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Small molecule inhibitors of the bromodomain and extraterminal domain (BET) family proteins have emerged as promising options not only for the treatment of multiple cancers but also for disturbing the process of sperm maturation with potential for use as viable contraceptive targets. In this study, we find that the BET family inhibitor NHWD870 and BRDT can bind well in vitro through bioinformatics software prediction and protein binding inhibition experiments. NHWD870 can produce a good contraceptive effect through animal experiments in vivo, and the fertility can be restored to normal after drug withdrawal. Transcriptomics and proteomics results suggest that NHWD870 affects pathways related to spermatogenesis and maturation, further contributing to the male infertility phenotype. Our results show that NHWD870 can induce a complete and reversible contraceptive effect in mice, which is stronger than that of JQ1 and its synthesized derivatives. This study is expected to eventually lead to clinical trials.

Aberrant energy metabolism not only endows tumor cells with unlimited proliferative capacity but also contributes to the establishment of the glucose-deficient/lactate-rich immunosuppressive tumor microenvironment (ITM) impairing antitumor immunity. Herein, a novel metabolic nanoregulator (D/B/CQ@ZIF-8@CS) was developed by enveloping 2-deoxy-d-glucose (2-DG), BAY-876, and chloroquine (CQ) into zeolitic imidazolate framework-8 (ZIF-8) to simultaneously deprive the energy/nutrition supply of tumor cells and relieve the ITM for synergetic tumor starvation-immunotherapy. Aerobic glycolysis, glucose uptake, and autophagy flux could be concurrently blocked by D/B/CQ@ZIF-8@CS, cutting off the nutrition/energy supply and the source of lactate. Furthermore, inhibition of glucose uptake and aerobic glycolysis could effectively reverse the glucose-deficient/lactate-rich ITM, thus functionally inactivating regulatory T cells and augmenting anti-CTLA-4 immunotherapy. Such a two-pronged strategy would provide new insights for the design of metabolic intervention-based synergistic cancer therapy.

Dose dependent effects of TPCA-1 on STAT3 activation.

TPCA-1 inhibits endogenous STAT3 activity with or without exogenous IL6 in NSCLC with EGFR mutation.

Abundance of IL6 and COX2 in NSCLC cells and TPCA-1 inhibits their transcription.

TPCA-1 blocks cell cycle in G2/M in HCC827 cells.

Epidermal growth factor receptor (EGFR) is a clinical therapeutic target to treat a subset of non–small cell lung cancer (NSCLC) harboring EGFR mutants. However, some patients with a similar kind of EGFR mutation show intrinsic resistance to tyrosine kinase inhibitors (TKI). It indicates that other key molecules are involved in the survival of these cancer cells. We showed here that 2-[(aminocarbonyl)amino]-5 -(4-fluorophenyl)-3- thiophenecarboxamide (TPCA-1), a previously reported inhibitor of IκB kinases (IKK), blocked STAT3 recruitment to upstream kinases by docking into SH2 domain of STAT3 and attenuated STAT3 activity induced by cytokines and cytoplasmic tyrosine kinases. TPCA-1 is an effective inhibitor of STAT3 phosphorylation, DNA binding, and transactivation in vivo. It selectively repressed proliferation of NSCLC cells with constitutive STAT3 activation. In addition, using pharmacologic and genetic approaches, we found that both NF-κB and STAT3 could regulate the transcripts of interleukin (IL)-6 and COX-2 in NSCLC harboring EGFR mutations. Moreover, gefitinib treatment only did not efficiently suppress NF-κB and STAT3 activity. In contrast, we found that treatment with TKIs increased phosho-STAT3 level in target cells. Inhibiting EGFR, STAT3, and NF-κB by combination of TKIs with TPCA-1 showed increased sensitivity and enhanced apoptosis induced by gefitinib. Collectively, in this work, we identified TPCA-1 as a direct dual inhibitor for both IKKs and STAT3, whereas treatment targeting EGFR only could not sufficiently repress NF-κB and STAT3 pathways for lung cancers harboring mutant EGFR. Therefore, synergistic treatment of TPCA-1 with TKIs has potential to be a more effective strategy for cancers. Mol Cancer Ther; 13(3); 617–29. ©2014 AACR.

EGFR silence inhibits STAT3 activation in MDA-MB-231 cells.

Supplementary method and figure legends

TPCA-1 inhibits STAT3 phosphorylation.

Combination of TPCA-1 increases sensitivity to gefitinib in TKI insensitive NSCLC.

