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In this paper, we investigate a Reconfigurable Intelligent Surface (RIS)-assisted secure Symbiosis Radio (SR) network to address the information leakage of the primary transmitter (PTx) to potential eavesdroppers. Specifically, the RIS serves as a secondary transmitter in the SR network to ensure the security of the communication between the PTx and the Primary Receiver (PRx), and simultaneously transmits its information to the PTx concurrently by configuring the phase shifts. Considering the presence of multiple eavesdroppers and uncertain channels in practical scenarios, we jointly optimize the active beamforming of PTx and the phase shifts of RIS to maximize the secrecy energy efficiency of RIS-supported SR networks while satisfying the quality of service requirement and the secure communication rate. To solve this complicated non-convex stochastic optimization problem, we propose a secure beamforming method based on Proximal Policy Optimization (PPO), which is an efficient deep reinforcement learning algorithm, to find the optimal beamforming strategy against eavesdroppers. Simulation results show that the proposed PPO-based method is able to achieve fast convergence and realize the secrecy energy efficiency gain by up to 22% when compared to the considered benchmarks.

Abstract Despite recent advances in extrusion bioprinting of cell‐laden hydrogels, using naturally derived bioinks to biofabricate complex elastic tissues with both satisfying biological functionalities and superior mechanical properties is hitherto an unmet challenge. Here, we address this challenge with precisely designed biological tough hydrogel bioinks featuring a double‐network structure. The tough hydrogels consisted of energy‐dissipative dynamically crosslinked glycosaminoglycan hyaluronic acid (o‐nitrobenzyl‐grafted hyaluronic acid) and elastin through Schiff's base reaction, and free‐radically polymerized gelatin methacryloyl. The incorporation of elastin further improved the elasticity, stretchability (∼170% strain), and toughness (∼45 kJ m−3) of the hydrogels due to the random coiling structure. We used this novel class of hydrogel bioinks to bioprint several complex elastic tissues with good shape retention. Furthermore, in vitro and in vivo experiments also demonstrated that the existence of elastin in the biocompatible bioinks facilitated improved cell behaviors and biological functions of bioprinted tissues, such as cell spreading and phenotype maintenance as well as tissue regeneration. The results confirmed the potential of the elastin‐containing tough hydrogel bioinks for bioprinting of 3D complex elastic tissues with biological functionalities, which may find widespread applications in elastic tissue regeneration.

In this paper, the detection methods and detection systems for the subwavelength focusing optical field of the micro-Fresnel zone plate (FZP) are experimentally studied. First, a comparison is made between the micro/nanofabrication methods for micro-FZP, namely, focused ion beam (FIB) and electron beam lithography, and the results show that FIB is better suited for the amplitude-type micro-FZP fabrication. Subsequently, the experimental detection devices based on the wide-field microscopy amplification (WFMA) imaging method (indirect detection method) and scanning near-field optical microscopy (direct detection method) are, respectively, constructed for the detection of the subwavelength focusing optical field of micro-FZP. The experimental results are compared and analyzed with theoretical calculation results, indicating that the WFMA method is more suitable for the detection of micro-FZP subwavelength focusing optical field that is not sensitive to radial components. This study provides an experimental reference for the micro/nanofocusing optical field detection of micro/nano-optical components similar to micro-FZP and promotes the practical application of micro-FZP.

