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A femtosecond soliton erbium-doped fiber ring laser with the symmetrical saturable absorber (SA) of graded index multimode fiber-step index multimode fiber-graded index multimode fiber (GIMF-SIMF-GIMF) is proposed and proved. Based on the nonlinear multimode interference (NL-MMI) effect of SA, the fiber laser achieved femtosecond soliton mode-locking operation and repetition rate tuning. The duration of soliton was 364 fs at 1562.5 nm and repetition rate was tunable from 10.29 MHz to 763.36 MHz. In the structure of SA, a short step index multimode fiber (SIMF) was inserted between two graded index multimode fibers (GIMFs) to generate more high-order modes, adjust the self-focusing length, and improve operation stability of mode-locked fiber laser. The SA also has the advantages of immunity to the external environment variation, high damage threshold and inoxidizability, which make the laser operate stably for a long time.

Pleomorphic xanthoastrocytoma (PXA), anaplastic pleomorphic xanthoastrocytoma (A-PXA), and epithelioid glioblastoma (E-GBM) show overlapping features. However, little is known about their clinical characteristics, molecular features and relationship with progression.Fourteen patients diagnosed at Nanfang Hospital from 2016 to 2019 were enroled, including eleven PXA patients, two A-PXA patients, and one E-GBM patient. All tumour tissue samples of the fourteen patients were examined by immunohistochemical staining (MGMT, VEGF, BRAF-V600E, etc.).The mean age of 13 patients with PXA or A-PXA was 25.4 years; twelve of these patients had tumours at supratentorial regions. VEGF positivity was detected in the tumour samples of 13 patients, MGMT positivity in 10 patients, and BRAF-V600E positivity in 7 patients. The recurrent tumour tissue of the patient with E-GBM arising from A-PXA was screened to detect 11 glioma markers (MGMT, BRAF-V600E, etc.) and chromosome 1p/19q by next-generation sequencing (NGS). For the tumour sample of the E-GBM patient who survived for up to 11 years after the fourth resection, BRAF V600E was wild type in the sample obtained from the first surgery, while it was mutant in the second, third, and fourth surgeries. In contrast, the promoter status of MGMT in the four surgeries was unmethylated. The NGS results showed that the mutation frequencies of BRAF V600E in the second, third and fourth surgeries were 14.06%, 9.13% and 48.29%, respectively.Collectively, the results suggest that patients with A-PXA may relapse multiple times and eventually progress to E-GBM with the BRAF-V600E mutation.

A Q -switched mode-locked square noise-like pulse (QMLSNLP) is generated in a nonlinear polarization rotation passively mode-locked fiber laser. When the pump power changes from 154 mW to 414 mW, the frequency of the Q -switched envelope varies from 21.7 kHz to 38.9 kHz, while the duration of the Q -switched envelope decreases from 5.1 µ s to 3.2 µ s , correspondingly. In the meantime, QMLSNLP keeps the fundamental repetition rate constant, and the pulse duration increases from 3.4 ns to 6.7 ns. By inserting different lengths of single-mode fiber into the ring cavity, the evolutions of QMLSNLP are measured and analyzed. According to the cavity parameters and experimental results, impacts of the cavity length on QMLSNLP are investigated in detail.

Patients suffering from glioblastoma have a dismal prognosis, indicating the need for new therapeutic targets. Here we provide evidence that the DNA damage kinase HIPK2 and its negative regulatory E3-ubiquitin ligase SIAH1 are critical factors controlling temozolomide-induced cell death. We show that HIPK2 downregulation (HIPK2kd) significantly reduces the level of apoptosis. This was not the case in glioblastoma cells expressing the repair protein MGMT, suggesting that the primary DNA lesion responsible for triggering HIPK2-mediated apoptosis is O6-methylguanine. Upon temozolomide treatment, p53 becomes phosphorylated whereby HIPK2kd had impact exclusively on ser46, but not ser15. Searching for the transcriptional target of p-p53ser46, we identified the death receptor FAS (CD95, APO-1) being involved. Thus, the expression of FAS was attenuated following HIPK2kd, supporting the conclusion that HIPK2 regulates temozolomide-induced apoptosis via p-p53ser46-driven FAS expression. This was substantiated in chromatin-immunoprecipitation experiments, in which p-p53ser46 binding to the Fas promotor was regulated by HIPK2. Other pro-apoptotic proteins such as PUMA, NOXA, BAX, and PTEN were not affected in HIPK2kd, and also double-strand breaks following temozolomide remained unaffected. We further show that downregulation of the HIPK2 inactivator SIAH1 significantly ameliorates temozolomide-induced apoptosis, suggesting that the ATM/ATR target SIAH1 together with HIPK2 plays a proapoptotic role in glioma cells exhibiting p53wt status. A database analysis revealed that SIAH1, but not SIAH2, is significantly overexpressed in glioblastomas. Implications: The identification of a novel apoptotic pathway triggered by the temozolomide-induced DNA damage O6-methylguanine supports the role of p53 in the decision between survival and death and suggests SIAH1 and HIPK2 as new therapeutic targets.

