Age-Dependent Female Survival Advantage in Hepatocellular Carcinoma: A Multicenter Cohort Study.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) has a higher incidence in males, but the association of sex with survival remains controversial. This study aimed to examine the effect of sex on HCC survival and its association with age. METHODS: Among 33,238 patients with HCC from 12 Chinese tertiary hospitals, 4175 patients who underwent curative-intent hepatectomy or ablation were analyzed. Cancer-specific survival (CSS) was analyzed using Cox regression and Kaplan-Meier methods. Two propensity score methods and multiple mediation analysis were applied to mitigate confounding. To explore the effect of estrogen, a candidate sex-specific factor that changes with age, female participants' history of estrogen use, and survival were analyzed. RESULTS: There were 3321 males and 854 females included. A sex-related disparity of CSS was present and showed a typical age-dependent pattern: a female survival advantage over males appeared at the perimenopausal age of 45 to 54 years (hazard risk [HR], 0.77; 5-year CSS, 85.7% vs 70.6%; P = .018), peaked at the early postmenopausal age of 55 to 59 years (HR, 0.57; 5-year CSS, 89.8% vs 73.5%; P = .015), and was not present in the premenopausal (<45 y) and late postmenopausal groups (≥60 y). Consistent patterns were observed in patients after either ablation or hepatectomy. These results were sustained with propensity score analyses. Confounding or mediation effects accounted for only 19.5% of sex survival disparity. Female estrogen users had significantly longer CSS than nonusers (HR, 0.74; 5-year CSS, 79.6% vs 72.5%; P = .038). CONCLUSIONS: A female survival advantage in HCC depends on age, and this may be associated with age-dependent, sex-specific factors.

Silicon-Carbon Dots-Loaded Mesoporous Silica Nanocomposites (mSiO2@SiCDs): An Efficient Dual Inhibitor of Cu2+-Mediated Oxidative Stress and Aß Aggregation for Alzheimer's Disease.

The redox-active metal ions, especially Cu2+, are highly correlated to Alzheimer's disease (AD) by causing metal ion-mediated oxidative stress and toxic metal-bound ß-amyloid (Aß) aggregates. Numerous pieces of evidence have revealed that the regulation of metal homeostasis could be an effective therapeutic strategy for AD. Herein, in virtue of the interaction of both amino-containing silane and ethylenediaminetetraacetic acid disodium salt for Cu2+, the silicon-carbon dots (SiCDs) are deliberately prepared using these two raw materials as the cocarbon source; meanwhile, to realize the local enrichment of SiCDs and further maximize the chelating ability to Cu2+, the SiCDs are feasibly loaded to the biocompatible mesoporous silica nanoparticles (mSiO2) with the interaction between residual silane groups on SiCDs and silanol groups of mSiO2. Thus-obtained nanocomposites (i.e., mSiO2@SiCDs) could serve as an efficient Cu2+ chelator with satisfactory metal selectivity and further modulate the enzymic activity of free Cu2+ and the Aß42-Cu2+ complex to alleviate the pathological oxidative stress with an anti-inflammatory effect. Besides, mSiO2@SiCDs show an inspiring inhibitory effect on Cu2+-mediated Aß aggregation and further protect the neural cells against the toxic Aß42-Cu2+ complex. Moreover, the transgenic Caenorhabditis elegans CL2120 assay demonstrates the protective efficacy of mSiO2@SiCDs on Cu2+-mediated Aß toxicity in vivo, indicating its potential for AD treatment.

Safety and efficacy of microwave ablation for the treatment of low-risk papillary thyroid microcarcinoma: a prospective multicenter study.