Abstract Streptomyces species have a complex life cycle and are the producers of ~70% of commercial antibiotics. Global regulators AfsR and AfsS are widespread among Streptomyces and have been identified as key activators of antibiotic production in several species. However, their roles as repressors of antibiotic production are unclear; in particular, nothing is known regarding the regulatory mechanism of AfsS, despite many decades of research, because it has no DNA‐binding domain. Here, we demonstrate that AfsR and AfsS negatively regulate avermectin production and morphological development in the industrially important species S. avermitilis. AfsR directly represses ave structural genes (aveA1, aveA4), cluster‐situated activator gene aveR, and eight key developmental genes, whereas it directly activates afsS, aco (for autoregulator avenolide biosynthesis), and avaR1 (encoding avenolide receptor). GST pull‐down, microscale thermophoresis, co‐immunoprecipitation, and chromatin immunoprecipitation‐quantitative PCR assays demonstrated that AfsS interacts with AfsR to co‐regulate target genes involved in avermectin production and development and that this interaction requires intact AfsS repeated sequences and enhances the binding affinity of AfsR to target promoters. AfsR/AfsS interaction also occurs in model species S. coelicolor and S. roseosporus (producer of daptomycin, a cyclic lipopeptide antibiotic widely used for the treatment of human infections), suggesting that such interaction is conserved in Streptomyces species. The master developmental repressor BldD acts as a direct activator of both afsR and afsS. Deletion of afsR or afsS strongly enhances avermectin production in wild‐type and industrial S. avermitilis strains. Our findings demonstrate novel regulatory roles and mechanisms of AfsR and AfsS in Streptomyces and facilitate methods for antibiotic overproduction.

Tolerogenic dendritic cells (tolDCs) facilitate the suppression of autoimmune responses by differentiating regulatory T cells (Treg). The dysfunction of immunotolerance results in the development of autoimmune diseases, such as rheumatoid arthritis (RA). As multipotent progenitor cells, mesenchymal stem cells (MSCs), can regulate dendritic cells (DCs) to restore their immunosuppressive function and prevent disease development. However, the underlying mechanisms of MSCs in regulating DCs still need to be better defined. Simultaneously, the delivery system for MSCs also influences their function. Herein, MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ, maximizing efficacy in vivo. The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines. In the collagen-induced arthritis (CIA) mice model, alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39+CD73+ on MSCs. These enzymes hydrolyze ATP to adenosine and activate A2A/2B receptors on immature DCs, further promoting the phenotypic transformation of DCs to tolDCs and regulating naïve T cells to Tregs. Therefore, encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression. This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.

The focusing performances of high-numerical-aperture (NA) Fresnel zone plates (FZP) under different immersion media are investigated by combining the vectorial angular spectrum (VAS) theory and the finite-difference time-domain method. It has been found that as the refractive index deviation increases, the focus approximately linearly shifts along the positive z-axis. Simultaneously, the transverse size of the focusing spot gradually decreases, and super-resolution focusing is realized. However, the peak intensity declines with an increase in the refractive index. In addition, when the deviation of the refractive index of the actual immersion medium from the design value is less than about 30%, VAS theory can correctly estimate the focusing light field distribution, except when the FZP has only one or two transparent annuli. On the contrary, VAS theory cannot achieve an accurate prediction when the deviation is larger. These findings will benefit the practical application of high-NA FZPs.

Abstract Bacterial infection can cause delay in wound healing, and reactive oxygen species (ROS) was accumulated in wounds, which threaten patients’ lives. Therefore, it needs to develop a multifunctional hydrogel for infected wound healing. Here, a multifunctional QAS‐CS@GA‐GM hydrogel with antibacterial and antioxidant property, established by the self‐adaptive covalent bond, is prepared aiming to eradicate bacteria and eliminate ROS. It is observed that QAS‐CS@GA‐GM hydrogel displays remarkable ability of clearing ROS and killing bacteria in vitro. With its antibacterial and antioxidant activity, QAS‐CS@GA‐GM hydrogel significantly accelerates the MRSA‐infected wound closure and reduces inflammatory, when QAS‐CS@GA‐GM hydrogel was applied to wound sites. Collectively, the research suggests that a self‐adaptive QAS‐CS@GA‐GM hydrogel is a promising wound dressing as antibacterial and ROS‐scavenging dressing for bacterial‐infected wound.

