous reactive oxygen species in the circulatory system. To this end, the interactions between the different hemoglobin (Hb) subunits and peroxiredoxin 2, which is a ubiquitous member of the antioxidant enzymes that also controls the cytokine-induced peroxide levels, were assessed. We predicted by the increment of diversity with quadratic discriminant analysis (IDQD) that peroxiredoxin2 (Prx2) could interact with the hemoglobin alpha, beta and gamma subunits but not with the delta subunit. Coimmunoprecipitation (co-IP), electrospray ionization quadrupole time of flight (ESI-Q-TOF) mass spectrometry, Western blotting and X-ray absorption fine structure (XAFS) spectroscopy were performed to verify these predictions. The results showed that Prx2 was a member of the beta-globin immunoprecipitating complex that existed in hemoglobin A, hemolysate-hemoglobin A, hemoglobin A-hemoglobin A2, hemolysate-hemoglobin A-hemoglobin A2 and hemoglobin A2 but not in hemolysate-hemoglobin A2. Adding Prx2 to hemoglobin A altered the second shell of iron embedded in hemoglobin A. Therefore, Prx2 interacts with hemoglobin A (Alpha2Beta2) and hemoglobin F (Alpha2Gamma2) but not with hemoglobin A2 (Alpha2Delta2).

Chemoresistance mechanisms of breast cancer and their countermeasures.

Chemoresistance is one of the major challenges for the breast cancer treatment. Owing to its heterogeneous nature, the chemoresistance mechanisms of breast cancer are complicated, and not been fully elucidated. The existing treatments fall short of offering adequate solution to drug resistance, so more effective approaches are desperately needed to improve existing therapeutic regimens. To overcome this hurdle, a number of strategies are being investigated, such as novel agents or drug carriers and combination treatment. In addition, some new therapeutics including gene therapy and immunotherapy may be promising for dealing with the resistance. In this article, we review the mechanisms of chemoresistance in breast cancer. Furthermore, the potential therapeutic methods to overcome the resistance were discussed.

Naturally Occurring Mutations within HBV Surface Promoter II Sequences Affect Transcription Activity, HBsAg and HBV DNA Levels in HBeAg-Positive Chronic Hepatitis B Patients.

Mutations in hepatitis B virus (HBV) surface promoter II (SPII) have not been well studied in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. We aimed to investigate SPII mutations in such patients and their biological and clinical impacts. Direct sequencing was used to detect SPII mutations in 106 HBeAg-positive treatment-naïve CHB patients with genotype C (82.1% (87/106) was C2) HBV infection. Results showed that mutation frequency in transcription factor (TF) unbinding region was significantly higher than that in TF binding region of SPII (C1: 3.4% vs. 1.3%; C2: 2.6% vs. 1.3%; p < 0.0001). Luciferase assay revealed distinct promoter activities among SPII mutants; especially SPII of G120A mutant had a 15-fold higher activity than that of wild-type (p < 0.001). In vitro experiments in HepG2 cells showed that G82A, A115C and G120A mutants increased the hepatitis B surface antigen (HBsAg) levels, while C18T had an opposite effect. G82A, A115C and G120A mutants boosted the intracellular HBV total RNA level. G120A mutation resulted in an increased HBV DNA level in vitro, consistent with the serological results in patients. Thus, novel SPII mutations would affect promoter activity, HBsAg, HBV DNA and HBV total RNA levels, suggesting their potential biological and clinical significances.