A disposable ultrasensitive immunosensor based on MXene/NH2-CNT modified screen-printed electrode for the detection of ovarian cancer antigen CA125.

Cancer antigen 125 (CA125) is the gold standard biomarker for clinical diagnosis of ovarian cancer, with a threshold value of 35 U/mL in serum. In this paper, a disposable ultrasensitive immunosensor based on Ti3C2Tx-MXene/amino-functionalized carbon nanotube (NH2-CNT) modified screen-printed carbon electrode (SPCE) was constructed for the detection of the ovarian cancer antigen CA125. By optimizing the mass ratio of Ti3C2Tx to NH2-CNT, Ti3C2Tx/NH2-CNT composite with excellent electrochemical properties was prepared, which is beneficial for amplifying the initial electrochemical signal. The positively charged NH2-CNT effectively alleviated the stacking problem of Ti3C2Tx, and its amino group also facilitated the covalent immobilization of the capture antibody. Meanwhile, chitosan (CS) with excellent film-forming ability was also used to successfully enhance the adsorption of electrode material, thus improving the stability of the sensor. In addition, CS could further enhance the current signal. The prepared immunosensor exhibited excellent performance in CA125 detection with a wide linear range from 1 mU/mL to 500 U/mL, and good selectivity, reproducibility and lomg-term stability. Furthermore, the immunosensor showed satisfactory results for the detection of CA125 in clinical serum samples, which is promising for the clinical screening, early diagnosis and prognostic examination of ovarian cancer.

Unintentional emissions of polychlorinated naphthalenes in China: Sources, composition, and historical trends.

Polychlorinated naphthalenes (PCNs) are detrimental to human health and the environment. With the commercial production of PCNs banned, unintentional releases have emerged as a significant environmental source. However, relevant information is still scarce. In this study, provincial emissions for eight PCNs homologues from 37 sources in the Chinese mainland during the period of 1960-2019 were estimated based on a source-specific and time-varying emission factor database. The results showed that the total PCNs emissions in 2019 reached 757.0 kg with Hebei ranked at the top among all the provinces and iron & steel industry as the biggest source. Low-chlorinated PCNs comprised 90% of emissions by mass, while highly chlorinated PCNs dominated in terms of toxicity, highlighting divergent priorities for mitigating emissions and safeguarding human health. The emissions showed an overall upward trend from 1960 to 2019 driven by emission increase from iron & steel industry in terms of source, and from North China and East China in terms of geographic area. Per-capita emissions followed an inverted U-shaped environmental Kuznets curve while emission intensities decreased with increasing per-capita Gross Domestic Product (GDP) following a nearly linear pattern when log-transformed.

Tumor treating induced fields: a new treatment option for patients with glioblastoma.

Purpose: Currently, a range of electromagnetic therapies, including magnetic field therapy, micro-currents therapy, and tumor treating fields, are under investigation for their potential in central nervous system tumor research. Each of these electromagnetic therapies possesses distinct effects and limitations. Our focus is on overcoming these limitations by developing a novel electric field generator. This generator operates by producing alternating induced currents within the tumor area through electromagnetic induction. Methods: Finite element analysis was employed to calculate the distribution of electric fields. Cell viability was assessed using the CCK-8 assay. Tumor volumes and weights served as indicators to evaluate the effectiveness of TTIF. The in-vivo imaging system was utilized to confirm tumor growth in the brains of mice. Results: TTIF significantly inhibited the proliferation of U87 cells both in vitro and in vivo. Conclusion: TTIF significantly inhibited the proliferation of U87 cells both in vitro and in vivo. Consequently, TTIF emerges as a potential treatment option for patients with progressive or metastatic GBM.

The role of biophysical cues and their modulated exosomes in dental diseases: from mechanism to therapy.

