Hippocampal excitation-inhibition balance underlies the 5-HT2C receptor in modulating depressive behaviours.

The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) in depression is a topic of debate, and the underlying mechanisms remain largely unclear. We now elucidate hippocampal excitation-inhibition (E/I) balance underlies the regulatory effects of 5-HT2CR in depression. Molecular biological analyses showed that chronic mild stress (CMS) reduced the expression of 5-HT2CR in hippocampus. We revealed that inhibition of 5-HT2CR induced depressive-like behaviors, reduced GABA release and shifted the E/I balance towards excitation in CA3 pyramidal neurons by using behavioral analyses, microdialysis coupled with mass spectrum, and electrophysiological recording. Moreover, 5-HT2CR modulated neuronal nitric oxide synthase (nNOS)-carboxy-terminal PDZ ligand of nNOS (CAPON) interaction through influencing intracellular Ca2+ release, as determined by fiber photometry and coimmunoprecipitation. Notably, disruption of nNOS-CAPON by specific small molecule compound ZLc-002 or AAV-CMV-CAPON-125C-GFP, abolished 5-HT2CR inhibition-induced depressive-like behaviors, as well as the impairment in soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly-mediated GABA vesicle release and a consequent E/I imbalance. Importantly, optogenetic inhibition of CA3 GABAergic neurons prevented the effects of AAV-CMV-CAPON-125C-GFP on depressive behaviors in the presence of 5-HT2CR antagonist. Conclusively, our findings disclose the regulatory role of 5-HT2CR in depressive-like behaviors and highlight the hippocampal nNOS-CAPON coupling-triggered E/I imbalance as a pivotal cellular event underpinning the behavioral consequences of 5-HT2CR inhibition.

NiCo2O4 Nanowires Immobilized on Nitrogen-Doped Ti3C2Tx for High-Performance Wearable Magnesium-Air Batteries.

Flexible magnesium (Mg)-air batteries provide an ideal platform for developing efficient energy-storage devices toward wearable electronics and bio-integrated power sources. However, high-capacity bio-adaptable Mg-air batteries still face the challenges in low discharge potential and inefficient oxygen electrodes, with poor kinetics property toward oxygen reduction reaction (ORR). Herein, spinel nickel cobalt oxides (NiCo2O4) nanowires immobilized on nitrogen-doped Ti3C2Tx (NiCo2O4/N-Ti3C2Tx) are reported via surface chemical-bonded effect as oxygen electrodes, wherein surface-doped pyridinic-N-C and Co-pyridinic-N moieties accounted for efficient ORR owing to increased interlayer spacing and changed surrounding environment around Co metals in NiCo2O4. Importantly, in polyethylene glycol (PVA)-NaCl neutral gel electrolytes, the NiCo2O4/N-Ti3C2Tx-assembled quasi-solid wearable Mg-air batteries delivered high open-circuit potential of 1.5 V, good flexibility under various bent angles, high power density of 9.8 mW cm-2, and stable discharge duration to 12 h without obvious voltage drop at 5 mA cm-2, which can power a blue flexible light-emitting diode (LED) array and red smart rollable wearable device. The present study stimulates studies to investigate Mg-air batteries involving human-body adaptable neutral electrolytes, which will facilitate the application of Mg-air batteries in portable, flexible, and wearable power sources for electronic devices.

Application of Functionalized Zn-Based Metal-Organic Frameworks (Zn-MOFs) with CuO in Heterocycle Synthesis via Azide-Alkyne Cycloaddition.

The main goal of this article is to discuss the expansion of click chemistry. A new catalyst composed of CuO nanoparticles embedded in Zn-MOF with the ligand 2,4,6-tris(4-carboxyphenoxy)-1,3,5-triazine (H3L) is presented. The incorporation of CuO nanoparticles into the Zn-MOF structure led to desirable morphology and catalytic properties. The designed catalyst was evaluated for its catalytic role in the multicomponent reaction and copper-catalyzed azide-alkyne cycloaddition (CuAAC) for preparation of triazole rings with 80-91% yield. The catalyst demonstrated an appealing architecture and exhibited robustness, high efficiency, and environmental friendliness. Characterization of the catalyst was performed using various techniques, including Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission electron microscopes (TEM), high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray spectroscopy (EDX), elemental mapping, and X-ray diffraction (XRD). The results suggest that this novel catalyst has the potential to be a valuable tool in the development of new synthetic approaches for a wide range of applications.

