Glioblastoma stem cells deliver ABCB4 transcribed by ATF3 via exosomes conferring glioblastoma resistance to temozolomide.

Glioblastoma stem cells (GSCs) play a key role in glioblastoma (GBM) resistance to temozolomide (TMZ) chemotherapy. With the increase in research on the tumour microenvironment, exosomes secreted by GSCs have become a new focus in GBM research. However, the molecular mechanism by which GSCs affect drug resistance in GBM cells via exosomes remains unclear. Using bioinformatics analysis, we identified the specific expression of ABCB4 in GSCs. Subsequently, we established GSC cell lines and used ultracentrifugation to extract secreted exosomes. We conducted in vitro and in vivo investigations to validate the promoting effect of ABCB4 and ABCB4-containing exosomes on TMZ resistance. Finally, to identify the transcription factors regulating the transcription of ABCB4, we performed luciferase assays and chromatin immunoprecipitation-quantitative PCR. Our results indicated that ABCB4 is highly expressed in GSCs. Moreover, high expression of ABCB4 promoted the resistance of GSCs to TMZ. Our study found that GSCs can also transmit their highly expressed ABCB4 to differentiated glioma cells (DGCs) through exosomes, leading to high expression of ABCB4 in these cells and promoting their resistance to TMZ. Mechanistic studies have shown that the overexpression of ABCB4 in GSCs is mediated by the transcription factor ATF3. In conclusion, our results indicate that GSCs can confer resistance to TMZ in GBM by transmitting ABCB4, which is transcribed by ATF3, through exosomes. This mechanism may lead to drug resistance and recurrence of GBM. These findings contribute to a deeper understanding of the mechanisms underlying drug resistance in GBM and provide novel insights into its treatment.

Effect of Dl-3-n-Butylphthalide on olfaction in rotenone-induced Parkinson's rats.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Olfactory dysfunction (OD) is an important nonmotor feature of PD. Dl-3-n-Butylphthalide (NBP) is a synthetic compound isolated from Apium graveolens seeds. The present study was conducted to investigate the effect of NBP on olfaction in rotenone-induced Parkinson's rats to explore the mechanism and pathway of OD in PD. Methods: The PD model was established using rotenone-induced SD rats, divided into blank control, model, and treatment groups. A sham group was also established, with 10 rats in each group. The treatment group was given NBP (1 mg/kg, 10 mg/kg, and 100 mg/kg, dissolved in soybean oil) intragastrically for 28 days. Meanwhile, the control group rats were given intra-gastrically soybean oil. After behavioral testing, all rats were executed, and brain tissue was obtained. Proteomics and Proteomic quantification techniques (prm) quantification were used to detect proteomic changes in rat brain tissues. Results: Compared with the control group, the model group showed significant differences in behavioral tests, and this difference was reduced after treatment. Proteomics results showed that after treatment with high-dose NBP, there were 42 differentially expressed proteins compared with the model group. Additionally, the olfactory marker (P08523) showed a significant upregulation difference. We then selected 22 target proteins for PRM quantification and quantified 17 of them. Among them, the olfactory marker protein was at least twofold upregulated in the RTH group compared to the model group.

Curcumol: a review of its pharmacology, pharmacokinetics, drug delivery systems, structure-activity relationships, and potential applications.

Curcumol (Cur), a guaiane-type sesquiterpenoid hemiketal, is an important and representative bioactive component extracted from the essential oil of the rhizomes of Curcumae rhizoma which is also known as "Ezhu" in traditional Chinese medicine. Recently, Cur has received considerable attention from the research community due to its favorable pharmacological activities, including anti-cancer, hepatoprotective, anti-inflammatory, anti-viral, anti-convulsant, and other activities, and has also exerted therapeutic effect on various cancers, liver diseases, inflammatory diseases, and infectious diseases. Pharmacokinetic studies have shown that Cur is rapidly distributed in almost all organs of rats after intragastric administration with high concentrations in the small intestine and colon. Several studies focusing on structure-activity relationship (SAR) of Cur have shown that some Cur derivatives, chemically modified at C-8 or C-14, exhibited more potent anti-cancer activity and lower toxicity than Cur itself. This review aims to comprehensively summarize the latest advances in the pharmacological and pharmacokinetic properties of Cur in the last decade with a focus on its anti-cancer and hepatoprotective potentials, as well as the research progress in drug delivery system and potential applications of Cur to date, to provide researchers with the latest information, to highlighted the limitations of relevant research at the current stage and the aspects that should be addressed in future research. Our results indicate that Cur and its derivatives could serve as potential novel agents for the treatment of a variety of diseases, particularly cancer and liver diseases.

