Search

Central post-stroke pain (CPSP) is a highly refractory form of central neuropathic pain that has been poorly studied mechanistically. Recent observations have emphasized the critical role of the spinal dorsal horn in CPSP. However, the underlying mechanisms remain unclear. In this study, rats were subjected to thalamic hemorrhage to investigate the role of spinal monocyte chemoattractant protein-1 (MCP-1) and C-C motif chemokine receptor 2 (CCR2) in the development of CPSP. Immunohistochemical staining and ELISA were used to assess the expression changes of c-Fos, Iba-1, GFAP, MCP-1, and CCR2 in the dorsal horn of the lumbar spinal cord following thalamic hemorrhage, and the involvement of spinal MCP-1 in CPSP was examined by performing intrathecal anti-MCP-1 mAb injection to neutralize the spinal extracellular MCP-1. We demonstrated that intra-thalamic collagenase microinjection induced persistent bilateral mechanical pain hypersensitivity and facilitated the spontaneous pain behaviors evoked by intraplantar bee venom injection. Accompanying CPSP, the expression of c-Fos, Iba-1, and GFAP in the lumbar spinal dorsal horn was significantly increased up to 28 days post-intra-thalamic collagenase microinjection. Intrathecal injection of minocycline and fluorocitrate dramatically reverses the bilateral mechanical pain hypersensitivity. Moreover, intra-thalamic collagenase microinjection dramatically induced the up-regulation of MCP-1 but had no effect on the expression of CCR2 in the bilateral lumbar spinal dorsal horn, and MCP-1 was primarily localized in the neuron. Intrathecal injection of anti-MCP-1 mAb was also able to reverse CPSP and reduce the expression of c-Fos, Iba-1, and GFAP in the lumbar spinal dorsal horn. These findings indicated that spinal MCP-1 contributes to CPSP by mediating the activation of spinal neurons and glial cells following thalamic hemorrhage stroke, which may provide insights into pharmacologic treatment for CPSP.

Due to the increasing use of local anesthetic techniques in various healthcare settings, local anesthetic toxicity still occurs. Seizures are the most common symptom of local anesthetic toxicity. The relationship between local anesthetic-induced seizures and the sensation of pain has not been established till now. Here, we assessed the development of pain hypersensitivity after ropivacaine-induced seizures (RIS) and the influence of RIS on incision-induced postsurgical pain and formalin-induced acute inflammatory pain. In addition, the involvement of spinal 5-HT/5-HT

Intracerebral hemorrhage (ICH) is a common subtype of stroke and places a great burden on the family and society with a high mortality and disability rate and a poor prognosis. Many findings from imaging and pathologic studies have suggested that cerebral ischemic lesions visualized on diffusion-weighted imaging (DWI) in patients with ICH are not rare and are generally considered to be associated with poor outcome, increased risk of recurrent (ischemic and hemorrhagic) stroke, cognitive impairment, and death. In this review, we describe the changes in cerebral blood flow (CBF) and DWI lesions after ICH and discuss the risk factors and possible mechanisms related to the occurrence of DWI lesions, such as cerebral microangiopathy, cerebral atherosclerosis, aggressive early blood pressure lowering, hyperglycemia, and inflammatory response. We also point out that a better understanding of cerebral DWI lesions will be a key step toward potential therapeutic interventions to improve long-term recovery for patients with ICH.