OBJECTIVES: To assess the safety and efficacy of ultrasound-guided thermal ablation for low-risk papillary thyroid microcarcinoma (PTMC) via a prospective multicenter study. METHODS: From January 2017 through June 2021, low-risk PTMC patients were screened. The management details of active surveillance (AS), surgery, and thermal ablation were discussed. Among patients who accepted thermal ablation, microwave ablation (MWA) was performed. The main outcome was disease-free survival (DFS). The secondary outcomes were tumor size and volume changes, local tumor progression (LTP), lymph node metastasis (LNM), and complication rate. RESULTS: A total of 1278 patients were included in the study. The operation time of ablation was 30.21 ± 5.14 min with local anesthesia. The mean follow-up time was 34.57 ± 28.98 months. Six patients exhibited LTP at 36 months, of whom 5 patients underwent a second ablation, and 1 patient received surgery. The central LNM rate was 0.39% at 6 months, 0.63% at 12 months, and 0.78% at 36 months. Of the 10 patients with central LNM at 36 months, 5 patients chose ablation, 3 patients chose surgery and the other 2 patients chose AS. The overall complication rate was 1.41%, and 1.10% of patients developed hoarseness of the voice. All of the patients recovered within 6 months. CONCLUSIONS: Thermal ablation of low-risk PTMC was observed to be safe and efficacious with few minor complications. This technique may help to bridge the gap between surgery and AS as treatment options for patients wishing to have their PTMC managed in a minimally invasive manner. CLINICAL RELEVANCE STATEMENT: This study proved that microwave ablation is a safe and effective treatment method for papillary thyroid microcarcinoma. KEY POINTS: Percutaneous US-guided microwave ablation of papillary thyroid microcarcinoma is a very minimally invasive treatment under local anesthesia during a short time period. The local tumor progression and complication rate of microwave ablation in the treatment of papillary thyroid microcarcinoma are very low.

Congo Red-Derived Carbon Dots: Simultaneously as Fluorescence Probe for Protein Aggregates, Inhibitor for Protein Aggregation, and Scavenger of Free Radicals.

The pathological aggregation of some proteins is claimed to be highly related to several human diseases, such as ß-amyloid 1-42 (Aß42 ) to Alzheimer's disease (AD), islet amyloid polypeptide, and insulin to type 2 diabetes mellitus. Therefore, it is in desperate need to develop effective methods for detection of protein aggregates and inhibition of abnormal aggregation. Herein, to construct all-in-one probe with both diagnosis and treatment potentials for protein aggregation diseases, Congo red (CR), a classical staining reagent with red fluorescence signal output for protein aggregates, is deliberately adopted to react with three different reductive carbon sources and ammonium persulfate to generate three CR-derived carbon dots (CDs). The obtained CDs exhibit the capabilities of turn-on red fluorescence imaging of protein aggregates, and/or inhibition of protein aggregation as well as scavenging of free radicals. Among them, CA-CDs, using citric acid as the reductive carbon source, demonstrate the superiority to the other two studied CDs in integrating all of these functions, and particularly exert excellent cytoprotection effect against toxic Aß42 species, possessing tremendous potential in diagnosis and treatment of AD for future study. The present study paves a new way to develop all-in-one CDs for the protein disease research.

Period-Dependent Survival Benefit of Percutaneous Microwave Ablation for Hepatocellular Carcinoma: A 12-Year Real-World, Multicentric Experience.

Introduction: Although microwave ablation (MWA) is a promising technique for hepatocellular carcinoma (HCC) treatment, its 10-year efficacy is unknown. Objective: The objective of the study was to assess whether the advances in MWA for HCC translated into a real-world survival benefit. Methods: This retrospective study included 2,354 patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 to B from 5 hospitals, with at least 2 years of follow-up for all the patients. Recurrence and survival were analyzed using the Kaplan-Meier method with time-period stratification. Results: A total of 5,326 HCCs (mean diameter, 2.9 cm ± 1.2) underwent 4,051 sessions of MWA with a median follow-up of 61.3 (0.6-169.5 range) months during 3 periods (2007-2010, 2011-2014, and 2015-2018). Technical success was achieved in 5,194 (97.5%) tumors with significant improvement over time, especially for >3.0-cm HCC (p < 0.001). Local tumor progression (LTP) showed no period-dependent advance, with >3.0-cm HCC and perivascular location being the risk factors for LTP. The median intrahepatic metastasis time was 27.6 (95% confidence interval [CI]: 25.2-28.8) months, with 5- and 10-year occurrence rates of 68.8% and 79.4%, respectively. The 5- and 10-year overall survivals were 63.9% and 41.1%, respectively, and BCLC stage 0, A, and all B patients showed an observable survival improvement over time (p < 0.001). The median disease-free survival time increased from 19.4 (95% CI: 16.5-22.6) months in 2007-2010 to 28.1 (95% CI: 25.9-32.3) months in 2015-2018. The improved survival for early recurrent (≤2 years) patients was period-dependent, as verified by Cox regression analyses. The major complications rate per procedure was 3.0% (122/4,051). Conclusions: These real-world data show that MWA provided an upward trend in survival for HCC patients with BCLC stage 0-B over a 12-year follow-up period. An encouraging clear survival benefit in early recurrent patients was also observed.

