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Background: Subarachnoid hemorrhage (SAH) is a serious cerebrovascular emergency. The incidence of SAH and hazard ratio of death increase with age. Objective: In this study, we aimed to observe the effects and potential mechanisms of olfactory three needle (OTN) on cognitive impairment, neuronal activity, and neural stem cell differentiation in SAH rats. Methods: Sprague-Dawley (SD) rats were randomly divided into five groups: Sham, SAH group, SAH + Nimodipine (NMP) group, and SAH + OTN group. The rats in the SAH + OTN group received the OTN electroacupuncture treatment. For treatment with recombinant DKK1 (a Wnt/β-catenin inhibitor), mice were injected with DKK1. Results: Our results found that OTN improved cognitive impairment and hippocampal neuron damage in SAH rats. Furthermore, OTN promoted the proliferation of neural stem cells in SAH rats. Mechanistically, OTN activated Wnt/β-catenin signaling in SAH rats, as indicated by the increased expression levels of Wnt1, β-Catenin, LMNB1, and p-GSK-3β. DKK1 reversed the improvement effect of OTN on cognitive impairment and neuronal damage in SAH rats. Meanwhile, DKK1 blocked the promoting effect of OTN on the proliferation of NSCs in SAH rats. Conclusions: OTN electroacupuncture may be an effective therapeutic strategy for SAH.

To better tap into the potential of distributed renewable energy generation, microgrid system has become an emerging technology. As the bridge of microgrids, the inverters can flexibly convert distributed DC power input into AC power output. It is verified that the traditional droop control strategy for microgrid inverters has inherent defects of uneven reactive power distribution. To this end, this paper proposes a droop control strategy as a multi-objective optimization problem while considering the deviations of bus voltage and reactive power distributions of microgrids. Then, the optimization problem is further formulated as a Markov decision process and solved by a deep reinforcement learning (DRL) algorithm called deep deterministic policy gradient to obtain a dynamic optimal droop coefficient control strategy. Simulation results demonstrated that our DRL-based strategy eliminates the uneven reactive power distribution without voltage drop.

Gastric perforation refers to the complete rupture of the gastric wall, leading to the extravasation of gastric contents into the thoracic cavity or peritoneum. Without timely intervention, the expulsion of gastric contents may culminate in profound discomfort, exacerbating the inflammatory process and potentially triggering perilous sepsis. In clinical practice, surgical suturing or endoscopic closure procedures are commonly employed. Magnetic-driven microswarms have also been employed for sealing gastrointestinal perforation. However, surgical intervention entails significant risk of bleeding, while endoscopic closure poses risks of inadequate closure and the need for subsequent removal of closure clips. Moreover, the efficacy of microswarms is limited as they merely adhere to the perforated area, and their sealing effect diminishes upon removal of the magnetic field. Herein, we present a Fe&Mg@Lard-Paraffin micromotor (LPM) constructed from a mixture of lard and paraffin coated with magnesium (Mg) microspheres and iron (Fe) nanospheres for sutureless sealing gastric perforations. Under the control of a rotating magnetic field, this micromotor demonstrates precise control over its movement on gastric mucosal folds and accurately targets the gastric perforation area. The phase transition induced by the high-frequency magnetothermal effect causes the micromotor composed of a mixed oil phase of lard and paraffin to change from a solid to a liquid phase. The coated Mg microspheres are subsequently exposed to the acidic gastric acid environment to produce a magnesium protonation reaction, which in turn generates hydrogen (H2) bubble recoil. Through a Mg-based micropower traction, part of the oil phase could be pushed into the gastric perforation, and it would then solidify to seal the gastric perforation area. Experimental results show that this can achieve long-term (>2 h) gastric perforation sealing. This innovative approach holds potential for improving outcomes in gastric perforation management.

“On‐the‐fly” molecule enrichment by micro/nanomotors obviously improves heterogeneous catalysis, trace detection, and environmental monitoring, yet faces challenges of the trade‐off between collection range and interaction time. Inspired by the versatile foraging process of predators, this work demonstrates that micromotors doing spontaneous multipattern motion with microvortex can greatly enhance “on‐the‐fly” enrichment, demonstrated by highly sensitive surface‐enhanced Raman scattering detection. It leverages an axis‐asymmetric bowl‐shaped structure and the nonlinear Ag–AgCl reaction, realizing alternating low‐velocity swinging forward and accelerated steering motions for prolonged interaction and large work area. Moreover, the bowl‐shaped microstructure bestows a micro‐vortex above the Ag side due to the competition of electric potential and pressure gradient, also extending interaction time during the acceleration. Consequently, it exhibits at least an order of magnitude larger enhancement of detection signals than the counterparts. This proof‐of‐concept study highlights the significance of motion mode and structure design in guiding flow field, offering substantial benefits for applications.

