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Abstract Profiling antibiotic resistance genes (ARGs) in the Yellow River of China’s Henan Province is essential for understanding the health risks of antibiotic resistance. The profiling of ARGs was investigated using high-throughput qPCR from water samples in seven representative regions of the Yellow River. The absolute and relative abundances of ARGs and moble genetic elements (MGEs) were higher in summer than in winter (ANOVA, p

ABSTRACT: Four experiments were performed to investigate the role of the mitogen-activated protein kinase (MAPK) signaling pathway in intestinal absorption of phosphorus (P) and calcium (Ca) in broiler chickens. Experiment 1 assessed how dietary levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) influence the gene expression of intestinal P and Ca transporters in broilers. Experiment 2 evaluated the effects of 1,25(OH)2D3 administered via intraperitoneal injection on the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38MAPK) signaling pathways. Experiments 3 and 4 investigated the effect of ERK and p38MAPK inhibitors on the expression of intestinal P and Ca transporters. The findings demonstrated that broilers (1–21 days old) fed a 1,25(OH)2D3-deficient diet (0.625 µg/kg) exhibited reduced body weight, tibia P and Ca levels, and mRNA levels of P transporters (NaPi-IIb, PiT-1, and PiT-2), Ca transporters (NCX1, PMCA1b, and CaBP-D28k), vitamin D receptors (VDR), ERK, and p38MAPK in the duodenum (Experiment 1) (P < 0.05). By comparison, the growth, bone quality, and mRNA levels of genes (except for duodenal NaPi-IIb) in broilers were similar to those in broilers fed the control diet when dietary 1,25(OH)2D3 was adequate (5 µg/kg) (Experiment 1) (P > 0.05). After intraperitoneal injection of 1,25(OH)2D3, the mRNA level of jejunal NaPi-IIb and the protein level of p-p38MAPK/t-p38MAPK in broilers (9–14 days old) decreased (P < 0.05), whereas the mRNA level of CaBP-D28k and the protein level of p-ERK/t-ERK increased (Experiment 2) (P < 0.05). The mRNA and protein expression of jejunal NaPi-IIb and the protein expression of CaBP-D28k in broilers (9–17 days old) treated with the ERK inhibitor PD98059 were greater than those in the control group (Experiment 3) (P < 0.05). Similarly, compared with control broilers, broilers (9–17 days old) treated with the p38MAPK inhibitor SB203580 showed elevated mRNA expression of jejunal NaPi-IIb and CaBP-D28k (Experiment 4) (P < 0.05). These results suggest that adequate supplementation with 1,25(OH)2D3 (5 µg/kg) can restore broiler growth and bone quality by upregulating the transcription of genes involved in intestinal P and Ca absorption. Additionally, the ERK and p38MAPK signaling pathways are implicated in the modulatory effect of 1,25(OH)2D3 on the absorption of P and Ca in broilers.

Sepsis is a serious life-threatening health disorder with high morbidity and mortality rates that burden the world, but there is still a lack of more effective and reliable drug treatment. Liang-Ge-San (LGS) has been shown to have anti-inflammatory effects and is a promising candidate for the treatment of sepsis. However, the anti-sepsis mechanism of LGS has still not been elucidated. In this study, a set of genes related to inflammatory chemotaxis pathways was downloaded from Encyclopedia of Genes and Genomes (KEGG) and integrated with sepsis patient information from the Gene Expression Omnibus (GEO) database to perform differential gene expression analysis. Glycogen synthase kinase-3β (GSK-3β) was found to be the feature gene after these important genes were examined using the three algorithms Random Forest, support vector machine recursive feature elimination (SVM-REF), and least absolute shrinkage and selection operator (LASSO), and then intersected with possible treatment targets of LGS found through the search. Upon evaluation, the receiver operating characteristic (ROC) curve of GSK-3β indicated an important role in the pathogenesis of sepsis. Immune cell infiltration analysis suggested that GSK-3β expression was associated with a variety of immune cells, including neutrophils and monocytes. Next, lipopolysaccharide (LPS)-induced zebrafish inflammation model and macrophage inflammation model was used to validate the mechanism of LGS. We found that LGS could protect zebrafish against a lethal challenge with LPS by down-regulating GSK-3β mRNA expression in a dose-dependent manner, as indicated by a decreased neutrophils infiltration and reduction of inflammatory damage. The upregulated mRNA expression of GSK-3β in LPS-induced stimulated RAW 264.7 cells also showed the same tendency of depression by LGS. Critically, LGS could induce M1 macrophage polarization to M2 through promoting GSK-3β inactivation of phosphorylation. Taken together, we initially showed that anti-septic effects of LGS is related to the inhibition on GSK-3β, both in vitro and in vivo.