Antibacterial surfaces are surfaces that can resist bacteria, relying on the nature of the material itself. It is significant for safe food and water, human health, and industrial equipment. Biofilm is the main form of bacterial contamination on the material surface. Preventing the formation of biofilm is an efficient way to develop antibacterial surfaces. The strategy for constructing the antibacterial surface is divided into bacteria repelling and bacteria killing based on the formation of the biofilm. Material surface wettability, adhesion, and steric hindrance determine bacteria repelling performance. Bacteria should be killed by surface chemistry or physical structures when they are attached to a material surface irreversibly. Killing approaches are usually in the light of the cell membrane of bacteria. This review summarizes the fabrication methods and applications of antibacterial surfaces from the view of the treatment of the material surfaces. We also present several crucial points for developing long-term stability, no drug resistance, broad-spectrum, and even programable antibacterial surfaces.

Background: Inflammation process is an important determinant for subsequent changes in cardiac function and remodeling after acute myocardial infarction (MI). Recent studies have implicated that ALK4 haplodeficiency improves cardiac function after MI. However, it remains unknown if the beneficial effects are partly attributed to ALK4 haplodeficiency-induced modulation on inflammatory response in the inflammatory phase of MI. In this research, we aimed to explore the mechanism of ALK4 haplodeficiency in the inflammatory stage of MI. Methods: ALK4, CD16, and CD14 were detected in peripheral blood mononuclear cells (PBMCs) isolated from MI patients and healthy volunteers. ALK4 haplodeficiency (ALK4+/-) mice and wild-type (WT) littermates were randomly divided into the sham group and the MI group. Inflammation cytokines and chemokines were measured. Echocardiography and intracardiac electrophysiological recordings were performed on the 3rd day and the 7th day after MI operation. ALK4 expression and inflammation cytokines were also detected in LPS- or IL-4-stimulated bone marrow-derived macrophages (BMDM) from the ALK4+/- mice and WT littermates. Results: ALK4 gene expression in circulating monocytes of MI patients was higher than that in those of healthy volunteers. Cardiac inflammation and vulnerability of ventricular arrhythmia after acute myocardial injury are significantly alleviated in ALK4+/- mice as compared to WT littermates. On the 3rd day post-MI, the level of M1 macrophages were decreased in ALK4+/- mice as compared to WT littermates, while the level of M2 macrophages were increased on the 7th day post-MI. BMDM isolated from ALK4+/- mice displayed reduced secretion of pro-inflammation cytokines after stimulation by LPS in hypoxic condition and increased secretion of anti-inflammation cytokines after stimulation by IL-4. As a result, the haplodeficiency of ALK4 might be responsible for reduced inflammation response in the post-MI stage. Conclusions: ALK4 haplodeficiency reduces cardiac inflammation, improves cardiac function, and finally reduces the vulnerability of ventricular arrhythmia in the inflammatory stage after MI.

This study aims to compare and analyze the clinical features, diagnosis, treatment and prognosis of culture-negative and culture-positive primary pyogenic spondylitis.In a retrospective analysis, 202 cases of adult primary pyogenic spondylitis with complete clinical data in our hospital from January 2013 to January 2020 were divided into two groups according to bacterial culture results: culture negative (The culture positive rate was 37.62% (76/202). There were no significant differences in age, gender, affected segment, spinal abscess, diabetes mellitus, course of disease, surgery, recurrence, and follow-up time between the two groups (The culture-negative group's admission WBC, admission ESR, admission CRP, discharge ESR, discharge CRP, ESR decline rate, CRP decline rate, and hospital stay were lower than the culture positive group, the difference was statistically significant (

A dual-site controlled pH probe, which is composed of gold nanoparticles and modified with rhodamine and fluorescein derivatives, was applied to sensitively monitor intracellular pH changes in sperm. The pH probe revealed the intracellular pH of sperm under different conditions and demonstrated the lower pH in asthenozoospermia patients as compared to healthy individuals. Importantly, the pH probe can help screen for healthy sperm.

