Optomechanical Microwave-to-Optical Photon Transducer Chips: Empowering the Quantum Internet Revolution.

The first quantum revolution has brought us the classical Internet and information technology. Today, as technology advances rapidly, the second quantum revolution quietly arrives, with a crucial moment for quantum technology to establish large-scale quantum networks. However, solid-state quantum bits (such as superconducting and semiconductor qubits) typically operate in the microwave frequency range, making it challenging to transmit signals over long distances. Therefore, there is an urgent need to develop quantum transducer chips capable of converting microwaves into optical photons in the communication band, since the thermal noise of optical photons at room temperature is negligible, rendering them an ideal information carrier for large-scale spatial communication. Such devices are important for connecting different physical platforms and efficiently transmitting quantum information. This paper focuses on the fast-developing field of optomechanical quantum transducers, which has flourished over the past decade, yielding numerous advanced achievements. We categorize transducers based on various mechanical resonators and discuss their principles of operation and their achievements. Based on existing research on optomechanical transducers, we compare the parameters of several mechanical resonators and analyze their advantages and limitations, as well as provide prospects for the future development of quantum transducers.

Molecular characterization of hybrid virulence plasmids in ST11-KL64 KPC-2-producing multidrug-resistant hypervirulent Klebsiella pneumoniae from China.

Introduction: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-HvKP) strains combining virulence and multidrug resistance (MDR) features pose a great public health concern. The aim of this study is to explore the evolutionary characteristics of virulence in CR-HvKP by investigating the genetic features of resistance and virulence hybrid plasmids. Methods: The resistance and virulence phenotypes were determined by using antimicrobial susceptibility testing and the mouse bacteremia infection model, respectively. Plasmid profiles were investigated by S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting, conjugation assay, and whole genome sequencing (WGS). Bioinformatics tools were used to uncover the genetic features of the resistance and virulence hybrid plasmids. Results: Two ST11-KL64 CRKP clinical isolates (KP18-3-8 and KP18-2079), which exhibited enhanced virulence compared with the classic CRKP, were detected positive for blaKPC-2 and rmpA2. The virulence level of the hypermucoviscous strain KP18-3-8 was higher than that of KP18-2079. S1-PFGE, Southern hybridization and WGS analysis identified two novel hybrid virulence plasmids in KP18-3-8 (pKP1838-KPC-vir, 228,158 bp) and KP18-2079 (pKP1838-KPC-vir, 182,326 bp), respectively. The IncHI1B/repB-type plasmid pKP1838-KPC-vir co-harboring blaKPC-2 and virulence genes (rmpA2, iucABCD and iutA) but lacking type IV secretion system could transfer into non-hypervirulent ST11 K. pneumoniae with the assistance of a helper plasmid in conjugation. The IncFII/IncR-type virulence plasmid pKP18-2079-vir may have been generated as a result of recombination between a typical pLVPK-like virulence plasmid and an MDR plasmid. Conclusion: Our studies further highlight co-evolution of the virulence and resistance plasmids in ST11-CRKP isolates. Close surveillance of such hybrid virulence plasmids in clinical K. pneumoniae should be performed.

Machine-Learning-Guided Engineering of an NADH-Dependent 7ß-Hydroxysteroid Dehydrogenase for Economic Synthesis of Ursodeoxycholic Acid.