Background Astrocytoma and glioblastoma (GBM) are the two main subtypes of glioma, with the 2016 World Health Organization Classification of Tumors of the Central Nervous System (CNS WHO) classifying them into different grades. GBM is the most malignant among all CNS tumors with a 5-year survival rate of less than 5%. Although the prognosis of patients with astrocytoma is better than that of GBM in general, patients with anaplastic astrocytoma (AA) and isocitrate dehydrogenase (IDH) wild type have a similar prognosis as GBM and entail a high risk of progression. Exploring the molecular driving force behind the malignant phenotype of astrocytoma and GBM will help explain the diversity of glioma and discover new drug targets. Methods We enrolled 12 patients with astrocytoma and 12 patients with GBM and performed whole-exome sequencing (WES) and RNA sequencing analysis on tumor samples from the patients. Results We found that the somatic mutation of KRT18, which is associated with cell apoptosis and adhesion by interacting with receptor 1-associated protein (TRADD) and pinin, was significantly enriched in astrocytoma, but rare in GBM. Copy number loss of MTAP, which is closely related to a poor prognosis of glioma, was found to be significantly enriched in GBM. In addition, different somatic copy number alteration (SCNA), gene expression, and immune cell infiltration patterns between astrocytoma and GBM were found. Conclusions This study revealed the distinct characteristics of astrocytoma and GBM at the DNA and RNA level. Somatic mutation of KRT18 and copy number loss of MTAP, two key genetic alterative genes in astrocytoma and GBM, have the potential to become therapeutic targets in glioma.

We designed an erbium-doped fiber laser based on a semiconductor saturable absorber mirror. The switch of Q-switched mode-locking and continuous-wave mode-locking was obtained by adjusting the pump power.

Background Analysis of mutational signatures is becoming routine in cancer genomics, with implications for pathogenesis, classification, and prognosis. Among the signatures cataloged at COSMIC, mutational signature 4 has been linked to smoking. However, the distribution of signature 4 in Chinese lung cancer patients has not been evaluated, and its clinical value has not been evaluated. Here we survey mutational signatures in Chinese lung cancer patients and explore the relationship between signature 4 and other genomic features in the patients. Methods We extracted mutational signatures from whole-exome sequencing data of Chinese non-small cell lung cancer patients. The data included 401 lung adenocarcinoma (LUAD) and 92 squamous cell carcinoma (LUSC). We then performed statistical analysis to search for genomic and clinical features that can be linked to mutation signatures. Results We found signature 4 is the most frequent mutational signature in LUSC and the second most frequent in LUAD. Fifty-six LUAD and thirty-five LUSC patients were named with high signature 4 similarities (cosine similarity >0.7). These patients have shorter survival and higher tumor mutational burden comparing to those with low signature 4 similarities. Dozens of genes with single nucleotide variation, index mutations, and copy number variations were differentially enriched in the patients with high signature 4 similarities. Among these genes, CSMD3, LRP1B, TP53, SYNE1, SLIT2, FGF4, and FGF19 are common in both LUADs and LUSCs with high signature 4 similarities, showing that these genes are tightly associated with signature 4. Conclusions The present study is the first to report a comparison in Chinese NSCLC patients with or without COSMIC mutational signature 4. These results will help find the Signature 4 related mutational process in NSCLC.

Background: Pleomorphic xanthoastrocytoma (PXA), anaplastic pleomorphic xanthoastrocytoma (A-PXA), and epithelioid glioblastoma (E-GBM) show overlapping features. However, little is known about their clinical characteristics, molecular features and progression relationship. Methods: Fourteen patients diagnosed at Nanfang Hospital from 2016 to 2019 were enrolled, including eleven PXA patients, two A-PXA patients, and one E-GBM patient. All tumor tissue samples of fourteen patients were examined by immunohistochemistry staining (MGMT, VEGF, BRAF-V600E, etc.). The recurred tumor tissue of the E-GBM patient arising from A-PXA was detected for 11 glioma markers (MGMT, BRAF-V600E, etc.) and chromosome 1p/19q by next generation sequencing (NGS). Results: The mean age of 13 patients with PXA or A-PXA was 25.4 years, twelve of whom were burdened with tumors at supratentorial regions. VEGF showed positive expression in the tumor samples of 13 patients, MGMT positive in 10 patients, and BRAF-V600E positive in 7 patients. As for the tumor sample of the E-GBM patient survived for up to 10 years after the fourth resections, BRAF V600E was wild-type in the sample obtained from the first surgery while it was mutant in the second, third, and fourth surgery. In the contrast, the promoter status of MGMT in four operations were unmethylated. The NGS results showed that the mutation frequencies of BRAF V600E in the second surgery, the third surgery and the fourth surgery were 14.06%, 9.13% and 48.29% respectively. Conclusions: Collectively, the results suggest that patients with A-PXA may relapse multiple times and eventually progress to E-GBM with BRAF-V600E mutation.

