Development and validation of HBV surveillance models using big data and machine learning.

BACKGROUND: The construction of a robust healthcare information system is fundamental to enhancing countries' capabilities in the surveillance and control of hepatitis B virus (HBV). Making use of China's rapidly expanding primary healthcare system, this innovative approach using big data and machine learning (ML) could help towards the World Health Organization's (WHO) HBV infection elimination goals of reaching 90% diagnosis and treatment rates by 2030. We aimed to develop and validate HBV detection models using routine clinical data to improve the detection of HBV and support the development of effective interventions to mitigate the impact of this disease in China. METHODS: Relevant data records extracted from the Family Medicine Clinic of the University of Hong Kong-Shenzhen Hospital's Hospital Information System were structuralized using state-of-the-art Natural Language Processing techniques. Several ML models have been used to develop HBV risk assessment models. The performance of the ML model was then interpreted using the Shapley value (SHAP) and validated using cohort data randomly divided at a ratio of 2:1 using a five-fold cross-validation framework. RESULTS: The patterns of physical complaints of patients with and without HBV infection were identified by processing 158,988 clinic attendance records. After removing cases without any clinical parameters from the derivation sample (n = 105,992), 27,392 cases were analysed using six modelling methods. A simplified model for HBV using patients' physical complaints and parameters was developed with good discrimination (AUC = 0.78) and calibration (goodness of fit test p-value >0.05). CONCLUSIONS: Suspected case detection models of HBV, showing potential for clinical deployment, have been developed to improve HBV surveillance in primary care setting in China. (Word count: 264).

This study has developed a suspected case detection model for HBV, which can facilitate early identification and treatment of HBV in the primary care setting in China, contributing towards the achievement of WHO's elimination goals of HBV infections.We utilized the state-of-art natural language processing techniques to structure the data records, leading to the development of a robust healthcare information system which enhances the surveillance and control of HBV in China.

Mapping gender networks of music self-concept and music emotions: A network analysis study of music majors in China.

BACKGROUND: Students' music self-concept and music emotions are becoming prominent topics within the area of music education. AIMS, SAMPLES AND METHODS: The majority of previous research on self-concept and music emotions has examined the two constructs independently and focused on gender differences in externalizing behaviours in music learning, but has neglected the internal interactions between individual music self-concept and music emotions. Network analysis is a promising method for visually examining music self-concept and music emotions as part of a network of interactions to identify core features and interrelationships among nodes in the network. In this study, 515 students majoring in music from a Chinese university were recruited. RESULTS: The results showed that high music self-concept and boredom were the common features at the core of the network for both men and women college students. The boredom exhibited by women differed from that of men in that men's boredom was directed at the entire music course, while boredom in women manifested as daydreaming and boredom with learning materials. CONCLUSIONS: This study is the first to explore gender differences in the music self-concept and music emotions from a holistic perspective. The findings could help music teachers gain insight into the complex system of music self-concept and music emotions. Music teachers could capture the respective features of men and women to design individualized teaching strategies.

Enhancing Cytochrome C Recognition and Adsorption through Epitope-Imprinted Mesoporous Silica with a Tailored Pore Size.

We have reported the synthesis of epitope-imprinted mesoporous silica (EIMS) with an average pore size of 6.2 nm, which is similar to the geometrical size of the target protein, cytochrome C (Cyt c, 2.6 × 3.2 × 3.3 nm3), showing great recognition and large-scale adsorption performance. The characteristic fragment of Cyt c was used as a template and docked onto the surface of C16MIMCl micelles via multiple interactions. Nitrogen adsorption-desorption and transmission electron microscopy confirmed the successful preparation of EIMS. Due to the ordered pore structure, larger pore size, and high specific surface area, the prepared EIMS show superior specificity (IF = 3.8), excellent selectivity toward Cyt c, high adsorption capacity (249.6 mg g-1), and fast adsorption equilibrium (10 min). This study demonstrates the potential application of EIMS with a controllable pore size for high-effective and large-scale separation of Cyt c, providing a new approach for effective biomacromolecular recognition.

CAMBA framework: Unveiling the brain asymmetry alterations and longitudinal changes after stroke using resting-state EEG.