Malignant ascites is a common complication of some advanced cancers. Although intraperitoneal (IP) administration of chemotherapy drugs is routinely used to treat cancerous ascites, conventional drugs have poor retention and therefore need to be administered frequently to maintain a sustained anti-tumor effect. In this study, a thermosensitive hydrogel composite loaded with norethindrone nanoparticles (NPs) and oxaliplatin (N/O/Hydrogel) was developed to inhibit ascites of hepatocellular carcinoma (HCC) through IP injection. N/O/Hydrogel induced apoptosis in the H22 cells in vitro, and significantly inhibited ascites formation, tumor cell proliferation and micro-angiogenesis in a mouse model of advanced HCC with ascites, and prolonged the survival of tumor-bearing mice. Histological examination of the major organs indicated that the hydrogel system is safe. Taken together, the N/O/Hydrogel system is a promising platform for in-situ chemotherapy of malignant ascites.

Chemotherapy is the primary treatment for advanced non-small-cell lung cancer (NSCLC). However, related dose-dependent toxicity limits its clinical use. Therefore, it is necessary to explore new strategies for improving the clinical outcomes while reducing the side effects of chemotherapy in the treatment of NSCLC. In this study, we designed and synthesized epidermal growth factor (EGF)-modified doxorubicin nanoparticles (EGF@DOX-NPs) that selectively targets the epidermal growth factor receptor (EGFR) overexpressed in lung tumor cells. When administered in combination with low-dose X-ray radiotherapy (RT), the NPs preferentially accumulated at the tumor site due to radiation-induced outburst of the local intra-tumoral blood vessels. Compared with DOX alone, EGF@DOX-NPs significantly decreased the viability and migration and enhanced the apoptosis rates of tumor cells in vitro. Also, the EGF@DOX-NPs significantly inhibited tumor growth in vivo, increasing the survival of the tumor-bearing mice without apparent systemic toxic effects through RT-induced aggregation. The tumor cell proliferation was greatly inhibited in the RT + EGF@DOX-NPs group. Contrarily, the apoptosis of tumor cells was significantly higher in this group. These results confirm the promising clinical application of radiotherapy in combination with EGF@DOX-NPs for lung cancer treatment.

Ulcerative colitis (UC) is an incurable and highly complex digestive disease affecting millions of people worldwide. Compared to the current therapeutic drugs, bioactive peptides are more promising and safe substances as functional foods or drugs for the prevention and treatment of UC. The alcohol-soluble components from fermentation broth by fresh wheat germ and apple (AC-WGAF) were found to be effective in UC prevention in dextran sulfate sodium-induced mice in vivo. Herein, 4 novel peptides are identified from AC-WGAF by membrane ultrafiltration, recycling preparative high-performance liquid chromatography, and matrix-assisted laser desorption–ionization time-of-flight/time-of-flight mass spectrometry, possessing anti-colitis activity via using an in vitro model. One of those peptides named T24 (PVLGPVRGPFPLL) exhibited the most remarkable anti-colitis activity by preventing tight junction protein loss, maintaining epithelial barrier integrity, and promoting cell proliferation during in vitro and in vivo studies by regulating mitogen-activated protein kinase signaling pathways. Thus, T24 is a promising peptide as a functional food or novel drug for UC prevention and treatment.

With the development of new energy technology, the distributed generation has attracted more and more attention. In order to enhance the inertia of distributed generator system to improve its stability, the control technology of virtual synchronous generator (VSG) is proposed. However, the traditional VSG control technology often has poor flexibility and long dynamic adjustment time. In this context, a deep deterministic policy gradient (DDPG) algorithm based adaptive controller is designed to realize the adaptive control of inertia and damping coefficient in the system, so that the parameters can be adjusted adaptively under different operating conditions. Next, a simulation model of VSG isolated island single machine operation model is built in MATLAB Simulink, and the implementation of DDPG algorithm is given and verified by simulation. The results show that the VSG parameter adaptive system controlled by DDPG has stronger ability to resist disturbance and achieves better performance than the traditional VSG adaptive system. The DRL model only takes 0.448 s to return to stable, but the other two models need 0.632 s and 0.818 s respectively.