Background Central post-stroke pain (CPSP) is an intractable and disabling central neuropathic pain that severely affects patients’ lives, well-being, and socialization abilities. However, CPSP has been poorly studied mechanistically and its treatment remains challenging. Here, we used a rat model of CPSP induced by thalamic hemorrhage to investigate its underlying mechanisms and the effect of stellate ganglion block (SGB) on CPSP and emotional comorbidities. Methods Thalamic hemorrhage was produced by injecting collagenase IV into the ventral-posterolateral nucleus (VPL) of the right thalamus. The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Behavioral tests were carried out to examine depressive and anxiety-like behaviors including the open field test (OFT), elevated plus maze test (EPMT), novelty-suppressed feeding test (NSFT), and forced swim test (FST). The peri-thalamic lesion tissues were collected for immunofluorescence, western blotting, and enzyme-linked immunosorbent assay (ELISA). Genetic knockdown of thalamic hypoxia-inducible factor-1α (HIF-1α) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) with microinjection of HIF-1α siRNA and NLRP3 siRNA into the VPL of thalamus were performed 3 days before collagenase injection into the same regions. Microinjection of lificiguat (YC-1) and MCC950 into the VPL of thalamus were administrated 30 min before the collagenase injection in order to inhibited HIF-1α and NLRP3 pharmacologically. Repetitive right SGB was performed daily for 5 days and laser speckle contrast imaging (LSCI) was conducted to examine cerebral blood flow. Results Thalamic hemorrhage caused persistent mechanical allodynia and anxiety- and depression-like behaviors. Accompanying the persistent mechanical allodynia, the expression of HIF-1α and NLRP3, as well as the activities of microglia and astrocytes in the peri-thalamic lesion sites, were significantly increased. Genetic knockdown of thalamic HIF-1α and NLRP3 significantly attenuated mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Further studies revealed that intra-thalamic injection of YC-1, or MCC950 significantly suppressed the activation of microglia and astrocytes, the release of pro-inflammatory cytokines, the upregulation of malondialdehyde (MDA), and the downregulation of superoxide dismutase (SOD), as well as mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. In addition, repetitive ipsilateral SGB significantly restored the upregulated HIF-1α/NLRP3 signaling and the hyperactivated microglia and astrocytes following thalamic hemorrhage. The enhanced expression of pro-inflammatory cytokines and the oxidative stress in the peri-thalamic lesion sites were also reversed by SGB. Moreover, LSCI showed that repetitive SGB significantly increased cerebral blood flow following thalamic hemorrhage. Most strikingly, SGB not only prevented, but also reversed the development of mechanical allodynia and anxiety- and depression-like behaviors induced by thalamic hemorrhage. However, pharmacological activation of thalamic HIF-1α and NLRP3 with specific agonists significantly eliminated the therapeutic effects of SGB on mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Conclusion This study demonstrated for the first time that SGB could improve CPSP with comorbid anxiety and depression by increasing cerebral blood flow and inhibiting HIF-1α/NLRP3 inflammatory signaling.

Intracerebral hemorrhage (ICH) is an acute cerebrovascular disease with high disability and mortality rates. Recombinant tissue plasminogen activator (rtPA) is commonly applied for hematoma evacuation in minimally invasive surgery (MIS) after ICH. However, rtPA may contact directly with brain tissue during MIS procedure, which makes it necessary to discuss the safety of rtPA. We found that, in the in vivo ICH model induced by VII-type collagenase, rtPA treatment improved the neurological function of ICH mice, alleviated the pathological damage and decreased the apoptosis and autophagy level of the peri-hematoma tissue. In the in-vitro model of ICH induced by hemin, the administration of rtPA down-regulated neuronal apoptosis, autophagy, and endoplasmic reticulum stress of neurons. Transcriptome sequencing analysis showed that rtPA treatment upregulated the PI3K/AKT/mTOR pathway in neurons, and PI3K inhibitor (LY294002) can reverse the protective effects of rtPA in inhibiting excessive apoptosis, autophagy and ER-stress. Epidermal growth factor receptor inhibitor (AG-1487) reversed the effect of rtPA on PI3K/AKT/mTOR pathway, which might indicate that the EGF domain played an important role in the activation of PI3K/AKT/mTOR pathway.

The aim was to examine the effect of role overload, work addiction and leader-member exchange on missed nursing care.A cross-sectional study.Chinese registered nurses from five Sichuan province public hospitals were studied from March 2022-May 2022. The measurements were derived from a questionnaire on role overload, work addiction, missed nursing care, leader-member exchange and a sociodemographic datasheet. Descriptive statistics and inferential statistics were conducted (N = 403).Role overload was associated with missed nursing care, and work addiction played a mediation role. Leader-member exchange negatively predicted work addiction and played a moderating role between role overload and work addiction. The effect of role overload on work addiction was attenuated when the level of leader-member exchange was higher. Promoting leader-member exchange could mitigate how role overload undermines missed nursing care.