Dual External Field Strategy in Regulating the Superhalogen Characteristics of the Non-Noble Metal Constituted Tantalum Oxide Clusters.

The identification of the non-noble metal constituted TaO cluster as a potential analogue to the noble metal Au is significant for the development of tailored materials. It leverages the superatom concept to engineer properties with precision. However, the impact of incrementally integrating TaO units on the electronic configurations and properties within larger TaO-based clusters remains to be elucidated. By employing the density functional theory calculations, the global minima and low-lying isomers of the TanOn (n = 2-5) clusters were determined, and their structural evolution was disclosed. In the cluster series, Ta5O5 was found to possess the highest electron affinity (EA) with a value of 2.14 eV, based on which a dual external field (DEF) strategy was applied to regulate the electronic property of the cluster. Initially, the electron-withdrawing CO ligand was affixed to Ta5O5, followed by the application of an oriented external electric field (OEEF). The CO ligation was found to be able to enhance the Ta5O5 cluster's electron capture capability by adjusting its electron energy levels, with the EA of Ta5O5(CO)4 peaking at 2.58 eV. Subsequently, the introduction of OEEF further elevated the EA of the CO-ligated cluster. Notably, OEEF, when applied along the +x axis, was observed to sharply increase the EA to 3.26 eV, meeting the criteria for superhalogens. The enhancement of EA in response to OEEF intensity can be quantified as a functional relationship. This finding highlights the advantage of OEEF over conventional methods, demonstrating its capacity for precise and continuous modulation of cluster EAs. Consequently, this research has adeptly transformed tantalum oxide clusters into superhalogen structures, underscoring the effectiveness of the DEF strategy in augmenting cluster EAs and its promise as a viable tool for the creation of superhalogens.

A New Surgical Assistance Aid for Mesiodens Extraction Based on the Ideal Approach.

BACKGROUND: To date, the classification of mesiodens has been based on the location, crown orientation, and morphology; however, there is no assistance aid focusing on choosing surgical approach. PURPOSE: This study aimed to introduce and evaluate a new surgical assistance aid for mesiodens extraction based on surgical approach. STUDY DESIGN, SETTING, SAMPLE: For the retrospective trial part of this study, case data from mesiodens patients who had surgery at the Affiliated Stomatological Hospital was collected, and a new surgical assistance aid was developed. A prospective randomized controlled trial was conducted on mesiodens patients who were seen in our department (patients with one mesiodens were included). PREDICTOR VARIABLE: The predictor variable was surgical approach either with or without the surgical assistance aid. Subjects were randomized to one of the two study groups. For subjects assigned to the group using the surgical assistance guide, the approach was selected according to the aid detailed in this study. For subjects assigned to the group without the surgical assistant aid, 2 residents chose an approach based on their judgment and review of relevant imaging and physical examination. MAIN OUTCOME VARIABLES: The preoperative evaluation time, operative time, and complications associated with surgery were recorded separately for the two groups. COVARIATES: The age and sex were also recorded. ANALYSES: Variables were analyzed using the independent t-test and χ2 test. The level of statistical significance is P < .05. RESULTS: In the retrospective trial part, a new surgical assistance aid for mesiodens extraction was developed based on the ideal surgical approach. In the prospective randomized controlled trial, the experimental group (n = 50) was statistically significant in preoperative evaluation time (4.51 ± 0.34 mins vs 5.43 ± 0.34 mins) and operative time (31.87 ± 5.57 mins vs 36.32 ± 5.28 mins) compared to the control group (n = 50) (P < .001). There was no significant intergroup difference in complications associated with surgery (P > .05). CONCLUSION AND RELEVANCE: The new surgical assistance aid developed in this study guides surgeons to ease the selection of surgical approaches and shorten the operative time.