In this paper, we employ a symmetrical graded index multimode fiber-step index multimode fiber-graded index multimode fiber (GIMF-SIMF-GIMF) structure as artificial saturable absorber to achieve mode-locked operation in an Erbium-doped fiber laser. After optimizing the cavity length, pump power and orientation of polarization controller, noise-like pulse (NLP) is built in anomalous dispersion region experimentally. It is worth noting that except for the traditional NLP, a special NLP with unique features is obtained whose temporal and spectral properties are different from the known case on NLP reported before. According to the experimental results, we also acquire and compare properties of subpulse within NLP envelope with the change of pump power. Last but not least, harmonic of the peculiar NLP is found under appropriate cavity conditions.

We report on the experimental observation of various bound states of solitons in an erbium-doped fiber laser mode-locked by a graded index multimode fiber-step index multimode fiber-graded index multimode fiber (GIMF-SIMF-GIMF) saturable absorber (SA). Based on the nonlinear multimode interference (NL-MMI) effect of the GIMF-SIMF-GIMF SA, not only various bound single-pulse solitons (BSSs) can be obtained, but various bound twin-pulse solitons (BTSs) can also be achieved by adjusting the pump power and PC. The BSSs are formed by single soliton bound together, the BTSs are formed by multiple second-order tightly bound state of solitons.

A rapid and precise phase-retrieval method based on Lissajous ellipse fitting and ellipse standardization is demonstrated. It only requires two interferograms without pre-filtering, which reduces its complexity and shortens the processing time. The elliptic coefficients obtained by ellipse fitting are used for ellipse standardization. After compensating phase-shift errors by ellipse standardization, the phase distribution is extracted with high precision. It is suitable for fluctuation, noise, tilt-shift, simple and complex fringes. This method is effective for the number of fringes less than 1. The reliability of the method is verified by simulations and experiments, indicating high accuracy and less time consumption.

We demonstrated an experimental observation of bright-dark pulse pair and soliton bunch in mode-locked erbium-doped fiber ring laser with the saturable absorber (SA) of graded index multimode fiber-step index multimode fiber-graded index multimode fiber (GIMF-SIMF-GIMF), which utilizes nonlinear multimode interference inside the multimode fiber to realizing mode locking of fiber laser. During the experiment, we observed a fascinating phenomenon of dualwavelength bright-dark pulse pair, in which the wavelengths of the two wavelengths are 1558.5 nm and 1560.1 nm, respectively, and the wavelength interval is 1.6 nm. The PBS filter was used to verify that the bright and dark pulses are orthogonal to each other in polarization. We also obtained multiple set of soliton bunches running at the fundamental frequencies of 100.5 ns, and when we increase the pump power we could find that the number of optical solitons increases in a single soliton bunch, which experimental phenomenon is in appropriate agreement with the theory. Based on the observation and understanding of these experimental phenomena, it is beneficial to explore the rich nonlinear effects in the mode-locked fiber laser.

A wavelength tunable, dark pulse, and bright pulse-switched dual-wavelength fiber ring laser is reported. Through adding high nonlinear optical fiber as a nonlinear medium in the fiber ring cavity, the double-wavelength dark-bright pulse pair can be formed. The separation of dark-bright pulse pair can be achieved by polarization beam splitter. The dark pulse and bright pulse with orthogonal polarization correspond to different wavelengths, respectively. Then, via tunable optical filter and polarization controller to filter out the wavelength we need and adjust the polarization, we achieved the interconversion of dark pulse and bright pulse in the same wavelength and the tunableness of wavelengths of dark pulse and bright pulse in our laser.

Using the saturated absorption and the high nonlinearity of the molybdenum disulfide (MoS2) saturable absorber (SA), a three-component bright–dark–bright (BDB) vector pulse fiber laser is reported. By using polarization resolved measurement and spectral filtering, it can be found that the dark pulse component and one of bright pulses components constitute the dark–bright​ pulse pair with the same polarization state. The dark–bright pair and another bright pulse are orthogonally polarized. In other words, the single BDB pulse can be also considered to be composed of the orthogonal a bright pulse and a dark–bright pulse pair. The time interval between the bright pulse and the dark–bright pulse pair remained unchanged as the pump power was increased. The experimental results clearly show the existence of a new BDB vector pulse in fiber laser.

