Enhanced Broadband Manipulation of Acoustic Vortex Beams Using 3-bit Coding Metasurfaces through Topological Optimization.

The acoustic coding metasurfaces (ACMs) have the ability to manipulate complex acoustic behavior by reconstructing the coding sequence. In particular, the design of broadband coding enhances the versatility of ACMs. ACMs offer significant advantages over traditional metasurfaces, including a limited number of units and flexible wave control performance. The unit quantity is determined by 2n, with 1-bit utilizing 2 units, 2-bit using 4 units, and 3-bit employing 8 units. Utilizing multiple bits allows for precise control over the phase of sound waves and enables the realization of more intricate acoustic functions. To address the requirements of broadband multi-bit applications, this paper presents the development of novel 3-bit broadband reflected acoustic coding metasurfaces (BACMs) with eight coding units. These metasurfaces are systematically designed using the bottom-up topology optimization method. A constant phase difference of 45° can be achieved across all eight coding units within a broad frequency range. Additionally, the spiral distribution of phase differences enables the construction of an acoustic vortex metasurface. Moreover, by combining the convolution method, the strategies are outlined for constructing vortex-focusing metasurfaces and vortex beam manipulation metasurfaces. These 3-bit coding metasurfaces possess significant potential in the fields of acoustic particle suspension and acoustic communication.

SNX-3 mediates retromer-independent tubular endosomal recycling by opposing EEA-1-facilitated trafficking.

Early endosomes are the sorting hub on the endocytic pathway, wherein sorting nexins (SNXs) play important roles for formation of the distinct membranous microdomains with different sorting functions. Tubular endosomes mediate the recycling of clathrin-independent endocytic (CIE) cargoes back toward the plasma membrane. However, the molecular mechanism underlying the tubule formation is still poorly understood. Here we screened the effect on the ARF-6-associated CIE recycling endosomal tubules for all the SNX members in Caenorhabditis elegans (C. elegans). We identified SNX-3 as an essential factor for generation of the recycling tubules. The loss of SNX-3 abolishes the interconnected tubules in the intestine of C. elegans. Consequently, the surface and total protein levels of the recycling CIE protein hTAC are strongly decreased. Unexpectedly, depletion of the retromer components VPS-26/-29/-35 has no similar effect, implying that the retromer trimer is dispensable in this process. We determined that hTAC is captured by the ESCRT complex and transported into the lysosome for rapid degradation in snx-3 mutants. Interestingly, EEA-1 is increasingly recruited on early endosomes and localized to the hTAC-containing structures in snx-3 mutant intestines. We also showed that SNX3 and EEA1 compete with each other for binding to phosphatidylinositol-3-phosphate enriching early endosomes in Hela cells. Our data demonstrate for the first time that PX domain-only C. elegans SNX-3 organizes the tubular endosomes for efficient recycling and retrieves the CIE cargo away from the maturing sorting endosomes by competing with EEA-1 for binding to the early endosomes. However, our results call into question how SNX-3 couples the cargo capture and membrane remodeling in the absence of the retromer trimer complex.

[Detection of drug-resistance genes of Mycoplasma pneumoniae in bronchoalveolar lavage fluid of children with refractory Mycoplasma pneumoniae pneumonia].