Surveillance of SARS-CoV-2 in wastewater by quantitative PCR and digital PCR: a case study in Shijiazhuang city, Hebei province, China.

In this study, we reported the first long-term monitoring of SARS-CoV-2 in wastewater in Mainland China from November 2021 to October 2023. The city of Shijiazhuang was employed for this case study. We developed a triple reverse transcription droplet digital PCR (RT-ddPCR) method using triple primer-probes for simultaneous detection of the N1 gene, E gene, and Pepper mild mottle virus (PMMoV) to achieve accurate quantification of SARS-CoV-2 RNA in wastewater. Both the RT-ddPCR method and the commercial multiplex reverse transcription quantitative polymerase chain reaction (RT-qPCR) method were implemented for the detection of SARS-CoV-2 in wastewater in Shijiazhuang City over a 24-month period. Results showed that SARS-CoV-2 was detected for the first time in the wastewater of Shijiazhuang City on 10 November 2022. The peak of COVID-19 cases occurred in the middle of December 2022, when the concentration of SARS-CoV-2 in the wastewater was highest. The trend of virus concentration increases and decreases forming a "long-tailed" shape in the COVID-19  outbreak and recession cycle. The results indicated that both multiplex RT-ddPCR and RT-qPCR are effective in detecting SARS-CoV-2 in wastewater, but RT-ddPCR is capable of detecting low concentrations of SARS-CoV-2 in wastewater which is more efficient. The SARS-CoV-2 abundance in wastewater is correlated to clinical data, outlining the public health utility of this work.HighlightsFirst long-term monitoring of SARS-CoV-2 in wastewater in Mainland ChinaCOVID-19 outbreak was tracked in Shijiazhuang City from outbreak to containmentWastewater was monitored simultaneously using RT-ddPCR and RT-qPCR methodsTriple primer-probe RT-ddPCR detects N1 and E genes of SARS-CoV-2 and PMMoV.

Rapid authentication of characteristic milk powders by recombinase polymerase amplification assays.

The authentication of dairy species has great significance for food safety. This study focused on a more rapid method for identifying major dairy species, and specific recombinase polymerase amplification (RPA)-based assays for cattle, goat, sheep, camel and donkey were developed. Through the developed RPA-based assays, goats and sheep could be simultaneously identified and bovine families could be differentiated. The performances of the RPA assays were validated using 37 milk powder samples, of which 16.2% (6/37) were suspected of being adulterated and 24.3% (9/37) were potentially at risk of being wrongly identified as adulteration. The effectiveness of the developed assays for crude DNA detection was also validated by a rapid nucleic acid extraction kit, and results showed that the presence of large amounts of protein and fat did not affect the qualitative results. Therefore, these assays could combine with the rapid nucleic acids extraction methods for being used in field detection.

IFITM3 promotes glioblastoma stem cell-mediated angiogenesis via regulating JAK/STAT3/bFGF signaling pathway.