Objective In the present study, we aimed to describe the clinical features, diagnosis, treatment, and prognosis of spinal epidural abscess (SEA). Methods The complete clinical data of 11 SEA patients who were treated in our hospital system from January 2015 to June 2018 were retrospectively analyzed. Moreover, the clinical features, diagnosis, treatment, and prognosis of 642 SEA cases collected from the foreign literature from 2010 to 2019 were also investigated. Results Among our 11 SEA patients, nine cases had purulent inflammation, two cases had tuberculosis, two cases had infection caused by Staphylococcus aureus, one case had infection caused by Streptococcus constellatus, one case had infection caused by Klebsiella pneumoniae, five cases showed negative bacterial culture, and two cases had Mycobacterium tuberculosis. All 11 cases showed focal spinal pain, eight cases exhibited neurological deficits, and six cases experienced fever. Nine of the 11 cases involved the lumbosacral spine, one case involved the thoracic spine, and one case involved the cervical spine. Eight patients had a longer course of disease (>2 weeks), all 11 patients had vertebral osteomyelitis, and nine patients had intervertebral discitis. One patient had motor dysfunction of arms and legs, one patient had lower limb motor dysfunction, one patient had limb numbness, one patient experienced relapse after the conservative treatment, and one patient experienced relapse after the surgical treatment. The follow-up time was 15-24 months. Conclusion The classic diagnosis of triads (focal spine pain, neurological deficit, and fever) was less specific for SEA. MRI examination, blood culture, tissue culture, and biopsy could be used for the diagnosis for SEA. Suppuritis was a common cause of SEA. Early detection, early diagnosis and early treatment, as well as the selection of the most suitable treatment regimen based on comprehensive evaluation, played crucial roles in a better prognosis of SEA. There was no statistically significant difference in terms of the general condition, diagnosis, treatment and prognosis between the patients with negative and positive culture results (P>0.05). For SEA patient with negative culture, antibiotic treatment should be used empirically.

How to precisely reprogram tumor-associated macrophages (TAMs) and combine them with immunogenic cell death (ICD) is still a great challenge in enhancing the antitumor immunotherapeutic effect. Here, we developed a localized drug delivery system with a step-by-step cell internalization ability based on a hierarchical-structured fiber device. The chemotherapeutic agent-loaded nanomicelles are encapsulated in the internal chambers of the fiber, which could first be internalized by actively targeting tumor cells to induce ICD. Next, the rod-like microparticles can be gradually formed from long to short shape through hydrolysis of the fiber matrix in the tumor microenvironment and selectively phagocytosed by TAMs but not to tumor cells when the length becomes less than 3 μm. The toll-like receptors 7 (TLR7) agonist imiquimod could be released from these microparticles in the cytoplasm to reprogram M2-like TAMs. The

Typical glucose oxidase (GOx)-based starvation therapy is a promising strategy for tumor treatment; however, it is still difficult to achieve an effective therapeutic effect via a single starvation therapy. Herein, we designed a pH-sensitive polymeric vesicle (PV) self-assembled by histamine-modified chondroitin sulfate (CS-his) for codelivery of GOx and l-buthionine sulfoximine (BSO). GOx can consume glucose to induce the starvation therapy after the PVs reach cancer cell. Moreover, the product H2O2 will be reduced by a high concentration of glutathione (GSH) in the tumor cell, resulting in a reduction of the GSH content. The released BSO finally further reduced the GSH level. As a result, the signaling pathway of the ferroptosis will be activated. The in vivo results demonstrated that GOx/BSO@CS PVs exhibit a good inhibitory effect on the growth of 4T1 tumors in mice. Thus, this work provides a facile strategy to prepare pH-sensitive nanomedicine for synergistic starvation-ferroptosis therapy of tumor.

Immunomagnetic beads have been widely explored as an important analytical tool for the rapid and sensitive detection of circulating tumor cells (CTCs). However, their clinical application is seriously hindered by the tedious preparation procedures and heterogeneous nature of CTCs. To this end, a designed multifunctional platform named Fe3O4@TA/CuII superparamagnetic nanoparticles (SPMNPs) is expected to have the following features: (i) the formation of a tannic acid-copper (II) ion (TA/CuII) coating which could be accomplished by a one-step method is very simple; (ii) the TA/CuII coating shows high affinity for heterogeneous CTCs and good resistance to nonspecific adhesion of blood cells; (iii) "self-release" of the captured cells could be achieved as the TA/CuII coating gradually degrades in the cell culture environment without any additional interventions. Therefore, the resulting Fe3O4@TA/CuII SPMNPs could capture various CTCs (MCF-7, HepG2 and HeLa cells) with different expression levels of the epithelial cell adhesion molecule (EpCAM). And the capture efficiency and cell purity can reach 88% and 87%, respectively. In addition, 68% of the captured cells are self-released after 6 h of incubation and most of the released cells show high cell proliferation activity. In particular, Fe3O4@TA/CuII SPMNPs can successfully detect 1-13 CTCs from 1 mL of blood of 14 patients with 6 types of cancers. Hence, we expect that the as-prepared Fe3O4@TA/CuII SPMNPs with simple, efficient, and universal yet cost-efficient characteristics could act as a promising analytical tool for clinical CTC detection.