Histidine Protonation Behaviors on Structural Properties and Aggregation Properties of Aß(1-42) Mature Fibril: Approaching by Edge Effects.

The histidine behavior plays a crucial role in the structural and aggregation properties of protein folding and misfolding. Understanding the histidine behavior at the edge of the protein structure is critical for finding ways to disrupt fibril elongation and growth, but this impact remains poorly understood. In the current study, we used molecular dynamics simulations to investigate the edge substitution effect of histidine protonation on the structural and aggregation properties. Our data showed that ΔG1 contributed the most to binding affinity compared to ΔG2 and ΔG3. The different protonation states at the edge chain significantly impacted the secondary structure properties of the edge chain. Specifically, we found that such protonation behavior significantly affected specific regions, particularly the N-terminus (G9-Q15) and C-terminus (K28-A30). Further analysis confirmed that H6, H13, and H14 were directly involved in H-bonding networks with the C1_H14//C2_H13 interchain interactions critical for maintaining the interchain stability. Furthermore, we confirmed that H6, H13, and H14 were directly involved in the loss of the carbon skeleton contact in the N-terminus. Our findings indicate that the edge condition is more susceptible to changes in structural properties than the middle condition. The current study is helpful for understanding the histidine behavior hypothesis in related misfolding diseases.

Template-free efficacious morphology of electrosynthesized polyaniline/ß-cyclodextrin host-guest complex on Au/rGO modified electrode for removal and recovery of rare-earth and heavy elements from seawater.

Global water pollution and scarcity of water resources are turning increasingly into serious threats to the survival of all living organisms on Earth. This study offers an influent strategy for the electrosynthesis of reduced graphene oxide/polyaniline/ß-cyclodextrin (rGO/PAni/ßCD) nanocomposite and its application to the removal/recovery of heavy elements (HEs) and rare-earth elements (REEs). Besides physicochemical and electrochemical studies, the surface morphological and statistical properties of fabricated nanocomposite electrode were examined. The textural and morphological characteristics of nanocomposite electrode were investigated via AFM data based on statistical, stereometric, and fractal theory. The cohesive, porous, and well-developed morphology of fabricated nanocomposite electrode has enabled the electrodeposition technique to achieve significant simultaneous removal/recovery efficiency of HE and REE ions such as Pb(II), Cu(II), Cd(II), Hg(II), Ce(IV), and Nb(V). Therefore, using rGO/PAni/ßCD, considerable removal of HEs and REEs was achieved under optimized pH, 0.1 M KNO3, and 35 mg L-1 metal ion initial concentration during 20 min. Removal capacity of the nanocomposite electrode is preserved subsequent to 10 cycles of electrodeposition/desorption, according to the desorption investigation through eluted adsorbent at time intervals in deionized water and adjusted acidic pH values. Then, using rGO/PAni/CD nanocomposite, simulated seawater remediation was accomplished successfully. This interdisciplinary approach reveals that the removal/recovery efficiency enhance linearly along with the improvement of well-developed morphology for electrosynthesized composites. Thus, these results suggest how the morphological features of the polymer composites could improve remediation of water resources.

Edge Substitution Effects of Histidine Tautomerization Behaviors on the Structural Properties and Aggregation Properties of Aß(1-42) Mature Fibril.

Histidine behaviors play critical roles in folding and misfolding processes due to the changes in net charge and the various N/N-H orientations on imidazole rings. However, the effect of histidine tautomerization (HIE (Nε-H, ε) and HID (Nδ-H, δ) states) behaviors on the edge chain of Aß mature fibrils remains inadequately understood, which is critical for finding a strategy to disturb fibril elongation and growth. In the current study, eight independent molecular dynamics simulations were conducted to investigate such impacts on the structural and aggregation properties. Our results from three different binding models revealed that the binding contributions of edge substitution effects are primarily located between chains 1 and 2. Histidine states significantly influence the secondary structure of each domain. Further analysis confirmed that the C1_H6//C1_E11 intrachain interaction is essential in maintaining the internal stability of chain 1, while the C1_H13//C2_H13 and C1_H14//C2_H13 interchain interactions are critical in maintaining the interchain stability of the fibril structure. Our subsequent analysis revealed that the current edge substitution leads to the loss of the C1_H13//C1_E11 intrachain and C1_H13//C2_H14 interchain interactions. The N-terminal regularity was significantly directly influenced by histidine states, particularly by the residue of C1_H13. Our study provides valuable insights into the effect of histidine behaviors on the edge chain of Aß mature fibril, advancing our understanding of the histidine behavior hypothesis in misfolding diseases.