Hemispheric asymmetry or lateralization is a fundamental principle of brain organization. However, it is poorly understood to what extent the brain asymmetries across different levels of functional organizations are evident in health or altered in brain diseases. Here, we propose a framework that integrates three degrees of brain interactions (isolated nodes, node-node, and edge-edge) into a unified analysis pipeline to capture the sliding window-based asymmetry dynamics at both the node and hemisphere levels. We apply this framework to resting-state EEG in healthy and stroke populations and investigate the stroke-induced abnormal alterations in brain asymmetries and longitudinal asymmetry changes during poststroke rehabilitation. We observe that the mean asymmetry in patients was abnormally enhanced across different frequency bands and levels of brain interactions, with these abnormal patterns strongly associated with the side of the stroke lesion. Compared to healthy controls, patients displayed significant alterations in asymmetry fluctuations, disrupting and reconfiguring the balance of inter-hemispheric integration and segregation. Additionally, analyses reveal that specific abnormal asymmetry metrics in patients tend to move towards those observed in healthy controls after short-term brain-computer interface rehabilitation. Furthermore, preliminary evidence suggests that baseline clinical and asymmetry features can predict poststroke improvements in the Fugl-Meyer assessment of the lower extremity (mean absolute error of about 2). Overall, these findings advance our understanding of hemispheric asymmetry. Our framework offers new insights into the mechanisms underlying brain alterations and recovery after a brain lesion, may help identify prognostic biomarkers, and can be easily extended to different functional modalities.

Distribution and ecological risk assessment of heavy metals in sediments of Dajiuhu Lake Wetland in Shennongjia, China.

The rapid development of modern society has resulted in discharge of large, heavy metal quantities into wetlands that have been continuously accumulating, causing severe pollution. Dajiuhu, located in the Shennongjia Forest District of Hubei Province in China, is a wetland of significant value internationally, serving as a model wetland ecosystem with heightened scientific research value. In this study, 27 surface sediment samples from nine sub-lakes in Dajiuhu were collected in August 2020. The concentrations of Cd, Cr, Cu, Ni, Pb, and Zn in the sediments were determined. The heavy metal occurrence and speciation characteristics were analyzed by an improved BCR (European Community Bureau of Reference) extraction method. Four methods were used to evaluate heavy metals' pollution degree and ecological risk. The possible source of heavy metals was inferred using correlation analysis and principal component analysis. The heavy metal content in the lake sediments of Dajiuhu wetland was from the highest to the lowest concentration as follows: Zn [Formula: see text] Cr [Formula: see text] Ni [Formula: see text] Pb [Formula: see text] Cu [Formula: see text] Cd. The average Cd content exceeded the national nature reserve threshold values, while the other heavy metals measured were below their respective threshold values. However, due to the occurrence of Pb and Cd in different forms, they still pose certain pollution and ecological risk to the lake wetlands. On the other hand, Zn, Cr, Ni, and Cu do not pose an ecological risk in the lakes of the Dajiuhu wetland. The spatial distribution of heavy metal content in the nine sub-lakes did vary significantly. Regarding the heavy metal sources in the lake sediments, Ni, Cr, and Cu originate from natural factors, and Cd and Pb have mainly anthropogenic origins. In contrast, Zn has both natural and anthropogenic origins. This study provides further insights into the study of heavy metal pollution in lake wetlands. It provides a framework and a direction for managing heavy metal pollution in the Dajiuhu wetland.

Modified constraint-induced movement therapy enhances cortical plasticity in a rat model of traumatic brain injury: a resting-state functional MRI study.