OBJECTIVE: To study the drug resistance of Mycoplasma pneumoniae (MP) in the bronchoalveolar lavage fluid (BALF) of children with refractory Mycoplasma pneumoniae pneumonia (RMPP) and the distribution of drug-resistance genes, as well as the association of alleles at 2063 locus of 23SrRNA V region central ring with resistance to antimicrobial drugs. METHODS: BALF specimens were collected from 245 children with RMPP who were admitted to the Children's Hospital Affiliated to Zhengzhou University from March 2016 to December 2020. A rapid cultured drug sensitivity assay was used to detect the resistance of MP isolates to nine commonly used antimicrobial drugs. The real-time PCR was used to measure MP DNA. The direct sequencing was used to detect gene mutations in MP 23SrRNA V region central ring. RESULTS: Among the 245 BALF specimens, 207 tested positive for MP DNA, with a positive rate of 84.5%. The results of drug susceptibility test showed that the children with RMPP had a resistance rate of > 70% to macrolide antimicrobial drugs, with the highest resistance rate to clarithromycin, followed by roxithromycin, clindamycin, acetylspiramycin, erythromycin, and azithromycin, and these children had a resistance rate of < 5% to quinolone antimicrobial drugs. Among the 207 MP DNA-positive specimens, 41 (19.8%) had no drug-resistance gene mutations and 166 (80.2%) had drug-resistance gene mutations, among which 154 (74.4%) had an A→G mutation at 2063 locus of 23SrRNA V region central ring, 7 (3.4%) had an A→G mutation at 2064 locus, and 5 (2.4%) had mutations in both 2063 and 2064 loci. Among the 166 specimens with point mutations of the MP 23SrRNA gene, 159 (95.8%) had point mutations at 2063 locus. The A→G point mutation at 2063 locus of 23SrRNA V region central ring had a great impact on resistance to macrolide antimicrobial drugs. There was a significant difference in the distribution of alleles at 2063 locus between the children with resistance to clarithromycin, roxithromycin, clindamycin, acetylspiramycin, erythromycin, and azithromycin (P < 0.05). CONCLUSIONS: MP in the BALF of children with RMPP has a relatively high resistance rate to macrolide antimicrobial drugs. Resistance to macrolide antimicrobial drugs is closely associated with the A→G point mutation in the 23SrRNA gene, and the point mutation at 2063 locus of 23SrRNA V region central ring may affect the drug-resistance mechanism of MP.

Cultivation of Spirulina platensis for nutrient removal from piggery wastewater.

The discharge of livestock wastewater without appropriate treatment causes severe harm to the environment and human health. In the pursuit of finding solutions to this problem, the cultivation of microalgae as feedstock for biodiesel and animal feed additive using livestock wastewater coupled with the removal of nutrients from wastewater has become a hot research topic. In this study, the cultivation of Spirulina platensis using piggery wastewater for the production of biomass and the removal of nutrients were studied. The results of single factor experiments confirmed that Cu2+ seriously inhibit the growth of Spirulina platensis, while the influences of nitrogen, phosphorous, and zinc on the growth of Spirulina platensis can all be described as "low promotes high inhibits." Spirulina platensis grew well in the 4-fold dilution of piggery wastewater supplemented with moderate sodium bicarbonate, which indicated that it is the limiting nutrients for Spirulina platensis growth in piggery wastewater. The biomass concentration of Spirulina platensis reached 0.56 g/L after 8 days of culture at the optimal conditions proposed by the response surface method, which were as follows: 4-fold dilution of piggery wastewater, 7 g/L sodium bicarbonate, pH of 10.5, initial OD560 of 0.63, light intensity of 3030 lx, and light time/dark time of 16 h/8 h. Spirulina platensis cultured in the diluted piggery wastewater contained 43.89% protein, 9.4% crude lipid, 6.41 mg/g chlorophyll a, 4.18% total sugar, 27.7 mg/kg Cu, and 246.2 mg/kg Zn. The removal efficiency for TN, TP, COD, Zn, and Cu from the wastewater by Spirulina platensis was 76%, 72%, 93.1%, 93.5%, and 82.5%, respectively. These results demonstrated the feasibility of piggery wastewater treatment by the cultivation of Spirulina platensis.

Downregulation of microRNA­221 facilitates H1N1 influenza A virus replication through suppression of type­IFN response by targeting the SOCS1/NF­κB pathway.