Acute promyelocytic leukemia (APL) has become curable over 95% patients under a complete chemo-free treatment with all-trans retinoic acid (ATRA) and arsenic trioxide in low-risk patients. Minimizing chemotherapy has proven feasible in high-risk patients. We evaluated oral arsenic and ATRA without chemotherapy as an outpatient consolidation therapy and no maintenance for high-risk APL. We conducted a multicenter, single-arm, phase 2 study with consolidation phases. The consolidation therapy included Realgar–Indigo naturalis formula (60 mg/kg daily in an oral divided dose) in a 4-week-on and 4-week-off regimen for 4 cycles and ATRA (25 mg/m2 daily in an oral divided dose) in a 2-week-on and 2-week-off regimen for 7 cycles. The primary end point was the disease-free survival (DFS). Secondary end points included measurable resident disease, overall survival (OS), and safety. A total of 54 participants were enrolled at seven centers from May 2019. The median age was 40 years. At the median follow-up of 13.8 months (through April 2022), estimated 2-year DFS and OS were 94% and 100% in an intention-to-treat analysis. All the patients achieved complete molecular remission at the end of consolidation phase. Two patients relapsed after consolidation with a cumulative incidence of relapse of 6.2%. The majority of adverse events were grade 1–2, and only three grade 3 adverse events were observed. Oral arsenic plus ATRA without chemotherapy was active as a first-line consolidation therapy for high-risk APL.Trial registration: chictr.org.cn number, ChiCTR1900023309.

Purpose Vascular cognitive impairment (VCI) has been one of the major types of cognitive impairment. Blood-brain barrier damage plays an essential part in the pathogenesis of VCI. At present, the treatment to VCI mainly focused on prevention, with no drug clinically approved for the treatment of VCI. This study aimed to investigate the effects of DL-3-n-butylphthalide (NBP) on VCI rats. Methods A modified bilateral common carotid artery occlusion (mBCCAO) model was applied to mimic VCI. The feasibility of the mBCCAO model was verified by laser Doppler, 13N-Ammonia-Positron Emission Computed Tomography (PET) and Morris Water Maze. Subsequently, Morris water maze experiment, Evans blue staining and western blot of tight junction protein were performed to evaluate the effect of different doses of NBP (40mg/kg, 80mg/kg) on the improvement of cognitive impairment and BBB disruption induced by mBCCAO. Immunofluorescence was employed to examine the changes of pericyte coverage in mBCCAO model and the effect of NBP on pericyte coverage were preliminarily explored. Results mBCCAO surgery led to obvious cognitive impairment and the decrease of whole cerebral blood flow, among which the blood flow in cortex, hippocampus and thalamus brain regions decreased more significantly. High-dose NBP (80 mg/kg) improved long-term cognitive function in mBCCAO rats, alleviated Evans blue leakage and reduced the loss of tight junction proteins (ZO-1, Claudin-5) in the early course of the disease, thereby exerting a protective effect on the blood-brain barrier. No significant changes in pericyte coverage were observed after mBCCAO. Conclusions High-dose NBP improved cognitive function in mBCCAO rats. High-dose NBP protected the integrity of BBB by upregulating TJ protein expression, rather than regulating pericyte coverage ratio. NBP could be a potential drug for the treatment of VCI.

Background: Ferrous ion, a degradation product of hematomas, induces inflammatory reactions and other secondary injuries after intracerebral hemorrhage (ICH). Our study aimed to investigate the specific neuroprotective mechanism of adipose‐derived stem cells (ADSCs) on ferrous ion‐induced neural injury in vitro. Methods: ADSCs were co‐cultured with primary cortical neurons in a transwell system treated with ferrous sulfate to generate an in vitro ICH model. ADSCs and cortical neurons were cultured in the upper and lower chambers, respectively. Neuron apoptosis was determined by flow cytometry. The levels of insulin‐like growth factor‐1 (IGF‐1), malondialdehyde (MDA) and nitric oxide synthase (NOS) activity in neuron culture medium were detected with commercial kits. In neurons, protein expression in phosphatidylinositol‐3‐kinase (PI3K)/protein kinase B (Akt) signaling pathway, nuclear factor erythroid 2‐related factor 2 (Nrf2)/heme oxygenase‐1 (HO‐1) signaling pathway and apoptosis‐related proteins were detected by western blot. Results: ADSCs attenuated neural apoptosis, reduced MDA levels and NOS activity induced by ferrous sulfate. In neurons, IGF‐1 was increased, as were p‐PI3K, p‐Akt, Nrf2, HO‐1, and Bcl‐2 while cleaved caspase 3 was down‐regulated. Conclusions: ADSCs exert neuroprotective effects against ferrous iron‐induced neuronal damage by secreting IGF‐1 and increasing the levels of Akt‐dependent Nrf2/ARE signaling pathway.