Interferon-induced transmembrane protein 3 (IFITM3) has been previously verified to be an endosomal protein that prevents viral infection. Recent findings suggested IFITM3 as a key factor in tumor invasion and progression. To clarify the role and molecular mechanism of IFITM3 in Glioblastoma multiforme (GBM) progression, we investigated the expression of IFITM3 in glioma datasets culled from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). Primary GBM stem cells (GSCs) were cultured and identified in vitro. Loss-of-function and gain-of-function experiments were established by using shRNAs and lentiviral vectors targeting IFITM3. Co-culture system of GSCs and vascular endothelial cells was constructed in a Transwell chamber. Tube formation and spheroid-based angiogenesis assays were performed to determine the angiogenic capacity of endothelial cells. Results revealed that IFITM3 is elevated in GBM samples and predictive of adverse outcome. Mechanistically, GSCs-derived IFITM3 causes activation of Jak2/STAT3 signaling and leads to robust secretion of bFGF into tumor environment, which eventually results in enhanced angiogenesis. Taken together, these evidence indicated IFITM3 as an essential factor in GBM angiogenesis. Our findings provide a new insight into mechanism by which IFITM3 modulates GBM angiogenesis.

Integrated Diffusion Tensor Imaging and Renal Parenchymal Volume for Early Detection and Grading of Split Renal Functional Impairment in Lupus Nephritis.

RATIONALE AND OBJECTIVES: To investigate the effectiveness of combining split diffusion tensor imaging (DTI) measurements with split renal parenchymal volume (RPV) for assessing split renal functional impairment in patients with lupus nephritis (LN). MATERIALS AND METHODS: Seventy-four participants [48 LN patients and 26 healthy volunteers (HV)] were included in the study. All participant underwent conventional MR and DTI (b = 0, 400, and 600 s/mm2) examinations using a 3.0 T MRI scanner to determine the split renal DTI measurements and split RPV. In LN patients, renography glomerular filtration rate (rGFR) was measured using 99mTc-DTPA scintigraphy based on Gates' method, serving as the reference standard to categorize all split kidneys of LN patients into LN with mild impairment (LNm, n = 65 kidneys) and LN with moderate to severe (LNms, n = 31 kidneys) groups according to the threshold of 30 ml/min in spilt rGFR. All statistical analyses were performed using SPSS 25.0 and MedCalc 20.0 software packages. RESULTS: Only split medullary fractional anisotropy (FA) and the product of split medullary FA and RPV could distinguish pairwise subgroups among the HV and each LN subgroup (all p < 0.05). ROC curve analysis demonstrated that split medullary FA (AUC = 0.866) significantly outperformed other parameters in differentiating HV from LNm groups, while the product of split medullary FA and split RPV was superior in distinguishing LNm and LNms groups (AUC = 0.793) than other parameters. The combination of split medullary FA and split RPV showed best correlation with split rGFR (r = 0.534, p < 0.001). CONCLUSION: Split medullary FA, and its combination with split RPV, are valuable biomarkers for detecting early functional changes in renal alterations and predicting disease progression in patients with LN.

CircRNA Larp4b/miR-298-5p/Mef2c Regulates Cardiac Hypertrophy Induced by Angiotensin II.

Cardiac hypertrophy (CH) is an early marker in the clinical course of heart failure. Circular RNAs (circRNAs) play important roles in human disease. However, the role of circ_Larp4b in myocardial hypertrophy has not been studied. Angiotensin II (Ang II) treated HL-1 cells to induce a CH cell model. Quantitative real-time polymerase chain reaction was used to detect the expression of circ_Larp4b, microRNA-298-5p, and myocyte enhancer factor 2 (Mef2c). Western blot detected the protein level of alpha-actinin-2 (ACTN2), beta-myosin heavy chain (ß-MHC), atrial natriuretic peptide (ANP), and Mef2c. The relationship between miR-298-5p and circ_Larp4b or Mef2c was verified by dual-luciferase reporter assay and RNA pull-down assay. Circ_Larp4b and Mef2c were upregulated in HL-1 cells treated with Ang II. Moreover, circ_Larp4b down-regulation regulated the progress of CH induced by Ang II. MiR-298-5p was a target of circ_Larp4b, and Mef2c was a target of miR-298-5p. Overexpressed Mef2c reversed the cell size inhibited by miR-298-5p in Ang II-induced HL-1 cells. Circ_Larp4b regulated CH progress by regulating miR-298-5p/Mef2c axis.