Dental diseases such as caries and periodontitis have been common public health problems. Dental disease treatment can be achieved through stem cell-based dental regeneration. Biophysical cues determine the fate of stem cells and govern the success of dental regeneration. Some studies have manifested exosomes derived from stem cells could not only inherit biophysical signals in microenvironment but also evade some issues in the treatment with stem cells. Nowadays, biophysical cue-regulated exosomes become another promising therapy in dental regenerative medicine. However, methods to improve the efficacy of exosome therapy and the underlying mechanisms are still unresolved. In this review, the association between biophysical cues and dental diseases was summarized. We retrospected the role of exosomes regulated by biophysical cues in curing dental diseases and promoting dental regeneration. Our research also delved into the mechanisms by which biophysical cues control the biogenesis, release, and uptake of exosomes, as well as potential methods to enhance the effectiveness of exosomes. The aim of this review was to underscore the important place biophysical cue-regulated exosomes occupy in the realm of dentistry, and to explore novel targets for dental diseases.

SEC31a-ATG9a Interaction Mediates the Recruitment of COPII Vesicles for Autophagosome Formation.

Autophagy plays an important role in determining stem-cell differentiation. During the osteogenic differentiation of mesenchymal stem cells (MSCs), autophagosome formation is upregulated but the reason is unknown. A long-standing quest in the autophagy field is to find the membrane origin of autophagosomes. In this study, cytoplasmic coat protein complex II (COPII) vesicles, endoplasmic reticulum-derived vesicles responsible for the transport of storage proteins to the Golgi, are demonstrated to be a critical source of osteoblastic autophagosomal membrane. A significant correlation between the number of COPII vesicle and the autophagy level is identified in the rat bone tissues. Disruption of COPII vesicles restrained osteogenesis and decreased the number and size of autophagosomes. SEC31a (an outer coat protein of COPII vesicle) is found to be vital to regulate COPII vesicle-dependent autophagosome formation via interacting with ATG9a of autophagosomal seed vesicles. The interference of Sec31a inhibited autophagosome formation and osteogenesis in vitro and in vivo. These results identified a novel mechanism of autophagosome formation in osteogenic differentiation of stem cells and identified SEC31a as a critical protein that mediates the interplay between COPII and ATG9a vesicles. These findings broaden the understanding of the regulatory mechanism in the osteogenic differentiation of MSCs.

Comparison of staggered and conventional posterior single-door laminoplasty.

OBJECTIVE: This study aimed to delineate the clinical and radiological outcomes between two different single-door laminoplasty techniques, the staggered approach and the conventional one-sided approach, in treating cervical spondylotic myelopathy (CSM). METHODS: This is a retrospective chart review that involved 67 patients who had CSM with symptoms lasting for ≥3 months, and underwent staggered laminoplasty (Group A, n=35) or conventional laminoplasty (Group B, n=32). Outcomes measures included intraoperative parameters, the Japanese Orthopaedic Association (JOA) score, visual analog scale (VAS) for pain, cervical curvature, cervical range of motion (ROM), and radiographic parameters that reflected the level of post-operative muscle atrophy. Follow-up assessments were available at 3-, 6-, and 12-months post-operation. RESULTS: The mean ages in Group A and Group B were 57.11 (SD, 8.02) and 55.28 (SD, 8.47) years, respectively, with a gender distribution of 40.00% female in Group A and 40.63% in Group B (P>0.05). The average operative times were 130.86 (SD, 11.80) and 129.84 (SD, 10.51) minutes, respectively (P>0.05). However, intraoperative blood loss in milliliters was significantly higher in Group A (196.06; SD, 32.69) compared to Group B (155.03; SD, 37.80) (P<0.001). JOA scores revealed no significant post-operative differences between the two groups. Nevertheless, Group A exhibited less VAS pain, reduced post-operative ROM loss at 6 and 12 months, and less alteration in cervical curvature and decreased severity in muscle atrophy at 3-, 6-, and 12-months post-surgery. CONCLUSION: Patients who underwent staggered single-door laminoplasty experienced more favorable outcomes in some metrics than those who received the conventional technique.