As a minimally invasive local cancer therapy, photothermal therapy (PTT) has aroused intensive interests in recent years. However, the therapeutic effect of PTT is still unsatisfying due to the production of heat shock proteins. Combination therapy has been regarded as a promising strategy to enhance therapeutic efficiency. In this study, a novel intelligent protoporphyrin (PpIX)-based polymer nanoplatform is developed for synergistic enhancement of cancer treatment through combined PTT and nitric oxide (NO) therapy. The core of the nanoparticle is composed of closely packed porphyrin-based NO donors and PpIX branches of the block copolymer. The prepared nanoparticles exhibit good photothermal conversion capability and high sensitivity to release NO under light illumination. And the produced high localized temperature and intracellular NO concentration could efficiently inhibit cancer cells both in vitro and in vivo. More important, this therapeutic nanoplatform can fundamentally eliminate the emergence of multidrug resistance and overcome the hypoxia microenvironment in tumors because of the absence of chemotherapeutic drugs and the oxygen-independent process, thus opening up new ideas for multifunctional therapeutic agent design for treatment of multidrug-resistant cancer.

The fundamental understanding of the surface reconstruction induced by the applied potential is of great significance for enhancing the oxygen evolution reaction (OER). Here, we show that a previously overlooked discharge current in the low applied potential region also leads to in situ electrochemical activation of a nitrogen-doped nickel oxyhydroxide surface. We exploit the fact that doping of heteroatoms weakens the surface structure, and hence, a weak discharge current originating from the capacitive nature of nickel oxyhydroxide has a strong structure-reforming ability to promote the formation of nitrogen and oxygen vacancies. The current density at 1.4 V (vs. Hg/HgO) can dramatically increase by as much as 31.3 % after discharge in the low applied potential region. This work provides insight into in situ enhancement of the OER and suggests that the low applied potential region must be a primary consideration in evaluating the origin of the activity of electrocatalysts.