Accumulating data has indicated that host microRNAs (miRNAs/miRs) play essential roles in innate immune responses to viral infection; however, the roles and the underlying mechanisms of miRNAs in influenza A virus (IAV) replication remain unclear. The present study examined on the effects of miRNAs on hemagglutinin (H)1 neuraminidase (N)1 replication and antiviral innate immunity. Using a microarray assay, the expression profiles of miRNA molecules in IAV­infected A549 cells were analyzed. The results indicated that miR­221 was significantly downregulated in IAV­infected A549 cells. It was also observed that IAV infection decreased the expression levels of miR­221 in A549 cells in a dose­ and time­dependent manner. Functionally, upregulation of miR­221 repressed IAV replication, whereas knockdown of miR­221 had an opposite effect. Subsequently, it was demonstrated that miR­221 overexpression could enhance IAV­triggered IFN­α and IFN­ß production and IFN­stimulated gene expression levels, while miR­221­knockdown had the opposite effect. Target prediction and dual luciferase assays indicated that suppressor of cytokine signaling 1 (SOCS1) was a direct target of miR­221 in A549 cells. Furthermore, knockdown of SOCS1 efficiently abrogated the influences caused by miR­221 inhibition on IAV replication and the type­I IFN response. It was also found that the miR­221 positively regulated NF­κB activation in IAV­infected A549 cells. Taken together, these data suggested that miR­221­downregulation promotes IAV replication by suppressing type­I IFN response through targeting SOCS1/NF­κB pathway. These findings suggest that miR­221 may serve as a novel potential therapeutic target for IAV treatment.

The long non-coding RNA LSINCT5 promotes malignancy in non-small cell lung cancer by stabilizing HMGA2.

Long non-coding RNAs (lncRNAs) can actively participate in tumorigenesis in various cancers. However, the involvement of lncRNA long stress induced non-coding transcripts 5 (LSINCT5) in non-small cell lung cancer (NSCLC) remains largely unknown. Here we showed a novel lncRNA signature in NSCLC through lncRNA profiling. Increased LSINCT5 expression positively correlates with malignant clinicopathological features and poor survival. LSINCT5 can promote migration and viability of various NSCLC cells in vitro and also enhance lung cancer progression in vivo. RNA immunoprecipitation followed by mass spectrometry has identified that LSINCT5 interacts with HMGA2. This physical interaction can increase the stability of HMGA2 by inhibiting proteasome-mediated degradation. Therefore, LSINCT5 may possibly contribute to NSCLC tumorigenesis by stabilizing the oncogenic factor of HMGA2. This novel LSINCT5/HMGA2 axis can modulate lung cancer progression and might be a promising target for pharmacological intervention.

Serum microRNA-365 in combination with its target gene TTF-1 as a non-invasive prognostic marker for non-small cell lung cancer.

BACKGROUND: MicroRNA (miR)-365 functions as a tumor suppressor in non-small cell lung cancer (NSCLC) cells by targeting thyroid transcription factor 1 (TTF-1). AIM: To investigate miR-365 and TTF-1 mRNA expression in serum of NSCLC and their associations with patients' prognosis. METHODS: MiR-365 and TTF-1 mRNA expression in 100 NSCLCs and 100 healthy control sera were detected by quantitative real-time PCR (qRT-PCR). RESULTS: MiR-365 expression level was significantly lower in NSCLC serum samples than in healthy control serum samples (P<0.001), while TTF-1 mRNA expression level was significantly increased in NSCLC serum samples compared to healthy control serum samples (P<0.001). In addition, low miR-365 expression and high TTF-1 expression, alone or in combination, were all significantly associated with poor differentiation (P=0.008, 0.008 and 0.001, respectively), advanced TNM stage (P=0.001, 0.005 and <0.001 respectively) and positive lymph node metastasis (P=0.02, 0.02 and 0.01, respectively) of NSCLC patients. Notably, NSCLC patients with combined low miR-365 expression and high TTF-1 expression (miR-365-low/TTF-1-high) had shortest overall survival (P<0.001). Furthermore, multivariate analysis showed that miR-365 expression (P=0.01), TTF-1 expression (P=0.01), and combined expression of miR-365 and TTF-1 (miR-365/TTF-1, P=0.001) were all independent prognostic factors for overall survival in NSCLC patients. CONCLUSIONS: Our data reveal that preoperative serum miR-365 and TTF-1 mRNA levels may be both effective indicators of tumor aggressiveness in human NSCLC. More interestingly, miR-365 and its target gene TTF-1 appear to be synergistic risk factors for the reduction in overall survival of patients with NSCLC.