Phase change materials have attracted significant attention owing to their promising applications in many aspects. However, it is seriously restricted by some drawbacks such as obvious leakage, relatively low thermal conductivity, and easily flame properties. Herein, a novel flame retardant form-stable composite phase change material (CPCM) with polyethylene glycol/epoxy resin/expanded graphite/magnesium hydroxide/zinc hydroxide (PEG/ER/EG/MH/ZH) has been successfully prepared and utilized in the battery module. The addition of MH and ZH (MH:ZH = 1:2) as flame retardant additions can not only greatly improve the flame retardant effect but also maintain the physical and mechanical properties of the polymer. Further, the EG (5%) can provide the graphitization degree of residual char which is beneficial to building a more protective barrier. This designation of CPCM can exhibit leakage-proof, high thermal conductivity (increasing 400%–500%) and prominent flammable retardant performance. Especially at 3C discharge rate, the maximum temperature is controlled below 54.2 °C and the temperature difference is maintained within 2.2 °C in the battery module, which presents a superior thermal management effect. This work suggests an efficient and feasible approach toward exploiting a multifunctional phase change material for thermal management systems for electric vehicles and energy storage fields.

Abstract Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) might be involved in the activation of important pathways related to tumor immune escape, along with programmed death-ligand 1 (PD-L1). Here, we aimed to investigate the correlation between the expression of Siglec-15 and PD-L1 in nasopharyngeal carcinoma (NPC) patients. We determined the expression of PD-L1 via immunohistochemical staining and that of Siglec-15 via immunofluorescence staining in 182 NPC tissue samples. A significant correlation was identified between the PD-L1 and Siglec-15 expression (P = 0.000). Moreover, Kaplan–Meier survival curves showed that PD-L1 expression was associated with improved overall survival (OS) (P = 0.025) and Siglec-15 expression was associated with improved distant failure-free survival (D-FFS) (P = 0.048). Moreover, multivariate Cox analysis showed that PD-L1 and Siglec-15 were independent predictors of OS (P = 0.020) and D-FFS (P = 0.047), respectively. The results of the log-rank test and Cox regression analyses showed that patients exhibiting no PD-L1/Siglec-15 expression had significant advantages regarding OS, compared to other groups (P = 0.037). PD-L1 and Siglec-15 may represent novel biomarkers for predicting the prognosis of NPC patients. Siglec-15 may be considered as a potential target for the development of therapeutics for NPC treatment in the future.

ObjectiveEvidence from observational studies suggests that Sjögren’s syndrome (SS) may contribute to an elevated risk of Parkinson’s disease (PD) and dementia. However, few studies have been undertaken to summarize and assess the consistency of the data quantitatively. Therefore, we evaluated the risk of dementia and PD in SS patients through a systematic review and meta-analysis approach.MethodsTwo reviewers independently conducted a systematic search of PubMed, Embase, and Web of Science databases (updated to February 14, 2022) to identify published literature on the association between SS and dementia or PD. The risk estimates of dementia or PD in patients with SS were pooled using fixed or random-effects models.ResultsOf the 631 studies initially searched, 10 were eventually included. Pooled results suggested that the risk of developing dementia significantly increased in patients with SS (HR = 1.24, 95% CI: 1.15–1.33, P < 0.001), and such risk in females with SS was similar to that in males. The risk of PD was 1.36 times higher in SS (HR = 1.36, 95% CI: 1.23–1.50, P < 0.001). The association between SS and PD risk appeared to occur primarily in female patients (female: HR = 1.28, 95% CI: 1.21–1.35; P < 0.001 vs. male: HR = 1.00, 95% CI: 0.87–1.16, P = 0.962, respectively). No significant effect of age was observed on the risk of developing PD and dementia in SS patients.ConclusionOur study supports that people with SS are at higher risk of PD and dementia than the general population. Further studies are needed to elucidate the underlying mechanisms and to assess whether interventions for SS have the potential to affect dementia and PD development.