Prevalence of visual abnormalities detected through paediatric vision screening in Queensland, Australia.

BACKGROUND: Vision screening programs can provide epidemiological information regarding visual impairment in children. This study aims to report the characteristics of visual abnormalities diagnosed through the Primary School Nurse Health Readiness Program (PSNHRP) in Queensland, Australia. METHODS: A retrospective review of vision screening records from the PSNHRP between January 2017 and December 2020 was undertaken. Children aged between 4 and 7 who underwent vision screening were included for review. Children with a visual acuity of worse than 6/9-1 using the Parr 4 m letter-matching chart or those who failed the SPOT Vision Screener were referred to an optometrist or ophthalmologist for review. RESULTS: 164 890 children underwent vision screening. 12148 children failed visual screening (7.4%) and were referred for an eye assessment. 6011 (69.4%) of the 8659 children who attended ophthalmic review had a confirmed visual abnormality. Of 164 890 screened children, 1187 (0.72%) were confirmed to have anisometropia, 3843 (2.33%) had refractive error, 194 (0.12%) had strabismus, 755 (0.46%) had anisometropic amblyopia, 136 (0.08%) had strabismic amblyopia, and 1356 (0.82%) had an unspecific abnormality. There was no statistically significant difference in the age at screening between any visual abnormality (p = 0.94). Anisometropia, refractive error, and strabismus were significantly more common in females than males (p = 0.03, p < 0.01, and p = 0.03 respectively), whereas anisometropic amblyopia was more common in males (p < 0.01). CONCLUSIONS: We report the prevalence of visual abnormalities detected through the PSNHRP vision screening program. Identification of medical or socioeconomic risk factors that are likely to be associated with visual abnormalities can help to optimise vision screening programs.

Magnesium Nanocomposite Hydrogel Reverses the Pathologies to Enhance Mandible Regeneration.

The healing of bone defects after debridement in medication-related osteonecrosis of the jaw (MRONJ) is a challenging medical condition with impaired angiogenesis, susceptible infection, and pro-inflammatory responses. Magnesium (Mg) nanocomposite hydrogel is developed to specifically tackle multiple factors involved in MRONJ. Mg-oxide nanoparticles tune the gelation kinetics in the reaction between N-hydroxysuccinimide-functionalized hyperbranched poly (ethylene glycol) and proteins. This reaction allows an enhanced mechanical property after instant solidification and, more importantly, also stable gelation in challenging environments such as wet and hemorrhagic conditions. The synthesized hydrogel guides mandible regeneration in MRONJ rats by triggering the formation of type H vessels, activating Osterix+ osteoprogenitor cells, and generating anti-inflammatory microenvironments. Additionally, this approach demonstrates its ability to suppress infection by inhibiting specific pathogens while strengthening stress tolerance in the affected alveolar bone. Furthermore, the enhanced osteogenic properties and feasibility of implantation of the hydrogel are validated in mandible defect and iliac crest defect created in minipigs, respectively. Collectively, this study offers an injectable and innovative bone substitute to enhance mandible defect healing by tackling multiple detrimental pathologies.

Large scale analysis of the SARS-CoV-2 main protease reveals marginal presence of nirmatrelvir-resistant SARS-CoV-2 Omicron mutants in Ontario, Canada, December 2021-September 2023.