Comparative Effectiveness of Robot-Assisted Training Versus Enhanced Upper Extremity Therapy on Upper and Lower Extremity for Stroke Survivors: A Multicentre Randomized Controlled Trial.

OBJECTIVE: Robot-assisted neuro-rehabilitation therapy plays a central role in upper extremity recovery of stroke. However, the efficacy of robotic training on the upper extremity is not yet well defined, and little attention has been devoted to its potential effect on the lower extremity. The aim of this study was to compare the efficacy of robot-assisted training and therapist-mediated enhanced upper extremity therapy on the upper and lower extremities. METHODS: A randomized clinical trial involving 172 stroke survivors was conducted in China. All participants received either robot-assisted training or enhanced upper extremity therapy for 3 weeks. Fugl-Meyer assessment upper extremity subscale (FMA-UE), Fugl-Meyer assessment lower extremity subscale (FMA-LE), and Modified Barthel Index were administered at baseline, mid-treatment (1 week after treatment start), and post-treatment. RESULTS: Participants in the robot-assisted training group showed a significant improvement in the hemiplegia extremity, which was non-inferior to the enhanced upper extremity therapy group in FMA-UE (p < 0.05), while suggesting greater motor recovery of lower extremity in FMA-LE (p < 0.05) compared with the enhanced upper extremity therapy group. A marked increase in Modified Barthel Index was observed within groups; however, no significant difference was found between groups. CONCLUSION: Robot-assisted training is non-inferior but not better in reducing impairment of the upper extremity and appears to be superior in reducing impairment of the lower extremity compared with enhanced upper extremity therapy for stroke survivors.

A multicenter 10-year oncologic outcome of ultrasound-guided percutaneous microwave ablation of clinical T1 renal cell carcinoma: will it stand the test of time?

OBJECTIVES: We updated the experience on percutaneous microwave ablation for renal cell carcinoma with five-center data and long-term follow-up. METHODS: This retrospective study reviewed the T1N0M0 renal cell carcinoma patients who underwent microwave ablation between April 2006 and December 2019. Clinicopathological and procedural data were collected. Technical effectiveness and complications were assessed, and the Kaplan-Meier method was used for cancer-specific survival, disease-free survival, overall survival, and local neoplastic process analyses. RESULTS: A total of 323 consecutive patients (mean age, 62.9 years ± 14.0) with 371 biopsy-proved tumors (mean diameter, 2.9 cm ± 1.2) were enrolled, and 42.6% of the tumors were located adjacent to collecting system/bowel and technical effectiveness was achieved in 360 (97.0%) tumors. For 275 cT1a patients, during median follow-up time of 66.0 months (IQR, 58.4-73.6), 10-year local neoplastic processes, cancer-specific survival, disease-free survival, and overall survival rates were 1.9%, 87.4%, 71.8, and 67.5%, respectively. For 48 cT1b patients, during the median follow-up time of 30.4 months (IQR, 17.7-44.8), 5-year local tumor progression, cancer-specific survival, disease-free survival, and overall survival rates were 11.3%, 91.4%, 69.1, and 89.2%, respectively. Major complications showed no differences between cT1a (3.5%) and cT1b (6.9%) patients (p = 0.28). A clinical risk stratification system was developed based on multivariable model to predict DFS and CSS with c-indexes of 0.78 (95% CI: 0.71-0.85) and 0.77 (95% CI: 0.65-0.90), respectively. CONCLUSIONS: With matured follow-up at five institutions, ultrasound-guided percutaneous microwave ablation is a reliable treatment option for cT1a renal cell carcinoma even in dangerous location and appears to be promising for cT1b tumors. KEY POINTS: • To our knowledge, this is the first multicenter cohort of long-term oncologic outcomes with percutaneous MWA of cT1 RCC. • The predicting model we developed is accurate to predict the long-term DFS and CSS, which can help to provide a better MWA prognostication over routinely available clinical information. • The available evidence shows that microwave ablation of clinical stage T1 RCC is safe and reliable with promising long-term oncologic outcomes, especially for cT1a RCC with excellent 10-year results.