Hippocampal HDAC5-mediated histone acetylation underlies stress susceptibility in mice exposed to chronic social defeat stress.

Chronic stress leads to social avoidance and anhedonia in susceptible individuals, a phenomenon that has been observed in both human and animal models. Nevertheless, the underlying molecular mechanisms underpinning stress susceptibility and resilience remain largely unclear. There is growing evidence that epigenetic histone deacetylase (HDAC) mediated histone acetylation is involved in the modulation of depressive-related behaviors. We hypothesized that histone deacetylase 5 (HDAC5), which is associated with stress-related behaviors and antidepressant response, may play a vital role in the susceptibility to chronic stress. In the current study, we detected the levels of HDAC5 and acetylation of histone 4 (H4) in the hippocampus subsequent to chronic social defeat stress (CSDS) in C57BL/6J mice. We found that CSDS induces a notable increase in HDAC5 expression, concomitant with a reduction in the acetylation of histone H4 at lysine 12 (H4K12) in the hippocampus of susceptible mice. Meanwhile, intrahippocampal infusion of HDAC5 shRNA or HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) both reversed the depression susceptibility in susceptible mice that subjected to CSDS. Furthermore, HDAC5 overexpression was sufficient to induce depression susceptibility following microdefeat stress, accompanied by a significant reduction in H4K12 level within the hippocampus of mice. Additionally, the Morris water maze (MWM) results indicated that neither CSDS nor HDAC5 exerted significant effects on spatial memory function in mice. Taken together, these investigations indicated that HDAC5-modulated histone acetylation is implicated in regulating the depression susceptibility, and may be serve as potential preventive targets for susceptible individuals.

Beyond Shell-Filling: Strong Enhancement of Electron Affinity of Metal Clusters through a Noninvasive Oriented External Electric Field.

Traditional electron counting rules, like the Jellium model, have long been successfully utilized in designing superhalogens by modifying clusters to have one electron less than a filled electronic shell. However, this shell-filling approach, which involves altering the intrinsic properties of the clusters, can be complex and challenging to control, especially in experiments. In this letter, we theoretically establish that the oriented external electric field (OEEF) can substantially enhance the electron affinity (EA) of diverse aluminum-based metal clusters with varying valence electron configurations, leading to the creation of superhalogen species without altering their shell arrangements. This OEEF approach offers a noninvasive alternative to traditional superatom design strategies, as it does not disrupt the clusters' geometrical structures and superatomic states. These findings contribute a vital piece to the puzzle of constructing superalkalis and superhalogens, extending beyond conventional shell-filling strategies and potentially expanding the range of applications for functional clusters.

Tuning molecular assembly behavior to amplify the sonodynamic activity of porphyrins for efficient antibacterial therapy.

Sonodynamic therapy (SDT) is a promising strategy to treat deep-seated bacterial infections with good tissue penetration and spatiotemporal controllability. However, the low ROS generation efficiency of current sonosensitizers limits the development of SDT. Herein, we report a porphyrin derivative, TAPyPP-2, the sonodynamic activity of which is enhanced with less oxygen dependence by tuning its molecular assembly behavior. TAPyPP-2 can spontaneously form an ultra-small nano-assembly with a diameter of 6 nm in water by conjugation with primary amine salt-decorated pyridinium via π-π staking. The ultra-small assembly behavior can lower the energy gap between singlet and triplet states to 0.01 eV and promote the separation of holes and electrons, which facilitates ROS generation under ultrasound irradiation, in particular type I ROS. The unique hydrophilic ratio and positive charges endow TAPyPP-2 with superior abilities to interact with Staphylococcus aureus, resulting in extremely high sonodynamic antibacterial activity. Therefore, TAPyPP-2 successfully kills Staphylococcus aureus bacteria in the enclosed cavity of synovial joint and achieves effective SDT of septic arthritis. This work is anticipated to motivate enormous interest in the development of efficient SDT.