Abstract Background Distal duodenal resections are sometimes necessary for radical surgery, but how to restore duodenal continuity is still unclear. This study aimed at determining which style of anastomosis was more suitable for the duodenojejunostomy after resection of distal duodenum. Patients and methods We retrospectively identified 34 patients who underwent distal duodenum resection at our center between January 2014 and December 2021. According to whether the end or the side of the proximal duodenum was involved in reconstruction, duodenojejunostomy were classified as End style (E-style) and Side style (S-style). Demographic data, clinicopathological details, and postoperative complications were analyzed between two groups. Results Thirteen patients (38.2%) received E-style duodenojejunostomy, and 21 patients (62.8%) received S-style duodenojejunostomy. Comparative analysis showed that in group of E-style, patients had a lower rate of multivisceral resection(5/13 vs 18/21; P = 0.008), delayed gastric emptying (DGE) (1/13 vs 11/21; P = 0.011) and intraperitoneal infection (2/13 vs 12/21; P = 0.03). In this study, the incidence of major complications was up to 35.3% (12/34) and no patient died of complication in perioperative period. In two group, there was no difference in the incidence of major complications (E-style vs S-style: 3/13 vs 9/21; P = 0.292). Conclusions The E-style duodenojejunostomy for the reconstruction of distal duodenum resection is safe and feasible. The E-style anastomosis may have potential value in decreasing the occurrence of complications such as DGE and intraperitoneal infection, and the definitive advantages still need to be verified.

In order to address the challenge of low offloading rate caused by the obstacles blocking in the links between unmanned aerial vehicle (UAV) and ground users (GU) in urban scene, a partial task offloading scheme for UAV-enabled mobile edge computing with the aid of reconfigurable intelligence surface was proposed.A nonconvex and multivariable coupling stochastic optimization problem was formulated by the joint design of the computation task allocation, the transmit power of GU, the phase shift of RIS, UAV computation resource, and UAV trajectory, aiming at maximizing the minimum average data throughput of GU.By leveraging the properties of mathematical expectation, the stochastic optimization problem was transformed into a deterministic optimization problem.Then, the deterministic optimization problem was decomposed into three subproblems by using the block coordinate descent (BCD) algorithm.By introducing auxiliary variables, the nonconvex problems were transformed into convex optimization problems via the successive convex approximation and semidefinite relaxation, and then the approximate suboptimal solution of the original problem was obtained.The simulation results show that the proposed algorithm has good convergence performance and effectively improves the average data throughput of GU.

Tissue engineering provides a promising strategy for auricular reconstruction. Although the first international clinical breakthrough of tissue-engineered auricular reconstruction has been realized based on polymer scaffolds, this approach has not been recognized as a clinically available treatment because of its unsatisfactory clinical efficacy. This is mainly since reconstruction constructs easily cause inflammation and deformation. In this study, we present a novel strategy for the development of biological auricle equivalents with precise shapes, low immunogenicity, and excellent mechanics using auricular chondrocytes and a bioactive bioink based on biomimetic microporous methacrylate-modified acellular cartilage matrix (ACMMA) with the assistance of gelatin methacrylate (GelMA), poly(ethylene oxide) (PEO), and polycaprolactone (PCL) by integrating multi-nozzle bioprinting technology. Photocrosslinkable ACMMA is used to emulate the intricacy of the cartilage-specific microenvironment for active cellular behavior, while GelMA, PEO, and PCL are used to balance printability and physical properties for precise structural stability, form the microporous structure for unhindered nutrient exchange, and provide mechanical support for higher shape fidelity, respectively. Finally, mature auricular cartilage-like tissues with high morphological fidelity, excellent elasticity, abundant cartilage lacunae, and cartilage-specific ECM deposition are successfully regenerated in vivo, which provides new opportunities and novel strategies for the fabrication and regeneration of patient-specific auricular cartilage.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12871-024-02448-2.