Effect of Avastin on the number and structure of tumor blood vessels of nude mice with A549 lung adenocarcinoma.

The aim of the present study was to investigate the effect of Avastin on the number and structure of tumor blood vessels of nude mice with A549 lung adenocarcinoma. A total of 30 nude mice were randomly divided into three groups, namely the control, the Avastin I (Avastin 3 mg/kg) and the Avastin II (Avastin 6 mg/kg) groups. Following treatment, ELISA was used to detect the expression level of vascular endothelial growth factor (VEGF) in tumor tissues. The microvascular density in tumor tissues and tumor vascular pericyte coverage was detected by immunofluorescence. The tumor growth and survival rate of mice in the three groups were also analyzed. Compared with the control group, the Avastin I and II groups exhibited significantly decreased VEGF levels and microvascular density in the tumor tissues, with the decrease in the Avastin II group being more prominent (P<0.05). After 7 days of treatment, the vascular pericyte coverage in the tumor tissues of mice in the Avastin I and II groups was significantly increased compared with that in the control group mice (P<0.05). Compared with the control group, the mice in the Avastin I and II groups exhibited a significantly decreased tumor growth rate and this effect was dose-dependent. The survival rate of mice in the Avastin I and II groups was significantly increased compared with that of the mice in the control group (P<0.05). In conclusion, Avastin significantly decreased the microvascular density of the tumor in nude mice with A549 lung adenocarcinoma and also significantly increased tumor vascular pericyte coverage, inhibited tumor growth and increased the survival rate of the mice, through its potent antiangiogenic activity.

Prognostic potential of microRNA-138 and its target mRNA PDK1 in sera for patients with non-small cell lung cancer.

microRNA (miR)-138 has been recognized as a potential tumor suppressor via regulating 3-phosphoinositide-dependent protein kinase-1 (PDK1) expression in non-small cell lung cancer (NSCLC) cells. The aim of this study was to investigate miR-138 and PDK1 mRNA expression in serum of NSCLC and their associations with patients' prognosis. miR-138 and PDK1 mRNA expressions in 100 NSCLCs and 100 healthy control sera were detected by quantitative real-time PCR. miR-138 expression level was significantly lower in NSCLC serum samples than in healthy control serum samples (P < 0.001), while PDK1 mRNA expression level was significantly increased in NSCLC serum samples compared to healthy control serum samples (P < 0.001). In addition, miR-138 downregulation and PDK1 upregulation were both significantly associated with advanced tumor-node-metastasis (TNM) stage (both P = 0.002) and positive lymph node metastasis (both P = 0.01) of NSCLC patients. Moreover, the overall survival of NSCLC patients with low miR-138 expression or high PDK1 mRNA expression was obviously shorter than those with high miR-138 expression or low PDK1 mRNA expression (both P < 0.001). Notably, NSCLC patients with combined miR-138 downregulation and PDK1 upregulation (miR-138-low/PDK1-high) had shortest overall survival (P < 0.001). Furthermore, multivariate analysis showed that miR-138 expression (P = 0.01), PDK1 expression (P = 0.01), and combined expression of miR-138 and PDK1 (miR-138/PDK1, P = 0.001) were all independent prognostic factors for overall survival in NSCLC patients. Deregulation of miR-138/PDK1 cascade may be implicated in carcinogenesis and cancer progression of human NSCLC. More importantly, miR-138 and PDK1 may synergistically predict patients' prognosis and their combination may represent a promising prognostic biomarker of human NSCLC.