Enzymatic synthesis of ursodeoxycholic acid (UDCA) catalyzed by an NADH-dependent 7ß-hydroxysteroid dehydrogenase (7ß-HSDH) is more economic compared with an NADPH-dependent 7ß-HSDH when considering the much higher cost of NADP+/NADPH than that of NAD+/NADH. However, the poor catalytic performance of NADH-dependent 7ß-HSDH significantly limits its practical applications. Herein, machine-learning-guided protein engineering was performed on an NADH-dependent Rt7ß-HSDHM0 from Ruminococcus torques. We combined random forest, Gaussian Naïve Bayes classifier, and Gaussian process regression with limited experimental data, resulting in the best variant Rt7ß-HSDHM3 (R40I/R41K/F94Y/S196A/Y253F) with improvements in specific activity and half-life (40 °C) by 4.1-fold and 8.3-fold, respectively. The preparative biotransformation using a "two stage in one pot" sequential process coupled with Rt7ß-HSDHM3 exhibited a space-time yield (STY) of 192 g L-1 d-1, which is so far the highest productivity for the biosynthesis of UDCA from chenodeoxycholic acid (CDCA) with NAD+ as a cofactor. More importantly, the cost of raw materials for the enzymatic production of UDCA employing Rt7ß-HSDHM3 decreased by 22% in contrast to that of Rt7ß-HSDHM0, indicating the tremendous potential of the variant Rt7ß-HSDHM3 for more efficient and economic production of UDCA.

A 3D tetrathiafulvalene-based metal-organic framework with intramolecular charge transfer for efficient near-infrared photothermal conversion.

The selection of metal centers can endow donor-metal-accepter (D-M-A) type MOFs with progressive framework dimensions. 3D Cd-based MOFs with intramolecular charge transfer caused by D-M-A exhibit a satisfactory photothermal conversion efficiency of 35.7%, with the temperature rapidly rising from 25 °C to 201 °C in 7 s under 808 nm laser irradiation.

Identification of tmexC3-tmexD3-toprJ1b in an XDR Providencia rettgeri clinical isolate co-producing NDM-1 and OXA-10 carbapenemases.

OBJECTIVES: Emergence of carbapenemase and tigecycline resistance genes in pathogens threatens the efficacy of last-resort antibiotics. High attention should be paid to the spread and convergence of such resistance genes. This study reports an extensively drug-resistant (XDR) Providencia rettgeri clinical strain co-harbouring carbapenemase genes blaNDM-1, blaOXA-10 and the tmexCD3-toprJ1b gene cluster. METHODS: The phenotype and genotype of P. rettgeri Pre20-95 were investigated by antimicrobial susceptibility testing, conjugation assay, stability testing and whole genome sequencing. Bioinformatics tools were used to uncover the genetic structures of its multidrug-resistant (MDR) plasmid pPre20-95-1 and SXT/R391 integrative and conjugative element ICEPreChn20-95. RESULTS: P. rettgeri strain Pre20-95 was isolated from a human clinical infection and displayed an extensively drug-resistant (XDR) phenotype. Whole genome sequencing (WGS) analysis identified a pPrY2001-like MDR plasmid, namely pPre20-95-1, co-harbouring blaNDM-1 and blaOXA-10 genes in Pre20-95. The multidrug resistance region of pPre20-95-1 was composed of a Tn6625-derived module and a ∆Tn1696 structure, and blaNDM-1 and blaOXA-10 were located in a composite Tn structure consisting of insertion sequences ISCR1 and ISAba125 and an In125-like class 1 integron, respectively. Furthermore, the novel RND efflux pump gene cluster tmexCD3-toprJ1b was identified on the SXT/R391 ICE ICEPreChn20-95 of its chromosome, and reverse PCR showed that it could form a circular intermediate for transmission. CONCLUSION: Our findings highlight further dissemination of the tmexCD3-toprJ1b gene cluster into a clinical isolate of P. rettgeri and convergence with multiple carbapenemase genes, which increases the risk of the emergence of XDR strains and threatens the treatment of Enterobacterales bacterial infections.

A Review of Myoelectric Control for Prosthetic Hand Manipulation.

Myoelectric control for prosthetic hands is an important topic in the field of rehabilitation. Intuitive and intelligent myoelectric control can help amputees to regain upper limb function. However, current research efforts are primarily focused on developing rich myoelectric classifiers and biomimetic control methods, limiting prosthetic hand manipulation to simple grasping and releasing tasks, while rarely exploring complex daily tasks. In this article, we conduct a systematic review of recent achievements in two areas, namely, intention recognition research and control strategy research. Specifically, we focus on advanced methods for motion intention types, discrete motion classification, continuous motion estimation, unidirectional control, feedback control, and shared control. In addition, based on the above review, we analyze the challenges and opportunities for research directions of functionality-augmented prosthetic hands and user burden reduction, which can help overcome the limitations of current myoelectric control research and provide development prospects for future research.