BackgroundLiposarcomas (LPS) are mesenchymal malignancies with four principal subtypes presenting distinct molecular and clinical features. Pleomorphic liposarcoma (PLPS) is one of the rarest and most aggressive subtypes of LPS. Surgical resection is currently a preferred curative approach for localized PLPS. However, the prognosis of unresectable PLPS is extremely poor, and there is no standard treatment.Case presentationA 59-year-old Chinese woman was diagnosed with unresectable PLPS. The case was discussed and managed by specialists from a multidisciplinary team at Fudan Zhongshan Hospital. Preoperative radiotherapy (RT) of intensity-modulated radiation therapy (IMRT) at 50 Gy/25 Fx concurrently with the angiogenesis inhibitor anlotinib (8 mg, days 1–14, every 3 weeks) was prescribed to the patient. The dosage of anlotinib was increased to 10 mg after RT. After 6 months of treatment, the tumor had significantly shrunk and was successfully resected. Examination of the surgical specimens showed a pathological complete response (pCR). Until the latest follow-up (April 2022), no recurrence was observed, and disease-free survival has exceeded 14 months.ConclusionThis case sheds light on the probability that perioperative RT combined with an angiogenesis inhibitor can be effectively used in PLPS, which is resistant to chemotherapy and usually considered to have a poor prognosis. Further studies with randomized controlled clinical trials will improve our knowledge of this preoperative treatment strategy.

The electroosmosis effect is a complement to the theory of the traditional capillary penetration of cutting fluid. In this study, based on the electric double layer (EDL) characteristics at friction material/solution interfaces, the influences of additives and their concentrations on capillary electroosmosis were investigated, and a water-based cutting-fluid formulation with consideration to the electroosmosis effect was developed. The lubrication performance levels of cutting fluids were investigated by a four-ball tribometer. The results show that the EDL is compressed with increasing ionic concentration, which suppresses the electroosmotic flow (EOF). The specific adsorption of OH− ions or the dissociation of surface groups is promoted as pH rises, increasing the absolute zeta potential and EOF. The polyethylene glycol (PEG) additive adsorbed to the friction material surface can keep the shear plane away from the solid surface, reducing the absolute zeta potential and EOF. The electroosmotic performance of cutting fluid can be improved by compounding additives with different electroosmotic performance functions. Furthermore, electroosmotic regulators can adjust the zeta potential by the electrostatic adsorption mechanism, affecting the penetration performance of cutting fluid in the capillary zone at the friction interface. The improvement in the tribological performance of cutting fluid developed with consideration given to the electroosmosis effect is attributed to the enhancement of the penetration ability of the cutting fluid and the formation of more abundant amounts of lubricating film at the interface.

Emerging evidence has shown that long non-coding RNAs (lncRNAs) play crucial roles in human cancers. However, systematic characterization of lncRNAs and their roles in gastrointestinal stromal tumor (GIST) therapy have been lacking. We performed high-throughput RNA sequencing (RNA-seq) of 20 GIST and paired adjacent normal samples. We characterized the transcriptional landscape and dysregulation of lncRNAs in GIST. We identified 866 upregulated and 1,268 downregulated lncRNAs in GIST samples, the majority of which were GIST-specific over other cancer types. Most hallmarks were found to be dysregulated in GIST samples, and lncRNAs were highly associated with cancer-related hallmarks. RP11-616M22.7 was identified to increase in imatinib-resistant samples compared to those in non-resistant samples. Further analysis revealed that RP11-616M22.7 was closely associated with the Hippo signaling pathway. By treating GIST cells with different doses of imatinib, we verified that RP11-616M22.7 knockdown promotes the sensitivity of tumor cells, whereas RP11-616M22.7 overexpression induces resistance to imatinib. We further confirmed reducing of resistance to imatinib by knocking down RP11-616M22.7 in vivo. Additionally, RP11-616M22.7 was observed to interact with RASSF1 protein. Our study revealed that deficiency of RP11-616M22.7 was able to reduce resistance of the GIST cell response to imatinib treatment both in vitro and in vivo.