Summary Protective efficiency of a combination of four recombinant Brucella abortus (B. abortus) proteins, namely, ribosomal protein L7/L12, outer membrane protein (OMP) 22, OMP25 and OMP31, was evaluated as a combined subunit vaccine (CSV) against B. abortus infection in RAW 264.7 cell line and murine model. Four proteins were cloned, expressed and purified, and their immunocompetence was analysed. BALB/c mice were immunized subcutaneously with single subunit vaccines (SSVs) or CSV. Cellular and humoral immune responses were determined by ELISA. Results of immunoreactivity showed that these four recombinant proteins reacted with Brucella‐positive serum individually but not with Brucella‐negative serum. A massive production of IFN‐γ and IL‐2 but low degree of IL‐10 was observed in mice immunized with SSVs or CSV. In addition, the titres of IgG2a were heightened compared with IgG1 in SSV‐ or CSV‐immunized mice, which indicated that SSVs and CSV induced a typical T‐helper‐1‐dominated immune response in vivo. Further investigation of the CSV showed a superior protective effect in mice against brucellosis. The protection level induced by CSV was significantly higher than that induced by SSVs, which was not significantly different compared with a group immunized with RB51. Collectively, these antigens of Brucella could be potential candidates to develop subunit vaccines, and the CSV used in this study could be a potential candidate therapy for the prevention of brucellosis.

An improved moments estimation algorithm used in a newly developed K-band wind profiler to obtain accurate 3-D profiles of wind velocity along the altitude is described. The signal-to-noise ratio (SNR) of turbulent echoes detected by millimeter-wave radar is usually low, making it becomes a challenging task to determine accurate Doppler profiles. And if wind profilers can provide quick estimates of wind, they will have greater applicability in automated, real-time environments. The improved method combines the concepts of adaptive Doppler windows and profile chain construction, reduces the search range of prospective spectral peaks by using adaptive Doppler windows, and designs new multiparameter cost functions to determine velocity profiles by studying the wind shear in the surface boundary layer. The algorithm can effectively identify the atmospheric echo components of each range bin even under the condition of low SNR, and the computational time is decreased by at least 18% compared with the previous algorithms. The proposed method is tested on the real wind radar datasets to verify its robustness and reliability. The wind information obtained by four different algorithms is compared with the data obtained from the meteorological mast of the Gaoyou wind farm in China. The comparison results indicate that the proposed method shows a nicer match with the data of the mast, and it derives the winds more accurately in the atmosphere of the surface boundary layer.

Social insurance is an essential component of a contemporary social security system since it protects people's fundamental well-being, but it also incurs a heavy cost for businesses. If social security costs are excessively high, business profitability will suffer, and innovation will be discouraged. The most affected companies would be those in labor-intensive industries and medium-sized enterprises. Chinese businesses have suffered severe losses as a result of the COVID-19 outbreak. Given the circumstance, China enacted additional tax cuts and preferential social insurance premium plans. This article suggests a lower ratio of contribution as a strategy to cut the cost of social insurance premiums for businesses, given the growth of the social security fund in recent years and the proportion of participants to recipients in pension funds. It would be possible to increase firm profitability and lessen the impact of COVID-19 on industries by minimizing this operation burden. In order to compare the financial performance of state-owned manufacturers (SOMs) to that of their non-state-owned peers, who have a lower ratio of contribution, this study uses a multiple regression model. The ratio of contributions was inversely correlated with an enterprise's financial performance. In other words, financial performance will improve as the ratio of contribution lowers; nevertheless, this effect is more pronounced in SOMs. The final section of this study proposed optimized approaches for social insurance premiums reform.