BackgroundThe association between shift work, night work, and the risk of dementia are conflicting in the literature.ObjectivesThis study was performed to obtain evidence on the potential relationship between shift work, night work, and dementia.MethodsTo investigate the link between shift work, night work, and dementia, we systematically searched PubMed, Embase, and Web of Science from inception to January 1, 2022. The eligibility of the retrieved records and extracted data were independently reviewed by two researchers. The Preferred Reporting Items for Systematic Evaluations and Meta-Analyses (PRISMA) statement was followed. STATA 16.0 was used to conduct the meta-analysis.ResultsA total of four studies involving 103,104 participants were included in this meta-analysis. Pooled results indicated that night shift workers had a 12% increased risk of dementia compared to subjects without night work (HR = 1.12, 95% CI 1.03–1.23, P = 0.094). Shift work was not significantly associated with dementia risk (HR: 1.09, 95% CI: 0.83–1.43, P = 0.546), but the effect of shift work on dementia risk appeared to increase with age, with a correlation observed among workers older than 50 years (HR = 1.31; 95% CI: 1.03–1.68, P = 0.030).ConclusionThe data presented in our study suggest that night work may be a risk factor for dementia. More prospective studies with objective exposure measurements are required to further confirm this result.Systematic review registrationhttps://doi.org/10.37766/inplasy2022.6.0079, identifier: INPLASY202260079.

Abstract Deep reinforcement learning has achieved some remarkable results in self‐driving. There is quite a lot of work to do in the area of autonomous driving with high real‐time requirements because of the inefficiency of reinforcement learning in exploring large continuous motion spaces. A deep imitation reinforcement learning (DIRL) framework is presented to learn control policies of self‐driving vehicles, which is based on a deep deterministic policy gradient algorithm (DDPG) by vision. The DIRL framework comprises two components, the perception module and the control module, using imitation learning (IL) and DDPG, respectively. The perception module employs the IL network as an encoder which processes an image into a low‐dimensional feature vector. This vector is then delivered to the control module which outputs control commands. Meanwhile, the actor network of the DDPG is initialized with the trained IL network to improve exploration efficiency. In addition, a reward function for reinforcement learning is defined to improve the stability of self‐driving vehicles, especially on curves. DIRL is verified by the open racing car simulator (TORCS), and the results show that the correct control strategy is learned successfully and has less training time.

Outbreak of COVID-19 is ongoing all over the world. Spine trauma is one of the most common types of trauma and will probably be encountered during the fight against COVID-19 and resumption of work and production. Patients with unstable spine fractures or continuous deterioration of neurological function require emergency surgery. The COVID-19 epidemic has brought tremendous challenges to the diagnosis and treatment of such patients. To coordinate the diagnosis and treatment of infectious disease prevention and spine trauma so as to formulate a rigorous diagnosis and treatment plan and to reduce the disability and mortality of the disease, multidisciplinary collaboration is needed. This expert consensus is formulated in order to (1) prevent and control the epidemic, (2) diagnose and treat patients with spine trauma reasonably, and (3) reduce the risk of cross-infection between patients and medical personnel during the treatment.

Subarachnoid hemorrhage (SAH) is a common disease with high morbidity and mortality, which can cause pathological, physiological, and biological reactions. SAH causes a series of responses such as neuronal and cerebral cortex damage, which in turn leads to inflammation and apoptosis. Traditional Chinese medicine has a strong anti-inflammatory effect, such as Alantolactone (ATL). However, studies on ATL therapy for SAH have not been reported. We observed the neurological scores, brain water content, Evans blue (EB) extravasation, neuroinflammation, and apoptosis via performing an enzyme-linked immunosorbent assay (ELISA), western blotting, immunofluorescence staining, and other methods after SAH. In this study, we found that ATL treatment attenuated the neurologic deficits, inhibited neuronal apoptosis and inflammatory reaction, promoted polarization of microglia toward the M2 phenotype, and activated the PI3K/Akt signaling pathway. ATL can reduce the neurons and cerebral cortex damage of SAH rats through activating PI3K/Akt signaling pathway.

Fracture induced failure of plates in hull structures subjected to in-plane biaxial low-cycle fatigue loading are generally a combination of accumulative plasticity and biaxial low-cycle fatigue damage. A biaxial low-cycle fatigue crack growth analysis of a hull structure that accounts for the accumulative plasticity effect can be suitable for the actual evaluation of the overall fracture induced failure of the hull structure in severe sea conditions. An analytical model of biaxial low-cycle fatigue crack propagation with a control parameter for the J integral was presented for hull inclined-crack plate. The test was conducted for cruciform specimens made of Q235 steel with an inclined crack to validate the presented analysis. The biaxial accumulative plasticity behaviour and the effects of the biaxiality and stress ratios were investigated by numerical analysis. The results of this study reveal a strong dependence of biaxial low-cycle fatigue crack propagation on biaxial accumulated plasticity.