Diagnostic Value of Structural MRI in Spinocerebellar Ataxia Type 3 / 中山大学学报(医学科学版)

ObjectiveTo explore the role of structural MRI in the diagnosis of spinocerebellar ataxia type 3 （SCA3） and further evaluate its correlation with disease severity and disease duration. MethodsWe prospectively enrolled 81 genetically diagnosed SCA3 patients ［59 symptomatic （sym-SCA3） and 22 pre-symptomatic （pre-SCA3）］ and 35 age- and sex-matched healthy controls （HCs）. MRI structural images （3D T1 MPRAGE） and clinical data of all subjects were collected. Three observers with different radiological experience measured the width of the superior， middle and inferior cerebellar peduncle （SCP， MCP and ICP）， the anterior-posterior diameters of the pons and spinal cord at the levels of the foramen magnum and upper edge of the 3rd-5th cervical vertebra. One observer performed the measurements again 2 months later to assess for the intra- and inter-observer reliability， respectively. One-way ANOVA， rank-sum test， ROC curve and Random Forest were used to evaluate the diagnostic value of the above metrics for SCA3， and the correlation between the metrics and clinical variables was analyzed. ResultsNot depending on the radiological experience， the metrics based on morphological MRI showed high intra- and inter-observer reliability， among which bilateral superior and middle cerebellar peduncles performed best. The diameters of bilateral SCP， MCP， ICP， pons and spinal cord （except spinal cord at the level of the upper edge of the 5th cervical vertebra） decreased successively in HCs， pre-SCA3 and sym-SCA3 with a statistical difference （P<0.017）. ROC analysis revealed that the left MCP had the highest diagnostic value for pre-SCA3 （AUC=0.911）， with sensitivity， specificity and a cut-off value of 85.7%， 95.5% and 10.15 mm， respectively. In contrast， the right SCP had the highest diagnostic value for sym-SCA3 （AUC=0.999）， with sensitivity， specificity and a cut-off value of 100%， 98.3% and 2.62 mm， respectively. The Random Forest model based on the above metrics also had high diagnostic efficiency （AUC= 0.970， specificity=93.1%）， and the left MCP contributed the most. Correlation analysis showed that the above metrics had a significantly or moderately negative correlation with the Scale for the Assessment and Rating of Ataxia （SARA） and disease duration （P<0.05）. ConclusionNot depending on radiological experience， measurements of brain structure based on morphological MRI are reliable， which can help diagnose SCA3 and predict disease severity and duration. The left MCP and the right SCP perform best for predicting pre-SCA3 and sym-SCA3， respectively. Therefore， the structural MRI is recommended for assisting the clinical diagnosis of SCA3.

Research progress of therapeutic exosomes / 药学学报

Exosomes are a kind of endosomal vesicles that are secreted by most if not all living cells. Due to their capability of delivering a variety of cargos, such as tissue- or cell-specific proteins, lipids, and genetic materials, and their broad biological activities, exosomes have gained substantial attention as emerging therapeutics. Exosomes derived from mesenchymal stem cells (MSCs) and dendritic cells (DCs) are two types of exosomes that are widely studied. Many preclinical and clinical studies have shown that they have a satisfactory treatment effect in lung diseases, liver diseases, nervous system diseases, tumors, and other diseases. In addition, exosomes from macrophages, tumor cells, plant cells, and many other cells are getting more attention due to their therapeutic potential. Besides natural exosomes, research on engineered exosomes has also made plenty of progress. There have been several engineering methods of exosomes, such as targeting modification and loading of active ingredients. In this review, we summarize the research progress of therapeutic exosomes from different sources, and further discusses the application prospects of exosomes and possible challenges in the future.