Aim To assess the effects of workplace fun on nurse innovative behaviour and to confirm the intermediary function of affective commitment. Background Employee innovative behaviour has a crucial function in survival and development of an organisation. On the basis of the theory of social exchange, there has been inadequate study of the influence of workplace fun on nurse innovative behaviour mediated by affective commitment. Methods A cross-sectional, descriptive correlational research design was conducted for 331 Chinese nurses from five public hospitals. The measurements were obtained from a questionnaire on workplace fun, affective commitment, nurse innovative behaviour and a sociodemographic datasheet. Descriptive statistics were used to analyse the personal profile, and inferential statistics were used to test hypotheses. Results We identified a positive correlation between workplace fun and nurse innovative behaviour. Affective commitment had a mediating effect. Conclusion Workplace fun and affective commitment can promote nurse innovative behaviour. Implications for nursing management Managers need to provide measures that promote workplace fun and affective commitment to enhance nurse innovative behaviour.

Background: The clinical efficiency of terpenoids in treating human acute lung injury (ALI) is yet to be determined. The lipopolysaccharide-induced rat model of ALI is a well-established and widely used experimental model for studying terpenoids’ effects on ALI. Using a systematic review and meta-analysis, the therapeutic efficiency of terpenoid administration on the lung wet-to-dry weight ratio in rats was investigated.Methods: Using the Cochrane Library, Embase, and PubMed databases, a comprehensive literature search for studies evaluating the therapeutic efficacy of terpenoids on ALI in rats was conducted. The lung wet-to-dry weight ratio was extracted as the main outcome. The quality of the included studies was assessed using the Systematic Review Center for Laboratory Animal Experimentation’s risk of bias tool.Results: In total, 16 studies were included in this meta-analysis. In general, terpenoids significantly lowered the lung wet-to-dry weight ratio when compared with the control vehicle (p = 0.0002; standardized mean difference (SMD): −0.16; 95% confidence interval (CI): −0.24, −0.08). Subgroup analysis revealed that low dose (≤10 μmol/kg) (p < 0.0001; SMD: −0.68; 95% CI: −1.02, −0.34), intraperitoneal injection (p = 0.0002; SMD: −0.43; 95% CI: −0.66, −0.20), diterpenoid (p = 0.004; SMD: −0.13; 95% CI: −0.23, −0.04), and triterpenoid (p = 0.04; SMD: −0.28; 95% CI: −0.54, −0.01) significantly lowered the lung wet-to-dry weight ratio when compared with the control vehicle.Conclusion: A low dose of diterpenoid and triterpenoid administered intraperitoneally is effective in alleviating ALI. This systematic review and meta-analysis provides a valuable mirror for clinical research aiming at the advancement of terpenoids for preventive and therapeutic use.Systematic Review Registration: CRD42022326779

Surface electromyography (sEMG) is a kind of valuable bioelectric signal and very potential in the field of human–machine interaction. Ideal interactions require sEMG based patterns recognition not only with high accuracy but also with good rapidity. However, too much real-time feature-related computation will greatly slow down the interaction, especially for multichannel sEMG. To decrease the feature-related time consumption, the paper formulates the feature reduction as an optimization problem, and develops a double-phases particle swarm optimization (PSO) with hybrid coding to solve the problem. In the research, the initial feature data set with 31 kinds of feature is built firstly based on eight subjects’ 16 channels forearm sEMG signals, then PSO is introduced to conduct the feature reduction of 31 × 16 dimensions through the feature and channel optimization in double phases. During the optimization, two improved k-nearest neighbor (KNN) methods such as weighted representation based KNN (WRKNN) and weighted local mean representation based KNN (WLMRKNN) are introduced to classify the gestures, and the classification accuracy is used to evaluate the particles of PSO. Experimental results and comparison analysis show that PSO based feature reduction methods outperform genetic algorithm (GA), ant colony optimization (ACO) and principal component analysis (PCA) based feature reduction methods. With the optimized feature data subset by PSO, WRKNN and WLMRKNN are superior to KNN, quadratic discriminant analysis (QDA), and naive bayes (NB) greatly. The proposed method can be applied in the pattern recognition of high dimensional sEMG with multichannel or high-density channels for the purpose of rapidity and without a decline of accuracy in real-time control. Further, it can be used to reduce the economic cost of the personalized customization equipment through the optimal channels for any subjects in the future.