The Impact of SARS-CoV-2 Infection on Patients with Aortic Stenosis.

OBJECTIVE: To investigate the potential treatments for aortic stenosis and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using bioinformatics and systems biology. STUDY DESIGN: Observational study. Place and Duration of the Study: Jiading District Central Hospital affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China, from August to December 2022. METHODOLOGY: GSE147507 was chosen as the SARS-CoV-2 infection dataset from the Biotechnology Information (NCBI) GEO database, while GSE153555 was chosen as the dataset of patients with aortic stenosis (AS). This analysis predicted protein-drug interactions (PDIs) and found therapeutic compounds for AS and COVID-19. RESULTS: One hundred and four DEGs were shared between the two datasets. Researchers built a PPI network to identify 10 hub genes from the network. Researchers discovered that COVID-19 and AS shared certain pathogenic pathways and found a relationship between hub genes and transcription factors and miRNAs, as well as a connection between hub genes and proposed treatments. CONCLUSION: Hub genes were identified as potential pathogenic pathways in SARS-CoV-2 infection and AS. In addition, new prescription medication options for treating both illnesses were provided. KEY WORDS: SARS-CoV-2 infection, COVID-19, Aortic stenosis, Differentially expressed genes, Hub genes, Gene-disease, Drug molecule.

Associations of adverse childhood experiences with common psychiatric disorder in later life: results from the China mental health survey.

BACKGROUND: Associations between adverse childhood experiences (ACEs) and common psychiatric disorders among older Chinese individuals have not been well reported. The objectives of this study are to examine the prevalence of ACEs and the associations of ACEs with common psychiatric disorders among older adults in China. METHODS: The study used data from the China Mental Health Survey (CMHS), a nationally representative epidemiological survey, which used computer-assisted personal interviewing (CAPI), logistic regression models were used to examine community-based adult psychiatric disorders and associated risk factors. Finally, 2,317 individuals aged 60 years or over were included in the CMHS. The national prevalence of ACEs in older adults were estimated and logistic regression were used to analyse the association between ACEs and past-year psychiatric disorders. RESULTS: Prevalence of ACEs among older adults in China was 18.1%. The three most common types of ACEs were neglect (11.6%), domestic violence (9.2%), and parental loss (9.1%). This study proved the association between ACEs and common past-year psychiatric disorders in older adults. ACEs increased the risk of past-year psychiatric disorders in older adults. After adjustment for age, sex, marital status, employment status, education, rural or urban residence, region, and physical diseases, the association between ACEs and past-year psychiatric disorders were still significant. CONCLUSIONS: ACEs are linked to an increased risk for past-year psychiatric disorders in older adults. ACEs may have long-term effects on older adults' mental well-being. Preventing ACEs may help reduce possible adverse health outcomes in later life.

Lewis base-catalyzed cascade [4 + 2]-annulation reaction of N-alkoxy acrylamides and acyl isothiocyanates: facile access to 2-imino-1,3-thiazinone derivatives.

A formal [4 + 2]-cycloaddition reaction of N-alkoxy acrylamides and acyl isothiocyanates was developed via a Lewis base-catalyzed cascade aza-nucleophilic addition/thio-Michael addition process under mild conditions. This study provides a facile approach for preparing 2-imino-1,3-thiazinone derivatives in moderate to excellent yields and enriches the field of heterocyclic acrylamide chemistry. The reported method features metal-free reaction conditions, high atom economy, and easy operation. Moreover, the reaction was successfully scaled up and derivatization reactions were successfully performed.

Synthesis of Polycyclic Imidazolidinones via Cascade [3 + 2]-Annulation of ß-Oxo-acrylamides with Cyclic N-Sulfonyl Imines.