Abstract Background Treating patients with advanced sarcomas is challenging due to great histologic diversity among its subtypes. Leiomyosarcoma (LMS) and de-differentiated liposarcoma (DDLPS) are two common and aggressive subtypes of soft tissue sarcoma (STS). They differ significantly in histology and clinical behaviors. However, the molecular driving force behind the difference is unclear. Methods We collected 20 LMS and 12 DDLPS samples and performed whole exome sequencing (WES) to obtain their somatic mutation profiles. We also performed RNA-Seq to analyze the transcriptomes of 8 each of the LMS and DDLPS samples and obtained information about differential gene expression, pathway enrichment, immune cell infiltration in tumor microenvironment, and chromosomal rearrangement including gene fusions. Selected gene fusion events from the RNA-seq prediction were checked by RT-PCR in tandem with Sanger sequencing. Results We detected loss of function mutation and deletion of tumor suppressors mostly in LMS, and oncogene amplification mostly in DDLPS. A focal amplification affecting chromosome 12q13–15 region which encodes MDM2, CDK4 and HMGA2 is notable in DDLPS. Mutations in TP53, ATRX, PTEN, and RB1 are identified in LMS but not DDLPS, while mutation of HERC2 is only identified in DDLPS but not LMS. RNA-seq revealed overexpression of MDM2, CDK4 and HMGA2 in DDLPS and down-regulation of TP53 and RB1 in LMS. It also detected more fusion events in DDLPS than LMS (4.5 vs. 1, p = 0.0195), and the ones involving chromosome 12 in DDLPS stand out. RT-PCR and Sanger sequencing verified the majority of the fusion events in DDLPS but only one event in LMS selected to be tested. The tumor microenvironmental signatures are highly correlated with histologic types. DDLPS has more endothelial cells and fibroblasts content than LMS. Conclusions Our analysis revealed different recurrent genetic variations in LMS and DDLPS including simultaneous upregulation of gene expression and gene copy number amplification of MDM2 and CDK4. Up-regulation of tumor related genes is favored in DDLPS, while loss of suppressor function is favored in LMS. DDLPS harbors more frequent fusion events which can generate neoepitopes and potentially targeted by personalized immune treatment.

A bucket structure optimization method based on compound digging trajectory and limit digging force was proposed for the problem that the real digging resistance of excavators is difficult to measure and difficult to use as bucket load for structure optimization. The uncertainty of the digging resistance in the actual digging process of the excavator was analyzed, and a digging trajectory was obtained by active digging using the compound digging action. Based on the limit digging force model, the digging force and its variation law were calculated, and analyzed for different hydraulic cylinder’s active digging in the trajectory. Based on the bucket shape line equation, a parametric model of the bucket was established using APDL language, and the bucket stress variation under different digging actions was analyzed. The bucket stress and mass were reduced by 4.59% and 5.84% respectively after optimization.