Modified constraint-induced movement therapy (mCIMT) has shown beneficial effects on motor function improvement after brain injury, but the exact mechanism remains unclear. In this study, amplitude of low frequency fluctuation (ALFF) metrics measured by resting-state functional magnetic resonance imaging was obtained to investigate the efficacy and mechanism of mCIMT in a control cortical impact (CCI) rat model simulating traumatic brain injury. At 3 days after control cortical impact model establishment, we found that the mean ALFF (mALFF) signals were decreased in the left motor cortex, somatosensory cortex, insula cortex and the right motor cortex, and were increased in the right corpus callosum. After 3 weeks of an 8-hour daily mCIMT treatment, the mALFF values were significantly increased in the bilateral hemispheres compared with those at 3 days postoperatively. The mALFF signal values of left corpus callosum, left somatosensory cortex, right medial prefrontal cortex, right motor cortex, left postero dorsal hippocampus, left motor cortex, right corpus callosum, and right somatosensory cortex were increased in the mCIMT group compared with the control cortical impact group. Finally, we identified brain regions with significantly decreased mALFF values at 3 days postoperatively. Pearson correlation coefficients with the right forelimb sliding score indicated that the improvement in motor function of the affected upper limb was associated with an increase in mALFF values in these brain regions. Our findings suggest that functional cortical plasticity changes after brain injury, and that mCIMT is an effective method to improve affected upper limb motor function by promoting bilateral hemispheric cortical remodeling. mALFF values correlate with behavioral changes and can potentially be used as biomarkers to assess dynamic cortical plasticity after traumatic brain injury.

A Transferable Deep Learning Prognosis Model for Predicting Stroke Patients' Recovery in Different Rehabilitation Trainings.

Since the underlying mechanisms of neurorehabilitation are not fully understood, the prognosis of stroke recovery faces significant difficulties. Recovery outcomes can vary when undergoing different treatments; however, few models have been developed to predict patient outcomes toward multiple treatments. In this study, we aimed to investigate the potential of predicting a treatment's outcome using a deep learning prognosis model developed for another treatment. A total of 15 stroke survivors were recruited in this study, and their clinical and physiological data were measured before and after the treatment (clinical measurement, biomechanical measurement, and electroencephalography (EEG) measurement). Multiple biomarkers and clinical scale scores of patients who had completed manual stretching rehabilitation training were analyzed. Data were used to train deep learning prognosis models, yielding an 87.50% prognosis accuracy. Pre-trained prognosis models were then applied to patients who completed robotic-assisted stretching training, yielding a prognosis accuracy of 91.84%. Interpretation of the deep learning models revealed several key factors influencing patients' recoveries, including the plantar-flexor active range of movement (r = 0.930, P = 0.02), dorsiflexor strength (r = 0.932, P = 0.002), plantar-flexor strength (r = 0.930, P = 0.002), EEG power spectrum density and EEG functional connectivities in the occipital, central parietal, and parietal areas. Our results suggest (i) that deep learning can be a promising method for accurate prediction of the recovery potential of stroke patients in clinical scenarios and (ii) that it can be successfully applied to different rehabilitation trainings with explainable factors.

EEG Microstate-Specific Functional Connectivity and Stroke-Related Alterations in Brain Dynamics.

The brain, as a complex dynamically distributed information processing system, involves the coordination of large-scale brain networks such as neural synchronization and fast brain state transitions, even at rest. However, the neural mechanisms underlying brain states and the impact of dysfunction following brain injury on brain dynamics remain poorly understood. To this end, we proposed a microstate-based method to explore the functional connectivity pattern associated with each microstate class. We capitalized on microstate features from eyes-closed resting-state EEG data to investigate whether microstate dynamics differ between subacute stroke patients (N = 31) and healthy populations (N = 23) and further examined the correlations between microstate features and behaviors. An important finding in this study was that each microstate class was associated with a distinct functional connectivity pattern, and it was highly consistent across different groups (including an independent dataset). Although the connectivity patterns were diminished in stroke patients, the skeleton of the patterns was retained to some extent. Nevertheless, stroke patients showed significant differences in most parameters of microstates A, B, and C compared to healthy controls. Notably, microstate C exhibited an opposite pattern of differences to microstates A and B. On the other hand, there were no significant differences in all microstate parameters for patients with left-sided vs. right-sided stroke, as well as patients before vs. after lower limb training. Moreover, support vector machine (SVM) models were developed using only microstate features and achieved moderate discrimination between patients and controls. Furthermore, significant negative correlations were observed between the microstate-wise functional connectivity and lower limb motor scores. Overall, these results suggest that the changes in microstate dynamics for stroke patients appear to be state-selective, compensatory, and related to brain dysfunction after stroke and subsequent functional reconfiguration. These findings offer new insights into understanding the neural mechanisms of microstates, uncovering stroke-related alterations in brain dynamics, and exploring new treatments for stroke patients.

Free amino acids, carbon and nitrogen isotopic compositions responses to cadmium stress in two castor (Ricinus communis L.) species.