Additional file 1: Supporting Information. Figure S1. SEM images of SA-CNTs. A) Low-magnitude and B) high-magnitude SEM images of SA-CNTs. SEM, scanning electron microscope. Scale bar: 100μm (A), Scale bar: 1μm (B). Figure S2. A schematic representation of the epicardial outgrowth culture from embryonic mouse hearts. Figure S3. Identification of epicardial cells. A, B) Epicardial cells are identified with immunolabeling of A) characteristic mesothelial marker (nuclear Wilms-tumor1, WT1, and B) organized epithelial tight junctions (Zonula occludens-1, ZO1) at day3 of culture. Figure S4. Representative images indicate that epicardial outgrow from the embryonic mouse heart to both Coverglass and SA-CNTs can be observed within 24 hours after explant planting, using phase contrast light microscopy. Figure S5. A-C) Representative phase contrast light microscopy images indicating that epicardial cells outgrowing from heart explants placed on Coverglass (control) formed a tightly packed sheet of epithelial cells at Day2. B and C): the enlarged image of a selected zone in A. D-F) Epicardial cells from explants placed on SA-CNTs (begin to exhibit a lamellipodia (arrowed) and migratory behavior at Day2. E and F): the enlarged image of a selected zone in D. Scale bars, 500μm. Figure S6. Schematic illustration demonstrating the isolation of primary epicardial cells using an outgrowth culture assay and the cells migration manner on different substrates. A, D) E12.5 heart ventricles placed on Epicardial outgrowth on Coverglass (control, A) and SA-CNTs (D). B, E) Epicardial cells outgrowing from heart at day2, epicardial outgrowth from heart explants placed on Coverglass (control) formed a tightly packed sheet of epithelial cells displaying cobblestoned morphology (B), while many cells on SA-CNTs exhibit an a lamellipodia with elongated fibroblast-like shape, particularly those cells at periphery of epithelial sheets (E). C, F) Different cell migration manner on Coverglass and SA-CNTs. At day3, the foremost cells of epicardial outgrowth on Coverglass stuck to the substrate and stopped moving forward, resulting in a formation of “Dam”, until the trapped outgrowing cells accumulate and broke through the “Dam” and poured out (C), in comparison, this phenomenon is rarely observed in the SA-CNTs group, with the peripheral cells of the outgrowth on SA-CNTs migrating far away from the central cells (F). Figure S7. Migration patterns of epicardial cells outgrowing from heart explants placed on Coverglass. Typical image after 4 day of culture showing that the cells on Coverglass spread around in a non-directional manner. Figure S8. Quantitation of migration distance of epicardial cells grown out from heart explant on control and SA-CNTs after 4 day of culture, showing that epicardial cells on SA-CNTs tend to migrate along the CNT-aligned direction (La), while the cells on Coverglass spread around in a non-directional manner. n = 7 for control sample and n = 13 for SA-CNTs from 5 independent experiments. *p < 0.05. Figure S9. Migration patterns of epicardial cells outgrowing from heart explants placed on E-SA-CNTs (SA-CNTs plus external electrical stimulation). Typical image after 4 day of culture showing that the cells on E-SA-CNTs tend to migrate along the CNT-aligned direction (La). Figure S10. Biocompatibility evaluation of SA-CNTs on epicardial cells using TUNEL staining. A) Representative confocal images of epicardial cells outgrowing on Coverglass (Control), SA-CNTs and E-SA-CNTs being labelled with TUNEL assay for apoptotic cells (green), and co-stained with DAPI (blue) for cell nuclei. B) Quantitative apoptotic nuclei in total DAPI+ for epicardial cells outgrowing on Coverglass (Control), SA-CNTs and E-SA-CNTs. E-SA-CNTs, SA-CNTs plus external electrical stimulation. n = 6 for each sample. n.s., not significant. Figure S11. An image of an MPS in larger size covering the ventricles of a Tyrode's solution perfused rabbit heart. Scale bar: 1cm. Figure S12. Cross section SEM images of the electromechanical actuator. A) Low-magnitude and B) high-magnitude of the device without PDMS packing. C) Low-magnitude and D) high-magnitude of the device with PDMS packing. Blue indicates the gel electrolyte area. Scale bar: 25μm. Figure S13. SEM images of CNT-film. A) Low-magnitude and B) high-magnitude SEM images of CNT-film. Scale bar: 10μm (A), Scale bar: 1μm (B). Figure S14. An actuator petal (0.0036 g) lifting/pushing objects sticked on the top of the petal during deformation. A) Lifting a weight of 0.0170 g. B) Pushing a weight of 0.1271 g. C) Force / Weight Ratio of adult human heart and actuator petal. Figure S15. Typical CV curves of one actuator petal at different scan rates (from 1 to 20 V s-1) with voltage window of ± 2 V. Figure S16. Images of a flower-shaped power assist unit with heart mimicked systolic and diastolic behavior. A and B) At the scan rate of 5 V s-1 with the voltage alternating window of ± 2.0 V. C and D) At the scan rate of 5 V s-1 with the voltage alternating window of ± 2.5 V. Contraction ratio (CR) was defined as (end diastolic dimension (EDD) – end systolic dimension (ESD))/ EDD×100 %. Figure S17. Images of a flower-shaped power assist unit with heart mimicked systolic and diastolic behavior at different scan rates with voltage window of ± 2.5 V. Figure S18. Three-electrode testing system. A) Illustration of the performed method. Working electrode: CNT-film strip. Reference electrode: Ag/AgCl electrode. Counter electrode: Pt wire. Electrolyte: 10% sulfuric acid aqueous solution. B) Typical CV curves of A. Figure S19. The computer simulated structure deformation maps of a flower-shaped power assist unit (scan rate: 1V s-1, voltage window: ± 2.5 V). The tip area reveals larger position shifting, while the change of position shifting is mainly concentrated in the middle and lower area. Left, top view; Right, bottom view. Figure S20. A) Images of the mechanical property test by Instron. B) A typical resulted stress-strain curve. Figure S21. The computer simulated stress distribution maps of flower-shaped power assist units with different Yong’s modulus, showing that the bottom of the flower-shaped device has a larger stress with a smaller deformation, while the top part of each petal reveals a small stress with large position shifting. The strength of the petal increases with the augment of its Yong’s modulus, which can be seen from the stress distribution legend of each simulation. For example, when the Yong’s modulus is 267.2 MPa, the green area represents 2.724 e+1 to 5.444 e+1; when the Yong’s modulus is 400.8 MPa, the green area represents 4.086e+1 to 8.165 e+1.Figure S22. Schematic illustration demonstrating the setup of ex vivo testing the MPS pacing function. MPS, multifunctional power assist system. Figure S23. Hematoxylin/eosin staining of tissue section of Control (A and C, without implantation) and MPS (B and D) group after 2 and 4 weeks of subcutaneous implantation. * indicates the space left by MPS implant (MPS implant was washed way during staining). Arrow indicates the SA-CNTs left after staining. Scale bar: 500 μm (left), 50 μm (right). Table S1 Table of sequences for upstream and downstream primer for genes analyzed using qRT-PCR