Background: Immune checkpoint inhibitors (ICIs) are employed to treat various cancers, including soft tissue sarcomas (STSs), and less than 20% of patients benefit from this treatment. Vascular endothelial growth factor (VEGF) promotes the immunosuppressive tumor microenvironment and contributes to ICI-resistant therapy. Anti-VEGF receptor tyrosine-kinase inhibitors (TKIs) combined with ICIs have shown antitumor activity in patients with alveolar soft-part sarcoma (ASPS). However, they have not been extensively studied to treat other STS subtypes, such as leiomyosarcoma (LMS), dedifferentiated liposarcoma (DDLPS), undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), and angiosarcoma (AS).Methods: In this retrospective study, we collected data from 61 patients who were diagnosed with advanced STS based on imaging and histology, including LMS, DDLPS, and UPS. Among them, 41 patients were treated with ICIs combined with TKIs and 20 patients received ICI therapy. The endpoints of progression-free survival (PFS) and overall response rate (ORR) were analyzed in the two groups, and the overall response [partial response (PR), stable disease (SD), and progressive disease (PD)] of each patient was determined using RECIST 1.1 evaluation criteria.Results: In total, 61 STS patients had the following subtypes: LMS (n = 20), DDLPS (n = 17), UPS (n = 8), ASPS (n = 7), MFS (n = 7), and AS (n = 2). The median PFS (mPFS) was significantly prolonged after ICI treatment in combination with TKIs (11.74 months, 95% CI 4.41–14.00) compared to ICI treatment alone (6.81 months, 95% CI 5.43–NA) (HR 0.5464, p = 0.043). The 12-month PFS rates of patients who received ICI–TKI treatment were increased from 20.26% (95% CI 0.08–0.53) to 42.90% (95% CI 0.27–0.68). In the combination therapy group, 12 patients (30%) achieved PR, 25 patients (62.5%) achieved SD, and 3 patients (7.5%) achieved PD for 3 months or longer. In the non-TKI-combination group, 2 patients (9.5%) achieved PR, 14 patients (66.7%) achieved SD, and 5 patients (23.8%) achieved PD within 3 months. The ORRs in the two groups were 30.0% (ICI–TKI combination) and 9.5% (ICI only), respectively. A notable ORR was observed in the ICI–TKI combination group, especially for subtypes ASPS (66.7%), MFS (42.9%), and UPS (33.3%). The PD-L1 expression (n = 33) and tumor mutation burden (TMB, n = 27) were determined for each patient. However, our results showed no significant difference in PFS or response rates between the two groups.Conclusion: This study suggests that ICI–TKI treatment has antitumor activity in patients with STS, particularly the ASPS and MFS subtypes. Moreover, effective biomarkers to predict clinical outcomes are urgently needed after combination therapy in the STS subtypes.

Liposarcoma (LPS) is a rare and heterogeneous malignancy of adipocytic origin. Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are two of the most common subtypes, showing similar genetic characterizations but distinct biological behaviors and clinical prognosis. Compared to WDLPS, DDLPS is more aggressive and has the potential of metastasis, as the malignant adipocytic tumor’s metabolic changes may have taken place during the tumorigenesis of LPSs. Therefore, to investigate the lipid alterations between the two subtypes, high-resolution liquid chromatography tandem mass spectrometry (LC-MS/MS) based untargeted lipidomic analysis was performed onto LPS tissues from 6 WDLPS and 7 DDLPS patients. The lipidomic analysis showed the upregulated phosphatidylcholines and phosphoethanolamines in DDLPS, and the upregulated triglycerides and diglycerides in WDLPS, which might be due to the uncompleted adipocytic dedifferentiation leading to such tumorigenesis. Such a finding was also confirmed by the similarity comparison of two LPS subtypes to the transcriptome of stromal vascular fraction at different differentiation stages. Transcriptomic analysis also demonstrated that metabolic pathways including the pentose phosphate pathway (PPP) were upregulated in WDLPS compared to DDLPS. Therefore, the cell line LPS853 was treated with the PPP inhibitor 6-aminonicotinamide ex vivo and the proliferation and invasion of LPS853 was significantly promoted by PPP inhibition, suggesting the potential role of PPP in the development and differentiation of LPS. In conclusion, this study described the altered lipid profiles of WDLPS and DDLPS for the first time, revealing the different differentiation stages of the two subtypes and providing a potential metabolic target for LPS treatment.

Understanding the effects of electrical double layers (EDL) and tribo-induced electric fields on the electroosmotic behaviors of lubricants is important for developing high-performance water-based lubricants. In this study, EDL conductivities of aqueous lubricants containing a surfactant of 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS) or cetyltrimethylammonium bromide (CTAB) were analyzed. The interfacial zeta potentials of the synthesized lubricants and Al2O3 ceramic-alloy steel contacts were measured, and frictional potentials of ceramic and steel surfaces were determined using a modified ball-on-disc configuration. The distribution characteristics of the tribo-induced electric field of the ceramic-steel sliding contact were numerically analyzed. The electroosmotic behaviors of the lubricants were investigated using a four-ball configuration. It was found that an EDL and tribo-induced electric field was a crucial enabler in stimulating the electroosmosis of lubricants. Through altering EDL structures, CHAPS enhanced the electroosmosis and penetration of the water-based lubricant, thus resulting in improved lubrication.