Recent developments in the removal of metal-based engineered nanoparticles from the aquatic environments by adsorption.

Nowadays, metal-based engineered nanoparticles (m-ENPs) are ubiquitous in aquatic environments for their wide applications in all walks of life. m-ENPs have been demonstrated to exert ecotoxicity, cytotoxicity and genotoxicity towards organisms and even humans. Therefore, the removal of m-ENPs from water has recently become a hot global concerned issue. Adsorption is widely investigated for this purpose, owing to its advantages of low cost, easy operation, high removal efficiency and potential recycling use of both the adsorbents and adsorbates. As the adsorption and related technologies were hardly comprehensively overviewed for the removal of m-ENPs, herein, the present review particularly focuses on this topic. The fundamentals to the technology, including adsorption isotherm, adsorption dynamics, the adsorption process with the special emphasis on the relationship between surface area and porosity of the adsorbent and the adsorption capacity, etc., are fully discussed. As the kernel of the adsorption method, adsorbents with diversified chemical and physical properties in different types are comprehensively elaborated. The primary factors affecting the adsorption, and adsorption mechanisms are well summarized. Particularly, the regeneration of the adsorbents and the reuse of adsorbed m-ENPs are highlighted for the sustainability. Finally, challenges and prospects in this field are outlined. Overall, this review aims to provide valuable references for the development of new adsorbents with more efficient and practical applications to remove m-ENPs and direct the future study.

Hydrophilic silicon nanoparticles as a turn-off and colorimetric fluorescent probe for curcuminoids detection in food samples and cell imaging.

Hydrophilic fluorescent silicon nanoparticles (SiNPs) with good pH stability, salt-tolerance and anti-photobleaching were for the first time prepared from hydrophobic 3-glycidoxypropyltrimethoxysilane. Employing SiNPs as the fluorescence probe, selective quantification of curcuminoids based on the quenching effect was realized with a linearity of 0.046-7.4 µg/mL and a limit of detection of 17.6 ng/mL. Moreover, in light of fluorescence redshift of SiNPs corresponding to the elevated concentration of curcuminoids, a fluorescence colorimetric method was established based on only one extra probe, i.e. herein SiNPs. Thus, semi-quantification of curcuminoids (0-14.7 µg/mL) was visualized from blue to yellow color. Both the developed quantitative and semi-quantitative probe were successfully applied to determine curcuminoids in various actual food samples. Furthermore, SiNPs possessed low cytotoxicity and succeeded in intracellular curcuminoids imaging. The proposed SiNPs could be a promising fluorescence probe for multiple applications.

Structural elucidation and antidiabetic activity of fucosylated chondroitin sulfate from sea cucumber Stichopus japonicas.

A fucosylated chondroitin sulfate was isolated from the body wall of sea cucumber Stichopus japonicus (FCSsj), whose structure was characterized by NMR spectroscopy and HILIC-FTMS. At the ratio of 1.00:0.26:0.65, three fucosyl residues were found: 2,4-disulfated-fucose (Fuc2,4S), 4-sulfated-fucose (Fuc4S) and 3,4-disulfated-fucose (Fuc3,4S), which were only linked to the O-3 of glucuronic acid residues (GlcA). Besides mono-fucosyl moieties, di-fucosyl branches, namely Fuc2,4Sα(1→3)Fuc4S, were also found to be attached to the O-3 of GlcA. The antidiabetic activity of FCSsj was evaluated using glucosamine induced insulin resistant (IR) Hep G2 cells in vitro. It was found that FCSsj significantly promoted the glucose uptake and glucose consumption of IR-Hep G2 cells in a dose-dependent manner, and could alleviate the cell damage. Furthermore, FCSsj could promote the glycogen synthesis in the glucosamine-induced IR-Hep G2 cells. These results provided a supplement for studying the antidiabetic activity of FCSsj.

