Weighted Gene Co-Expression Network Analysis of Oxymatrine in Psoriasis Treatment.

Purpose: Psoriasis is a common, chronic, inflammatory, recurrent, immune-mediated skin disease. Oxymatrine is effective for treating moderate and severe psoriasis. Here, transcriptional changes in skin lesions before and after oxymatrine treatment of patients with psoriasis were identified using full-length transcriptome analysis and then compared with those of normal skin tissues. Patients and Methods: Co-expression modules were constructed by combining the psoriasis area and severity index (PASI) score with weighted gene co-expression network analysis to explore the action mechanism of oxymatrine in improving clinical PASI. The expression of selected genes was verified using immunohistochemistry, quantitative real-time PCR, and Western blotting. Results: Kyoto Encyclopedia of Gene and Genome pathway analysis revealed that oxymatrine treatment reversed the abnormal pathways, with an improvement in lesions and a reduction in PASI scores. Gene Ontology (GO) analysis revealed that oxymatrine treatment led to altered GO terms being regulated with a decrease in the PASI score in patients. Therefore, oxymatrine treatment may improve the skin barrier, differentiation of keratinocytes, and alleviate abnormality of organelles such as desmosomes. Protein-protein interaction network interaction analysis revealed that the top five hub genes among many interrelated genes were CNFN, S100A8, SPRR2A, SPRR2D, and SPRR2E, associated with the epidermal differentiation complex (EDC). EDC regulates keratinocyte differentiation. This result indicates that oxymatrine treatment can restore keratinocyte differentiation by regulating the expression of EDC-related genes. Conclusion: Oxymatrine can improve erythema, scales, and other clinical symptoms of patients with psoriasis by regulating EDC-related genes and multiple pathways, thereby promoting the repair of epithelial tissue and maintaining the dynamic balance of skin keratosis.

Reconfigurable radar signal generator based on phase-quantized photonic digital-to-analog conversion.

A novel, to the best of our knowledge, scheme for reconfigurable radar signal generation is proposed based on the principle of photonic phase-quantized digital-to-analog conversion. Multi-level digital phase modulation with different modulation depths is combined to convert multi-channel digital data to the phase of an optical carrier. Frequency-modulated or phase-modulated radar signals are generated by beating the phase-synthesized optical carrier with a coherent reference light. The proposed radar signal generator features a simple structure, highly reconfigurable modulation format, and flexibly tunable frequency. A 3-bit photonic phase-quantized digital-to-analog converter with a 10-GSa/s sampling rate is constructed experimentally. The generation of linear frequency-modulated, nonlinear frequency-modulated, frequency-stepped, frequency-hopping, binary phase-coded, and polyphase-coded waveforms is demonstrated.

Research progress of catalysts for synthesis of low-carbon alcohols from synthesis gas.

In recent years, the application value of low-carbon alcohols (C1-C6 alcohols) in the fuel, chemical, environmental protection and other fields has become increasingly prominent. Catalytic conversion of synthesis gas to low-carbon alcohol is one of the important ways to realize the industrial production of low-carbon alcohol. Lack of high-performance catalysts is the main reason that restricts the industrial development of producing low-carbon alcohols from synthesis gas. The construction of a dual active-center catalyst with high activity and stability, and the study of its function and catalytic mechanism have become significantly important. In this paper, the characteristics of the reaction process of syngas to low-carbon alcohols, and the catalytic mechanism and preparation methods of different catalyst systems were reviewed, which provide the basis for further research on high performance catalysts.

Tunable 360° photonic radio frequency phase shifter based on optical quadrature double-sideband modulation and differential detection.

We propose a novel structure of a photonic RF phase shifter based on the vector-sum principle. The optical signal with quadrature double-sideband modulation passes through a dual-output Mach-Zehnder interferometer (MZI), and the two outputs are differentially detected. Two phase-quadrature RF terms are generated, and their amplitudes can be controlled in a triangularly complementary way by changing the phase of the MZI. A full tuning range of 0°-360° at 14 GHz is demonstrated experimentally accompanied by nearly constant RF amplitude. The validity of using our scheme in all-optical RF phase modulation is also verified.