Abstract Most breast cancers at an advanced stage exhibit an aggressive nature, and there is a lack of effective anticancer options. Herein, the development of patient‐derived organoids (PDOs) is described as a real‐time platform to explore the feasibility of tailored treatment for refractory breast cancers. PDOs are successfully generated from breast cancer tissues, including heavily treated specimens. The microtubule‐targeting drug‐sensitive response signatures of PDOs predict improved distant relapse‐free survival for invasive breast cancers treated with adjuvant chemotherapy. It is further demonstrated that PDO pharmaco‐phenotyping reflects the previous treatment responses of the corresponding patients. Finally, as clinical case studies, all patients who receive at least one drug predicate to be sensitive by PDOs achieve good responses. Altogether, the PDO model is developed as an effective platform for evaluating patient‐specific drug sensitivity in vitro, which can guide personal treatment decisions for breast cancer patients at terminal stage.

Dihydroartemisinin (DHA) is a potent anti-cancer drug that has limited clinical applications due to poor water solubility and low bioavailability. We designed a biodegradable poly(ethylene glycol) methyl ether-poly(ε-caprolactone) (MPEG-PCL) micelle carrier for DHA using the self-assembly method. The DHA/MPEG-PCL nanoparticles were spherical with an average particle size of 30.28 ± 0.27 nm, and released the drug in a sustained manner in aqueous solution. The drug-loaded nanoparticles showed dose-dependent toxicity in HeLa cells by inducing cycle arrest and apoptosis. Furthermore, compared to free DHA, the DHA/MPEG-PCL nanoparticles showed higher therapeutic efficacy and lower toxicity in vivo, and significantly inhibited tumor growth and prolonged the survival of tumor-bearing nude mice. In addition, the tumor tissues of the DHA/MPEG-PCL-treated mice showed a marked decline in the in situ expression of proliferation and angiogenesis markers. Taken together, the self-assembled DHA/MPEG-PCL nanoparticles are a highly promising delivery system for targeted cancer treatment.

Skin repair remains a common problem in plastic surgery. Wound dressing plays an important role in promoting local skin healing and has been widely studied. This study aimed to manufacture a composite film (CPCF) containing curcumin nanoparticles, collagen, and polyvinyl alcohol (PVA) to effectively promote the healing of skin wounds. Sustained drug release from the composite film provides long-term protection and treatment for skin wounds. Both antibacterial property and good histocompatibility of the CPCF were examined by analyzing antibacterial activity and cytotoxicity to validate its applicability for wound management. Moreover, in vivo studies proved that the CPCF had a rapid healing rate of 98.03%±0.79% and mature epithelialization on day 15 after surgery. Obvious hair follicles and earlier re-epithelialization was also noticed in the CPCF group using H&E staining. The result of Masson’s trichrome staining confirmed that CPCF could promote the formation of collagen fibers. In summary, CPCF may be promising as a wound dressing agent in wound management owing to its rapid wound-healing effects.

In recent years, more and more theaters with rotating mechanisms have been built and used, such as theaters with rotating auditoriums. The rotation mechanism in this type of building may lead to the uncertainty of evacuation distances and routes, which undoubtedly poses a higher challenge to performance-based fire protection design. Taking the revolving auditorium theater as an example, this paper proposes a systematic method to solve the problem of randomness in evacuation scenarios. The numerical simulations based on FDS and Pathfinder were carried out, and two improved evacuation strategies for theaters with rotating auditorium were proposed. The results show that the blockage of evacuation exits is an important factor affecting the success of evacuation and the evacuation time. In addition, the establishment of emergency evacuation stairs and rotating auditoriums can effectively reduce the evacuation time.