The bacterial species Streptomyces avermitilis is an important industrial producer of avermectins, which are widely utilized as effective anthelmintic and insecticidal drugs. We used gene deletion, complementation, and overexpression experiments to identify SAV4189, a MarR-family transcriptional regulator (MFR) in this species, as an activator of avermectin biosynthesis. SAV4189 indirectly stimulated avermectin production by altering expression of cluster-situated activator gene aveR, and directly repressed the transcription of its own gene (sav_4189) and adjacent cotranscribed gene sav_4190 (which encodes an unknown transmembrane efflux protein). A consensus 13-bp palindromic sequence, 5′-TTGCCYKHRSCAA-3′ (Y = T/C; K = T/G; H = A/C/T; R = A/G; S = C/G), was found within the SAV4189-binding sites of its own promoter region, and shown to be essential for binding. The SAV4189 regulon was thus predicted based on bioinformatic analysis. Night new identified SAV4189 targets are involved in transcriptional regulation, primary metabolism, secondary metabolism, and stress response, reflecting a pleiotropic role of SAV4189. sav_4190, the important target gene of SAV4189, exerted a negative effect on avermectin production. sav_4189 overexpression and sav_4190 deletion in S. avermitilis wild-type and industrial strains significantly increased avermectin production. SAV4189 homologs are widespread in other Streptomyces species. sav_4189 overexpression in the model species S. coelicolor also enhanced antibiotic production. The strategy of increasing yield of important antibiotics by engineering of SAV4189 homologs and target gene may potentially be extended to other industrial Streptomyces species. In addition, SAV4189 bound and responded to exogenous antibiotics hygromycin B and thiostrepton to modulate its DNA-binding activity and transcription of target genes. SAV4189 is the first reported exogenous antibiotic receptor among Streptomyces MFRs.

Abstract Background At present, sevoflurane inhalation anesthesia used on infants is well-known. But long-time exposure to inhalation anesthetic could cause neurologic disorder, especially nerve degeneration in infant and developing brain. The central nervous system degeneration of infants could affect the memory and cognitive function. γ-Aminobutyric acid (GABA) is a known inhibitory neurotransmitter in central nervous system. Inhalation anesthetic sevoflurane may activate GABAA receptor to inhibit central nervous system, leading to apoptosis of neural degeneration, cognitive dysfunction in the critical period of brain development. Methods Neural stem cells were derived from Wistar embryos, cultured in vitro. Third generation of neural stem cells were randomly divided into four groups according to cultured suspension: Sevoflurane group (Group S), GABAA receptor antagonists, Bicuculline group (Group B), Sevoflurane + GABAA receptor antagonists, Bicuculline group (Group S + B), dimethyl sulphoxide (DMSO) group (Group D). Group B and Group D did not receive sevoflurane preconditioning. Group S and Group S + B were pretreated with 1 minimum alveolar concentration (MAC) sevoflurane for 0 h, 3 h, 6 h, and 12 h. Group S + B and Group B were pretreated with bicuculline (10 uM). Group D was treated with DMSO (10 uL/mL). After treatments above, all groups were cultured for 48 h. Then we measured the cells viability by Cell Counting Kit (CCK-8) assay, cytotoxicity by Lactate Dehydrogenase (LDH) assay, apoptosis ratio with Annexin V/propidium iodide (PI) staining by flow cytometry, and the expression of GABAAR, anti-apoptotic protein Bcl-2, pro-apoptotic protein Bax and Caspase-3 by western blotting. Results After exposing to sevoflurane for 0 h, 3 h, 6 h, and 12 h with 1MAC, we found that cell viability obviously decreased and cytotoxicity increased in time-dependent way. And Annexin V/PI staining indicated increased apoptosis ratio by flow cytometry. The protein level of GABAA receptor, pro-apoptotic protein Bax and apoptosis protein Caspase-3 increased; while anti-apoptotic protein Bcl-2 decreased. And bicuculline could reverse all detrimental results caused by sevoflurane. Conclusion Sevoflurane can inhibit the central nervous system by activating GABAA, resulting in apoptosis of neural stem cells, thus leading to the NSCs degeneration.