Cadmium (Cd) toxicity induce various disturbances in metabolic processes and impair plant establishment. The composition of carbon and nitrogen stable isotopes (δ13C and δ15N) and free amino acids (FAAs) can reflect the response of plants to environmental stress. In the present study, a solution culture experiment was carried out, and the secretion characteristics of FAAs as well as δ13C and δ15N were evaluated as indicative of the functional performance of two castor species (Zibo-3 and Zibo-9) under various Cd concentrations stress (0, 1, 2, and 5 mg L-1). The results indicated that: 1) The treatment of the plants with 5 mg L-1 of a Cd solution resulted in a significant decline of biomasses by 22.4% and 11.6% in Zibo-3 and Zibo-9, respectively, relative to controls; additionally, the accumulation levels for Cd in Zibo-9 were higher than those in Zibo-3, thus Zibo-9 showed higher tolerance and enrichment ability to Cd. 2) The exposure of castor to Cd treatments results in significant modifications in individual FAAs, suggesting a differential sensitivity of each biosynthetic pathway to this stress; however, a positive correlation was found between the accumulation of total FAAs and Cd treatment dosages; higher proportion of asparagine and glutamate in total amino acids for Zibo-9, and abundant secretion of arginine in Cd treated Zibo-9 may be associated with the higher Cd-tolerance and Cd-accumulation in Zibo-9. 3) Cd stress increased leaf δ13C and δ15N values regardless of the castor species; δ13C and δ15N could be used as monitoring tools for heavy metal stress in plants.

Postoperative cytokine levels and their predictive value in critical patients after major abdominal surgery: a retrospective cohort study.

BACKGROUND: It remains uncertain as to what impact cytokine expression level has on patient outcomes. The association of serum levels of interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), and procalcitonin with critically ill patient outcomes after major abdominal surgery still need to be explored. METHODS: From January 1, 2018 to June 30, 2019, a retrospective cohort study was conducted on patients admitted to the surgical intensive care unit (SICU). Levels of IL-1ß, IL-2, IL-6, IL-8, IL-10, TNF-α, and procalcitonin were assessed in 1,228 patients undergoing major abdominal surgery with blood samples drawn within 24 h after surgery. RESULTS: Of the 1,228 patients admitted to the SICU for the first time, 1,152 survived and 76 patients died, with a mortality rate of 6.2% (76/1,228). The results of univariate and multivariate analyses revealed that non-survivors had higher levels of IL-1ß (OR =2.438, P<0.001) and IL-2 (OR =1.561, P=0.006). Of 62 (5.0%) readmitted to the SICU, the data of 59 were collected, and showed 46 patients survived and 13 died, giving a mortality rate of 22.0% (13/59), which was 3.5 times higher than the mortality rate during the first SICU admission. Serum IL-6 level associated with SICU readmission (OR =1.37, P=0.029). Furthermore, non-survivors had a longer SICU stay and higher rates of mechanical ventilation and continuous renal replacement therapy (CRRT). CONCLUSIONS: High levels of IL-1ß and IL-2 were associated with mortality, and a high level of IL-6 was a risk factor for SICU readmission in critically ill patients who underwent major abdominal surgery. The mortality rate was higher during the second SICU stay.

Shengbai decoction enhances the anti-tumor efficacy of cyclophosphamide on hepatoma 22-bearing mice.

Combination therapies with chemotherapy and traditional Chinese medicines are attracted increasing attentions for cancer treatment in China. Shengbai decoction (SBD) is a traditional Chinese compound medicine, composed of 6 traditional Chinese herbs. The aim of this study was to investigate the synergistic anti-tumor activity of SBD with cyclophosphamide (CTX) and the possibly underlying mechanisms in treating the hepatoma 22 (H22) -bearing mice. The liver cancer models in C57BL/6 mice were established by injecting with mouse H22 cancer cells. Results showed that combination treatment with SBD and CTX processed a significantly synergistic anti-tumor effect in H22 tumor-bearing mice. Moreover, SBD could not only improve leukopenia caused by CTX, but prolong the survival time of the mice. Furthermore, SBD could upregulate the expressions of the pro-apoptotic genes, including p53, BAD, Cas3 and Bax, and suppress the expression of anti-apoptotic gene Bcl-2. These results suggested that the combination treatment with SBD and CTX had health improving function and less side effects compared with the administration of CTX alone, and SBD could be a promising adjunct agent for liver cancer chemotherapy.