Debridement effectiveness of infected bone tissue of chronic hematogenous osteomyelitis in the lower extremities under the guidance of 99mTc-MDP SPECT/CT fused images / 中华创伤杂志

Objective:To explore the debridement effectiveness of infected bone tissue of chronic hematogenous osteomyelitis in the lower extremities under the guidance of 99mTc-MDP SPECT/CT fused images. Methods:A retrospective case series analysis was conducted on 21 patients with chronic hematogenous osteomyelitis in the lower extremities treated at Southwest Hospital of Army Medical University from May 2017 to June 2020. There were 8 males and 13 females, with the age range of 10-62 years [23(18, 37)years]. The tibial infections were found in 16 patients, and femoral infections in 5 patients. The duration of bone infection was 4-480 months [120(42, 228)months]. According to the Cierny-Mader anatomico-physiological system, 4 patients were classified as type I, 14 as type III, 3 as type IV; 18 patients were classified as type A and 3 as type B. Intraoperative debridement of infected bone tissue was operated at stage I on the region of interest (ROI) where the isocontour(ISO) value was between 30%-40%, using the preoperative 99mTc-MDP SPECT/CT fused images as the reference. The stage II bone defect reconstruction was based on autologous and / or allogeneic bone. To observe the frequency of operations regarding bone infection control in stage I. The preoperative white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), intraoperative bacterial culture and pathological examination were compared at stages I and II. The skin redness and swellings, pain, sinus tract in the infected limbs, and ossification of grafted bones in the original bone defect part were observed at stage II. The accuracy rate between ISO value in the region of interest (ROI) and set ISO figure was checked. The difference of longitudinal length of the bone debridement area in ROI area with the actual bone debridement area was observed under the coronal position. Results:All patients were followed up for 6-36 months [11(9, 29)months] after stage II operation. All of the 21 patients had undergone operations of infection control with an average number of 1.04 times in stage I. 1 patient's intraoperative frozen section indicated that neutrophils were>5/HP. The bone graft at stage II had been completed after another debridement. Comparison of preoperative inflammatory markers at stages I and II: the WBC was decreased from (5.9±1.6)×10 9/L to (5.4±1.5)×10 9/L ( P>0.05), the ESR decreased from 9(5, 26)mm/h to 4(2, 10)mm/h ( P<0.05), and the CRP decreased from 2.8(2.3, 7.7)mg/L to 2.3(1.4, 3.0)mg/L ( P>0.05). The results of bacterial culture of tissue at stage I were positive in 12 patients and negative in 9 patients. The pathological examination indicated neutrophils and lymphocyte infiltration. The results of bacterial culture of tissue at stage II were all negative. A modicum of plasmacyte and lymphocyte infiltration and the neutrophils (<5 per/Hp) had been found in the intraoperative frozen section and pathological examination. No redness, swelling or sinus tract was found in the skin after stage II surgery and ossification of grafted bone was good. The accuracy rate between ISO value in the ROI and set ISO figure was 90.5%. The comparison between longitudinal debridement scope of ROI [(86.8±31.1)mm] and actual bone tissue debridement scope [(86.0±31.3)mm] at stage I showed no significant difference ( P>0.05). Conclusions:99mTc-MDP SPECT/CT fused images can be used as an effective means to define the debridement scope of infected bone tissue preoperatively. The method can not only avoid excessive debridement, but also improve the cure rate of hematogenous osteomyelitis in the lower extremities.