One-pot synthesis of gamma-graphyne supported Pd nanoparticles with high catalytic activity.

As a unique member of the graphyne family, gamma-graphyne (γ-graphyne) is a novel kind of 2D carbon allotrope with potential high carrier mobility and large surface area. It remains a great challenge to synthesize graphynes with targeted topologies and good performance. Herein, a novel one-pot method was applied to the synthesis of γ-graphyne using hexabromobenzene and acetylenedicarboxylic acid via a Pd-catalyzed decarboxylative coupling reaction, which is easy to perform with mild reaction conditions, facilitating the possibility of mass production. As a result, the synthesized γ-graphyne reveals a two-dimensional γ-graphyne structure consisting of 1 : 1 sp/sp2 hybridized carbon atoms. Furthermore, γ-graphyne as a carrier for Pd (Pd/γ-graphyne) displayed a superior catalytic activity for the reduction of 4-nitrophenol with a short reaction time and high yields, even in aqueous media under aerobic conditions. Compared with Pd/GO, Pd/HGO, Pd/CNT, and commercial Pd/C, Pd/γ-graphyne showed more excellent catalytic performance with lower palladium loadings. Thus we expect that the novel approach for the synthesis of γ-graphyne will boost research on the design and application of graphyne-type functional materials for catalysis.

Characterization of a Conjugative Hybrid Plasmid Coharboring blaKPC-2 and blaIMP-4 in a Klebsiella quasipneumoniae Clinical Isolate.

Generation of hybrid MDR plasmids accelerated the evolution and transmission of resistance genes. In this study, we characterized a blaKPC-2- and blaIMP-4-coharboring conjugative hybrid plasmid constituted of an IncHI5 plasmid-like region, an IncFII(Yp)/IncFIA plasmid-like region, and a KPN1344 chromosome-like region from a clinical ST852-KL18 Klebsiella quasipneumoniae strain. The blaIMP-4 gene was captured by a novel integron In1965, and the blaKPC-2 gene was located on a new non-Tn4401 group I NTEKPC element. Both blaKPC-2- and blaIMP-4-containing genetic architectures were distinguished from classical structures, highlighting the constant evolution of these genetic elements. IMPORTANCE The emergence of carbapenem-resistant Enterobacterales (CRE) that coexpress serine- and metallo-carbapenemases is a severe threat to the efficacy of ceftazidime-avibactam (CZA), which has been proven to be extremely effective against KPC-producing Enterobacterales strains. Our study described the cooccurrence of KPC-2, a serine ß-lactamase, and IMP-4, a metallo-ß-lactamase (MBL), on a conjugative hybrid plasmid from a clinical carbapenem-resistant K. quasipneumoniae strain, and it revealed an alternative route for IncHI5 plasmid to evolve by recombining with other plasmids to form a hybrid plasmid. Moreover, this hybrid plasmid can be transferred into other Klebsiella species and stably persist during passage. The propagation of two important carbapenemase genes with a new genetic background using well-evolved plasmids in the clinical setting promotes the emergence of superbugs that require careful monitoring.

Development of biaromatic core-linked antimicrobial peptide mimics: Substituent position significantly affects antibacterial activity and hemolytic toxicity.