An Et3N-catalyzed cascade [3 + 2]-annulation of ß-oxo-acrylamides with cyclic N-sulfonyl ketimines or sulfamate-derived imines is developed under mild reaction conditions, which provides a concise and efficient route to access valuable sultam- or sulfamidate-fused imidazolidinone derivatives in good to excellent yields (80-95% yields) with excellent diastereoselectivities (>20:1 drs). The current protocol features atom economy, a transition-metal-free process, and broad functional group tolerance. Moreover, the asymmetric variant of the [3 + 2]-cycloaddition reaction was achieved in the presence of diphenylethanediamine or quinine-based bifunctional squaramide organocatalysts C-1 and C-11, giving the corresponding chiral polycyclic imidazolidinones in 68-90% yields with 25-94% ees and >20:1 drs in all cases.

Curcumin alleviates orofacial allodynia and improves cognitive impairment via regulating hippocampal synaptic plasticity in a mouse model of trigeminal neuralgia.

OBJECTIVE: Cognitive impairment, one of the most prevalent complications of trigeminal neuralgia, is troubling for patients and clinicians due to limited therapeutic options. Curcumin shows antinociception and neuroprotection pharmacologically, suggesting that it may have therapeutic effect on this complication. This study aimed to investigate whether curcumin alleviates orofacial allodynia and improves cognitive impairment by regulating hippocampal CA1 region synaptic plasticity in trigeminal neuralgia. METHODS: A mouse model of trigeminal neuralgia was established by partially transecting the infraorbital nerve (pT-ION). Curcumin was administered by gavage twice daily for 14 days. Nociceptive thresholds were measured using the von Frey and acetone test, and the cognitive functions were evaluated using the Morris water maze test. Dendritic spines and synaptic ultrastructures in the hippocampal CA1 area were observed by Golgi staining and transmission electron microscopy. RESULTS: Curcumin intervention increased the mechanical and cold pain thresholds of models. It decreased the escape latency and distance to the platform and increased the number of platform crossings and dwell time in the target quadrant of models, and improved spatial learning and memory deficits. Furthermore, it partially restored the disorder of the density and proportion of dendritic spines and the abnormal density and structure of synapses in the hippocampal CA1 region of models. CONCLUSION: Curcumin alleviates abnormal orofacial pain and cognitive impairment in pT-ION mice by a mechanism that may be related to the synaptic plasticity of hippocampal CA1, suggesting that curcumin is a potential strategy for repairing cognitive dysfunction under long-term neuropathic pain conditions.

Non-immune cell components in tumor microenvironment influencing lung cancer Immunotherapy.

Lung cancer (LC) is one of the leading causes of cancer-related deaths worldwide, with a significant morbidity and mortality rate, endangering human life and health. The introduction of immunotherapies has significantly altered existing cancer treatment strategies and is expected to improve immune responses, objective response rates, and survival rates. However, a better understanding of the complex immunological networks of LC is required to improve immunotherapy efficacy further. Tumor-associated antigens (TAAs) and tumor-specific antigens (TSAs) are significantly expressed by LC cells, which activate dendritic cells, initiate antigen presentation, and activate lymphocytes to exert antitumor activity. However, as tumor cells combat the immune system, an immunosuppressive microenvironment forms, enabling the enactment of a series of immunological escape mechanisms, including the recruitment of immunosuppressive cells and induction of T cell exhaustion to decrease the antitumor immune response. In addition to the direct effect of LC cells on immune cell function, the secreting various cytokines, chemokines, and exosomes, changes in the intratumoral microbiome and the function of cancer-associated fibroblasts and endothelial cells contribute to LC cell immune escape. Accordingly, combining various immunotherapies with other therapies can elicit synergistic effects based on the complex immune network, improving immunotherapy efficacy through multi-target action on the tumor microenvironment (TME). Hence, this review provides guidance for understanding the complex immune network in the TME and designing novel and effective immunotherapy strategies for LC.

Single-Cell Analysis of circRNA Using ddPCR.