A wideband dual-polarized antenna is proposed for 4G and 5G communication applications. The antenna element consists of a pair of opened-loop dipoles for dual-polarization and its three inherent resonant modes are shifted closer to form a wide bandwidth. With additional U-shaped slots etched around the feed point, the input impedance of the antenna element is matched to 50 Ohm. The fabricated antenna element operates from 1.8 to 4.0 GHz, having 75.9% (VSWR ≤ 2) impedance bandwidth and high port-to-port isolation (>25 dB). It also achieves a 67±1° beamwidth in H-plane and 68.7 ± 3.3° in V-plane with 8.5 ± 1 dBi gain across the supported bands. By using six antenna elements and designing RF phase shifting module (RFPSM) based on vector modulators, a six-element dual-polarized array with electrically downtilt is also fabricated and measured, realizing a peak gain of 16.8 dBi, a similar beamwidth in H-plane as single antenna element and an electrically downtilt in V-plane from 0° to 12° which is preferred in communication applications. This antenna array could be used for future 5G communication and other applications.

In this paper, we have introduced a compact eight-element antenna array for triple-band MIMO (multi-input multi-output) operation in 5G (fifth generation) mobile terminals, which consists of two symmetric four-element sub-arrays disposed, respectively, along two long side-edges of the system ground plane of the mobile terminal. This antenna element can operate at two dual-wideband of 3250-3820 MHz and 4790-6200 MHz with three resonance frequencies which can fully cover 5G NR (New Radio) BandN78 (3300-3800 MHz), China 5G-Band of 4800-5000 MHz and LTE Band-46 (5150-5925 MHz). The main parameters that characterize the performance of the proposed MIMO antenna system, such as bandwidth, reflection coefficient, isolation (more than 10.5 dB), total radiation efficiency (more than 43%), ECC (envelope correlation coefficient, less than 0.12) and CC (channel capacity, 34.9-37.6 bps/Hz), are analyzed and presented in this paper. Besides, the effects of single-hand and dual-hand on performance of the MIMO antenna system are also discussed. The structure of antenna element is only 15 mm × 3 mm (0.175 λ0 × 0.035 λ0, λ0 is the free-space wavelength at the frequency of 3.5 GHz) with a very small ground clearance of 13 mm × 2 mm on the main board of the proposed mobile terminal. The antenna system has the possibility to be used in 5G mobile terminals with triple-band operation, narrow frame and large display. The corresponding antennas prototype is fabricated and measured; and a quite good agreement between simulation and measurement is obtained.

PurposeThe three positron emission tomography (PET) imaging compounds: (2S,4R)-4-[18F]Fluoroglutamine ([18F]FGln), L-[methyl-11C]Methionine ([11C]Met), and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) were investigated to contrast their ability to image orthotopic BT4C gliomas in BDIX rats. Two separate small animal imaging systems were compared for their tumor detection potential. Dynamic acquisition of [18F]FGln was evaluated with multiple pharmacokinetic models for future quantitative comparison.ProceduresUp to four imaging studies were performed on each orthotopically grafted BT4C glioma-bearing BDIX rat subject (n = 16) on four consecutive days. First, a DOTAREM® contrast enhanced MRI followed by attenuation correction CT and dynamic PET imaging with each radiopharmaceutical (20 min [11C]Met, 60 min [18F]FDG, and 60 min [18F]FGln with either the Molecubes PET/CT (n = 5) or Inveon PET/CT cameras (n = 11). Ex vivo brain autoradiography was completed for each radiopharmaceutical and [18F]FGln pharmacokinetics were studied by injecting 40 MBq into healthy BDIX rats (n = 10) and collecting blood samples between 5 and 60 min. Erythrocyte uptake, plasma protein binding and plasma parent-fraction were combined to estimate the total blood bioavailability of [18F]FGln over time. The corrected PET-image blood data was then applied to multiple pharmacokinetic models.ResultsAverage BT4C tumor-to-healthy brain tissue uptake ratios (TBR) for PET images reached maxima of: [18F]FGln TBR: 1.99 ± 0.19 (n = 13), [18F]FDG TBR: 1.41 ± 0.11 (n = 6), and [11C]Met TBR: 1.08 ± 0.08, (n = 12) for the dynamic PET images. Pharmacokinetic modeling in dynamic [18F]FGln studies suggested both reversible and irreversible uptake play a similar role. Imaging with Inveon and Molecubes yielded similar end-result ratios with insignificant differences (p > 0.25).ConclusionsIn orthotopic BT4C gliomas, [18F]FGln may offer improved imaging versus [11C]Met and [18F]FDG. No significant difference in normalized end-result data was found between the Inveon and Molecubes camera systems. Kinetic modelling of [18F]FGln uptake suggests that both reversible and irreversible uptake play an important role in BDIX rat pharmacokinetics.