Under the concept of “Ubiquitous Electric Internet of Things”, the protection of key equipment in the state grid is facing a drastic revolution. Although recent progress has been achieved in the field of transformer condition monitoring via vibro-acoustic-based methods, there is not enough evidence for the detection of transformer insulation aging procedures with vibration monitoring. Indeed, reliable insulation is the functional last sovereign for an onsite transformer, and thus insulation breakdown is regarded as the determinate event for the failure of a transformer unit, among all its damage forms. In this paper, the feasibility of online vibration analysis as a potential method for insulation aging detection is demonstrated. Firstly, the authors designed 3 fatigue test platforms, including thermal, mechanical, and electrical factors, and launched a series of fatigue tests on the winding insulation materials. The results show that paper stiffness evolution can be seriously accelerated with multi-physical aging factors, especially with low-frequency harmonic loads. Accordingly, the modeling of these evaluative procedures in terms of stiffness variation was discussed, and extended to the feasibility analysis of this trend with a coupled beam model.

Purpose：In the present study, we aimed to compare and analyze the clinical features, diagnosis, treatment and prognosis of primary pyogenic spondylitis caused by Gram-positive and Gram-negative bacteria.Methods: A retrospective analysis consisting of 76 cases of primary pyogenic spondylitis with complete clinical information was carried out from January 2013 to January 2020 in our hospital. The patients were divided into two groups according to Gram staining: Gram-negative group (n=33) and Gram-positive group (n=43). The clinical characteristics, diagnosis, treatment and prognosis of the two groups were compared and analyzed.Results: Staphylococcus aureus accounted for the highest proportion of the Gram-positive group, while Escherichia coli accounted for the highest proportion of the Gram-negative group. Before treatment, there were no significant differences in terms of age, gender, affected segment, spinal abscess, diabetes mellitus, course of disease, admission erythrocyte sedimentation rate (ESR), admission C-reactive protein (CRP), and admission white blood cell (WBC) count between the two groups (P>0.05). After treatment, there were no statistically significant differences in discharge ESR, discharge CRP, ESR decline rate, CRP decline rate, surgery, recurrence, follow-up time, hospital stay, and body temperature ≥38℃ between the two groups (P>0.05). The body temperature of the Gram-negative group was higher compared with the Gram-positive group, and the number of patients with urinary tract infection in the Gram-negative group was significantly greater compared with the Gram-positive group (PConclusions: The body temperature of the Gram-negative group was higher compared with the Gram-positive group, and there were significantly more cases with urinary tract infection in the Gram-negative group compared with the Gram-positive group (P

Objectives This study aims to compare and analyze the clinical features, diagnosis, treatment and prognosis of culture-negative and culture-positive primary pyogenic spondylitis. Methods A retrospective analysis of 202 cases of adult primary pyogenic spondylitis with complete clinical data in our hospital from January 2013 to January 2020 were divided into 2 groups according to the bacterial culture results: culture negative group (n = 126), culture Positive group (n = 76). Compare the clinical characteristics, diagnosis, treatment and prognosis of patients with different culture results. Results The culture positive rate was 37.62% (76/202). There were no significant differences in age, gender, affected segment, spinal abscess, diabetes mellitus, course of disease, surgery, recurrence, and follow-up time between the two groups (P > 0.05). Two groups of hospital admission erythrocyte sedimentation rate (erythrocyte sedimentation rate, ESR), admission C-reactive protein (C-reactive protein, CRP), admission white blood cell count (white blood cell, WBC), discharge ESR, discharge CRP, ESR decline rate, CRP There were statistically significant differences in the rate of decline, hospitalization days, and body temperature ≥ 38 °C (P

In the war against cancer, tremendous efforts have been made by using a nanoparticle-based anticancer drug system. However, it is still a great challenge to achieve complete cure and eradication of cancer through chemotherapy. Here, we present a new multifunctional liposomal nanoplatform simultaneously loaded with hydrophilic doxorubicin hydrochloride in the aqueous core and hydrophobic debydrochlorination doxorubicin in the lipid bilayer. Compared with the traditional nanoparticle-based drug delivery system, this nanocarrier has three unique functions including a high payload of the same therapeutic agents with different water-solubilities, highly selective delivery of cargos to tumor cells and long-acting time with tumors. An excellent in vitro antitumor potency can be achieved with an IC50 of 0.91 μg mL-1 for this liposome, which is only half the IC50 of free doxorubicin. More importantly, extremely good antitumor efficacy in vivo is achieved since the mean tumor volume of all xenografted tumors is respectively ∼20% and ∼10% of that of the commercial liposomal doxorubicin formulation and the single doxorubicin liposomes on day 17 after being intravenously injected with the liposome nanoformulation 4 times. Moreover, the tumors were completely cured and eradicated on day 60 with no recurrence and the survival rate still remained at 70% after 365 days. Therefore, this multifunctional binary-drug loaded liposome provides a great potential platform for winning the war against cancer.

