Retracted: microRNA-145 regulates tumor suppressor candidate 3 and mitogen-activated protein kinase pathway to inhibit the progression of colorectal cancer.

BACKGROUND: It has been reported that microRNA-145 (miR-145) is downregulated in various cancers, including colorectal cancer (CRC). However, the role of miR-145 in progress of CRC and its mechanism remains unclear. METHODS: The expressions of miR-145 and tumor suppressor candidate 3 (TUSC3) were determined in CRC tissues and cells by real-time quantitative polymerase chain reaction and Western blot analysis. The effects of miR-145 and TUSC3 on cell viability, migration, and invasion of CRC cells were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-trtrazolium bromide assay and trans-well chamber experiment, respectively. The interaction between miR-145 and TUSC3 was explored by bioinformatics analysis, luciferase reporter assay, and Western blot analysis. The abundances of mitogen-activated protein kinase (MAPK) signaling pathway-related proteins were measured by Western blot analysis. RESULTS: miR-145 expression was downregulated in CRC tissues and cell lines, and TUSC3 was upregulated in CRC tissues and correlated inversely with miR-145 abundance. Overexpression of miR-145 and knockdown of TUSC3 suppressed cell viability, migration, and invasion in LS174T and HCT116 cells. Moreover, TUSC3 was indicated as a novel target of miR-145 and its expression was negatively regulated by miR-145. Restoration of TUSC3 can partially reverse the inhibitory effects of miR-145 on phosphorylation of extracellular signal-regulated kinases 1 and 2 in CRC cells. CONCLUSION: miR-145 can inhibit the viability, migration, and invasion through addressing MAPK signaling pathway by targeting TUSC3 in CRC cells, providing a novel biomarker for treatment of CRC.

A highly potent and selective inhibitor Roxyl-WL targeting IDO1 promotes immune response against melanoma.

Indoleamine 2,3-dioxygenase 1 (IDO1) activity links to immune escape of cancers. Inhibition of IDO1 provides a new approach for cancer treatment. Most clinical IDO1 drugs show marginal efficacy as single agents. On basis of molecular docking and pharmacophore modelling, a novel inhibitor Roxyl-WL was discovered with a half maximal inhibitory concentration (IC50) value of 1 nM against IDO1 and 10-100-fold increased potent activity compared with IDO1 drugs in clinical trials. Roxyl-WL displayed excellent kinase spectrum selectivity with no activity out of the 337 protein kinases. In vitro, Roxyl-WL effectively augmented the proliferation of T cells and reduced the number of regulatory T cell (Tregs).When administered to melanoma (B16F10) tumor-bearing mice orally, Roxyl-WL significantly suppressed tumor growth and induced immune response.

Effect of combined medicated thread moxibustion plus needle picking therapy of Zhuang nationality medicine on antioxidant levels in a rat model of sciatica.

OBJECTIVE: To investigate the effect and underlying mechanisms of combined medicated thread moxibustion therapy plus needle picking therapy of Zhuang nationality medicine on antioxidant levels in a rat model of sciatica. METHODS: One hundred Wistar rats, of specific pathogen free level, were randomly divided into five groups: normal control group, model group, medicated thread moxibustion group, needle picking group, and combination group. Each group contained 20 rats. In the model, medicated thread moxibustion, needle picking, and combination groups, sciatica models were established through chronic constriction injury of the sciatic nerve. After the model was established, the rats in the medicated thread moxibustion, needle picking, and combination groups were given the corresponding therapies for 21 days. The control and model groups received no treatment. Reactive oxygen species, superoxide dismutase, malondialdehyde, and total antioxidant capacity changes were determined. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit NADPH oxidases 4 (NOX4) mRNA expression and the morphology of cells were observed to detect apoptosis of gamma- aminobutyric acid ergic (GABAergic) neurons. RESULTS: Compared with control group, reactive oxygen species and malondialdehyde levels rose significantly in the model group (P < 0.01), while superoxide dismutase and total antioxidant capacity levels were lowered (P < 0.05). Compared with the model group, reactive oxygen species and malondialdehyde decreased in the needle picking group (P < 0.05), while superoxide dismutase levels were increased (P < 0.05); reactive oxygen species and malondialdehyde significantly decreased in the combination group (P < 0.01). In addition, the model group had higher NOX4 mRNA expression than that of the control group (P < 0.05), and the combination group had lower expression levels than that of the model group (P < 0.05). Apoptosis of GABAergic neurons was observed in the model group, and was attenuated after combined therapy. CONCLUSION: The medicated thread moxibustion therapy plus needle picking therapy of Zhuang nationality medicine can prevent oxidative damage in the rat model of sciatica via down-regulating NOX4 expression, improving antioxidant capacity, and inhibiting the oxidative damage pathway of GABAergic neurons.