PH-domain-dependent selective transport of p75 by kinesin-3 family motors in non-polarized MDCK cells.

A key process during epithelial polarization involves establishment of polarized transport routes from the Golgi to distinct apical and basolateral membrane domains. To do this, the machinery involved in selective trafficking must be regulated during differentiation. Our previous studies showed that KIF5B selectively transports vesicles containing p75-neurotrophin receptors to the apical membrane of polarized, but not non-polarized MDCK cells. To identify the kinesin(s) responsible for p75 trafficking in non-polarized MDCK cells we expressed KIF-specific dominant-negative constructs and assayed for changes in post-Golgi transport of p75 by time-lapse fluorescence microscopy. Overexpression of the tail domains of kinesin-3 family members that contain a C-terminal pleckstrin homology (PH) domain, KIF1A or KIF1Bbeta, attenuated the rate of p75 exit from the Golgi in non-polarized MDCK cells but not in polarized cells. Analysis of p75 post-Golgi transport in cells expressing KIF1A or KIF1Bbeta with their PH domains deleted revealed that vesicle transport by these motors depends on the PH domains. Furthermore, purified KIF1A and KIF1Bbeta tails interact with p75 vesicles and these interactions require the PH domain. Knockdown of canine KIF1A also inhibited exit of p75 from the Golgi, and this was rescued by expression of human KIF1A. Together these data demonstrate that post-Golgi transport of p75 in non-polarized epithelial cells is mediated by kinesin-3 family motors in a PH-domain-dependent process.

Kinesin KIF4 regulates intracellular trafficking and stability of the human immunodeficiency virus type 1 Gag polyprotein.

Retroviral Gag proteins are synthesized as soluble, myristoylated precursors that traffic to the plasma membrane and promote viral particle production. The intracellular transport of human immunodeficiency virus type 1 (HIV-1) Gag to the plasma membrane remains poorly understood, and cellular motor proteins responsible for Gag movement are not known. Here we show that disrupting the function of KIF4, a kinesin family member, slowed temporal progression of Gag through its trafficking intermediates and inhibited virus-like particle production. Knockdown of KIF4 also led to increased Gag degradation, resulting in reduced intracellular Gag protein levels; this phenotype was rescued by reintroduction of KIF4. When KIF4 function was blocked, Gag transiently accumulated in discrete, perinuclear, nonendocytic clusters that colocalized with endogenous KIF4, with Ubc9, an E2 SUMO-1 conjugating enzyme, and with SUMO. These studies identify a novel transit station through which Gag traffics en route to particle assembly and highlight the importance of KIF4 in regulating HIV-1 Gag trafficking and stability.

Polarization-dependent selective transport to the apical membrane by KIF5B in MDCK cells.

Microtubule-based vesicular transport is well documented in epithelial cells, but the specific motors involved and their regulation during polarization are largely unknown. We demonstrate that KIF5B mediates post-Golgi transport of an apical protein in epithelial cells, but only after polarity has developed. Time-lapse imaging of EB1-GFP in polarized MDCK cells showed microtubule plus ends growing toward the apical membrane, implying that plus end-directed N-kinesins might be used to transport apical proteins. Indeed, time-lapse microscopy revealed that expression of a KIF5B dominant negative or microinjection of function-blocking KIF5 antibodies inhibited selectively post-Golgi transport of the apical marker, p75-GFP, after polarization of MDCK cells. Expression of other KIF dominant negatives did not alter p75-GFP trafficking. Immunoprecipitation experiments demonstrated an interaction between KIF5B and p75-GFP in polarized, but not in subconfluent, MDCK cells. Our results demonstrate that apical protein transport depends on selective microtubule motors and that epithelial cells switch kinesins for post-Golgi transport during acquisition of polarity.