ABSTRACT Phosphopantetheinyl hydrolase, PptH (Rv2795c), is a recently discovered enzyme from Mycobacterium tuberculosis that removes 4′-phosphopantetheine (Ppt) from holo-carrier proteins (CPs) and thereby opposes the action of phosphopantetheinyl transferases (PPTases). PptH is the first structurally characterized enzyme of the phosphopantetheinyl hydrolase family. However, conditions for optimal activity of PptH have not been defined, and only one substrate has been identified. Here, we provide biochemical characterization of PptH and demonstrate that the enzyme hydrolyzes Ppt in vitro from more than one M. tuberculosis holo-CP as well as holo-CPs from other organisms. PptH provided the only detectable activity in mycobacterial lysates that dephosphopantetheinylated acyl carrier protein M (AcpM), suggesting that PptH is the main Ppt hydrolase in M. tuberculosis. We could not detect a role for PptH in coenzyme A (CoA) salvage, and PptH was not required for virulence of M. tuberculosis during infection of mice. It remains to be determined why mycobacteria conserve a broadly acting phosphohydrolase that removes the Ppt prosthetic group from essential CPs. We speculate that the enzyme is critical for aspects of the life cycle of M. tuberculosis that are not routinely modeled. IMPORTANCE Tuberculosis (TB), caused by Mycobacterium tuberculosis, was the leading cause of death from an infectious disease before COVID, yet the in vivo essentiality and function of many of the protein-encoding genes expressed by M. tuberculosis are not known. We biochemically characterize M. tuberculosis’s phosphopantetheinyl hydrolase, PptH, a protein unique to mycobacteria that removes an essential posttranslational modification on proteins involved in synthesis of lipids important for the bacterium’s cell wall and virulence. We demonstrate that the enzyme has broad substrate specificity, but it does not appear to have a role in coenzyme A (CoA) salvage or virulence in a mouse model of TB.

Millimeter-Wave (mmWave) antennas for 5G mobile terminals require a wide bandwidth, large-angle beam scanning, low-profile design, and multi-substrate compatibility for module-level integration. In this paper, we propose one candidate design employing a patch structure with the shorting pin to particularly generate extra zero modes. By taking advantages of the 2nd zero-mode with the TM01 mode, we can obtain a wide bandwidth covering 23.5~28 GHz, a large-angle beam scanning with ±60°, as well as keep the substrate as low profile as 0.508 mm. Thanks to the zero-mode induced patch-type design, it is compatible to multi-layer configuration possessing the extensibility and flexibility for further module design. We experimentally valid the design of a 4 × 2 array with multi-layer configuration in a cell phone environment. Good RF performances with ±60° scanning in the wide bandwidth indicate this proposed design can be an appropriate candidate for 5G mobile terminals.

A dual-functional antenna array operating in the long term evolution (LTE) band 42 (3.4-3.6 GHz) and 5.8-GHz wireless wide area network (WLAN) band (5.725-5.875 GHz) for multiple-input multiple-output (MIMO) applications in 5G smartphones is proposed. The proposed 8-antenna array is composed of two different antenna elements, namely, the folded L-shaped antenna and couple-fed U-shaped antenna. It can be applied in the 8 × 8 (by using 8 antenna elements) and 4 × 4 (by using 4 antenna elements) MIMO system across the LTE band 42 and 5.8-GHz WLAN band, respectively. The quasi-orthogonal polarization, balanced mode excitation and pattern diversity are properly used to achieve high isolation within the operation bands. A prototype of the proposed antenna array was fabricated and measured. The measured isolations in the LTE band 42 (6-dB impedance matching) and 5.8-GHz WLAN band (10-dB impedance matching) are better than 17.1 dB and 34.6 dB, respectively. The total efficiencies are 45%-62% and 52%-59% in the two operation bands, respectively. Besides, the measured envelope correlation coefficients (ECCs) are less than 0.045 and 0.0001, the calculated peak ergodic channel capacities are 37.9 bps/Hz and 19.3 bps/Hz in the 8 × 8 or 4 × 4 MIMO system across the operation bands. Furthermore, user's hand and head effects are investigated and desirable results are obtained. The above results show that this proposed antenna array is a good candidate for MIMO applications in smartphones.