Rosmarinic acid protects rats against post-stroke depression after transient focal cerebral ischemic injury through enhancing antioxidant response.

Rosmarinic acid (RA), a natural polyphenol, possesses potent antioxidant and anti-inflammatory activities. To evaluate the ability of RA to cure ischemic stroke and post-stroke depression (PSD), rats were treated with various doses of RA after cerebral ischemia. Neurological deficits and infarct volume of the brain were measured. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) were examined at different time points. In addition, a forced swimming test and sucrose preference test were performed to detect the anti-depressive effects of RA. Our results revealed RA administration significantly alleviated neurological deficits and reduced infarct volumes. RA attenuated the decrease of SOD, CAT activities and GSH levels in the ischemic penumbra of the brain. Most importantly, RA treatment alleviated the depression behaviors. Increased expression of Nrf2 was also induced by RA, while down regulation Nrf2 by Nrf2-short-hairpin RNA sequences reversed the increasing activity of SOD and CAT induced by RA, as well as the protection against PSD. The present study indicates that RA exerts a potent neuroprotective effect against stroke and PSD, which could be a promising therapeutic intervention for stroke.

Micelles self-assembled by 3-O-ß-D-glucopyranosyl latycodigenin enhance cell membrane permeability, promote antibiotic pulmonary targeting and improve anti-infective efficacy.

BACKGROUND: Nanoparticle-based pulmonary drug delivery systems are commonly developed and applied for drug-targeted delivery. They exhibit significant advantages compared to traditional pulmonary drug delivery systems. However, developing the formulation of each drug is a time-consuming and laborious task. RESULTS: In this study, a universal lung-targeting nanoparticle was designed and constructed. The self-assembled micelles were composed of a platycodon secondary saponin, 3-O-ß-D-glucopyranosyl platycodigenin 682 (GP-682), based on its specific amphiphilic structure. The GP-682 micelles exhibited a relatively stable zeta potential with a particle size between 60 and 90 nm, and the critical micelle concentration (CMC) value was approximately 42.3 µg/mL. Preincubation of GP-682 micelles markedly enhanced their cell membrane permeability and improved drug uptake in vitro. The results were visualized using fluorescent dye tracing, transmission electron microscopy (TEM) observations and the lactate dehydrogenase (LDH) release assay. The obtained benefits enhanced the distribution of levofloxacin (Lev) in mouse lung tissue and reduced antibiotics overdosing. The acute lung injury mouse model induced by the Pseudomonas aeruginosa PA 14 strain demonstrated that preinjection of GP-682 micelles before antibiotic administration resulted in a higher survival rate and anti-infective efficacy in vivo. It also caused reductions in pulmonary injury, bacterial invasion and cytokine expression compared with treatment with Lev alone. CONCLUSIONS: GP-682 micelles are another nanoparticle-based pulmonary drug delivery system and provide a new lung-targeting therapy option.

A Predicting Nomogram for Mortality in Patients With COVID-19.

Background: The global COVID-19 epidemic remains severe, with the cumulative global death toll reaching more than 207,170 as of May 2, 2020 (1). Purpose: Our research objective is to establish a reliable nomogram to predict mortality in COVID-19 patients. The nomogram can help us distinguish between patients who are at high risk of death and need close attention. Patients and Methods: For the single-center retrospective study, we collected 21 cases of patients who died in the critical illness area of the Optical Valley Branch of Tongji Hospital, Huazhong University of Science and Technology, from February 9 to March 10. Additionally, we selected 99 patients discharged during this period for analysis. The nomogram was constructed to predict the mortality for COVID-19 patients using the primary group of 120 patients and was validated using an independent cohort of 84 patients. We used multivariable logistic regression analysis to construct the prediction model. The nomogram was evaluated for calibration, differentiation, and clinical usefulness. Results: The predictors included in the nomogram were c-reactive protein, PaO2/FiO2, and cTnI. The areas under the curves of the nomogram were 0.988 (95% CI: 0.972-1.000) and 0.956 (95% CI, 0.874-1.000) in the primary and validation groups, respectively. Decision curve analysis suggests that the nomogram may have clinical usefulness. Conclusion: This study provides a nomogram containing c-reactive protein, PaO2/FiO2, and cTnI that can be conveniently used to predict individual mortality in COVID-19 patients. Next, we will collect as many cases as possible from multiple centers to build a more reliable nomogram to predict mortality for COVID-19 patients.