Effect of Functional Electrical Stimulation Rehabilitation Cycling on Lower Limb Motor Function in Children with Spastic Cerebral Palsy / 中国康复理论与实践

Objective To explore the effect of functional electrical stimulation (FES) rehabilitation cycling on lower limb motor function in children with spastic cerebral palsy. Methods From November, 2017 to December, 2020, 36 children with spastic hemiplegia in Beijing Bo'ai Hospital were randomly divided into control group (n = 18) and observation group (n = 18). The control group received routine rehabilitation training twice a day, and the observation group received FES rehabilitation cycling in addition, for eight weeks. Before and after treatment, the muscle tension of gastrocnemius and hamstring muscles on hemiplegic side was evaluated by modified Ashworth Scale (MAS), the change of walking speed was evaluated by 10-meter walking speed, the change of walking endurance was evaluated by 6-minute Walking Test, the walking function was evaluated by areas D and E of Gross Motor Function Measure (GMFM), and the energy consumption was evaluated by physiological cost index (PCI) . Results Two cases dropped out in the observation group. After training, there was no significant difference in MAS score of gastrocnemius muscle in both groups (t < 1.145, P > 0.05), the MAS score of hamstring muscle significantly decreased in the observation group (t = 4.869, P < 0.001), and no significant change was found in the control group (t = 1.458, P > 0.05). After training, the 10-meter walking speed, 6-minute walking distance, the score of GMFM and PCI significantly improved in both groups (|t| > 6.241, P < 0.001), and were better in the observation group than in the control group (|t| > 2.097, P < 0.05). Conclusion FES rehabilitation cycling training can improve the lower limb motor function of children with spastic hemiplegia.

Effect of Functional Electrical Stimulation Rehabilitation Cycling on Lower Limb Motor Function in Children with Spastic Cerebral Palsy / 中国康复理论与实践

Objective To explore the effect of functional electrical stimulation (FES) rehabilitation cycling on lower limb motor function in children with spastic cerebral palsy. Methods From November, 2017 to December, 2020, 36 children with spastic hemiplegia in Beijing Bo'ai Hospital were randomly divided into control group (n = 18) and observation group (n = 18). The control group received routine rehabilitation training twice a day, and the observation group received FES rehabilitation cycling in addition, for eight weeks. Before and after treatment, the muscle tension of gastrocnemius and hamstring muscles on hemiplegic side was evaluated by modified Ashworth Scale (MAS), the change of walking speed was evaluated by 10-meter walking speed, the change of walking endurance was evaluated by 6-minute Walking Test, the walking function was evaluated by areas D and E of Gross Motor Function Measure (GMFM), and the energy consumption was evaluated by physiological cost index (PCI) . Results Two cases dropped out in the observation group. After training, there was no significant difference in MAS score of gastrocnemius muscle in both groups (t < 1.145, P > 0.05), the MAS score of hamstring muscle significantly decreased in the observation group (t = 4.869, P < 0.001), and no significant change was found in the control group (t = 1.458, P > 0.05). After training, the 10-meter walking speed, 6-minute walking distance, the score of GMFM and PCI significantly improved in both groups (|t| > 6.241, P < 0.001), and were better in the observation group than in the control group (|t| > 2.097, P < 0.05). Conclusion FES rehabilitation cycling training can improve the lower limb motor function of children with spastic hemiplegia.

Design, synthesis, and neuroprotective and anti-platelet aggregation research of 3-n-butylphthalide derivatives / 药学学报

Butylphthalide and ferulic acid exhibit excellent therapeutic effects in ischemic stroke. In this research, twelve 3-n-butylphthalide derivatives were designed by molecular hybridization strategy. The target compounds were obtained by nucleophilic substitution, reduction reaction, esterification reaction and elimination reaction, and the structure was confirmed by 1H NMR, 13C NMR and ESI-MS. All compounds were evaluated for neuroprotective activity against OGD/R-induced neurotoxicity in rat cortical neurons by MTT assay. The compounds with the best neuroprotective activity were biologically evaluated for their ability to inhibit platelet aggregation induced by arachidonic acid (AA) and adenosine diphosphate (ADP) via the Bron method．The results indicate that 7b exhibited potent neurocyte protective activity as well as prominent anti-platelet aggregation activity. Compound 7b has potential to be developed as a drug for ischemic stroke.