Application of marine natural products in drug research.

New diseases are emerging as the environment changes, so drug manufacturers are always on the lookout for new resources to develop effective and safe drugs. In recent years, many bioactive substances have been produced in the marine environment, which represents an alternative resource for new drugs used to combat major diseases such as cancer or inflammation. Many marine-derived medicinal substances are in preclinical or early stage of clinical development, and some marine drugs have been put on the market, such as ET743 (Yondelis®). This review presents the sources, activities, mechanisms of action and syntheses of bioactive substances based on marine natural products in clinical trials and on the market, which is helpful to understand the progress of drug research by application of marine natural products.

Painful tonic spasm in Chinese patients with neuromyelitis optica spectrum disorder: Prevalence, subtype, and features.

OBJECTIVES: Painful tonic spasm (PTS) is a common symptom in patients with neuromyelitis optica spectrum disorder (NMOSD). We herein aimed to explore the prevalence, subtype, and features of PTS in Chinese Han patients with NMOSD. METHODS: We retrospectively reviewed medical records and interviewed patients with NMOSD who were admitted to Huashan Hospital and the Jing'an District Center Hospital of Fudan University in Shanghai, China, from February 2017 to May 2019. The primary questionnaires included a Numerical Rating Scale (NRS), Spinal Cord Injury Health Questionnaire (SCI-HQ), Penn Spasm Frequency Scale (PSFS), and Patient Global Impression of Improvement (PGI-I). RESULTS: Sixty-seven of 153 (43.79%) patients with NMOSD showed PTS, only when spinal cord was involved. PTS had a negative impact on daily life in 97.01% (65/67) of the patients, and 92.54% (62/67) of the patients needed symptomatic treatment. Pain intensity and frequency of PTS were significantly different (P = 0.018 with NRS, P = 0.045 with PSFS) among flexor tonic spasm, extensor tonic spasm, isometric tonic spasm and complex tonic spasm subtype. Forty patients (59.71%) manifested complex tonic spasms, which indicated more severe pain and frequent spasms comparing to other subtypes. The locations of PTS were significantly different among the 5 subtypes (P<0.001), i.e.,77.78% (7/9) of flexor tonic spasms appeared in the upper extremity, 100% (9/9) of extensor tonic spasm occurred in the lower extremity, and isometric tonic spasms principally occurred in the trunk (87.5%). Forty-one patients (66.13%) demonstrated good responses to the symptomatic treatments, and there were no statistical differences with respect to the therapeutic responses among the 5 PTS subtypes (P = 0.509). CONCLUSIONS: PTS was associated with myelitis, and was a common symptom in NMOSD. Intensity, frequency and location were different among the PTS subtypes. Complex tonic spasm was the most common and serious subtype.

Highly efficient removal of silver nanoparticles by sponge-like hierarchically porous thiourea-formaldehyde resin from Water.

With the increasing production and rapid market penetration as well as the confirmation of the toxic effects, silver nanoparticles (AgNPs) are one kind of newly emerging environmental contaminants of high concern. It is urgent to develop the efficient method to remove them from the environment. In this study, the sponge-like hierarchically porous thiourea-formaldehyde (TF) resin rich with nitrogen and sulfur was for the first time proposed as the adsorbent to achieve this goal. With enormous interconnected layer structure and plentiful macropores, the porous TF resin provided abundant available interaction sites and fast mass transfer to adsorb citrate stabilized AgNPs (citrate-AgNPs). Fast adsorption rate and high adsorption capacity (2478 mg/g) were obtained based on the electrostatic and metal-ligand interactions. Heterogeneous aggregation and simultaneous adsorption contributed to this removal process. Furthermore, with the assistance of NaCl, the porous TF resin exhibited largely enhanced removal efficiency towards citrate-AgNPs up to 98.7 % in 5 min, possibly due to the co-operation of adsorption and coagulation. This study proposed a promising adsorbent to remove AgNPs and provided a referential strategy to design highly efficient adsorbents for removal of nanoparticles.