Versatile structures of wavelength-dependent bound solitons are obtained based on nonlinear polarization rotation (NPR) mode-locked technology in an anomalous-dispersion fiber laser. After optimizing the intra-cavity birefringence and finely adjusting the operating wavelength of the laser, both the conventional soliton and loosely bound-state soliton pairs can be generated and switched under different operating wavelengths. With the evolution of bound state, the spectral interference fringes show significant changes and the temporal separation between bound solitons varies accordingly. Altering initial settings of laser parameters, wavelength-dependent multiple-soliton bound states are also found experimentally. Moreover, the formation and evolution mechanism of the bound states are explored and analyzed in this work.

The formation and evolution of dip-type spectral sidebands are numerically and experimentally researched in a soliton fiber ring laser passively mode locked by the nonlinear polarization rotation (NPR) technique. We provide a theoretical model that can predict the positions of dip-type sidebands, and point out that the formation of the dip-type sidebands is due to the local destructive interference effect between the soliton and dispersive waves induced by the periodic soliton perturbations in the laser cavity. The expression describing the position of dip-type sidebands is strictly deduced, which indicates that the positions of dip-type sidebands on the spectrum can be changed with the pulse width variation. The reliability of the theoretical model of dip-type sidebands is verified by experiments and simulations; both the experimental observations and numerical simulations can well confirm the theoretical predictions.

The graded index multimode-fiber step-index multimode fiber-graded index multimode fiber (GIMF-SIMF-GIMF) structure was designed as a saturable absorber (SA). To obtain optical pulses that meet the requirements of different applications, the multistate transformations of a femtosecond fiber laser based on GIMF-SIMF-GIMF SA were numerically and experimentally researched. The fiber laser can self-start mode-locking; its fundamental repetition rate of fiber laser is 10.35 MHz. The fiber laser can deliver three different optical pulses, namely, the conventional soliton, second-order bound state, and noise-like pulse. The duration of soliton is 421.2 fs; the energy of noise-like pulse is 197.10 pJ. The experimental and simulated results show that the output states of the fiber laser can be switched by adjusting the pump power.

We report on the influence of the average nonlinear coefficient on noise-like pulse (NLP) in a figure-of-eight erbium-doped fiber laser. Since the nonlinear switching point of nonlinear amplifying loop mirror (NALM) shifts with distinct laser configurations, through changing the length of highly nonlinear fiber (HNLF) in NALM, properties of output pulse have been compared and analyzed. The spectral evolutions occur and the peak power of NLP presents a decline when the HNLF is lengthened in NALM. Also, the tuning range of the duration of NLP shows a difference based on the average nonlinear coefficient selected.

Introduction: Colorectal cancer patients with high-level microsatellite instability benefit more from immune checkpoint inhibitor therapy, but they only account for around 15% of all colorectal cancer patients. The remaining patients are still lack of effective therapeutic biomarkers. For patients in late stage without optimal treatment, it is essential to find novel biomarkers which can be used to select appropriate therapies and therefore improve patients' overall survival. Methods: We used whole-exome sequencing to analyze 114 colorectal cancer samples. The samples included 86 primary late stage tumors and 28 metastatic tumors from liver, lung and other organs. The primary samples were further divided into different groups based on their tumor location (sideness) and microsatellite status (MS) since these indications are of great significance in clinical presentation and treatment. We then assessed somatic genomic lesions, copy number variations, germline gene alterations and mutational signatures in the above three pairs of comparisons respectively (primary vs. metastatic, right- vs. left-sided, MS instable vs. stable). Results: There were significant differences between the analyzed pairs. For the primary and metastatic samples, the most prominent difference was the copy number variation which happened in 25 genes in the metastatic samples and only one gene in the primary samples (gain of IL12) (p = 0.036). For the right- and left-sided comparison, SNP/Indel mutations were the most prominent. They happened more frequently in the right-sided than the left-sided tumors and those are rare genes in colorectal cancer, including BCL11A (p = 0.018), DICER1 (p = 0.038), NR4A3 (p = 0.004), NIN (p = 0.008) and FBXW7 (p = 0.019). For the MSI-MSS comparison, tumor mutation burden (TMB) stands out high in the MSI group compared to the MSS group (p < 0.0001). In addition, dozens of significantly mutated genes were observed in the MSI samples (p < 0.0001), such as KMT2B, ACVR2A, KMT2D, ASXL1, TCF7L2 and etc. However, TP53 occurred mainly in the MSS patients (p = 0.0007). Conclusion: Our study enables a deeper understanding of the genomic characterization of colorectal cancer from an integrated view. Copy number variations, gene mutations, and TMB were found to be the most significant differences between the comparison groups of primary vs. metastatic samples, left vs. right sided samples, and MSI vs. MSS samples respectively. Genomic differences between metastatic and primary samples may be potential therapeutic targets for metastatic colorectal cancer. Citation Format: Jianxia Li, Qianchao Wu, Jianwei Zhang, Huabin Hu, Yue Cai, Jiayu Lin, Jun Liu, Yanhong Deng. Novel genomic characterization in late stage colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2523.