The development of bacterial resistance to the majority of clinically significant antimicrobials has made it more difficult to treat bacterial infections with conventional antibiotics. As part of ongoing research on antimicrobial peptide mimetics, a series of quaternary ammonium cationic compounds with various linkers were designed and synthesized, with some demonstrating high antibacterial activity against Gram-negative and Gram-positive bacteria. The structure-activity relationship study revealed that the spatial position of substituents had a significant impact on antibacterial activity and hemolytic toxicity. The best compound, 3e, has good antibacterial activity against Staphylococcus aureus [minimum inhibitory concentration (MIC = 1 µg/mL)] and the least hemolytic toxicity [hemolytic concentration (HC50 = 905 µg/mL)], is stable in mammalian body fluids, and rarely induces bacterial resistance. The mechanism study revealed that the membrane action mode may be its potential bactericidal mechanism, and it can effectively cause the accumulation of intracellular reactive oxygen species (ROS) for killing bacteria. Importantly, 3e can effectively reduce the load of methicillin-resistant Staphylococcus aureus (MRSA) in mouse skin and has a higher in vivo bactericidal efficiency than vancomycin. These findings highlight the significance of divergent linkers in quaternary ammonium cations as antimicrobial peptide mimics and the potential of these cations to treat bacterial infections.

Emergence of a novel hybrid mcr-1-bearing plasmid in an NDM-7-producing ST167 Escherichia coli strain of clinical origin.

Colistin is considered as an antibiotic of 'last resort' for the treatment of lethal infections caused by carbapenem-resistant Enterobacterales (CRE), dissemination of plasmid-borne colistin resistance gene mcr-1, particularly into CRE, resulting in the emergence of strains that approach pan-resistance. A wide variety of plasmid types have been reported for carrying mcr-1. Among which, large IncHI2-type plasmids were multidrug-resistant (MDR) plasmids harbored multiple resistance determinants in addition to mcr-1. Herein, we characterized a novel hybrid IncHI2-like mcr-1-bearing plasmid in an NDM-7-producing ST167 Escherichia coli strain EC15-50 of clinical origin. Antimicrobial susceptibility testing showed E. coli EC15-50 exhibited an extensively drug-resistant (XDR) profile that only susceptible to amikacin and tigecycline. S1-PFGE, Southern hybridization and Whole-genome Sequencing (WGS) analysis identified a 46,161 bp bla NDM-7-harboring IncX3 plasmid pEC50-NDM7 and a 350,179 bp mcr-1-bearing IncHI2/HI2A/N/FII/FIA plasmid pEC15-MCR-50 in E. coli EC15-50. Sequence detail analysis revealed the type IV coupling protein (T4CP) gene was absent on pEC15-MCR-50, explaining that pEC15-MCR-50 was a non-conjugative plasmid. Comparative genetic analysis indicated the hybrid plasmid pEC15-MCR-50 was probably originated from pXGE1mcr-like IncHI2/HI2A/N plasmid and pSJ_94-like IncFII/FIA plasmid, and generated as a result of a replicative transposition process mediated by IS26. Currently, the prevalent mcr-1-carrying IncHI2 plasmids were rarely reported to be fused with other plasmids. The identification of the novel hybrid plasmid pEC15-MCR-50 in this study highlighted the importance of close surveillance for the emergence and dissemination of such fusion MDR plasmids, particularly in NDM-producing Enterobacterales.

Scalable Manufacture of Curcumin-Loaded Chitosan Nanocomplex for pH-Responsive Delivery by Coordination-Driven Flash Nanocomplexation.

Metal coordination-driven nanocomplexes are known to be responsive to physiologically relevant stimuli such as pH, redox, temperature or light, making them well-suited for antitumor drug delivery. The ever-growing demand for such nanocomplexes necessitates the design of a scalable approach for their production. In this study, we demonstrate a novel coordination self-assembly strategy, termed flash nanocomplexation (FNC), which is rapid and efficient for the fabrication of drug-loaded nanoparticles (NPs) in a continuous manner. Based on this strategy, biocompatible chitosan (CS) and Cu2+ can be regarded anchors to moor the antitumor drug (curcumin, Cur) through coordination, resulting in curcumin-loaded chitosan nanocomplex (Cur-loaded CS nanocomplex) with a narrow size distribution (PDI < 0.124) and high drug loading (up to 41.75%). Owing to the excellent stability of Cur-loaded CS nanocomplex at neutral conditions (>50 days), premature Cur leakage was limited to lower than 1.5%, and pH-responsive drug release behavior was realized in acidic tumor microenvironments. An upscaled manufacture of Cur-loaded CS nanocomplex is demonstrated with continuous FNC, which shows an unprecedented method toward practical applications of nanomedicine for tumor therapy. Furthermore, intracellular uptake study and cytotoxicity experiments toward H1299 cells demonstrates the satisfied anticancer efficacy of the Cur-loaded CS nanocomplex. These results confirm that coordination-driven FNC is an effective method that enables the rapid and scalable fabrication of antitumor drugs.