Bidirectional multiband radio-over-fiber system based on polarization multiplexing and wavelength reuse.

A polarization multiplexing technique based on phase-shift-induced polarization modulation-to-intensity modulation (PloM-to-IM) convertor and a Mach-Zehnder modulator (MZM) is proposed to generate multi-band signals. Successful transmission of the traditional radio frequency, microwave (MW) and millimeter wave (MMW) signals is simultaneously achieved. Meanwhile, the intensity-constant optical carrier (OC) is reused for upstream 25-km transmission.

Long-term stability improvement of tunable optoelectronic oscillator using dynamic feedback compensation.

We propose and demonstrate a novel method to improve the long-term stability of the wideband tunable optoelectronic oscillator (OEO) where a dynamic compensation scheme is achieved to offset the parameter variation of the fiber. In our method, a 900 MHz calibration signal transmits in the fiber link of the OEO's feedback loop for establishing a servo system which can extract the time delay of the feedback loop. The time delay varies with the external environment because refractive index and length of the fiber fluctuate with ambient temperature variations. Taking the extracted information as the reference, the wavelength of the tunable laser used in the OEO can be controlled precisely and continually to offset the random delay fluctuation in the fiber. Consequently, the long-term stability of the microwave signal generated by the OEO can be optimized. The experiment results show that Allan deviation achieved in 1000-s averaging time is improved more than two orders of magnitude when the tunable OEO worked at 2.4 GHz.

Synthesis of directly fused porphyrin dimers through Fe(OTf)3-mediated oxidative coupling.

An efficient and general Fe(OTf)3-mediated oxidative coupling method was developed for the synthesis of doubly or triply linked porphyrin dimers. Besides the central metal and peripheral substituent, regioselectivity of the oxidative coupling was found to be closely relevant to the onset oxidation potential of the porphyrin substrate, and the reactant with higher E(onset(ox)) tends to generate meso-ß doubly fused porphyrin dimer.

Fiber-distributed Ultra-wideband noise radar with steerable power spectrum and colorless base station.

A fiber-distributed Ultra-wideband (UWB) noise radar was achieved, which consists of a chaotic UWB noise source based on optoelectronic oscillator (OEO), a fiber-distributed transmission link, a colorless base station (BS), and a cross-correlation processing module. Due to a polarization modulation based microwave photonic filter and an electrical UWB pass-band filter embedded in the feedback loop of the OEO, the power spectrum of chaotic UWB signal could be shaped and notch-filtered to avoid the spectrum-overlay-induced interference to the narrow band signals. Meanwhile, the wavelength-reusing could be implemented in the BS by means of the distributed polarization modulation-to-intensity modulation conversion. The experimental comparison for range finding was carried out as the chaotic UWB signal was notch-filtered at 5.2 GHz and 7.8 GHz or not. Measured results indicate that space resolution with cm-level could be realized after 3-km fiber transmission thanks to the excellent self-correlation property of the UWB noise signal provided by the OEO. The performance deterioration of the radar raised by the energy loss of the notch-filtered noise signal was negligible.

A dual-polarization coherent communication system with simplified optical receiver for UDWDM-PON architecture.