Background: Cervical squamous cell carcinoma (CESC) is one of the most frequent malignancies in women worldwide. The level of immune cell infiltration and immune-related genes (IRGs) can significantly affect the prognosis and immunotherapy of CESC patients. Thus, this study aimed to identify an immune-related prognostic signature for CESC.Methods: TCGA-CESC cohorts, obtained from TCGA database, were divided into the training group and testing group; while GSE44001 dataset from GEO database was viewed as external validation group. ESTIMATE algorithm was applied to evaluate the infiltration levels of immune cells of CESC patients. IRGs were screened out through weighted gene co-expression network analysis (WGCNA). A multi-gene prognostic signature based on IRGs was constructed using LASSO penalized Cox proportional hazards regression, which was validated through Kaplan–Meier, Cox, and receiver operating characteristic curve (ROC) analyses. The abundance of immune cells was calculated using ssGSEA algorithm in the ImmuCellAI database, and the response to immunotherapy was evaluated using immunophenoscore (IPS) analysis and the TIDE algorithm.Results: In TCGA-CESC cohorts, higher levels of immune cell infiltration were closely associated with better prognoses. Moreover, a prognostic signature was constructed using three IRGs. Based on this given signature, Kaplan–Meier analysis suggested the significant differences in overall survival (OS) and the ROC analysis demonstrated its robust predictive potential for CESC prognosis, further confirmed by internal and external validation. Additionally, multivariate Cox analysis revealed that the three IRGs signature served as an independent prognostic factor for CESC. In the three-IRGs signature low-risk group, the infiltrating immune cells (B cells, CD4/8 + T cells, cytotoxic T cells, macrophages and so on) were much more abundant than that in high-risk group. Ultimately, IPS and TIDE analyses showed that low-risk CESC patients appeared to present with a better response to immunotherapy and a better prognosis than high-risk patients.Conclusion: The present prognostic signature based on three IRGs (CD3E, CD3D, LCK) was not only reliable for survival prediction but efficient to predict the clinical response to immunotherapy for CESC patients, which might assist in guiding more precise individual treatment in the future.

Abstract Background Iliosacral screw fixation is a popular method for the management of posterior pelvic ring fractures or dislocations, providing adequate biomechanical stability. Our aim in this study was to describe the use of a new patient-specific external template to guide the insertion of iliosacral screws and to evaluate the efficacy and safety of this technique compared with the conventional fluoroscopy-guided technique. Methods This was a retrospective study of patients with incomplete or complete posterior pelvic ring disruptions who required iliosacral screw fixation. For analysis, patients were divided into two groups: the external template group (37 screws in 22 patients) and the conventional group (28 screws in 18 patients). The operative time per screw, radiation exposure time and the rate of screw perforation (accuracy) were compared between groups. In the external template group, the difference between the actual and planned iliosacral screw position was also compared. Results In the conventional group, the average operative time per screw was 39.7 ± 10.6 min, with an average radiation exposure dose of 1904.0 ± 844.5 cGy/cm2, with 4 cases of screw perforation. In the external template group, the average operative time per screw was 17.9 ± 4.7 min, with an average radiation exposure dose of 742.8 ± 230.6 cGy/cm2 and 1 case of screw perforation. In the template group, the mean deviation distance between the actual and planned screw position was 2.75 ± 1.0 mm at the tip, 1.83 ± 0.67 mm in the nerve root tunnel zone and 1.52 ± 0.48 mm at the entry point, with a mean deviation angle of 1.73 ± 0.80°. Conclusions The external template provides an accurate and safe navigation tool for percutaneous iliosacral screw insertion that could decrease the operative time and radiation exposure.

Background: Advances in antimalarial drug development are important for combating malaria. Among the currently identified antimalarial drugs, it is suggested that some interact directly with the malarial parasites while others interact indirectly with the parasites. While this approach leads to parasite elimination, little is known about how these antimalarial drugs impact immune cells that are also critical in malarial response. Methods: Herein, the effects of two common antimalarial drugs, chloroquine and quinine, on platelets were explored at both the bulk level, using high performance liquid chromatography, and the single cell level, using carbon-fiber microelectrode amperometry, to characterize any changes in chemical messenger secretion. Results: The data reveal that both drugs cause platelet activation and reduce the number of platelet exocytosis events as well as delay fusion pore opening and closing. Conclusions: This work demonstrates how chloroquine and quinine quantitatively and qualitatively impact in vitro platelet function. General significance: Overall, the goal of this work is to promote understanding about how antimalarial drugs impact platelets as this may affect antimalarial drug development as well as therapeutic approaches to treat malarial infection.

Mg-based micromotors have emerged as an extremely attractive artificial micro/nanodevice, but suffered from uncontrollable propulsion and limited motion lifetime, restricting the fulfillment of complex tasks. Here, we have demonstrated Mg-based micromotors composed of Mg microspheres asymmetrically coated with Pt and temperature-sensitive poly(N-isopropylacrylamide) (PNIPAM) hydrogel layers in sequence. They can implement different motion behaviors stemming from the driving mechanism transformation when encountering catalyzed substrates such as H2O2 and respond to both H2O2 concentration and temperature in aqueous environment. The as-constructed Mg-based micromotors are self-propelled by Pt-catalyzed H2O2 decomposition following the self-consuming Mg-H2O reaction. In this case, they could further generate bilateral bubbles and thus demonstrate unique self-limitation motion like hovering when the phase transformation of PNIPAM is triggered by decreasing temperature or when the H2O2 concentration after permeating across the PNIPAM hydrogel layer is high enough to facilitate bubble nucleation. Our work for the first time provides a stimuli-induced “hovering” strategy for self-propelled micromotors, which endows Mg-based micromotors with an intelligent response to the surroundings besides the significant extension of their motion lifetime.