Polyhedral oligomeric silsesquioxanes (POSS) and γ-glycidoxy propyl trimethoxy silane (KH560) were applied to modify boron nitride (BN) and boron nitride whisker (BNw), and modified BN (m-BN) and m...

High-temperature-resistant magnetic particles/SiCN (C) composite ceramics were prepared by the polymer derivation in this paper. The phase composition, microstructure, electromagnetic wave (EMW) absorption properties and EMW absorption mechanism were studied. The results show that magnetic particles/SiCN (C) composite ceramics have a wider EMW absorption bandwidth as compared to the SiCN (C) composite ceramics. When the thickness was 4 mm, Fe/SiCN (C) composite ceramics had a minimum reflection loss (RLmin) of − 15.7 dB and an effective absorption bandwidth (EAB, RL

Regeneration of neural tissue is limited following spinal cord injury (SCI). Successful regeneration of injured nerves requires the intrinsic regenerative capability of the neurons and a suitable microenvironment. However, the local microenvironment is damaged, including insufficient intraneural vascularization, prolonged immune responses, overactive immune responses, dysregulated bioenergetic metabolism and terminated bioelectrical conduction. Among them, the immune microenvironment formed by immune cells and cytokines plays a dual role in inflammation and regeneration. Few studies have focused on the role of the immune microenvironment in spinal cord regeneration. Here, we summarize those findings involving various immune cells (neutrophils, monocytes, microglia and T lymphocytes) after SCI. The pathological changes that occur in the local microenvironment and the function of immune cells are described. We also summarize and discuss the current strategies for treating SCI with tissue-engineered biomaterials from the perspective of the immune microenvironment.

To precisely determine the species of a carbapenem-resistantSingle-molecule real-time (SMRT) sequencing was carried out on strain 18091276 to obtain the complete chromosome and plasmid (pCN1276) sequences, and average nucleotide identity (ANI) was used for precise species identification. The ICEs in GenBank with the same integrase structure as ICEThis bacterium wasThe formation of

Strain SZW01 was isolated from sea sediment collected from Shenzhen in Guangdong province, China, and was later identified as Aspergillus fumigatus by16S rDNA sequence analysis. Various chromatogra...

Consider a discrete-time risk model with dependence structures, where claim sizes are assumed to follow a one-sided linear process whose innovations further obey a so-called bivariate upper tail in...

Ag2WO4/CdS composites with different concentrations of CdS nanoparticles were synthesized. The morphology of the as-synthesized particles was studied by SEM and TEM, and the surface chemical states and elemental composition were investigated by XPS. The photocatalytic properties of both Ag2WO4 and Ag2WO4/CdS were investigated by decomposing RhB under visible light. The conclusion indicated that the addition of CdS into Ag2WO4 could improve the photocatalytic performance, while an excessive amount of CdS could decrease the photocatalytic activity. The mechanism for the increased photocatalytic performance was investigated by UV–Vis absorption spectrum, EIS Nyquist plots, and transient photocurrent responses. The increased photocatalytic performance could be attributed to the increased electron/hole separation and charge carrier transfer, due to the presence of CdS on Ag2WO4.

The nano-sized neodymium doped aluminum lutetium garnet (LuAG:Nd) phosphors well crystallized with particle size of around 100–130 nm were successfully synthesized via microwave-induced solution combustion method. The optimal crystallization temperature of LuAG:Nd was determined at 900 °C based on controlled trials. XRD results showed an obvious distortion in lattice parameters of LuAG, which could be confirmed by the shift of diffraction peak towards lower degrees with Nd concentration increasing. Another evidence for successful doping of neodymium was the absorption line at around 808 nm in the absorption spectra, which could result from the Nd3+ 4I9/2-4F5/2 transition. Furthermore, the near-infrared spectra showed that the quenching concentration of Nd3+ in prepared LuAG:Nd polycrystalline samples with the highest intensity of 1064 nm was at 5 mol%.