A dual-polarization coherent heterodyne optical communication system using a simplified and low-cost demodulation scheme, for high-capacity UDWDM-PON access networks, is proposed and demonstrated. In this scheme, the signal light and reference light occupying each of the polarization modes are emitted simultaneously from the transmitter. The random phase fluctuations between the signal light and reference light are obviated completely by means of the application of the phase-correlated orthogonal lights. When the signal light in the each polarization mode is modulated with M-amplitude-shift keying (M-ASK) or M2-quadrature amplitude modulation (M2-QAM), the phase-stable intermediate frequency (IF) signal with M-ASK or M2-QAM modulation in the corresponding polarization mode is available for conversion in the electrical domain by beating the modulated signal light with the un-modulated reference light. A new IF signal with M2 or M4-QAM can be synthesized by the IF signals in both modes as long as the power ratio and time delay between the two-modes optical signals are set at the proper values. This is achieved without using polarization demultiplexing and complicated algorithms and the synthesized IF signal can be received and demodulated directly. A proof-of-concept transmission link with dual-polarization 2-ASK is demonstrated. The experimental results are consistent with theoretical predictions.

Photonic-assisted microwave frequency multiplier based on nonlinear polarization rotation.

A photonic-assisted microwave frequency multiplier (MFM) based on the Kerr shutter is proposed and demonstrated. In this MFM, the nonlinear polarization rotation in the high nonlinear optical fiber is used for the first time to implement the light-controlled optical-carrier-suppressed modulation. The frequency-doubled microwave signal with the frequency up to 144 GHz is generated. The results of the experiment are in accordance with the theoretical prediction.

Photonic microwave-signal-mixing technique using phase-coherent orthogonal optical carriers for radio-over-fiber application.

An optical-assisted microwave-mixing technique based on orthogonal and phase-coherent optical carriers is proposed and demonstrated. High-quality binary-phase-shift keying, amplitude-shift keying, and on-off keying microwave modulation at 20 GHz implemented in the optical domain have been tested. The ultra-high-bandwidth response of the proposed mixing device is also analyzed and compared. The phase stability of the photonic microwave signal in the radio-over-fiber system is improved by the proposed signal mixing technique.

Clawlike tripodal porphyrin trimer: ion-controlled on­off fullerene binding.

A practical method for the preparation of novel tripodal tris(porphyrinato-urea) TP3 1 was readily achieved. Because of its appreciable preorganized triangular cone-shaped cavity resulting from the intramolecular hydrogen bonds of the tripodal tris-urea backbone, this porphyrin trimer host was found to have a high affinity toward fullerenes to form stable inclusion complexes in solution. A 120-fold binding selectivity toward C70 (Kassoc = 1.81 × 10(7) M(­1)) over C60 (Kassoc = 1.51 × 10(5) M(­1)) was further achieved in toluene. Moreover, the dissociation of such inclusion complexes can be easily realized by introducing H2PO4(­), and recapturing of the fullerene can be achieved after withdrawing H2PO4(­) by Ca(2+). A recyclable process for the inclusion and release of fullerene was therefore built by alternately feeding H2PO4(­) and Ca(2+). Benefiting from this approach, TP3 1 was sequentially applied to isolate C70 from the C60-enriched fullerene mixture successfully.

Metal-free iodine(III)-promoted synthesis of isoquinolones.

A metal-free oxidative cycloaddition reaction of substituted benzamides and alkynes has been developed for the synthesis of isoquinolones by using bis(trifluoracetoxy)iodobenzene (PIFA) and trifluoroacetic acid (TFA). Under mild conditions, a wide variety of isoquinolones were conveniently prepared via oxidative annulation of simple N-methoxybenzamide and diarylacetylene or aryl/alkyl acetylene derivatives in yields up to 87%.

Switchable regioselectivity in the PIFA-BF3·Et2O mediated oxidative coupling of meso-brominated Ni(II) porphyrin.

A simple and efficient method has been developed for the switchable synthesis of directly linked meso-brominated Ni(II) porphyrin dimers through PIFA-BF3·Et2O mediated oxidative coupling. The respective syntheses of meso-meso or meso-ß singly, doubly, and triply linked porphyrin dimers can be easily realized with the same reagent system.

The effect of Aceria litchii (Keifer) infestation on the surface properties of litchi leaf hosts.