Antibiotic resistance gene profiling in response to antibiotic usage and environmental factors in the surface water and groundwater of Honghu Lake, China.

There is an increasing concern that aquaculture has been implicated in the formation of antibiotic resistance gene (ARG) reservoirs; however, little is known about the consequences of their presence in groundwater. In this study, 22 antibiotics, including four acetylated metabolites, and 27 ARGs were analyzed in fish pond water, surface water, and groundwater of the Honghu Lake in China. Correlations between conventional parameters, ionic composition, antibiotic concentration, and relative abundance of ARGs in water samples were analyzed. Among the three different sources of water, total antibiotic levels were the highest in fish pond water and the lowest in groundwater, with moderate levels in lake water. In surface water, sulfonamides and their metabolites accounted for the highest antibiotic content, whereas tetracyclines were the most frequently found in groundwater samples. Despite the near-undetectable levels of antibiotics in groundwater, the relative abundance of ARGs in groundwater samples was even higher than that in surface waters. The magnitude and extent of ARG migration are likely to be dependent on local antibiotic contamination levels as well as on the local environmental and hydrogeological conditions, with the class 1 integrons (intI1) being essential for the dissemination of such ARGs. The effects of environmental parameters such as antibiotics, dissolved oxygen, HCO3-, and pH on ARGs were highly significant, reflecting the potential impact of these factors on the abundance of ARGs. Our findings thus highlight the need for improved control of the spread of ARGs in and from aquaculture environments.

Brain Endothelial Cell-Derived Exosomes Induce Neuroplasticity in Rats with Ischemia/Reperfusion Injury.

Exosomes derived from the cerebral endothelial cells play essential roles in protecting neurons from hypoxia injury, but little is known regarding the biological effects and mechanisms of exosomes on brain plasticity. In this study, exosomes were isolated from rodent cerebral endothelial cells (bEnd.3 cells) by ultracentrifugation, either endothelial cell-derived exosomes (EC-Exo) or PBS was injected intraventricularly 2 h after the middle cerebral artery occlusion/reperfusion (MCAO/R) model surgery in the Exo group and control group, respectively. Sham group rats received the same surgical but not ischemic procedure. We evaluated the motor function of rats after MCAO/R, and the foot-fault rate of the Exo group was significantly lower than that of the control group within 23 days (p < 0.05); the Catwalk analysis also showed gait difference between two groups (p < 0.05). On day 28 after MCAO/R, we euthanized the rats, removed the motor cortex from the brain, and then sequenced the genes by using GO and KEGG to find transcriptome analysis of biological terms and functional annotations: The pathway enrichment revealed that the function of synaptic transmission, regulation of synaptic plasticity, and regulation of synaptic vesicle cycle was significantly enriched with the Exo group than control group. Furthermore, the upregulation of synapsin-I expression in the motor cortex (p < 0.05) as well as the increase of the length of the dendrites were found in the Exo group (p < 0.05) than the control group. We determined the content of exosome microRNA levels, and microRNA-126-3p was the highest (TPM) by transcriptome analysis. Moreover, the microRNA-126-3p protected PC12 cells from apoptosis and increased neurite outgrowth, illustrating the mechanism of how exosomes play a role in altering brain plasticity. This study demonstrated that EC-Exo promoted functional motor recovery in the MCAO/R model, exosomes were critical for the reconstruction of synaptic function in ischemic brain injury, and microRNA-126-3p from EC-Exo could serve as a treatment for nerve damage.

Vascular Endothelial Cell-derived Exosomes Protect Neural Stem Cells Against Ischemia/reperfusion Injury.