Background: In response to the COVID-19 pandemic, a new oral antiviral called nirmatrelvir-ritonavir (PaxlovidTM) was authorized for use in Canada in January 2022. In vitro studies have reported mutations in Mpro protein that may be associated with the development of nirmatrelvir resistance. Objectives: To survey the prevalence, relevance and temporal patterns of Mpro mutations among SARS-CoV-2 Omicron lineages in Ontario, Canada. Methods: A total of 93,082 Mpro gene sequences from December 2021 to September 2023 were analyzed. Reported in vitro Mpro mutations were screened against our database using in-house data science pipelines to determine the nirmatrelvir resistance. Negative binomial regression was conducted to analyze the temporal trends in Mpro mutation counts over the study time period. Results: A declining trend was observed in non-synonymous mutations of Mpro sequences, showing a 7.9% reduction (95% CI: 6.5%-‬9.4%; p<0.001) every 30 days. The P132H was the most prevalent mutation (higher than 95%) in all Omicron lineages. In vitro nirmatrelvir-resistant mutations were found in 3.12% (n=29/929) Omicron lineages with very low counts, ranging from one to 19. Only two mutations, A7T (n=19) and M82I (n=9), showed temporal presence among the BA.1.1 in 2022 and the BQ.1.2.3 in 2022, respectively. Conclusion: The observations suggest that, as of September 2023, no significant or widespread resistance to nirmatrelvir has developed among SARS-CoV-2 Omicron variants in Ontario. This study highlights the importance of creating automated monitoring systems to track the emergence of nirmatrelvir-resistant mutations within the SARS-CoV-2 virus, utilizing genomic data generated in real-time.

Optimizing the combination of chemotherapeutic drugs along with radiotherapy for extranodal NK/T-cell lymphoma.

Background: Extranodal natural killer/T-cell lymphoma (ENKTCL) has a unique treatment principle. However, the optimal combination of drugs along with radiotherapy (RT) is unknown. Design: Retrospective cohort study. Objectives: We screened multiple drug combinations to identify the most efficacious therapeutic combinations. Methods: We reviewed 3105 patients who received 40 chemotherapy regimens with different combinations of 9 drug classes and/or RT. Least absolute shrinkage and selection operator and multivariable Cox regression analyses were used to screen efficacious single drugs and identify optimal combinations for overall survival (OS). Inverse probability of treatment weighting (IPTW) and multivariable analyses were used to compare survival between treatment regimens. Results: Screening and validation revealed RT, asparaginase (ASP), and gemcitabine (GEM) to be the most efficacious single modality/drug. RT remained an important component of first-line treatment, whereas ASP was a fundamental drug of non-anthracycline (ANT)-based regimens. Addition of RT to non-ANT-based or ASP/GEM-based regimens, or addition of an ASP-drug into ANT-based or GEM/platinum-based regimens, improved 5-year OS significantly. Use of ASP/GEM-based regimens was associated with significantly higher 5-year OS (79.9%) compared with ASP/ANT-based (69.2%, p = 0.001), ASP/methotrexate-based (63.5%, p = 0.011), or ASP/not otherwise specified-based (63.2%, p < 0.001) regimens. The survival benefit of ASP/GEM-based regimens over other ASP-based regimens was substantial across risk-stratified and advanced-stage subgroups. The survival benefits of a combination of RT, ASP, and GEM were consistent after adjustment for confounding factors by IPTW. Conclusion: These results suggest that combining ASP/GEM with RT for ENKTCL is an efficacious and feasible therapeutic option and provides a rationale and strategy for developing combination therapies.

Baicalin Ameliorates Depression-like Behaviors via Inhibiting Neuroinflammation and Apoptosis in Mice.

Depression is a common neuropsychiatric disease which brings an increasing burden to all countries globally. Baicalin, a flavonoid extracted from the dried roots of Scutellaria, has been reported to exert anti-inflammatory, antioxidant, and neuroprotective effects in the treatment of depression. However, the potential biological mechanisms underlying its antidepressant effect are still unclear. In the present study, we conducted extensive research on the potential mechanisms of baicalin's antidepressant effect using the methods of network pharmacology, including overlapped terms-based analysis, protein-protein interaction (PPI) network topology analysis, and enrichment analysis. Moreover, these results were further verified through molecular docking, weighted gene co-expression network analysis (WGCNA), differential gene expression analysis, and subsequent animal experiments. We identified forty-one genes as the targets of baicalin in the treatment of depression, among which AKT1, IL6, TP53, IL1B, and CASP3 have higher centrality in the more core position. Meanwhile, the roles of peripheral genes derived from direct potential targets were also observed. Our study suggested that biological processes, such as inflammatory reaction, apoptosis, and oxidative stress, may be involved in the therapeutic process of baicalin on depression. These mechanisms were validated at the level of structure, gene, protein, and signaling pathway in the present study. Taken together, these findings propose a new perspective on the potential mechanisms underlying baicalin's antidepressant effect, and also provide a new basis and clarified perspective for its clinical application.