A dual-wavelength soliton fiber ring laser with adjustable repetition rate was reported. Through adding highly nonlinear fiber (HNLF) as nonlinear medium in the fiber ring cavity, the dual-wavelength bright-dark soliton pair can be formed. The 1st to 4th, 5th to 8th and 9th to 11th harmonics bright-dark solitons pairs were obtained by rotating the Polarization controller (PC) when the power are 160 mW, 230 mW and 340 mW, respectively. In order to investigate the influence of loss on the laser system, a variable optical attenuator (VOA) was embedded in the ring laser cavity. Then the dual-wavelength with Kelly sidebands was obtained by properly adjusting the PC and VOA. The center wavelengths of the dual-wavelength laser were located at 1557.8 nm and 1568.5 nm and the 3 dB bandwidths of two wavelengths are 2.2 nm and 2.1 nm, respectively. The spacing between the two wavelengths was 10.7 nm. Due to the existence of nonlinearity, the 1st to 22th harmonics bright solitons sequence (corresponding to the repetition rate tunable from 196.8 kHz to 4.33 MHz) was obtained by increasing the pump power. The intervals of bright-dark solitons pair and bright solitons all were $5.08\ \mu\mathrm{s}$ , which corresponds to fundamental repetition rates are 196.8 kHz. The signal-to-noise ratio of the bright solitons was approximately 58 dB, which means the operation of laser was stable.

We investigate the conversion of mode locking of bright pulses, dark pulses and dark-bright pulses in an Erbium-doped fiber laser (EDFL) based on a Molybdenum disulfide (MoS2) films saturable absorber (SA) experimentally. When the pump power is 150 mW, by changing the polarization controller (PC) to change the polarization state in the laser cavity， we observed the bright pulse trains, the dark pulse trains and the dark-bright pulses trains in turn. All pulse interval are about 58 ns, and the repetition frequency of pulse is 1.7 MHz. The study provides a method for the conversion among bright pulses, dark pulses and dark-bright pulses.

In order to improve the accuracy and expand the range of the phase-shifting algorithm application, a precise three-step phase retrieval algorithm suitable for the interferograms with less than one fringes numbers is proposed. The proposed method improves the accuracy, on the one hand because normalization and subtraction are introduced to reduce background intensity fluctuation, on the other hand because Lissajous ellipse fitting (LEF) method is introduced to reconstruct phase maps from the normalized and Gram-Schmidt (GS) orthonormalized maps. Because the approximation operations for cumulative sum aren’t used in the GS method, the proposed algorithm is suitable for not only interferograms that the fringes numbers are more than one but also interferograms that fringes numbers are less than one. Moreover, the proposed method can be applied to simple and complex patterns. Thus, the proposed algorithm has a wider range of applications. The proposed algorithm’s reliability and performance are confirmed by simulations and experiments.

We report on the generation of high-order solitons with order continuously adjustable in an erbium-doped fiber laser mode-locked by a graded index multimode fiber–step index multimode fiber–graded index multimode fiber (GIMF–SIMF–GIMF) saturable absorber (SA). The SA has advantages of high damage threshold, easy fabrication and low cost. The fundamental soliton to eleventh-order soliton were obtained by adjusting the pump power and PC. It was found that both increasing pump power and adjusting PC can affect the solitons splitting during experiment. The generation of high-order solitons is due to the peak power clamping effect of laser cavity and the pulse shaping effect of GIMF–SIMF–GIMF SA. Last but not least, this is the first time to adjust the order of solitons continuously from the first to eleventh in a fiber laser mode-locked by GIMF–SIMF–GIMF SA.

In this article, we numerically research the generation of Dissipative-Soliton-Resonance (DSR) pulse in anomalous dispersion regime based on spectral filtering effect. We find that a strong spectral filtering effect can limit the spectrum broadening and avoid the pulse breaking up in the high effective gain of the cavity, which leads to the formation of DSR pulse. Meanwhile, we also find that the peak power of DSR pulse increases with the saturation power, which is in line with the case in normal dispersion regime. As a comparison, the DSR pulse cannot be obtained in the absence of spectral filtering effect, which proves that the generation of DSR pulse needs strong spectral filtering effect in anomalous dispersion regime. We believe that our work can be served as a theoretically guideline to investigate the generation of DSR pulse in anomalous dispersion regime.