Vascular endothelial cells were activated during acute ischemic brain injury, which could induce neural progenitor cell proliferation and migration. However, the mechanism was still unknown. In the current study, we explored whether vascular endothelial cells promoted neural progenitor cell proliferation and whether migration occurs via exosome communication. The acute middle cerebral artery occlusion (MCAO) model was prepared, and exosomes were isolated from bEnd.3 cells by ultracentrifugation. In the exosome injection (Exos) group and PBS injection (control) group, exosomes or PBS were injected intraventricularly into rats' brains 2 h after MCAO surgery, respectively. Sham group rats received the same surgical but did not cause middle cerebral artery occlusion. The infarct volume was reduced on day 21 after ischemic brain injury by MRI, and neurobehavioral outcomes were improved on day 7, 14, and 21 by exosome injection compared with the control (p < 0.05). On the 21st day after MCAO, the animals were euthanized, and the number of BrdU/nestin-positive cells was measured by immunofluorescence. BrdU/nestin-positive cells in Exos group rats were significantly increased (p < 0.05) in the peri infarct area, the ipsilateral DG zone of the hippocampus, and the ventral sub-regions of SVZ when compared with the rats in the control group. Further, in vitro study demonstrated that neural progenitor cell proliferation and migration were activated after exosomes treatment, and cell apoptosis was attenuated compared to the control (p < 0.05). Our study suggested that exosomes should be essential for the reconstruction of neuronal vascular units and brain protection in an acute ischemic injured brain.

Combination of cyclophosphamide and shengbai decoction has synergistic effect against melanoma.

Shengbai decoction (SBD), a famous Chinese herbal prescription, has been used for treatment of leukopenia for decades in China. In this study, its synergistic antitumor effect in combination with cyclophosphamide (CTX) on melanoma-bearing mice was investigated. A total of forty C57BL/6 male mice successfully modeled (6-8 weeks old, 18-22 g) were randomly divided into 4 groups (n = 10): 1) the model group, 2) the CTX group, 3) the low dose of SBD (10.66 g/kg/d, raw medicine) and CTX group, and 4) the high dose of SBD (31.98 g/kg/d, raw medicine) and CTX group. Melanoma mice models were established by injection of 0.1 mL of melanoma cell suspension under the midline of the back of each C57BL/6 mouse. Treatment started five days after modeling. The results showed that SBD significantly alleviated histopathological damage, and reduced tumor growth and the concentrations of IL-6, IFN-γ and TNF-α in serum. Furthermore, the combined therapy increased the positive expression of NF-κB and promoted apoptosis compared with CTX alone. These results indicated that SBD could improve the antitumor effect of CTX on melanoma in vivo. And this combination treatment may be an ideal therapy against melanoma.

Green Hydrothermal Synthesis of N-doped Carbon Dots from Biomass Highland Barley for the Detection of Hg2.

Totally water-soluble N-doped Carbon dots (N-CDs) were synthesized by a green hydrothermal method from biomass using Highland barley as a carbon source and ethanediamine as nitrogen source. TEM and XRD showed the graphitic amorphous structure and narrow diameter distribution of these N-CDs. N-doping to the crystal lattice and carrying many hydrophilic groups on the surface of N-CDs were verified by XPS and FT-IR. The as-synthesized N-CDs emitted strong blue fluorescence at 480 nm and owned a relatively high quantum yield of 14.4%. The product also could sensitively and selectively detect Hg2+ ions in the range of 10-160 µM and the limit of detection was equal to 0.48 µM.

Highly Selective Fluorescence Sensing and Imaging of ATP Using a Boronic Acid Groups-Bearing Polythiophene Derivate.

A boronic acid groups-bearing polythiophene derivate (L) was designed and synthesized for highly sensitive fluorescence detection of ATP based on a multisite-binding coupled with analyte-induced aggregation strategy. L has a polythiophene backbone as fluorophores and two functional side groups, i.e., quaternary ammonium group and boronic acid group, as multibinding sites for ATP. When various structural analogues such as ADP, AMP, and various inorganic phosphates were added into the aqueous solution of L, only ATP caused a remarkable fluorescence quenching of about 60-fold accompanied by obvious color changes of solution from yellow to purple. The detection limit is estimated to be 2 nM based on 3σ/slope. With the advantage of good water solubility, low toxicity, and highly selective response to ATP, L was successfully utilized as a probe to real-time assay activity of adenylate kinase (ADK) and map fluorescent imaging of ATP in living cells.