BACKGROUND: The wettability of target crop surfaces affects pesticide wetting and deposition. The structure and properties of the leaf surface of litchi leaves undergo severe changes after infestation by Aceria litchii (Keifer). The objective of this study was to systematically investigate the surface texture and wettability of litchi leaves infested. RESULTS: Firstly, the investigation focused on the surface structure and physicochemical properties of litchi leaves infested with Aceria litchii. Subsequently, different levels of Contact Angle (CA) were measured individually on the infested litchi leaves. Lastly, Surface Free Energy (SFE) and its polar and dispersive components were calculated using the Owens-Wendt-Rabel-Kaelble (OWRK) method. The outcomes revealed distinctive 3D surface structures of the erineum at various stages of mycorrhizal growth. At stage NO. 1, the height of the fungus displayed a peaked appearance, with the skewness value indicating a surface characterized by more crests. In contrast, at stages NO. 2 and NO. 3, the surface appeared relatively flat. Furthermore, post-infestation of litchi leaves, the CA of droplets on the abaxial surface of diseased leaves exhibited an increase, while the SFE value on the abaxial surface of leaves decreased significantly, in contrast to the abaxial surface of healthy leaves. CONCLUSION: The infestation behavior of Aceria litchii changed the surface structure and chemistry of litchi leaves, which directly affected the CA value of foliar liquids and the SFE value of leaves, changing the surface wettability of litchi leaves from hydrophobic to superhydrophobic. This study provides useful information for improving the wetting and deposition behavior of liquid droplets on the surface of infested leaves. © 2024 Society of Chemical Industry.

Implementation of wavelength reusing upstream service based on distributed intensity conversion in ultrawideband-over-fiber system.

We propose and demonstrate a simple scheme for generating the ultrawideband (UWB) signals and reusing the wavelength for upstream service simultaneously by using a distributed polarization modulation-to-intensity modulation convertor. Through adjusting the static phase difference between transverse electric and transverse magnetic modes of the optical carrier (OC) and the angle between the polarization direction of the OC and the principal axis of the polarizers, the UWB doublet-like signals were generated. Meanwhile, the error-free transmission of the upstream signals with bit rate of 1.25 Gbit/s over 10 km fiber is achieved. The power penalty resulting from the interference of downstream signals is less than 0.3 dB.

Targeting mycobacterium protein tyrosine phosphatase B for antituberculosis agents.

Protein tyrosine phosphatases are often exploited and subverted by pathogenic bacteria to cause human diseases. The tyrosine phosphatase mPTPB from Mycobacterium tuberculosis is an essential virulence factor that is secreted by the bacterium into the cytoplasm of macrophages, where it mediates mycobacterial survival in the host. Consequently, there is considerable interest in understanding the mechanism by which mPTPB evades the host immune responses, and in developing potent and selective mPTPB inhibitors as unique antituberculosis (antiTB) agents. We uncovered that mPTPB subverts the innate immune responses by blocking the ERK1/2 and p38 mediated IL-6 production and promoting host cell survival by activating the Akt pathway. We identified a potent and selective mPTPB inhibitor I-A09 with highly efficacious cellular activity, from a combinatorial library of bidentate benzofuran salicylic acid derivatives assembled by click chemistry. We demonstrated that inhibition of mPTPB with I-A09 in macrophages reverses the altered host immune responses induced by the bacterial phosphatase and prevents TB growth in host cells. The results provide the necessary proof-of-principle data to support the notion that specific inhibitors of the mPTPB may serve as effective antiTB therapeutics.

What does Chinese BERT learn about syntactic knowledge?

Pre-trained language models such as Bidirectional Encoder Representations from Transformers (BERT) have been applied to a wide range of natural language processing (NLP) tasks and obtained significantly positive results. A growing body of research has investigated the reason why BERT is so efficient and what language knowledge BERT is able to learn. However, most of these works focused almost exclusively on English. Few studies have explored the language information, particularly syntactic information, that BERT has learned in Chinese, which is written as sequences of characters. In this study, we adopted some probing methods for identifying syntactic knowledge stored in the attention heads and hidden states of Chinese BERT. The results suggest that some individual heads and combination of heads do well in encoding corresponding and overall syntactic relations, respectively. The hidden representation of each layer also contained syntactic information to different degrees. We also analyzed the fine-tuned models of Chinese BERT for different tasks, covering all levels. Our results suggest that these fine-turned models reflect changes in conserving language structure. These findings help explain why Chinese BERT can show such large improvements across many language-processing tasks.

Lon peptidase 1 (LONP1)-dependent breakdown of mitochondrial 5-aminolevulinic acid synthase protein by heme in human liver cells.