In this article, the peak-power expression of dissipative-soliton-resonance (DSR) pulse is derived, in a normal-dispersion fiber laser, by using the equation for the resonance curve and the relationship between the parameters of cubic–quintic complex Ginzburg–Landau (CGLQ) equation and the cavity parameters. According to the peak-power expression, the peak power of DSR pulses is inversely proportional to the average dispersion and the square of the gain bandwidth, is proportional to the square of the saturation power. That is to say, we can improve the peak power of DSR pulse in three ways: Firstly, increase the saturation power in the case of sinusoidal-saturable-absorber transmission curve; secondly, decrease the gain bandwidth properly; thirdly, decrease the average dispersion suitably. In addition, the further results of numerical simulations are obtained by using pulse-tracing technique, which are in good agreement with the theoretical derivation of peak power of DSR pulses. This means that our work can serve as a guideline to design high-peak-power DSR fiber laser.

Asperuloside, an iridoid glycoside found in Herba Paederiae, is a component from traditional Chinese herbal medicine. In this study, we aimed to investigate the protective effects and potential mechanisms of asperuloside action on inflammatory responses in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells and an LPS-induced lung injury model. The pro-inflammatory cytokines and signaling pathways were measured by enzyme-linked immunosorbent assays (ELISA) and Western blotting to determine the effects of asperuloside. We found that asperuloside can significantly downregulate tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 levels in vitro and in vivo, and treatment with asperuloside significantly reduced the lung wet-to-dry weight, histological alterations and myeloperoxidase activity in a murine model of LPS-induced acute lung injury (ALI). In addition, Western blot analysis that pretreatment with asperuloside remarkably blunted the phosphorylation of inhibitor of nuclear factor kappa-B (IκBα), extracellular signal-related kinases 1 and 2 (ERK1/2), c-Jun. N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) in LPS-stimulated inflammation. These results indicate that asperuloside exerts its anti-inflammatory effect in correlation with inhibition of a pro-inflammatory mediator through suppressing nuclear factor kappa-B (NF-κB) nuclear translocation and MAPK phosphorylation in a dose-dependent manner.

A phase retrieval method from three interferograms based on normalized vector is proposed to achieve high accuracy and less time computation. It needn’t pre-filtering for the interferograms, which reduces its complexity and shortens the processing time. The difference maps are used to filter out the background intensity after compensating the fluctuation. Then, the normalized vector is used to obtain tested phase distribution with high precision. It is suitable for simple and complex fringes. Moreover, the phase can be correctly extracted when the fluctuation of background intensity and modulation amplitude is existed. The reliability of the algorithm is verified with simulated and experimental data.

In this paper, we reported on the experimental generation of dark pulses from a passively mode-locked fiber laser based on the interaction between the evanescent light and two dimensional material molybdenum disulfide (MoS 2 ) on the microfiber. The MoS 2 nanosheets are prepared through the liquid-phase exfoliation (LPE) method and transferred onto a tapered microfiber by the optical deposition method. The MoS 2 -deposited microfiber is the key mode-locker for dark pulse generation. In experiment, by properly adjusting the polarization controller and pump power, we obtained dark pulses output. The center wavelength of the laser is 1533.4 nm, the interval of the pulse train is 33.3 ns and repetition rate is measured to be 30 MHz.

D(-)-Salicin is a traditional medicine which has been known to exhibit anti-inflammation and other therapeutic activities. The present study aimed to investigate whether D(-)-Salicin inhibited the LPS-induced inflammation in vivo and in vitro. We evaluated the effect of D(-)-Salicin on cytokines (TNF-α, IL-1β, IL-6 and IL-10) in vivo and in vitro by enzyme-linked immunosorbent assay and signaling pathways (MAPKs and NF-κB) in vivo by Western blot. The results showed that D(-)-Salicin markedly decreased TNF-α, IL-1β and IL-6 concentrations and increased IL-10 concentration. In addition, western blot analysis indicated that D(-)-Salicin suppressed the activation of MAPKs and NF-κB signaling pathways stimulated by LPS. To examine whether D(-)-Salicin ameliorated LPS-induced lung inflammation, inhibitors of MAPKs and NF-κB signaling pathways were administrated intraperitoneally to mice. Interference with specific inhibitors revealed that D(-)-Salicin-mediated cytokine suppression was through MAPKs and NF-κB pathways. In the mouse model of acute lung injury, histopathologic examination indicted that D(-)-Salicin suppressed edema induced by LPS. So it is suggest that D(-)-Salicin might be a potential therapeutic agent against inflammatory diseases.