WWOX-related epileptic encephalopathy caused by a novel mutation in the WWOX gene: a case report.

Background: WWOX-related epileptic encephalopathy is an autosomal recessive disorder caused by mutations in the WW-containing oxidoreductase gene, characterized by the onset of refractory seizures in infants. Early-onset epilepsy, electroencephalography abnormalities, and developmental delay or degeneration are the main clinical manifestations. Early death can occur in severe cases. In the present study, a novel variant in WWOX was detected in a patient with epilepsy and his healthy parents. Case presentation: A 5-month-old boy presented with epilepsy. The main manifestations were intractable seizures, mental and motor retardation and hearing impairment. Subsequent genetic testing revealed the presence of an epilepsy-associated novel mutation: c.991C>A (amino acid change: p.Ser304Tyr) in the WWOX gene. Variants were inherited from parents with healthy phenotypes. Finally, a patient died at 6 months of age. Conclusion: The discovery of novel variants has enriched the existing database of WWOX gene variants and may expand the range of clinical options for treating WWOX-related disorders.

A systematic review and network meta-analysis on the optimal wavelength of low-level light therapy (LLLT) in treating knee osteoarthritis symptoms.

OBJECTIVES: To compare the efficacy of the various wavelengths of low-level light therapy (LLLT) in alleviating knee pain, dysfunction, and stiffness in patients with knee osteoarthritis (KOA), and to compare the effectiveness of LLLT versus sham treatment in reducing knee pain, dysfunction, and stiffness. METHODS: PubMed, Web of Science, EMBASE, and Cochrane Library were searched from inception to 12 December 2023. Randomized controlled trials that assessed the effects of different wavelengths of LLLT on alleviating pain of patients with KOA were included. A conventional meta-analysis and network meta-analysis were preformed, and standardized mean differences (SMD) with 95% confidence interval (CI) were calculated. RESULTS: Thirteen studies involving 673 participants with KOA met inclusion criteria. Overall, LLLT was superior to sham LLLT for relieving pain (SMD = 0.96, 95% CI 0.31-1.61) but not for improving function (SMD = 0.21, 95% CI - 0.11 to 0.53) or stiffness (SMD = 0.07, 95% CI - 0.25 to 0.39). Surface under the cumulative ranking curve (SUCRA) value ranking showed the most effective wavelength of LLLT in reducing KOA pain was 904-905 nm (SUCRA, 86.90%), followed by multi-wavelengths (MWL) (SUCRA, 56.43%) and 785-850 nm (SUCRA, 54.97%). Compared to sham LLLT, L2 (SMD = 1.42, 95% CI = 0.31-2.53) and L1 (SMD = 0.82; 95% CI = 0.11-1.50) showed a significant reduction in KOA pain. However, MWL (SMD = 0.83; 95% CI = - 0.06 to 1.72) showed similar KOA pain reduction compared to sham LLLT. The certainty of evidence showed that the quality of evidence regarding the effectiveness of overall LLLT versus sham, and 904-905 nm versus sham were low, while the quality of evidence for MWL versus sham, and 785-850 nm versus sham was very low. CONCLUSION: While the 904-905 nm wavelength showed potential benefits in reducing KOA pain, the overall quality of the evidence was low. LLLT with 904-905 nm or 785-850 nm wavelengths yielded significantly better reduction in KOA pain compared to sham LLLT, but further high-quality research is warranted to validate these findings.