5-Aminolevulinic acid synthase (ALAS-1) is the first rate controlling enzyme that controls cellular heme biosynthesis. Negative feedback regulation of ALAS-1 by the end product heme is well documented and provides the foundation for heme treatment of acute porphyrias, a group of diseases caused by genetic defects in the heme biosynthesis pathway and exacerbated by controlled up-regulation of ALAS-1. Heme is known to affect ALAS-1 activity by repressing gene transcription, accelerating mRNA degradation, and impeding pre-ALAS-1 mitochondrial translocation. In the current study, we examined the effect of heme on the rate of mature ALAS-1 protein turnover in human cells and tissues and explored the mediator involved in this new regulatory mechanism. We found that heme and other metalloporphyrins such as CoPP and CrPP decreased mitochondrial ALAS-1 protein through proteolysis. This degradative effect cannot be emulated by iron or free protoporphyrin, two major chemical components of the heme ring, and is independent of oxidative stress. Down-regulating the activity of mitochondrial LONP1, an ATP-dependent protease that controls the selective turnover of mitochondrial matrix proteins, with potent inhibitors and specific siRNA diminished the negative effect of heme on mitochondrial ALAS-1. Therefore, our data support the existence of a conserved heme feedback regulatory mechanism that functions on the mature form of ALAS-1 protein through the activity of a mitochondrial proteolytic system.

Probing language identity encoded in pre-trained multilingual models: a typological view.

Pre-trained multilingual models have been extensively used in cross-lingual information processing tasks. Existing work focuses on improving the transferring performance of pre-trained multilingual models but ignores the linguistic properties that models preserve at encoding time-"language identity". We investigated the capability of state-of-the-art pre-trained multilingual models (mBERT, XLM, XLM-R) to preserve language identity through language typology. We explored model differences and variations in terms of languages, typological features, and internal hidden layers. We found the order of ability in preserving language identity of whole model and each of its hidden layers is: mBERT > XLM-R > XLM. Furthermore, all three models capture morphological, lexical, word order and syntactic features well, but perform poorly on nominal and verbal features. Finally, our results show that the ability of XLM-R and XLM remains stable across layers, but the ability of mBERT fluctuates severely. Our findings summarize the ability of each pre-trained multilingual model and its hidden layer to store language identity and typological features. It provides insights for later researchers in processing cross-lingual information.

Zinc mesoporphyrin induces rapid proteasomal degradation of hepatitis C nonstructural 5A protein in human hepatoma cells.

BACKGROUND & AIMS: The nonstructural 5A (NS5A) protein of hepatitis C virus (HCV) plays a critical role in HCV replication and is an attractive target for the therapy of HCV infection. So far, little is known about the posttranslational regulation of NS5A protein and its precise role in HCV RNA replication. Our objectives were to elucidate the down-regulation of NS5A protein and HCV RNA replication by zinc mesoporphyrin (ZnMP) and the mechanism by which this process occurs. METHODS: Human hepatoma cells expressing HCV proteins were used to investigate the posttranslational regulation of ZnMP on NS5A protein by Western blots and immunoprecipitation. Real-time quantitative reverse transcription polymerase chain reaction was used to determine the effects of ZnMP on HCV RNA replication. RESULTS: ZnMP selectively and markedly down-regulated NS5A protein levels by increasing degradation of NS5A protein (half-life fell from 18.7 hours to 2.7 hours). The proteasome inhibitors epoxomicin and MG132 significantly abrogated degradation of NS5A protein by ZnMP without affecting levels of NS5A in the absence of ZnMP. Analysis of immunoprecipitates with an antiubiquitin antibody revealed polyubiquitination of NS5A, suggesting that ZnMP induces ubiquitination of NS5A protein. In addition, 10 micromol/L of ZnMP reduced HCV replication by approximately 63% in the Con1 replicon cells, approximately 70% in J6/Japanese fulminant hepatitis 1 HCV-transfected cells, and approximately 90% in J6/Japanese fulminant hepatitis 1 HCV-infected cells without affecting cell viability. CONCLUSIONS: ZnMP produces a rapid and profound down-regulation of the NS5A protein by enhancing its polyubiquitination and proteasome-dependent catabolism. ZnMP may hold promise as a novel agent to treat HCV infection.