Functional and emulsification characteristics of phospholipids and derived o/w emulsions from peony seed meal.

Peony seed phospholipids (PPLs), a kind of multifunctional plant-like phospholipids were extracted from peony seed meal. We investigated the functional properties of PPLs and compared their emulsification performance in corn oil-peony seed oil o/w emulsion systems with that of soy lecithin (DPLs). The PPLs were characterized with the higher content of phosphatidylcholine (PC) (416 ± 28 mg/g) and lyso-phosphatidylcholine (LPC) (43 ± 14 mg/g) fractions, and lower content of phosphatidylethanolamine (PE) (71 ± 13 mg/g). The polyunsaturated fatty acids showed higher content (83.25%), with the highest content of linoleic acid (46.05%) in PPLs. PPLs-emulsions showed smaller average particle size and higher loaded peony seed oil content at pH 5, temperature 50 °C, and about 60% corn oil content. PPLs-emulsions imparted better hydroxyl radical scavenging efficiency and reducing power than DPLs. Our results suggest that PPLs can be used as emulsifiers with improved antioxidant properties.

Genomic Epidemiology Insights on NDM-Producing Pathogens Revealed the Pivotal Role of Plasmids on blaNDM Transmission.

Incidences of nosocomial infections mediated by New Delhi metallo-ß-lactamase (NDM) enzyme-producing Enterobacterales are increasing globally, resulting in a great burden to public health. The carbapenem-resistant Enterobacterales (CRE) were collected from Henan, China during 2013-2016. The blaNDM-positive strains were characterized using PCR, antimicrobial susceptibility testing, conjugation assay, S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), Southern blot, whole-genome sequencing (WGS), and bioinformatics analysis. Eighty-one NDM-producing strains were identified among 391 nonduplicate CRE strains. Among them, four strains cocarried mcr and blaNDM genes, and two carried blaIMP-4 and blaNDM genes. The coexistence of blaNDM-5 and mcr-9 in Enterobacter hormaechei was found for the first time. In total, four blaNDM subtypes were identified. Among them, blaNDM-1 and blaNDM-5 were predominant. There was an obvious increasing trend in blaNDM-5 from 2013 to 2016. Thirteen different bacterial species were found among the 81 strains, and Escherichia coli was the dominant strain. blaNDM genes were located on nine different Inc-type plasmids, most of them on the IncX3 plasmids, except for the Pr-15-2-50 strain, which was located on the chromosome. We characterized two novel plasmids: the IncHI5-like plasmid carrying blaNDM-9 found in K. pneumonia, and the IncI1 blaNDM-5-positive plasmid. These findings provide the genomic basis for the widespread transmission of blaNDM and pave the way for the formulation of more effective monitoring and control methods. IMPORTANCE To control the emergence and transmission of CRE, it is important to perform retrospective genomic investigations. It is important to evaluate the plasmid diversity, genetic environment, and evolutionary relationships of the blaNDM-positive clinical strains in the early transmission stages. This study conducted an in-depth analysis of blaNDM-positive pathogens during a 4-year period using different methods for observing the high prevalence and active transmission of blaNDM-positive CRE. Moreover, we also explored the coexistence of the blaNDM and mcr, a clinically important mobile colistin resistance gene. This study shows that the prevalence of blaNDM-positive pathogens in Henan is high and the isolation rates increase each year. Moreover, plasmid-mediated horizontal transfer plays an important role in blaNDM dissemination. The co-occurrence of multiple resistance genes highlighted a long-lasting evolutionary pathway. Therefore, we have suggested the long-term continuous surveillance of clinical pathogens carrying blaNDM to learn the future transmission trend and curb the public health risk caused by CRE.