Dosimetric benefit and clinical feasibility of deep inspiration breath-hold and volumetric modulated arc therapy-based postmastectomy radiotherapy for left-sided breast cancer.

To evaluate the dosimetric benefits and clinical feasibility of deep inspiratory breath-hold (DIBH) combined with volumetric modulated arc therapy (VMAT) in left-sided postmastectomy radiotherapy (PMRT). Eligible patients with left-sided breast cancer undergoing DIBH-based PMRT were prospectively included. Chest wall, supra/infraclavicular fossa, and/or internal mammary node irradiation (IMNI) were planned with a prescription dose of 43.5 Gy in 15 fractions. VMAT plans were designed on free breathing (FB)-and DIBH-CT to compare dosimetric parameters in heart, left anterior descending artery (LAD) and lung. Cone-beam computed tomography (CBCT) was performed before and after treatment to evaluate inter- and intra-fractional setup errors. Heart position and dose variations during treatment were estimated by fusing CBCT with DIBH-CT scans.Twenty patients were included with 10 receiving IMNI. In total, 193 pre-treatment and 39 pairs pre- and post-treatment CBCT scans were analyzed. The Dmean, Dmax, and V5-40 of the heart, LAD, and left lung were significantly lower in DIBH than FB (p < 0.05 for all), except for V5 of LAD (p = 0.167). The cardiopulmonary dosimetric benefits were maintained regardless of IMNI. The inter- and intra-fractional setup errors were < 0.3 cm; and the overall estimated PTV margins were < 1.0 cm. During treatment, the mean dice similarity coefficient of heart position and the mean ratio of heart Dmean between CBCT and DIBH-CT plans was 0.95 (0.88-1.00) and 100% (70.6-119.5%), respectively. DIBH-VMAT could effectively reduce the cardiopulmonary doses with acceptable reproducibility and stability in left-sided PMRT regardless of IMNI.

Chaetocin inhibits the progression of neuroblastoma by targeting JAK2/STAT3 signaling pathway in SH-SY5Y cells.

Chaetocin is a fungal mycotoxin that extensively found in various natural products and has anticancer and anti­inflammatory activities. Herein, the anticancer effects of chaetocin against the progression of neuroblastoma were studied with SHSY-5Y human neuroblastoma cells and examined the underlying molecular mechanisms. The effects of chaetocin on cellular viability, apoptosis, cell migration, and invasion were investigated. The underlying mechanism of anticancer effects of chaetocin was found to mediate via activating JAK2/STAT3 signaling pathway. Furthermore, when SHSY-5Y cells were exposed to a higher concentration of chaetocin, the induction of cell apoptosis significantly increased by enhancing the expression of pro-apoptotic protein Bcl-2, resulting in anticancer activity against neuroblastoma. In addition, chaetocin significantly decreased the SHSY-5Y cell invasion and migration at 50 µM treatment. Moreover, it was shown that increasing chaetocin treatments greatly decreased the activity of proteins connected to the JAK2/STAT3 signaling pathway. In conclusion, chaetocin exhibits a diverse range of actions on neuroblastoma cells, including the inhibition of proliferation, induction of apoptosis, perturbation of cellular morphology, and modulation of critical signaling pathways, with a specific focus on the JAK/STAT3 pathway. These results contribute valuable insights that underscore the potential therapeutic utility of chaetocin in the context of neuroblastoma treatment, suggesting its multifaceted impact on key cellular processes involved in cancer progression.

Senolytic effect of triterpenoid complex from Ganoderma lucidum on adriamycin-induced senescent human hepatocellular carcinoma cells model in vitro and in vivo.