The construction of biocompatible and antibacterial surfaces is becoming increasingly important. However, most of the existing techniques require multi-step procedures, stringent conditions and specific substrates. We present here a facile method to create a biocompatible and antibacterial surface on virtually any substrate under ambient conditions. The strategy is based on casting a highly adherent elastomer, styrene-b-(ethylene-co-butylene)-b-styrene, from a solvent mixture of xylene and decanol, in which decanol acts as both a polymer precipitator to induce phase separation and a liquid template to stabilize the superhydrophobic structure. The stable and durable superhydrophobic surface shows good biocompatibility and antibacterial properties.

The hemolysis of erythrocytes is a big obstacle to the development of new non-plasticizer polymer containers for erythrocyte preservation. To construct a long-term anti-hemolytic surface of a plasticizer-free polymer, we coaxially electrospin core–shell structured D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)/poly(ethylene oxide) nanofibers on the surface of a styrene-b-(ethylene-co-butylene)-b-styrene (SEBS) elastomer that is covered with grafted poly(ethylene glycol) (PEG) chains. Our strategy is based on the fact that the grafted layers of PEG reduce mechanical damage to red blood cells (RBCs) while the TPGS released from the nanofibers on a blood-contacting surface can act as an antioxidant to protect RBCs from oxidative damage. We demonstrate that TPGS/PEO core–shell structured nanofibers have been well prepared on the surface of PEG modified SEBS; the controlled release of TPGS in distilled water is obtained and the release can last for almost 4 days at 4 °C; during RBC preservation, TPGS acts as the antioxidant to decrease the membrane oxidation and hemolysis of RBCs. Our work paves a new way for the development of non-plasticizer polymers for RBC preservation, which may be helpful for the fabrication of long-term anti-hemolytic biomaterials in vivo.

Objective In the present study, we aimed to describe the clinical features, diagnosis, treatment, and prognosis of spinal epidural abscess (SEA). Methods The complete clinical data of 11 SEA patients who were treated in our hospital system from January 2015 to June 2018 were retrospectively analyzed. Moreover, the clinical features, diagnosis, treatment, and prognosis of 642 SEA cases collected from the foreign literature from 2010 to 2019 were also investigated. Results Among our 11 SEA patients, nine cases had purulent inflammation, two cases had tuberculosis, two cases had infection caused by Staphylococcus aureus, one case had infection caused by Streptococcus constellatus, one case had infection caused by Klebsiella pneumoniae, five cases showed negative bacterial culture, and two cases had Mycobacterium tuberculosis. All 11 cases showed focal spinal pain, eight cases exhibited neurological deficits, and six cases experienced fever. Nine of the 11 cases involved the lumbosacral spine, one case involved the thoracic spine, and one case involved the cervical spine. Eight patients had a longer course of disease (>2 weeks), all 11 patients had vertebral osteomyelitis, and nine patients had intervertebral discitis. One patient had motor dysfunction of arms and legs, one patient had lower limb motor dysfunction, one patient had limb numbness, one patient experienced relapse after the conservative treatment, and one patient experienced relapse after the surgical treatment. The follow-up time was 15–24 months. Conclusion The classic diagnosis of triads (focal spine pain, neurological deficit, and fever) was less specific for SEA. MRI examination, blood culture, tissue culture, and biopsy could be used for the diagnosis for SEA. Suppuritis was a common cause of SEA. Early detection, early diagnosis and early treatment, as well as the selection of the most suitable treatment regimen based on comprehensive evaluation, played crucial roles in a better prognosis of SEA. There was no statistically significant difference in terms of the general condition, diagnosis, treatment and prognosis between the patients with negative and positive culture results (P>0.05). For SEA patient with negative culture, antibiotic treatment should be used empirically.