In this paper, a K-band antenna with ±60° beam scanning is proposed for a mmWave (millimeter-Wave) radar sensor. Especially, we take advantages of the magnetic dipole principle, and design the antenna by employing via holes in three sides, so as to form a cavity which can be equivalently considered as magnetic dipole, resulting in the 3 dB beam width as wide as 140° in E-plane. We cascade the mmWave antenna to 1×4 and 4×4 arrays for radar transmitting and receiving, respectively. The antenna array is fabricated and implemented to a K-band radar and its wide-angle beam scanning performance is evaluated by the radar's distance and angular detections.

A dual-polarized continuous transverse stub (CTS) K-band antenna with reconfigurable four beams and low profile is proposed based on substrate-integrated-waveguide (SIW) design. It consists of a line source generator (LSG) on the bottom surface, a spherical-wave to plane-wave transforming part on the middle layer, and CTS radiators on the top surface. Particularly, the LSG has four SIW-based H-plane horns, and a chip is integrated to switch among the two pairs of horns, so as to transfer the quasi-TEM waves on the bottom surface by a ±10° deflection angle to the middle layer for the CTS radiators on the top surface, resulting in four reconfigurable scanning beams with 10° for two polarizations. The measurements show that it realizes four reconfigurable beams with a 25.8 dBi gain at 24 GHz, verifying the design. The proposed antenna takes into account the advantages of reconfigurable multi-beam, dual polarization, low side lobes, low profile, and high gain, which can be applied to K-band sensing, especially for wind profile radars.

Wind profile radar systems require antennas with multiple radiation beams for detecting wind velocity, as well as with a low sidelobe and dual polarization for enhancing the sensitivity for the weak signal reflected from the turbulence. This paper proposes a lens antenna operating at 24 GHz with four reconfigurable beams for wind profile radars. This lens antenna includes 2 × 2 corrugated horn antennas for radiating 24 GHz waves in two polarizations, and the dielectric lens for modulating four radiation beams with a high gain and low sidelobe. Experiments demonstrate that this lens antenna can realize reconfigurable beams with deflections of ±15° in dual polarizations, meanwhile with the gain of 30.58 dBi and the sidelobe of −20 dB. This proposed lens antenna can be applied to mmWave wind profile radars of wind turbines for enhancing wind power efficiency.

Commensal microorganisms are essential to the normal development and function of many aspects of animal biology, including digestion, nutrient absorption, immunological development, behaviors, and evolution. The specific microbial composition and evolution of the intestinal tracts of wild pigs remain poorly characterized. This study therefore sought to assess the composition, distribution, and evolution of the intestinal microbiome of wild pigs. For these analyses, 16S rRNA V3-V4 regions from five gut sections prepared from each of three wild sows were sequenced to detect the microbiome composition. These analyses revealed the presence of 6,513 operational taxonomic units (OTUs) mostly distributed across 17 phyla and 163 genera in these samples, with Firmicutes and Actinobacteria being the most prevalent phyla of microbes present in cecum and jejunum samples, respectively. Moreover, the abundance of Actinobacteria in wild pigs was higher than that in domestic pigs. At the genus level the Bifidobacterium and Allobaculum species of microbes were most abundant in all tested gut sections, with higher relative abundance in wild pigs relative to domestic pigs, indicating that in the process of pig evolution, the intestinal microbes also evolved, and changes in the intestinal microbial diversity could have been one of the evolutionary forces of pigs. Intestinal microbial functional analyses also revealed the microbes present in the small intestine (duodenum, jejunum, and ileum) and large intestine (cecum and colon) of wild pigs to engage distinct metabolic spatial structures and pathways relative to one another. Overall, these results offer unique insights that would help to advance the current understanding of how the intestinal microbes interact with the host and affect the evolution of pigs.

A 12-port antenna array operating in the long term evolution (LTE) band 42 (3400-3600 MHz), LTE band 43 (3600-3800 MHz), and LTE band 46 (5150-5925 MHz) for 5G massive multiple-input multiple-output (MIMO) applications in mobile handsets is presented. The proposed MIMO antenna is composed of three different antenna element types, namely, inverted π-shaped antenna, longer inverted L-shaped open slot antenna, and shorter inverted L-shaped open slot antenna. In total, eight antenna elements are used for the 8×8 MIMO in LTE bands 42/43, and six antenna elements are designed for the 6×6 MIMO in LTE band 46. The proposed antenna was simulated, and a prototype was fabricated and tested. The measured results show that the LTE bands 42/43/46 are satisfied with reflection coefficient better than -6 dB, isolation lower than -12 dB, and total efficiencies of higher than 40%. In addition to that, the proposed antenna array has also shown good MIMO performances with an envelope correlation coefficient lower than 0.15, and ergodic channel capacities higher than 34 and 26.5 b/s/Hz in the LTE bands 42/43 and LTE band 46, respectively. The hand phantom effects are also investigated, and the results show that the proposed antenna array can still exhibit good radiation and MIMO performances when operating under data mode and read mode conditions.