Droplet digital polymerase chain reaction (ddPCR) is a new quantitative PCR method based on water-oil emulsion droplet technology. ddPCR enables highly sensitive and accurate quantification of nucleic acid molecules, especially when their copy numbers are low. In ddPCR, a sample is fractionated into ~20,000 droplets, and every nanoliter-sized droplet undergoes PCR amplification of the target molecule. The fluorescence signals of droplets are then recorded by an automated droplet reader. Circular RNAs (circRNAs) are single-stranded, covalently closed RNA molecules that are ubiquitously expressed in animals and plants. CircRNAs are promising as biomarkers for cancer diagnosis and prognosis and as therapeutic targets or agents to inhibit oncogenic microRNAs or proteins (Kristensen LS, Jakobsen T, Hager H, Kjems J, Nat Rev Clin Oncol 19:188-206, 2022). In this chapter, the procedures for the quantitation of a circRNA in single pancreatic cancer cells using ddPCR are described.

Post-traumatic stress disorder and traumatic events in China: a nationally representative cross-sectional epidemiological study.

Post-traumatic stress disorder (PTSD) is one of the most severe sequelae of trauma. But a nationally representative epidemiological data for PTSD and trauma events (TEs) was unavailable in China. This article firstly demonstrated detailed epidemiological information on PTSD, TEs, and related comorbidities in the national-wide community-based mental health survey in China. A total of 9,378 participants completed the PTSD-related interview of the CIDI 3.0. Lifetime prevalence and 12-month prevalence of PTSD in total respondents were 0.3% and 0.2%. while the conditional lifetime and 12-month prevalence of PTSD after trauma exposure were 1.8% and 1.1%. The prevalence of exposure to any type of TE was 17.2%. Among individuals with the exposed to TEs, younger, without regular work (being a homemaker or retried), and intimate relationship breakdown (separated/Widowed/Divorced), living rurally were associated with either the lifetime PTSD or the 12-month PTSD, while the count of a specific TE, the unexpected death of loved one, was related to both. Alcohol dependence was the most common comorbidity among male participants with PTSD but major depressive disorder (MDD) for female counterparts. Our study can provide a reliable reference for future identification and intervention for people with PTSD.

Interfacial Chemistry Effects in the Electrochemical Performance of Silicon Electrodes under Lithium-Ion Battery Conditions.

Understanding the solid electrolyte interphase (SEI) formation and (de)lithiation phenomena at silicon (Si) electrodes is key to improving the performance and lifetime of Si-based lithium-ion batteries. However, these processes remain somewhat elusive, and, in particular, the role of Si surface termination merits further consideration. Here, scanning electrochemical cell microscopy (SECCM) is used in a glovebox, followed by secondary ion mass spectrometry (SIMS) at identical locations to study the local electrochemical behavior and associated SEI formation, comparing Si (100) with a native oxide layer (SiOx /Si) and etched with hydrofluoric acid (HF-Si). HF-Si shows greater spatial electrochemical heterogeneity and inferior lithiation reversibility than SiOx /Si. This is attributed to a weakly passivating SEI and irreversible lithium trapping at the Si surface. Combinatorial screening of charge/discharge cycling by SECCM with co-located SIMS reveals SEI chemistry as a function of depth. While the SEI thickness is relatively independent of the cycle number, the chemistry - particularly in the intermediate layers - depends on the number of cycles, revealing the SEI to be dynamic during cycling. This work serves as a foundation for the use of correlative SECCM/SIMS as a powerful approach to gain fundamental insights on complex battery processes at the nano- and microscales.

Anticancer Effect of STING Agonist-Encapsulated Liposomes on Breast Cancer.

Breast cancer is one of the most common cancers worldwide, posing a serious threat to human health. Recently, innate immunity has become a widely discussed topic in antitumor research. The STING pathway is an important component of innate immunity, and several STING agonists have been developed and applied in antitumor research. Dimeric amidobenzimidazole (diABZI) is one STING agonist and is a nucleotide analog with low serological stability and cell membrane permeability. In this study, we prepared diABZI-encapsulated liposomes (dLNPs) using the ammonium sulfate gradient method. The average particle size of the dLNPs was 99.76 ± 0.230 nm, and the encapsulation efficiency was 58.29 ± 0.53%. Additionally, in vivo and in vitro assays showed that the dLNPs had a sustained-release effect and that the circulation time in vivo was longer than 48 h. The expression of IFN-ß and IFN-γ was elevated in mice treated with dLNPs. Moreover, we found that dLNPs can recruit CD8+ T cells to tumor tissue and exert antitumor effects. The dLNPs-treated group showed the most significant efficacy: the average tumor volume was 231.46 mm3, which decreased by 78.16% and 54.47% compared to the PBS group and diABZI group. Meanwhile, the hemolysis rate of the dLNPs was 2%, showing high biocompatibility. In conclusion, dLNPs can effectively suppress tumor growth and possess great potential in breast cancer therapy.