Abstract Background Human babesiosis is an infectious disease that is epidemic in various regions all over the world. The predominant causative pathogen of this disease is the intra-erythrocytic parasite Babesia microti. The thioredoxin system is one of the major weapons that is used in the resistance to the reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced by host immune system. In other intra-erythrocytic apicomplexans like the malaria parasite Plasmodium falciparum, anti-oxidative proteins are promising targets for the development of anti-parasitic drugs. However, to date, the sequences and biological properties of thioredoxins and thioredoxin-like molecules of B. microti remain unknown. Understanding the molecular characterization and function of B. microti thioredoxins may help to develop anti-Babesia drugs and controlling babesiosis. Methods The full-length B. microti thioredoxin 2 (BmTrx2) gene was obtained using a rapid amplification of cDNA ends (RACE) method, and the deduced BmTrx2 amino acid sequence was analyzed using regular bioinformatics tools. Recombinant BmTrx2 protein was expressed in vitro and purified using His-tag protein affinity chromatography resins. Reverse transcription PCR, quantitative real-time PCR and Western blot were employed to detect the expression and native proteins of BmTrx2. Indirect immunofluorescence assay was used to localize BmTrx2 in B. microti. Bovine insulin reduction assays were used to determine the enzyme activity of the purified recombinant BmTrx2 protein. Results The full-length BmTrx2 was 564 bp with a 408 bp open reading frame encoding a protein of 135 amino acids. The predicted molecular weight of the protein was 15.5 kDa. A conserved thioredoxin-like family domain was found in BmTrx2. The expression of BmTrx2 was upregulated on both the third and eighth day post-infection in mice, whereas expression was downregulated during the beginning and later stages. The results of Western blot analysis showed the native BmTrx2 in parasite lysates could be detected by mouse anti-BmTrx2 serum and that the recombinant BmTrx2 protein could be recognized by serum of B. microti-infected mice. Immunofluorescence microscopy showed that BmTrx2 localized in the cell cytoplasm of B. microti merozoites in B. microti-infected red blood cells. The results of bovine insulin reduction assay indicated the purified recombinant BmTrx2 protein possesses antioxidant enzyme activity. Dihydroartemisinin and quinine, known anti-malaria drugs, and clindamycin, a known anti-babesiosis drug, induced significantly higher upregulation of BmTrx2 mRNA. Conclusions Our results indicate that BmTrx2 is a functional enzyme with antioxidant activity and may be involved in the response of B. microti to anti-parasite drugs.

This paper generalizes the structural Markov properties for undirected decomposable graphs to arbitrary ones. This helps us to exploit the conditional independence properties of joint prior laws to analyze and compare multiple graphical structures, while being able to take advantage of the common conditional independence constraints. This work provides a theoretical support for full Bayesian posterior updating about the structure of a graph using data from a certain distribution. We further investigate the ratio of graph law so as to simplify the acceptance probability of the Metropolis–Hastings sampling algorithms. [ABSTRACT FROM AUTHOR]

Cytochrome P-450 epoxygenase (EPOX)-derived epoxyeicosatrienoic acids (EETs), 5-lipoxygenase (5-LO), and leukotriene B4 (LTB4), the product of 5-LO, all play a pivotal role in the vascular inflammatory process. We have previously shown that EETs can alleviate oxidized low-density lipoprotein (ox-LDL)-induced endothelial inflammation in primary rat pulmonary artery endothelial cells (RPAECs). Here, we investigated whether ox-LDL can promote LTB4 production through the 5-LO pathway. We further explored how exogenous EETs influence ox-LDL-induced LTB4 production and activity. We found that treatment with ox-LDL increased the production of LTB4 and further led to the expression and release of both monocyte chemoattractant protein-1 (MCP-1/CCL2) and intercellular adhesion molecule-1 (ICAM-1). All of the above ox-LDL-induced changes were attenuated by the presence of 11,12-EET and 14,15-EET, as these molecules inhibited the 5-LO pathway. Furthermore, the LTB4 receptor 1 (BLT1 receptor) antagonist U75302 attenuated ox-LDL-induced ICAM-1 and MCP-1/CCL2 expression and production, whereas LY255283, a LTB4 receptor 2 (BLT2 receptor) antagonist, produced no such effects. Moreover, in RPAECs, we demonstrated that the increased expression of 5-LO and BLT1 following ox-LDL treatment resulted from the activation of nuclear factor-κB (NF-κB) via the p38 mitogen-activated protein kinase (MAPK) pathway. Our results indicated that EETs suppress ox-LDL-induced LTB4 production and subsequent inflammatory responses by downregulating the 5-LO/BLT1 receptor pathway, in which p38 MAPK phosphorylation activates NF-κB. These results suggest that the metabolism of arachidonic acid via the 5-LO and EPOX pathways may present a mutual constraint on the physiological regulation of vascular endothelial cells.