Pasteurellosis caused by Pasteurella multocida manifest often as respiratory infection in farmed small ruminants. Although the incidence of pasteurellosis due to P. multocida mainly takes the form of pneumonia, there is limited information on host factors that play a role in disease pathogenesis in the milieu of host-pathogen interactions. Nuclear factor-erythroid 2 related factor 2 (Nrf-2), a critical regulator for various inflammatory and immune responses by controlling oxidative stress, may play an important role in the processes of inflammation induced by P. multocida. In this study, linalool, a natural compound of the essential oils in several aromatic plant species, elevated nuclear Nrf-2 protein translocation in the A549 lung cell line and in vivo. The P. multocida-induced pro-inflammatory cytokines expression was abrogated by Nrf-2 siRNA. Postponed treatment with linalool decreased lung neutrophil accumulation and enhanced clearance of P. multocida. Furthermore, linalool significantly increased the expression of antioxidant enzymes regulated by Nrf-2 and diminished lung tissue levels of several pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin (IL)-6. In addition, animals treated with linalool had a marked improvement in survival. These findings have uncovered that linalool acts as a novel Nrf-2 activator for a novel therapeutic strategy in pathogen-mediated lung inflammation.

Background Bornyl acetate is a bicyclic monoterpene present in numerous conifer oils. In this study, we aimed at clarifying the potential anti-inflammatory function and mechanism of bornyl acetate by using lipopolysaccharide (LPS)-induced acute lung injury murine model and RAW 264.7 cells. Materials and methods RAW 264.7 cells were pretreated with bornyl acetate 1 h before LPS stimulation and cell-free super supernatants were collected to measure cytokine concentrations. To induce acute lung injury, BALB/c mice were injected intranasally with LPS and treated with bornyl acetate 1 h before LPS stimulation. Seven hours after administration, the bronchoalveolar lavage fluid (BALF) was collected for measuring the cell count and cytokine production. We collected lungs for assaying wet-to-dry weight ratio, myeloperoxidase activity, and histologic changes. The extent of phosphorylation of mitogen-activated protein kinases and nuclear factor κB was detected by Western blot. Results Our results showed that bornyl acetate downregulated the levels of proinflammatory cytokines in vitro and in vivo; reduced the number of total cells, neutrophils, and macrophages in BALF; attenuated the histologic alterations in the lung; decreased the wet-to-dry weight ratio in BALF; and suppressed NF-kappa-B inhibitor alpha, extracellular regulated protein kinases, c-JunN-terminal kinase, p38 mitogen-activated protein kinase activation. Conclusions These findings suggested that bornyl acetate may be developed as a preventive agent for lung inflammatory diseases.

Acute lung injury (ALI), characterized by severe hypoxemia, pulmonary edema and neutrophil accumulation in the lung, is a common clinical problem associated with significant morbidity and mortality in shock, sepsis, ischemia reperfusion, etc.In this study, we aimed at investigating the protective effect of tubeimoside-1 (TBMS1) on inflammation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and a LPS-induced in vivo lung injury model.We evaluated the effect of TBMS1 on LPS-induced production of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in the culture supernatants of RAW 264.7 cells by enzyme-linked immunosorbent assay. LPS (0.5 mg/kg) was instilled intranasally in phosphate-buffered saline to induce ALI, and the severity of pulmonary injury was evaluated 6 h after LPS challenge.TBMS1 significantly inhibited the production of the pro-inflammatory cytokines, TNF-α, IL-6 and IL-1β in vitro and in vivo. Pretreatment with TBMS1 markedly attenuated the development of pulmonary edema, histological severities and inflammatory cells infiltration in mice with ALI. In addition, we further demonstrated that TBMS1 exerts an anti-inflammatory effect in vivo model of ALI through suppression of IκB activation and p38/extracellular signal-regulated kinase mitogen-activated protein kinases signaling in a dose-dependent manner.Overall, our data suggest that TBMS1 inhibits inflammation both in vitro and in vivo, and may be a potential therapeutic candidate for the prevention of inflammatory diseases.

Natural products have been used as potentially important sources of anti-inflammatory drugs. This study examined the effects of pinocembrin against lipopolysaccharide (LPS)-induced endotoxemia to ascertain whether pinocembrin could protect mice from ensuing death. Cytokine responses were also assessed in serum isolated from blood collected at 0, 2, 4, 6, 8, and 24 h after LPS administration of the mice (with or without drug treatment). The results showed that there was a lower production of TNFα, IL-6, and IL-1β in the serum of LPS-challenged mice that had been pre-treated with pinocembrin. In addition, pre-treatment with pinocembrin improved host survival against the LPS-induced lethal endotoxemia. These results suggest that this new flavonoid could potentially be a novel candidate for preventing development/mitigation progression of septic shock.