A multi-band 10-antenna array working at the sub-6-GHz spectrum (LTE bands 42/43 and LTE band 46) for massive multiple-input multiple-output (MIMO) applications in future 5G smartphones is proposed. To realize 10 × 10 MIMO applications in three LTE bands, 10 T-shaped coupled-fed slot antenna elements that can excite dual resonant modes are integrated into a system circuit board. Spatial and polarization diversity techniques are implemented on these elements so that the improved isolation and mitigated coupling effects can be achieved. The proposed antenna array was manufactured and experimentally measured. Desirable antenna efficiencies of higher than 42% and 62% were measured in the low band and high band, respectively. Vital results, such as the envelope correlation coefficient, channel capacity, and mean effective gain ratio, have also been computed and analyzed. The calculated ergodic channel capacities of the 10 × 10 MIMO system working in the LTE bands 42/43 and LTE band 46 reached up to 48 and 51.4 b/s/Hz, respectively.

Summary: Id helix-loop-helix (HLH) proteins (Id1–4) bind E protein bHLH transcription factors, preventing them from forming active transcription complexes that drive changes in cell states. Id proteins are primarily expressed during development to inhibit differentiation, but they become re-expressed in adult tissues in diseases of the vasculature and cancer. We show that the genetic loss of Id1/Id3 reduces ocular neovascularization in mouse models of wet age-related macular degeneration (AMD) and retinopathy of prematurity (ROP). An in silico screen identifies AGX51, a small-molecule Id antagonist. AGX51 inhibits the Id1-E47 interaction, leading to ubiquitin-mediated degradation of Ids, cell growth arrest, and reduced viability. AGX51 is well-tolerated in mice and phenocopies the genetic loss of Id expression in AMD and ROP models by inhibiting retinal neovascularization. Thus, AGX51 is a first-in-class compound that antagonizes an interaction formerly considered undruggable and that may have utility in the management of multiple diseases. : Wojnarowicz et al., describe the identification, by an in silico screen, and characterization of a small molecule, AGX51, that targets Id proteins. AGX51 treatment of cells lead to Id protein degradation, cell cycle arrest, and reduced cell viability. AGX51 inhibited pathologic ocular neovascularization in mouse models, phenocopying genetic Id loss. Keywords: Id proteins, protein-protein interactions, macular degeneration, retinopathy of prematurity, angiogenesis

Metamaterial antennas consisting of periodical units are suitable for achieving tunable properties by employing active elements to each unit. However, for compact metamaterials with a very limited number of periodical units, resonance blindness exists. In this paper, we introduce a method to achieve continuous tuning without resonance blindness by exploring hence, taking advantage of nonlinear properties of PIN diodes. First, we obtain the equivalent impedance of the PIN diode through measurements, then fit these nonlinear curves with mathematical expressions. Afterwards, we build the PIN diode model with these mathematical equations, making it compatible with implementing co-simulation between the passive electromagnetic model and the active element of PIN diodes and, particularly, the nonlinear effects can be considered. Next, we design a compact two-unit metamaterial antenna as an example to illustrate the electromagnetic co-simulation. Finally, we implement the experiments with a micro-control unit to validate this method. In addition, the nonlinear stability and the supplying voltage tolerance of nonlinear states for both two kinds of PIN diodes are investigated as well. This method of obtaining smooth tuning with nonlinear properties of PIN diodes can be applied to other active devices, if only PIN diodes are utilized.

A small-size reconfigurable loop antenna for mobile phone applications with a compact volume of 55 × 5 × 3 mm3 is proposed. In addition to the traditional three loop antenna modes, namely, 0.5-λ, 1-λ, and 1.5-λ modes, the proposed loop antenna also generates another 2-λ mode. To cover more operating bands with such compact antenna volume, the reconfigurable technique is therefore applied by inserting an RF switch at the end of the proposed antenna to improve bandwidth at the low band. By combining the four working states of RF switch, the proposed antenna can cover GSM850/900, DCS1800, PCS1900, UMTS2100, and LTE2300/2500 bands with low specific absorption rate and high efficiencies.