Thermochemical and Toxic Element Behavior during Co-Combustion of Coal and Municipal Sludge.

The thermochemical and kinetic behavior of co-combustion of coal, municipal sludge (MS) and their blends at different ratios were investigated by thermogravimetric analysis. Simulation experiments were performed in a vacuum tube furnace to determine the conversion behavior of toxic elements. The results show that the combustion processes of the blends of coal and municipal sludge are divided into three stages and the combustion curves of the blends are located between those of individual coal and municipal sludge samples. The DTGmax of the sample with 10% sludge addition reaches a maximum at the heating rate of 20 °C/min, indicating that the combustion characteristics of coal can be improved during co-combustion. Strong interactions were observed between coal and municipal sludge during the co-combustion. The volatilization rates of toxic elements decrease with an increasing proportion of sludge in the blends during co-combustion, which indicates that the co-combustion of coal and sludge can effectively reduce the volatilization rate of toxic elements. The study reflects the potential of municipal sludge as a blended fuel and the environmental effects of co-combustion of coal and municipal sludge.

Simultaneous or Staged Decompressions for Patients with Tandem Spinal Stenosis.

OBJECTIVE: To compare the clinical effects of cervical decompression first, lumbar decompression first, or simultaneous decompression of both lesions in the treatment of tandem spinal stenosis (TSS). METHODS: This is a retrospective analysis. From January 2013 to December 2018, 51 TSS patients underwent our surgery and postoperative investigation. Among the 51 subjects, 27 females and 24 males, aged 49-77 years with an average age of 66.3 ± 6.8, were selected. According to the different operation sequences, all patients were divided into three groups. In simultaneous operation group, five patients underwent cervical and lumbar vertebrae surgery at the same time. In first cervical surgery group, 28 patients underwent cervical vertebra surgery first, followed by lumbar spine surgery after a period of recovery. And in first lumbar surgery group, 18 patients underwent lumbar vertebrae surgery first. The choice for neck surgery is posterior cervical single-door vertebroplasty, the surgery of lumber is plate excision and decompression needle-rod system internal fixation. The outcome measures are visual analogue scale (VAS), Japanese Orthopaedic Association cervical (JOA-C) and lumbar (JOA-L) scores, which were assessed at 3 months and 1 year after the operation by telephone interview. In addition, operative time, estimated blood loss, and hospital stay were also recorded. RESULTS: All the patients in the study had surgery performed successfully by the same group of orthopaedic surgeons. The preoperative VAS scores of simultaneous operation group, first cervical surgery group, and first lumbar surgery group were 8.00 ± 1.00, 8.36 ± 0.68, and 8.17 ± 0.71 (P > 0.05). The preoperative JOA-C scores were 7.00 ± 2.35, 6.54 ± 1.53, and 7.83 ± 1.04 (P < 0.05). And the preoperative JOA-L scores were 7.20 ± 2.17, 4.64 ± 2.36, and 5.78 ± 1.22 respectively (P < 0.05). During the final 1-year follow-up, the JOA-C improvement rates of simultaneous operation group, first cervical surgery group, and first lumbar surgery group were 85.68% ± 5.44%, 84.27% ± 5.02%, and 83.34% ± 10.25%, respectively (P > 0.05), and the JOA-L improvement rates were 80.04% ± 3.35%, 81.65% ± 3.74%, and 80.21% ± 4.76% (P > 0.05). The difference among them was not statistically significant. In addition, operation time (OP), blood loss (BL), and hospital stay (HS) in the simultaneous operation group were 245.00 ± 5.00 min, 480.00 ± 27.39 mL, and 16.60 ± 0.55 days, respectively. While those parameters in the first cervical surgery group were 342.50 ± 18.18 min, 528.21 ± 43.97 mL, and 22.75 ± 2.15 days, and in the first lumbar surgery group they were 346.11 ± 24.77 min, 519.44 ± 43.99 mL, and 22.89 ± 1.64 days. The average blood loss in simultaneous operation group was less (P > 0.05); meanwhile, the operation time and hospital stay time were significantly shorter in the simultaneous operation group than in the first cervical surgery group and first lumbar surgery group (P < 0.05). Only one case of fat liquefaction occurred in first cervical surgery group, which healed spontaneously after a regular change of dressing for 1 month. CONCLUSIONS: Under the condition of ensuring the surgical effect, the choice of staged surgery or concurrent surgery according to the patients' own symptoms of cervical and lumbar symptoms could both obtain satisfactory results, and the damage of simultaneous surgery was less than that of staged surgery.