Acute effects of Kinesio Taping on lower-limb coordination of gait in hemiplegic patients.

BACKGROUND: Kinesio taping can effectively strengthen weakened muscles, increase walking speed, and improve dynamic balance in hemiplegic patients, but its effect on lower-limb coordination is not clear. Improving lower-limb coordination in hemiplegic patients can decrease risk of fall during walking. RESEARCH QUESTION: This study utilized continuous relative phase to depict the pattern and variability of lower-limb coordination in hemiplegic patients and healthy subjects during walking, and investigate whether it has the acute effect of Kinesio Taping on lower-limb coordination in hemiplegic patients during walking. METHODS: Gait was measured by a three-dimensional motion capture system for 29 hemiplegic patients (KT group) and 15 healthy subjects (control group). Mean continuous relative phase (MCRP) and mean continuous relative phase variability (MCRPV) were calculated to describe and evaluate lower-limb coordination. RESULTS: KT intervention only changed the coordination between the bilateral ankle joints in hemiplegic patients. Before the intervention, the MCRP of the two ankles (AA-MCRP) in the stance period of the control group was greater than the KT group (P < 0.001), the MCRPV of the two ankles (AA-MCRPV) in the swing period was lower than that in KT group (P < 0.001). After the intervention, the AA-MCRP in the stance period of the KT group increased (P < 0.001), the AA-MRPV in the swing period of KT group significantly decreased (P = 0.001). SIGNIFICANCE: Immediate ankle KT intervention can result in the in-phase or anti-phase coordination between the two ankles developing to out-of-phase coordination during the stance period of the affected limb during walking, and increase the stability of the out-of-phase coordination between the two ankles during the swing period of the affected limb. KT can be used in rehabilitation treatment for hemiplegic patients to improve acute coordination between the patients' ankles.

Preoperative administration of a biomimetic platelet nanodrug enhances postoperative drug delivery by bypassing thrombus.

The postoperative thrombus attached to the damaged blood vessels severely obstructs drugs from crossing the damaged blood-brain barrier (BBB) and targeting residual glioma cells around surgical margins, leading to glioblastoma (GBM) recurrence. A thrombus-bypassing, BBB-crossing, and surgical margin-targeted nanodrug is needed to address this phenomenon. Encouraged by the intrinsic damaged vascular endothelium chemotaxis of platelets, a platelet membrane-coated nanodrug (PM-HDOX) delivering doxorubicin (DOX) for postoperative GBM treatment is proposed and systematically investigated. Because surgery damages the vascular endothelium on the BBB around the surgical margin, the platelet membrane coating endows PM-HDOX with its inherent capacity to cross the broken BBB and target the surgical margin. Moreover, preoperative administration combined with fast-targeted PM-HDOX can realize the potential of bypassing thrombus. In GBM resection models, PM-HDOX with preoperative administration demonstrated significantly enhanced BBB-crossing and surgical margin-targeted efficacy. In particular, the PM-HDOX intensities around the surgical margins of the preoperative administration group were more than twice that of the postoperative administration group due to bypassing the thrombus formed in the broken BBB. In the antitumor experiment, the preoperative administration of PM-HDOX significantly inhibited the growth of postoperative residual tumors and prolonged the median survival time of mice. In conclusion, preoperative administration of a biomimetic platelet nanodrug can be an efficient and promising drug delivery strategy for residual GBM after surgery.