Background Bostrycin is a natural pigment product with anthraquinone skeleton, which has excellent inhibitory effect on a variety cancer cells. However, its suppression on tongue squamous cell carcinoma has not been reported. Methods We studied the effects of bostrycin on the cell growth and apoptosis of tongue squamous cell carcinoma in vitro, and explored its mechanism. Results Bostrycin could inhibit the proliferation and migration of tongue squamous cell carcinoma by arresting cell cycle at G2/M phase, and inducing cell apoptosis with mitochondrial membrane potential changes. West-blotting analysis also showed that bostrycin could inhibit the growth of tongue squamous cell carcinoma cells by activating the apoptosis-related signal proteins especially in mitochondrial apoptotic pathway. Conclusions Bostrycin can be used as a new anti-tumor candidate drug for further research. Our study provides reference for the potential application of bostrycin in the treatment of the tongue squamous cell carcinoma.

Biomineralization is characterized by the fact that the crystallization of inorganic minerals is guided by an in vivo biological interface. However, the interfaces that direct calcification are widely debated up to date. In this paper, it was found that the two-dimensional (2D) immiscible domain of cholesterol in the lipid bilayer can induce the deposition of calcium phosphate by rapidly promoting the nucleation of the hydroxyapatite (001) plane. This promotion effect is related to the high lattice matching degree between the 2D cholesterol immiscible domain and the (001) plane of hydroxyapatite (HAP), which leads to the heteroepitaxy of HAP. The lipid bilayer derived from cells or vesicles is the largest biological interface in the body, thus revealing whether the lipid bilayer can induce the deposition of calcium phosphate will facilitate the understanding of the important role of cells or vesicles in calcification.

Herein, silicon nitride (Si3N4) ceramic reinforced with multi-walled carbon nanotubes (MWCNT) was processed by hot press sintering using fluoride additives (AlF3 and MgF2). The X-ray diffraction patterns show that a SiC layer is formed owing to the reaction between Si and MWCNT, leading to a good bonding between MWCN and Si3N4 matrix. The microstructural results revealed that the fluoride additives lead to improve the densification and phase transformation through liquid phase mechanism. The effect of various concentrations of MWCNT on dielectric and microwave (MW) absorption properties of MWCNT/Si3N4 composites in a frequency range of 8.2 to 12.4 GHz (X-band) was investigated. The dielectric parameters have revealed that the complex permittivity of MWCNT/Si3N4 composites have also been enhanced with the addition of MWCNT content. Moreover, the MW absorption properties were improved with the addition of MWCNT, and the minimum value of reflection loss (RL) was achieved − 8.65 dB (~ 90% absorption), indicating that the MWCNT/Si3N4 composites might exhibit a promising prospect as MW absorber.

Carbon nanostructures (CNS) as a kind of reinforcement material can remarkably enhance the mechanical and thermal properties of ceramics. This research presents an analysis of the influence of CNS on the thermal conductivity and mechanical properties of SiCw/Si3N4 composites. The SiCw/Si3N4 composites containing various types of CNS e.g. carbon nanofibers (CNF), multi-walled carbon nanotubes (MWCNT) and graphene nano-platelets (GNP) were fabricated by hot-press sintering. XRD analysis confirmed a complete transformation of α-Si3N4 to β-Si3N4 and microstructural analysis shows a uniform distribution, as well as a pullout and bridging mechanism of CNS. The results revealed that the thermal conductivity and mechanical properties of SiCw/Si3N4 composites increased with the addition of CNS. Maximum values of fracture toughness (9.70 ± 0.8 MPa m1/2) and flexural strength (765 ± 58 MPa) have been achieved for the MWCNT-containing SiCw/Si3N4 composite, whereas the maximum values of Young's modulus (250 ± 3.8 GPa) and hardness (27.2 ± 0.9 GPa) have been achieved for the CNF-containing SiCw/Si3N4 composite. Moreover, thermal conductivity also improved with the addition of CNS and reached a maximum value of 110.6 W m−1 K−1 for the CNF-containing SiCw/Si3N4 composite. This work provides a useful approach for the fabrication of high-performance multifunctional composites for emerging engineering applications.