Structure-based discovery of novel 4-(2-fluorophenoxy)quinoline derivatives as c-Met inhibitors using isocyanide-involved multicomponent reactions.

The c-Met kinase has emerged as a promising target for the development of small molecule antitumor agents because of its close relationship with the progression of many human cancers, poor clinical outcomes and even drug resistance. In this study, two novel series of 6,7-disubstitued-4-(2-fluorophenoxy)quinoline derivatives containing α-acyloxycarboxamide or α-acylaminoamide scaffolds were designed, synthesized, and evaluated for their in vitro biological activities against c-Met kinase and four cancer cell lines (H460, HT-29, MKN-45, and MDA-MB-231). Most of the target compounds exhibited moderate to significant potency and possessed selectivity for H460 and HT-29 cancer cell lines. The preliminary structure-activity relationships indicated that α-acyloxycarboxamide or α-acylaminoamide as 5-atom linker contributed to the antitumor potency. Among these compounds, compound 10m (c-Met IC50 = 2.43 nM, a multitarget tyrosine kinase inhibitor) exhibited the most potent inhibitory activities against H460, HT-29 and MDA-MB-231 cell lines with IC50 of 0.14 ± 0.03 µM, 0.20 ± 0.02 µM and 0.42 ± 0.03 µM, which were 1.7-, 1.3- and 1.6-fold more active than foretinib, respectively. In addition, concentration-dependent assay and time-dependent assay indicated compound 10m can inhibit the proliferation of H460 cell in a time and concentration dependent manner. Moreover, docking studies revealed the common mode of interaction with the c-Met binding site, suggesting that 10m is a potential candidate for cancer therapy deserving further study.

Release of antidiabetic peptides from Stichopus japonicas by simulated gastrointestinal digestion.

Sea cucumber (Stichopus japonicus) is a high-protein food with the potential to release certain peptides through enzymolysis. This work is to explore the characteristics of peptides released from Stichopus japonicus protein in the process of digestion. Hydrolysates were obtained by gastrointestinal digestion and fractioned to <3, 3-10, 10-30 and >30 kDa fractions. Fifty-eight peptides from <3 kDa fraction were characterized using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Hydrolysates could improve glucose uptake of 3 T3-L1 cells and high insulin-induced insulin-resistant Hep G2 cells. Molecular docking showed that the released peptides had similar binding mode with anagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor. The <3 kDa fraction in gastro and intestinal digestion showed the greatest DPP-IV inhibitory potency (IC50 0.51 and 0.52 mg/mL, respectively). The results indicated that sea cucumber could be used as a functional food to release antidiabetic peptides through gastrointestinal digestion.

Direct oxidative coupling of N-acyl pyrroles with alkenes by ruthenium(ii)-catalyzed regioselective C2-alkenylation.

Ruthenium(ii)-catalyzed oxidative coupling by C2-alkenylation of N-acyl pyrroles with alkenes has been described. The acyl unit was found to be an effective chelating group for the activation of aryl C-H bonds ortho to the directing group. The alkenylation reaction of benzoyl pyrroles occurred regioselectively at the C2-position of the pyrrole ring, without touching the benzene ring. The reaction provides exclusively monosubstituted pyrroles under the optimized conditions. Disubstituted pyrroles could be obtained using higher loadings of the ruthenium(ii)-catalyst and the additives.

Contralateral seventh cervical nerve transfer can affect the pennation angle of the lower limb in spastic hemiplegia patients: An observational case series study.