Prime-O-glucosylcimifugin is an active chromone isolated from Saposhnikovia root which has been reported to have various activities, such as anti-convulsant, anticancer, anti-inflammatory properties. The purpose of this study was to evaluate the effect of prime-O-glucosylcimifugin on acute lung injury (ALI) induced by lipopolysaccharide in mice. BALB/c mice received intraperitoneal injection of Prime-O-glucosylcimifugin 1 h before intranasal instillation (i.n.) of lipopolysaccharide (LPS). Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and interleukin (IL)-6 in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Pulmonary histological changes were evaluated by hematoxylin–eosin, myeloperoxidase (MPO) activity in the lung tissue and lung wet/dry weight ratios were observed. Furthermore, the mitogen-activated protein kinases (MAPK) signaling pathway activation and the phosphorylation of IκBα protein were determined by Western blot analysis. Prime-O-glucosylcimifugin showed promising anti-inflammatory effect by inhibiting the activation of MAPK and NF-κB signaling pathway., Highlights • Prime-O-glucosylcimifugin regulated the expression of TNF-α, IL-1β, IL-6, and IL-10. • Prime-O-glucosylcimifugin inhibited the LPS-induced MAPK and NF-κB activation. • Prime-O-glucosylcimifugin protects mice from LPS-induced acute lung injury.

Imperatorin, a linear furanocoumarin, has many pharmacological effects such as antibacterial, anti-inflammatory and antiviral effects. The purpose of this study was to investigate the effect of Imperatorin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. BALB/c mice were pretreated with Imperatorin 1 h before LPS challenge. We found that the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the bronchoalveolar lavage fluid (BALF) were decreased significantly, and the level of interleukin-10 (IL-10) was up-regulated 8 h after Imperatorin treatment. Pretreatment with Imperatorin (15 or 30 mg/kg) decreased lung wet-to-dry weight (W/D) ratio, the number of inflammatory cells and myeloperoxidase (MPO) activities. Additionally, Imperatorin attenuated lung histopathological changes and significantly inhibited the phosphorylation of IκB, JNK, ERK and p38/MAPK. These findings demonstrate that Imperatorin protects against LPS-induced ALI in mice.

The objective of this study was to test the hypothesis that p-cymene can attenuate acute lung injury induced by lipopolysaccharide (LPS) in vivo. In the mouse model of LPS-induced acute lung injury, intraperitoneal preconditioning with p-cymene resulted in a significant reduction of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), lung water gain, inflammatory cell infiltration, lung tissue myeloperoxidase activity. In addition, p-cymene blocked the phosphorylation of IκBα protein and mitogen-activated protein kinases (MAPK) signaling pathway activation. Histopathologic examination of lung tissue indicated that p-cymene treatment markedly decreased focal thickening, congestion, pulmonary edema, and inflammatory cells infiltration. The results showed that p-cymene had a protective effect on LPS-induced ALI in mice.

Betulin, a naturally occurring triterpene, has shown anti-HIV activity, but details on the anti-inflammatory activity are scanty. In this study, we sought to investigate the effect of Betulin on LPS-induced activation of cell lines with relevance for lung inflammation in vitro and on lung inflammation elicited by either LPS or viable Escherichia coli (E. coli) in vivo. In vitro, Betulin inhibited LPS-induced tumor necrosis factor α (TNF-α) and (interleukin) IL-6 levels and up-regulated the level of IL-10. Also Betulin suppressed the phosphorylation of nuclear factor-κB (NF-κB) p65 protein in LPS-stimulated RAW 264.7 cells. In vivo, Betulin alleviated LPS-induced acute lung injury. Treatment with Betulin diminished pro-inflammatory cytokines, myeloperoxidase activity and bacterial loads in lung tissue during gram-negative pneumonia. Our findings demonstrated that Betulin inhibits pro-inflammatory responses induced by the gram-negative stimuli LPS and E. coli, suggesting that Betulin may represent a novel strategy for the treatment of lung inflammation.

We investigated whether p-synephrine exerts potent anti-inflammatory effects against acute lung injury (ALI) induced by lipopolysaccharide (LPS) in vivo, and we further investigated the inhibitory mechanism of p-synephrine in LPS-induced ALI. Lipopolysaccharide (0.5 mg/kg) was instilled intranasally in phosphate-buffered saline to induce acute lung injury, and 6, 24, and 48 h after LPS was given, bronchoalveolar lavage fluid was obtained to measure pro-inflammatory mediator. We also evaluated the effects of p-synephrine on LPS-induced the severity of pulmonary injury. The phosphorylation of nuclear factor-κB (NF-κB) p65 protein was analyzed by Western blotting. Our data showed that p-synephrine significantly reduced the amount of inflammatory cells, the lung wet-to-dry weight (W/D) ratio, reactive oxygen species, myeloperoxidase activity and enhanced superoxide dismutase (SOD) in mice with LPS-induced ALI. Tumor necrosis factor α and interleukin (IL)-6 concentrations decreased significantly while the concentration of IL-10 was significantly increased after p-synephrine pretreatment. In addition, p-synephrine suppressed not only the phosphorylation of NF-κB but also the degradation of its inhibitor (IκBα). These results suggested that the inhibition of NF-κB activation and the regulation of SOD are involved in the mechanism of p-synephrine’s protection against ALI.