AIM: To demonstrate the feasibility of mesenchymal stem cell (MSC)-mediated nano drug delivery, which was characterized by the “Trojan horse”-like transport of HIF-1α siRNA between MSCs and retinal pigment epithelial cells (RPE) under hypoxia environment.METHODS: Plasmid and lentivirus targeting the human HIF-1α gene were designed and constructed by Genechem company. HIF-1α siRNA was encapsulated into Poly (lactic-co-glycolic acid)(PLGA) nanoparticles(NPs) through the water-in-oil-in-water (W/O/W) multiple emulsion technique. MSCs were transfected with the NPs and the transfection efficacy was evaluated by flow cytometry. Then a transwell co-culture system of MSCs and RPE was constructed under hypoxia environment. The effects of MSC-loaded HIF-1α siRNA PLGA-NPs on proliferation, apoptosis, and migration of RPE cells were then evaluated. The effect on HIF-1α expression of RPE cells was analyzed by using quantitative polymerase chain reaction at the time point 24 h, 3 d and 7 d.RESULTS: The average diameter of PLGA-NPs loaded with HIF siRNA was 314.1nm and the zeta potential was﹣0.36 mV. The transfection efficiency of PLGA NPs was (67.3%±5.2%) into MSCs by using flow cytometry. Compared with the lentivirus group, the PLGA-NPs loaded with HIF-1α siRNA can effectively reduce the expression of HIF-1α mRNA up to 7 days in RPE (0.63±0.05 at 7d, P < 0.001). In the transwell co-culture system of MSCs and RPE, the abilities of proliferation(2.34±0.17 vs 2.40 ± 0.28 vs2.47±0.24 at 48h, F=0.23, P=0.80), apoptosis(14.83 ± 2.43% vs 12.94 ± 2.19% vs 12.39 ± 3.21%; F= 0.70, P=0.53) and migration(124.5± 7.78 vs 119.5± 5.32 vs 130±9.89, F =1.33, P=0.33) of the RPE cells had no differences between MSC-loaded HIF-1α siRNA PLGA-NPs group and other groups. The inhibition of PLGA on the HIF-1α mRNA expression in RPE cells could continue until the 7th day, the level of HIF-1α mRNA was lower than that of other groups (F=171.98, P CONCLUSION: The delivery of PLGA-NPs loaded with HIF-1α siRNA carried by MSCs is found to be beneficial temporally for HIF-1α mRNA inhibition in RPE cells under hypoxia environment. The MSC-based bio-mimetic delivery of HIF-1α siRNA nanoparticles is a potential method for therapy against choroidal neovascularization (CNV).

Supplemental material, sj-docx-1-tct-10.1177_15330338221114707 for Role of Long Noncoding RNA Regulator of Reprogramming in Colon Cancer Progression via Epidermal Growth Factor Receptor Signaling by Ying Chen, PhD, Li Yang, BA, Dian Yin, MM, Xiu Feng, Jing Jie, Phd, DengFu Yao, PhD, and JianRong Chen, PhD in Technology in Cancer Research & Treatment

Additional file 1. Figure S1. The treatment schema. The consolidation therapy included RIF (60 mg/kg daily in an oral divided dose) in a 4-week-on and 4-week-off regimen for 4 cycles and ATRA (25 mg/m2 daily in an oral divided dose) in a 2-week-on and 2-week-off regimen for 7 cycles. Of note, treatment cycles were counted according to the cycles of ATRA. Figure S2. Flow chart of participants enrollment, treatment and follow-up. 54 patients were enrolled in the clinical trial and an intention-to-treat analysis were performed. Seven patients had major protocol violation. Four of them suffered cerebral hemorrhage in induction therapy, so their physicians advised two cycles of chemotherapy for consolidation therapy and continued with RIF plus ATRA for 7 cycles. One of them changed protocol for a grade 3 hematochezia. One patient returned to his hometown hospital and changed his treatment plan. The last one did not give a specific reason for the change in treatment. Another seven patients were in consolidation process. Two patients were lost to follow-up and one of them had not completed the trial. Thus 39 patients were included in the per-protocol analysis. Figure S3. PML-RARA tested at 3, 5 and 7 months from the beginning of the induction therapy in ITT analysis.Table S1. Characteristics of the Patients. Table S2. Clinical characteristics and treatment of five patients with cerebral hemorrhage. Table S3. Treatment and outcomes of two relapsed patients. Patient No.1 had cerebral hemorrhage at the time of diagnosis. She had a molecular relapse at 11 months after remission and a central nervous system relapse at 13 months. Patient No.2 had a hematologic relapse at 13 months and achieved remission again after RIF plus ATRA reinduction and alive until last follow-up.