INTRODUCTION: We previously reported transferring seventh cervical (C7) nerve from unaffected side to affected side in patients with spastic hemiplegia due to chronic cerebral injury, to improve function and reduce spasticity of paralyzed upper limb. In the clinics, some patients also reported changes of spasticity in their lower limb, which could not be detected by routine physical examinations. Pennation angle of muscle can indirectly reflect the condition of spasticity. The purpose of this study was to evaluate whether this upper limb procedure may affect spasticity of lower limb, using ultrasonography to detect changes of muscle pennation angle (PA). METHODS: Twelve spastic hemiplegia patients due to cerebral injury including stroke, cerebral palsy, and traumatic brain injury, who underwent C7 nerve transfer procedure, participated in this study. B-mode ultrasonography was used to measure PA of the gastrocnemius medialis (GM) muscle at rest preoperatively and postoperatively. The plantar load distribution of the lower limbs was evaluated using a Zebris FDM platform preoperatively and postoperatively. RESULTS: The PA of the GM was significantly smaller on the affected side than that of unaffected side before surgery. On the affected side, the postoperative PA was significantly larger than preoperative PA. On the unaffected side, the postoperative PA was not significantly different compared to preoperative PA. The postoperative plantar load distribution of the affected forefoot was significantly smaller than preoperative load distribution, which was consistent with ultrasonography results. CONCLUSIONS: This study indicates that C7 nerve transfer surgery for improving upper limb function can also affect muscle properties of lower limb in spastic hemiplegia patients, which reveals a link between the upper and lower limbs. The interlimb interactions should be considered in rehabilitation physiotherapy, and the regular pattern and mechanism need to be further studied.

Ginkgolide K supports remyelination via induction of astrocytic IGF/PI3K/Nrf2 axis.

Although several therapies are approved, none promote re-myelination in multiple sclerosis (MS) patients, limiting their ability for sustained recovery. Thus, treatment development in MS has the opportunity to tackle the challenges, including experimental therapies targeting neuroprotection and re-myelination. Here, we provide a novel therapeutic target for Ginkgolide K (GK) that is now becoming a very critical natural compound to treat demyelination and neurodegeneration. GK improves behavioral dysfunction and demyelination in cuprizone (CPZ) model, followed by the migration and enrichment of astrocytes in the corpus callosum. Both in vitro and in vivo experiments demonstrates that GK triggers the upregulation of Nrf2/HO-1 in astrocytes and inhibition of p-NF-kB/p65, which is associated with the outcome of anti-inflammation and anti-oxidation by suppressing the production of IL-6 and TNFα as well as nitric oxide and iNOS in astrocytes. Further findings suggest that IGF/PI3K, but not BDNF, was induced in the corpus callosum after GK treatment, revealing that Nrf2 activation inhibited caspase-3 and apoptosis in O4+ oligodendrocytes possibly through IGF/PI3K signaling molecules. Since the current immunomodulatory therapies for MS have failed to prevent patients from entering the progressive phase of the disease, thus targeting Nrf2 in astrocytes with GK would be an ideal strategy for myelin protection and regeneration.

Fast reversed-phase liquid chromatographic separation of proteins by flow-through poly(styrene-co-divinylbenzene) microspheres.

With the explosive growth of the bioscience and biopharmaceuticals, the demand for high efficient analysis and separation of proteins is urgent. High-performance liquid chromatography is an appropriate technology for this purpose, and the stationary phase is the kernel to the separation efficiency. In this study, flow-through poly(styrene-co-divinylbenzene) microspheres characteristic of the binary pores, i.e. flow-through pores and mesopores, were synthesized; this special porous structure would benefit the convective mass transfer while guarantee the high specific surface area. Owing to the hydrophobic nature, poly(styrene-co-divinylbenzene) microspheres were suitable as the reversed-phase stationary phase for separation of proteins. For the high permeability of the poly(styrene-co-divinylbenzene) microspheres packed column, fast separation of the studied six proteins in ∼2 min was achieved. The recoveries of studied proteins were acceptable in the range of 79.0-99.4%. The proposed column had good pH stability of 1-13 and repeatability. Moreover, the column was applied for egg white fast separation, further demonstrating its applicability for complex bio-sample separation. The flow-through poly(styrene-co-divinylbenzene) microspheres were promising for fast separation of large molecules.