The inhibition of miR-17-5p promotes cortical neuron neurite growth via STAT3/GAP-43 pathway.

Spinal cord injury (SCI) is a devastating disease associated with locomotor function impair. The limited regenerative capability of the neural axon is one of the major factors that hinders the recovery of SCI. To enhance the regenerative ability of neuron is a promising strategy that repairs SCI. We previously proved miR-17-5p could target Signal Transducer and Activator of Transcription 3 (STAT3) in primary sensory neuron. We speculated that miR-17-5p was the miRNA that targets STAT3. The Dual-luciferase reporter assay indicated miR-17-5p could bind the 3'UTR of STAT3 mRNA. The RT-qPCR and Western blot assay showed miR-17-5p could not degenerate the mRNA of STAT3, but inhibit the expression of Signal Transducer and Activator of Transcription 3 (STAT3) via translation inhibition. MiR-17-5p inhibitor promoted the expression of STAT3, phosphorylated-STAT3 (p-STAT3) and Growth Associate Protein-43 (GAP-43), and this promotion was inhibited by STAT3 siRNA. MiR-17-5p mimics and inhibitor inhibited and promoted the neurite growth, respectively. MiR-17-5p inhibitor promoted the axon growth and AG490, the STAT3 phosphorylation inhibitor, inhibited this promotion. MiR-17-5p mimics inhibited the expression of STAT3, p-STAT3 and GAP-43, while the inhibitor promoted their expression. AG490 did not alter the expression of STAT3, while downregulated the expression both p-STAT3 and GAP-43 in miR-17-5p inhibitor&AG490 group. Taken together, these data indicated miR-17-5p could regulated cortical neuron axon growth via STAT3/GAP-43 pathway by targeting STAT3 mRNA 3'UTR. Therefore, miR-17-5p/STAT3/GAP-43 pathway plays a key role in regulating cortical neuron axon growth and could be a novel target to treat SCI.

The role of fibroblast activation protein in progression and development of osteosarcoma cells.

To investigate the expression levels of fibroblast activation protein (FAP) in human osteosarcoma tissues and its possible correlations with clinical pathological characteristics of patients with osteosarcoma, and to explore the potential effects of FAP on progression and development of osteosarcoma. Immunohistochemistry (IHC) assay was initially performed to detect the expression levels of FAP in 66 tumor tissues and adjacent non-tumor tissues. Patients were sequentially divided into two groups based on different expression levels of FAP. The correlations between the expression levels of FAP and the clinical pathological characteristics were investigated, and the role of FAP in proliferation, migration, and invasion of osteosarcoma cells was assessed via colony formation, MTT, wound healing, and transwell assays, respectively. The possible effects of FAP on tumor growth and metastasis were evaluated in vivo. We further attempted to reveal the underlying mechanism of FAP involved in tumor growth through bioinformatics and IHC assays. High expression levels of FAP were noted in human osteosarcoma tissues. It also was unveiled that FAP was significantly associated with the tumor size (P = 0.005*) and clinical stage (P = 0.017*). Our data further confirmed that knockdown of FAP remarkably blocked proliferation, migration, and invasion of osteosarcoma cells in vitro, and suppressed tumor growth and metastasis in mice via AKT signaling pathway. The possible role of FAP in progression and development of osteosarcoma could be figured out. Our data may be helpful to develop a novel therapeutic target for the treatment of osteosarcoma.

miR-155-5p Promotes Dorsal Root Ganglion Neuron Axonal Growth in an Inhibitory Microenvironment via the cAMP/PKA Pathway.