Chemical constituents from stems and leaves of Clausena emarginata / 中国中药杂志

The chemical constituents from the stems and leaves of Clausena emarginata were separated and purified by column chromatographies on silica gel,ODS,Sephadex LH-20,and PR-HPLC. The structures of the isolated compounds were identified on the basis of physicochemical properties and spectroscopic analysis,as well as comparisons with the data reported in the literature. Sixteen compounds were isolated from the 90% ethanol extract of the stems and leaves of C. emarginata,which were identified as siamenol( 1),murrastanine A( 2),3-formyl-1,6-dimethoxycarbazole( 3),3-methoxymethylcarbazole( 4),3-methylcarbazole( 5),murrayafoline A( 6),3-formylcarbazole( 7),3-formyl-1-hydroxycarbazole( 8),3-formyl-6-methoxycarbazole( 9),murrayanine( 10),murrayacine( 11),girinimbine( 12),nordentatin( 13),chalepin( 14),8-hydroxy-6-methoxy-3-pentylisocoumarin( 15) and ethyl orsellinate( 16). Compounds 1-4,14-16 were isolated from C. emarginata for the first time. Among them,compounds 1,2,15 and 16 were isolated from the genus Clausena for the first time. All isolated compounds were evaluated for their cytotoxic activities against five human cancer cell lines: HL-60,SMMC-7721,A-549,MCF-7 and SW480 in vitro. Compounds 12 and 14 showed significant inhibitory effects against various human cancer cell lines with IC_(50) values comparable to those of doxorubicin.

Treatment of calcaneal fracture by closed reduction and minimally invasive plate fixation assisted with bidirectional distractor distraction / 中国骨伤

<p><b>OBJECTIVE</b>To investigate clinical effects of calcaneal fracture with closed reduction and minimally invasive plate fixation assisted with bidirectional distractor distraction.</p><p><b>METHODS</b>From September 2015 to October 2016, 11 male patients(13 feet) with calcaneal fractures treated with bidirectional distractor distraction assisted with minimally invasive plate fixation were retrospectively studied. They were aged from 24 to 57 years old with an average of 36.4 years old;8 feet were type IIand 5 feet were type III according to Sanders classification. Postoperative incision, fracture healing, Böhler angle, Gissane angle were observed and Maryland scoring system was used to evaluate clinical effects.</p><p><b>RESULTS</b>All fractures healed well without incision inflammation and incision disunion. All patients were followed up from 12 to 15 months with an average of 13.5 months. Böhler angle were improved from (9.6±7.3)° before operation to (20.2±4.6) ° at 1 year after operation, and had statistical meaning; Gissane angle increased from (92.7 ±8.5)° before operation to (121.7 ±7.6) ° at 1 year after operation. Maryland score at 1 year after operation was 88.79±8.25, and 11 feet got excellent results and 2 feet moderate.</p><p><b>CONCLUSIONS</b>Bidirectional distractor distraction assisted with minimally invasive plate fixation could effectively fix calcaneal fractures, reduce postoperative complications, and get satisfied results of postoperative images and functional recovery. It is one of effective methods for treating Sanders II and III calcaneal fractures.</p>

Screening, preparation and biological activity of human monoclonal antibodies against postsynaptic short-chain neurotoxins fromLapemis curtus / 解放军医学杂志

Objective To prepare human anti-postsynaptic neurotoxin monoclonal antibody from phage antibody library using recombined postsynaptic short-chain neurotoxins ofLapemis curtus.Methods The three postsynaptic neurotoxins were expressed inEscherichia coli and phage antibodies against neurotoxins were screened. The obtained scFvs were further constructed to full antibodies. The antigen binding ability, biochemical and pharmacokinetic characteristics of the depurated antibodies were evaluated, and the anti-toxin effects of the antibody drugs were verifiedin vivo.Results Two positive scFvs with specific binding ability to all the three neurotoxins were obtained after 4 rounds of panning, and then the full antibodies were generated, expressed and purified. Antibody binding specificity was further confirmed. Pharmacokinetics of these two antibodies, SM-SD-911 and SM-SD-861 were similar to a conventional IgG molecule. SM-SD-911 and SM-SD-861 also showed strong antitoxin effectin vivo. Conclusionfull human anti-postsynaptic neurotoxin antibody has been successfully obtained by using recombinant neurotoxin technology and a large phage antibody library which may achieve clinical efficacy in navy medical applications.