We have developed a 3D smart binary polymer-brush pattern on the polymer substrate for inducing multiple cell microarrays aided by a lectin and temperature. The binary polymer-brush pattern composed of poly(N-isopropylacrylamide) (PNIPAM) and poly(D-gluconamidoethyl methacrylate) (PGAMA) brushes is fabricated by combining the photolithography technique with a surface-initiated photo-polymerization (SIPP) method. We demonstrate that well-defined binary polymer-brush patterns with high resolution are fabricated using this facile method. The patterned hierarchical PNIPAM brushes exhibit reversible switching to the adhesion of red blood cells (RBCs) induced by thermo-responsiveness. The PGAMA brush domains resist adhesion of RBCs but bind specifically with concanavalin A (Con A), forming a lectin pattern to capture RBCs in a site-specific manner. Therefore, multiple cell microarrays on a single platform are generated with the aid of Con A and temperature. This novel platform composed of a smart binary polymer-brush pattern is versatile and specific, which opens up pathways to potential applications such as microsensors, biochips and bioassays.

Alveolar bone resorption is a major cause of teeth loss and jeopardizes the osseointegration of dental implants, greatly affecting patient's quality of life and health. It is still a great challenge to completely regenerate the alveolar bone defect through traditional guided bone regeneration (GBR) membranes due to their limited bioactivity and regeneration potential. Herein, a new hierarchical-structured mineralized nanofiber (HMF) scaffold, which is combined with both anisotropic and isotropic nanofibrous surface topography and the mineralized particles, is fabricated via a simple template-assisted electrospinning technology and in situ mineralization method. This HMF scaffold can not only directly induce osteogenic differentiation of bone mesenchymal stem cells (osteoinduction), but also stimulate macrophage toward pro-healing (M2) phenotype-polarization with an elevated secretion of the pro-healing cytokines, eventually enhancing the osteogenesis (osteoimmunomodulation). The results of in vivo rat alveolar bone defect repair experiments demonstrate that as compared with the combination of commercial Bio-Gide and Bio-Oss, the single HMF scaffold shows comparable or even superior bone repair effect, with better tissue-integration and more suitable degradation time and accompanied by a simplified operation.

Escaping from primary tumors and entering into blood flow, circulating tumor cells (CTCs) contain significant information for both the original tumors and metastasis mechanisms. CTCs detection has become an effective liquid biopsy of tumors and shows great promise in early cancer detection, disease monitoring, prognosis and personalized medicine. Despite the urgent need from clinics, CTCs isolation from blood is still a huge challenge due to their extreme rareness in blood. Well‐defined micro/nanostructures and nature‐inspired hierarchical architectures offer unique avenues to address this challenge by matching well with the special physical properties of CTCs to sort cells or forming local topographic interactions to strengthen cell adhesion, thereby improving the CTC‐isolation performance. In this review, we first summarize researches on CTCs isolation with diverse micro/nanostructured substrates, which mainly include nanomaterials, microfluidics, DNA nanostructures, micromotors and in vivo detection devices. In sequence, various CTC‐isolation biomimetic architectures, which are inspired by different natural creatures (e.g., viruses, cells, extracellular matrix [ECM], plants, and animals), have been highlighted. At last, remaining challenges and future perspectives in designing CTC‐isolation platforms for clinical applications are also discussed.

We presented the fabrication of N doped NiS2 nanoarrays using NH3·H2O as the dopant precursor for the electrocatalytic OER. N doping primarily affects the configuration of electrons and the density of d-states near the Fermi level, together with the adsorption of the OER intermediate, thus overcoming the intrinsic limits of reaction kinetics.

Cell behaviors are influenced by the surrounding dynamic microenvironment where the extracellular matrix (ECM) composed of different micro/nano-structures plays a key role. Many micro/nano-structures have been developed to mimic the structure of ECM, but these structures are almost static, and fail to emulate the dynamicity and function of the ECM in vivo. Notably, certain micro/nano-structures based on shape-memory polymers (SMPs), including patterns, fibers, porous scaffolds and microspheres, have attracted increasing attention due to the unique spatiotemporal variations. The dynamical shifting of these biomimetic micro/nano-structures arising from the shape-memory effect endows the materials with unique functions, e.g., regulating cell behaviors and prompting tissue growth. Therefore, the dynamically tunable biomimetic micro/nano-structures based on SMPs can be an ideal platform to mimic dynamic changes in the ECM structure both in vitro and in vivo. This review summarizes the latest advances in the development of the methodologies for fabricating various SMP biomimetic micro/nano structures, spatiotemporal control of cell behaviors, and broad applications in biomedical engineering. Several crucial points for future research are presented.