Sensory dysfunction post spinal cord injury causes patients great distress. Sciatic nerve conditioning injury (SNCI) has been shown to restore sensory function after spinal cord dorsal column injury (SDCL); however, the underlying mechanism of this recovery remains unclear. We performed a microarray assay to determine the associated miRNAs that might regulate the process of SNCI promoting SDCL repair. In total, 13 miRNAs were identified according to our inclusion criteria, and RT-qPCR was used to verify the microarray results. Among the 13 miRNAs, the miR-155-5p levels were decreased at 9 h, 3 d, 7 d, 14 d, 28 d, 2 m and 3 m timepoints in the SDCL group, while the SNCI group had a smaller decrease. Thus, miR-155-5p was chosen for further study after a literature review and an analysis with the TargetScan online tool. Specifically, miR-155-5p targets PKI-α, and the expression pattern of PKI-α was opposite that of miR-155-5p in both the SDCL and SNCI groups. Interestingly, miR-155-5p could promote dorsal root ganglion (DRG) neuron axon growth via the cAMP/PKA pathway and in a TNF-α, IL-1ß or MAG inhibitory microenvironment in vitro. Furthermore, miR-155-5p could regulate the cAMP/PKA pathway and promote sensory conduction function recovery post dorsal column injury as detected by NF-200 immunohistochemistry, somatosensory-evoked potentials, BBB scale and tape removal test. Collectively, our results demonstrated that miR-155-5p participates in the molecular mechanism by which SNCI promotes the repair of SDCL and that upregulated miR-155-5p can repair SDCL by enhancing DRG neuron axon growth via the cAMP/PKA pathway. These findings suggest a novel treatment target for spinal cord injury.

Sorafenib promotes sensory conduction function recovery via miR-142-3p/AC9/cAMP axis post dorsal column injury.

Spinal cord injury results in sensation dysfunction. This study explored miR-142-3p, which acts a critical role in sciatic nerve conditioning injury (SNCI) promoting the repair of the dorsal column injury and validated its function on primary sensory neuron(DRG). miR-142-3p expression increased greatly in the spinal cord dorsal column lesion (SDCL) group and increased slightly in the SNCI group. Subsequently, the expression of adenylate cyclase 9 (AC9), the target gene of miR-142-3p, declined sharply in the SDCL group and declined limitedly in the SNCI group. The expression trend of cAMP was opposite to that of miR-142-3p. MiR-142-3p inhibitor improved the axon length, upregulated the expression of AC9, cAMP, p-CREB, IL-6, and GAP43, and downregulated the expression of GTP-RhoA. miR-142-3p inhibitor combined with AC9 siRNA showed shorter axon length, the expression of AC9, cAMP, p-CREB, IL-6, and GAP43 was decreased, and the expression of GTP-RhoA was increased. H89 and AG490, inhibitors of cAMP/PKA pathway and IL6/STAT3/GAP43 axis, respectively, declined the enhanced axonal growth by miR-142-3p inhibitor and altered the expression level of the corresponding proteins. Thus, a substitution therapy using Sorafenib that downregulates the miR-142-3p expression for SNCI was investigated. The results showed the effect of Sorafenib was similar to that of miR-142-3p inhibitor and SNCI on both axon growth in vitro and sensory conduction function recovery in vivo. In conclusion, miR-142-3p acts a pivotal role in SNCI promoting the repair of dorsal column injury. Sorafenib mimics the treatment effect of SNCI via downregulation of miR-142-3p, subsequently, promoting sensory conduction function recovery post dorsal column injury.