Background: Ganoderma lucidum (G. lucidum) is a famous medicinal mushroom that has been reported to prevent and treat a variety of diseases. Different extractions from G. lucidum have been used to manage age-related diseases, including cancer. Nevertheless, the senolytic activity of G. lucidum against senescent cancer cells has not been investigated. Although cellular senescence causes tumor growth inhibition, senescent cells promote the growth of the neighboring tumor cells through paracrine effects. Therefore, the elimination of senescent cells is a new strategy for cancer treatment. Methods: In this study, senescence was triggered in HCC cells by the chemotherapeutic agent Adriamycin (ADR), and subsequently, cells were treated with TC to assess its senolytic activity. Results: We found for the first time that the triterpenoid complex (TC) from G. lucidum had senolytic effect, which could selectively eliminate adriamycin (ADR)-induced senescent cells (SCs) of hepatocellular carcinoma (HCC) cells via caspase-dependent and mitochondrial pathways-mediated apoptosis and reduce the levels of senescence markers, thereby inhibiting the progression of cancers caused by SCs. TC could block autophagy at the late stage in SCs, resulting in a significant activation of TC-induced apoptosis. Furthermore, TC inhibited the senescence-associated secretory phenotype (SASP) in SCs through the inhibition of NF-κB, TFEB, P38, ERK, and mTOR signaling pathways and reducing the number of SCs. Sequential administration of ADR and TC in vivo significantly reduced tumor growth and reversed the toxicity of ADR. Conclusion: A triterpenoid complex isolated from G. lucidum may serve as a novel senolytic agent against SCs, and its combination with chemotherapeutic agents may enhance their antitumor efficacy.

Targeted recognition and enhanced biotransformation of phytochemicals by a dual-functional cellulose-based hydrogel bioreactor.

The combined technology of molecular imprinting and immobilization is a promising strategy for improving biocatalytic performance. In this work, a dual-functional cellulose-based hydrogel bioreactor with targeted recognition and transformation functions was innovatively designed by cellulose-based molecularly imprinted polymers (CM-MIPs) hydrogel coupled with layered double hydroxide immobilized enzyme (LDH-E). Firstly, CM-MIPs hydrogel was prepared by using phlorizin, 4-pinylpyridine, and cellulose microspheres as template molecule, functional monomer, and support material, respectively. Meanwhile, layered double hydroxide (LDH) taken as a carrier to immobilize ß-glucosidase. The prepared LDH was layered sheet-like structure with ultra-thin thickness of approximately only 1.5 nm, and ß-glucosidase was immobilized on both sides of the LDH. Further, the dual-functional bioreactor was constructed by the anion exchange, which possessed maximum targeted adsorption capacity to phlorizin of 15.25 mg/g, exhibited 1.2 folds higher transformation efficiency than LDH-E, and the phloretin content increased 26 folds to that in Lithocarpus litseifolius (Hance) Chu leaves extracts. Moreover, the transformation efficiency remained above 70 % even after five consecutive transformations. Overall, the dual-functional bioreactor has broad prospects for the application in targeted recognition and transformation of phytochemicals, and provides a new insight on multifunctional bio-based reactors in natural production field.

Clathrin-Mediated Endocytosis of Multiple Nanoparticles Tends to Be Less Cooperative: A Computational Study.

The internalization of nanoparticles is of great significance for their biological applications. Clathrin-mediated endocytosis (CME) is one of the main endocytic pathways. However, there is still a lack of a fundamental understanding regarding the internalization of multiple nanoparticles via CME. Therefore, in this study, we conducted computational investigations to uncover detailed molecular mechanisms and kinetic pathways for differently shaped nanoparticles in the presence of clathrin. Particular focus is given to understanding the CME of multiple-nanoparticle systems. We found that unlike receptor-mediated endocytosis, multiple nanoparticles did not get cooperatively wrapped by the membrane but tended to undergo independent endocytosis in the presence of clathrin. To further investigate the endocytosis mechanism, we studied the effects of clathrins, nanoparticle shape, nanoparticle size, nanoparticle arrangement, and membrane surface tension. The self-assembly of clathrin prefers independent endocytosis for multiple nanoparticles. Besides, the cooperative behavior is weak with increasing nanoparticle-shape anisotropy. However, when the membrane tension is reduced, the endocytosis pathway for multiple nanoparticles is cooperative endocytosis. Moreover, we found that the self-assembly of clathrins reduces the critical size of nanoparticles to undergo cooperative wrapping by the cell membrane. Our results provide valuable insights into the molecular mechanisms of multiple nanoparticles through CME and offer useful guidance for the design of nanoparticles as drug/gene delivery carriers.