ABSTRACT Peptidoglycan (PG), a polymer cross-linked by d-amino acid-containing peptides, is an essential component of the bacterial cell wall. We found that a fluorescent d-alanine analog (FDAA) incorporates chiefly at one of the two poles in Mycobacterium smegmatis but that polar dominance varies as a function of the cell cycle in Mycobacterium tuberculosis: immediately after cytokinesis, FDAAs are incorporated chiefly at one of the two poles, but just before cytokinesis, FDAAs are incorporated comparably at both. These observations suggest that mycobacterial PG-synthesizing enzymes are localized in functional compartments at the poles and septum and that the capacity for PG synthesis matures at the new pole in M. tuberculosis. Deeper knowledge of the biology of mycobacterial PG synthesis may help in discovering drugs that disable previously unappreciated steps in the process. IMPORTANCE People are dying all over the world because of the rise of antimicrobial resistance to medicines that could previously treat bacterial infections, including tuberculosis. Here, we used fluorescent d-alanine analogs (FDAAs) that incorporate into peptidoglycan (PG)—the synthesis of which is an attractive drug target—combined with high- and super-resolution microscopy to investigate the spatiotemporal dynamics of PG synthesis in M. smegmatis and M. tuberculosis. FDAA incorporation predominates at one of the two poles in M. smegmatis. In contrast, while FDAA incorporation into M. tuberculosis is also polar, there are striking variations in polar dominance as a function of the cell cycle. This suggests that enzymes involved in PG synthesis are localized in functional compartments in mycobacteria and that M. tuberculosis possesses a mechanism for maturation of the capacity for PG synthesis at the new pole. This may help in discovering drugs that cripple previously unappreciated steps in the process.

BackgroundGliosarcoma is one of the most common malignant brain tumors, and anti-angiogenesis is a promising approach for the treatment of gliosarcoma. However, chemotherapy is obstructed by the physical obstacle formed by the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). Honokiol has been known to possess potent activities in the central nervous system diseases, and anti-angiogenic and anti-tumor properties. Here, we hypothesized that honokiol could cross the BBB and BCSFB for the treatment of gliosarcoma.MethodologiesWe first evaluated the abilities of honokiol to cross the BBB and BCSFB by measuring the penetration of honokiol into brain and blood-cerebrospinal fluid, and compared the honokiol amount taken up by brain with that by other tissues. Then we investigated the effect of honokiol on the growth inhibition of rat 9L gliosarcoma cells and human U251 glioma cells in vitro. Finally we established rat 9L intracerebral gliosarcoma model in Fisher 344 rats and human U251 xenograft glioma model in nude mice to investigate the anti-tumor activity.Principal findingsWe showed for the first time that honokiol could effectively cross BBB and BCSFB. The ratios of brain/plasma concentration were respectively 1.29, 2.54, 2.56 and 2.72 at 5, 30, 60 and 120 min. And about 10% of honokiol in plasma crossed BCSFB into cerebrospinal fluid (CSF). In vitro, honokiol produced dose-dependent inhibition of the growth of rat 9L gliosarcoma cells and human U251 glioma cells with IC(50) of 15.61 µg/mL and 16.38 µg/mL, respectively. In vivo, treatment with 20 mg/kg body weight of honokiol (honokiol was given twice per week for 3 weeks by intravenous injection) resulted in significant reduction of tumor volume (112.70±10.16 mm(3)) compared with vehicle group (238.63±19.69 mm(3), P = 0.000), with 52.77% inhibiting rate in rat 9L intracerebral gliosarcoma model, and (1450.83±348.36 mm(3)) compared with vehicle group (2914.17±780.52 mm(3), P = 0.002), with 50.21% inhibiting rate in human U251 xenograft glioma model. Honokiol also significantly improved the survival over vehicle group in the two models (PConclusions/significanceThis study provided the first evidence that honokiol could effectively cross BBB and BCSFB and inhibit brain tumor growth in rat 9L intracerebral gliosarcoma model and human U251 xenograft glioma model. It suggested a significant strategy for offering a potential new therapy for the treatment of gliosarcoma.