This study designed a vertical take-off and landing tailsitter unmanned aerial vehicle (UAV) with a long endurance time. Nine parameters of the tailsitter UAV were investigated. Using a 2k full factorial test, 512 experiments on the nine parameters were conducted at their maximum and minimum values. The time coefficient and air resistance were calculated using the computational fluid dynamics (CFD) method under different parameter combinations. The analysis of variance determined that the specific factors influencing the time coefficient and air resistance were the root chord, wingtip chord, wingspan, and sweep angle. By carrying out a central composite design (CCD) test, 25 sample points of the four particular factors were constructed. The time coefficient and air resistance were simulated under different structural parameter combinations using the CFD method. CFD simulation was verified by carrying out a wind tunnel test, and the results revealed that the aerodynamic coefficient error was less than 5%, while the air resistance error was less than 6%. The response surface methodology (RSM) for the time coefficient and air resistance was established using a genetic aggregation method. A multi-objective genetic algorithm (MOGA) was used to optimize the parameters with regard to the maximum time coefficient and minimum air resistance. The optimal structural parameters were wing root chord length at 315 mm, wingtip chord length at 182 mm, wingspan length at 1198 mm, and sweep angle at 16°. Compared with the original layout and size, the time coefficient of the new design of the tailsitter UAV improved by 19.5%, while the air resistance reduced by 34.78%. The results obtained by this study are significant for the design of tailsitter UAVs.

We developed and tested an unmanned aerial vehicle-based gas sampling system (UGSS) for collecting gases and atmospheric particulate matter (PM). The system applies an alternative way of collecting both vertical and horizontal transects of trace gases in order to analyze them in the laboratory. To identify the best position of the UGSS intake port, aerodynamic flow simulations and experimental verifications of propeller airflow were conducted with an unmanned aerial vehicle (UAV) in hover mode. The UGSS will automatically replace the original gas in the system with gas from a target location to avoid the original gas being stored in the air bags. Experimental results show that the UGSS needs 5 s to replace the system’s own original gas using its pump. CO2 and PM2.5/10 above the corn field are used as the test species to validate the accuracy of the CO2 gas and PM concentrations collected by UGSS. Deming regression analyses showed good agreement between the measurements from the UGSS and the ground sampling station (y = 1.027x − 11.239, Pearson’s correlation coefficient of 0.98 for CO2; y = 0.992x + 0.704, Pearson’s correlation coefficient of 0.99 for PM).The UGSS provides a measuring method that actively collects gases and PM for manual analyses in the laboratory.

This study aims to explore the expression of GRP78, a marker of endoplasmic reticulum (ER) stress, in the cortex of rat brains acutely exposed to methylmercury (MeHg). Thirty Sprague-Dawley (SD) rats were randomly divided into six groups, and decapitated 6 hours (h) after intraperitoneal (i.p.) injection of MeHg (2, 4, 6, 8 or 10 mg/kg body weight) or normal saline. Protein and mRNA expression of Grp78 were detected by western blotting and real-time PCR, respectively. The results showed that a gradual increase in GRP78 protein expression was observed in the cortex of rats acutely exposed to MeHg (2, 4 or 6 mg/kg). Protein levels peaked in the 6 mg/kg group ( p < 0.05 vs. controls), decreased in the 8 mg/kg group, and bottomed below the control level in the 10 mg/kg group. Parallel changes were noted for Grp78 mRNA expression. It may be implied that acute exposure to MeHg induced hormetic dose-dependent changes in Grp78 mRNA and protein expression, suggesting that activation of ER stress is involved in MeHg-induced neurotoxicity. Low level MeHg exposure may induce GRP78 protein expression to stimulate endogenous cytoprotective mechanisms.