The role of c-Jun N-terminal kinases (JNKs) in the pathogenesis of cancer is well-known due to their involvement in carcinogenesis. Although previous studies have discussed different functions of JNKs depending on cell type, the present study aimed to investigate the function of JNKs in nasopharyngeal carcinoma (NPC) cells, as well as their involvement in chemotherapy sensitivity to Adriamycin. The present results showed that Adriamycin administration reduced cell viability and led to elevated expressions of c-Jun, phosphorylated JNK and phosphorylated c-Jun, indicating an activated JNK pathway. Notably, JNK inhibition by SP600125 also reduced cell growth. Thus, Adriamycin treatment combined with SP600125 was more effective on cell growth inhibition than each agent alone. The apoptosis analysis confirmed the reduction in cell growth. Therefore, these data provide evidence that the JNK pathway activity is negatively associated with cell viability, and its decline could sensitize NPC cells to Adriamycin. [ABSTRACT FROM AUTHOR]

• Multitude advances were found for V-rich Bi 2 S 3 nanowire than pristine Bi 2 S 3 photoelectrode. • V-rich Bi 2 S 3 nanowires achieve excellent photocurrent density for water splitting under visible light. • Deep insights on how the V-rich feature affects the PEC performance of Bi 2 S 3. Bi 2 S 3 is a n-type (negative type) semiconductor that has a narrow band gap and an ideal band edge position for hydrogen generation. However, high charge recombination rate, low photoelectrochemical (PEC) efficiency and poor stability are of major concerns of Bi 2 S 3 as a photoelectrode. Herein, we report an efficient Vanadium-rich Bi 2 S 3 nanowires (atomic ratio of V to Bi is 1/22) that have been prepared on fluorine-doped tin oxide (FTO) substrate by an in-situ solution-processed reaction with BiVO 4 film as precursor. The resulting V-rich photoelectrode demonstrates notably high charge separation efficiency and fast charge transport with respect to pristine Bi 2 S 3 nanowires. As a result, the photocurrent density of ca. 10 mA·cm−2 at -0.2 V vs Ag/AgCl is obtained under visible light illumination. In addition, V-rich Bi 2 S 3 generates IPCE (incident photocurrent-to-current conversion efficiency) of 50% at 460 nm and 45% at 760 nm, demonstrating a 2.0 and 2.8-fold increase, respectively, when compared with pristine Bi 2 S 3. This enhancement is probably due to increased light absorption, less charge recombination, and faster charge transfer. More importantly, in contrast to pristine Bi 2 S 3 sample that suffers detrimental photocorrosion in sulfide containing electrolyte, V-rich Bi 2 S 3 nanowires retain 84.6% of its initial photocurrent over the course of 1 h. These findings are expected to shed light on engineering high-performance and robust metal sulfide materials for photoelectrochemical application. [ABSTRACT FROM AUTHOR]

The aim of this study was to screen for polypeptides binding specifically to LoVo human colorectal cancer cells using a phage-displayed peptide library as a targeting vector for colorectal cancer therapy. Human normal colorectal mucous epithelial cells were applied as absorber cells for subtraction biopanning with a c7c phage display peptide library. Positive phage clones were identified by enzyme-linked immunosorbent assay and immunofluorescence detection; amino acid sequences were deduced by DNA sequencing. After 3 rounds of screening, 5 of 20 phage clones screened positive, showing specific binding to LoVo cells and a conserved RPM motif. Specific peptides against colorectal cancer cells could be obtained from a phage display peptide library and may be used as potential vectors for targeting therapy for colorectal cancer.