Edaravone Dexborneol provides neuroprotective effect by inhibiting neurotoxic activation of astrocytes through inhibiting NF-κB signaling in cortical ischemia.

Edaravone Dexborneol (EDB), comprised of edaravone and (+)- bornel, has been demonstrated to have synergistic effects of antioxidant and anti-inflammatory, which makes it to be applied for stroke as a protectant. However, the underlying mechanism of neuroprotection of EDB has not been fully elucidated. Increasing evidence has shown that neurotoxic A1 astrocytes were closely related to neuronal death after cerebral ischemia. However, whether EDB could provide neuroprotection by modulating the activation of astrocytes has not yet been elucidated. The present study aimed to explore whether EDB afforded neuroprotection by modulating A1 polarization of astrocytes and the down-stream signaling after cerebral ischemia. We first validated the neuroprotective effects of EDB in mice suffering focal cerebral ischemia via evaluating behavioral test, infarct volumes and neuronal survival. As for the down-stream signaling, our data further showed that EDB alleviated neuronal death by suppressing activation of neurotoxic A1 astrocytes via inhibition of NF-κB signaling pathway in vitro. Additionally, administration of EDB reduced the number of A1 reactive astrocytes in mice of focal cerebral ischemia. The above findings demonstrated that EDB provided neuroprotective effect by inhibiting neurotoxic activation of A1 astrocytes in animal model of cerebral ischemia, which indicated that EDB-mediated phenotypic regulation of astrocytes is a potential research direction to promote neurological recovery in central nervous system (CNS) diseases.

Increased choroidal stromal area in patients with active Graves' ophthalmopathy based on binarisation method of optical coherence tomographic images.

OBJECTIVE: To investigate the change in choroidal components of patients with Graves' ophthalmopathy (GO) with different degrees of disease activity and severity by using the image binarisation method of optical coherence tomography (OCT). METHODS: This cross-sectional study included 151 eyes of 90 patients with GO. Patients were grouped according to the clinical activity score (CAS) and disease severity. Total choroidal area (TCA), luminal area, stromal area (SA) and choroidal vascularity index (CVI) were acquired by image binarisation of the OCT. Ocular parameters between groups were compared using generalised estimating equations, accounting for intereye correlation and adjusting for relevant factors. RESULTS: As for the included eyes, 104 eyes were inactive GO and 47 eyes were active GO. Local choroidal thicknesses were thicker in active GO than in inactive GO. TCA and SA were significantly larger in active GO than in inactive GO group (3.44±0.91 mm2 vs 3.14±0.88 mm2, p=0.046; 1.16 (1.03-1.50) mm2 vs 1.10 (0.96-1.27) mm2, p=0.002, respectively). CAS was positively correlated with TCA (r=0.171, p=0.036) and SA (r=0.172, p=0.035), and negatively associated with CVI (r=-0.174, p=0.032). In multiple regression models, age, diopter and intraocular pressure (IOP) exhibited significant correlations with the SA (ß=-0.006, p=0.010; ß=0.076, p<0.001; ß=0.015, p=0.010, respectively). CONCLUSIONS: Thickened choroid was observed in active GO compared with inactive GO. The proportional increase of SA was augmented as the disease activity progressed. Age, diopter and IOP were independent factors that affected choroidal area and components in patients with GO. Multicentre prospective cohort studies with a large sample size are still needed.