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Amolops putaoensis is a recently described torrent frog species from A. monticola group that is known only from its type locality, northern Myanmar. We compared morphology and mitochondrial DNA sequence data from ten recently collected adult male specimens from the upper Dulong River System in Gongshan County, Yunnan Province, China, to the original description of A. putaoensis. Both datasets strongly supported referring the Chinese specimens to A. putaoensis, extending the known range of this species by approximately 133.7 km distance into China. Molecular phylogenetic analyses recovered A. putaoensis to be closely related to A. aniqiaoensis, A. kohimaensis, A. monticola, and A. adicola. We use the newly collected Chinese specimens to expand the morphological description of the species.

An amendment to this paper has been published and can be accessed via the original article.

Early diagnosis of hepatocellular carcinoma (HCC) lacks highly sensitive and specific protein biomarkers. Proteomics-driven discovery of tumor biomarkers is an important direction for omics study. Here, we described a staged mass spectrometry (MS)-based discovery-verification-validation proteomics workflow to explore serum proteomic biomarkers for HCC early diagnosis in 662 individuals (373 HCC patients and 289 non-HCC patients). Our workflow reproducibly quantified 451serum proteins using a data independent acquisition mass spectrometry (DIA-MS) strategy from discovery cohort, and proteins with significantly altered abundance in HCC were validated as candidates in an independent validation cohort using targeted proteomics based on parallel reaction monitoring (PRM). Machine learning models determined as P4 serum protein-panels (two serum proteomics biomarkers: HABP2, CD163 and two clinical used serum biomarkers: AFP, PIVKA-II) could clearly distinguish HCC patients from LC patients in an independent validation cohort (AUC 0.979, sensitivity 0.925, specificity 0.915), outperforming existing clinical prediction strategies (p

The N6-methyladenosine (m6A) RNA methyltransferase METTL16 is an emerging player in RNA modification landscape and responsible for the deposition of m6A in a few transcripts. AURKA (aurora kinase A) has been confirmed as an oncogene in cancer development including hepatocellular carcinoma (HCC). Nevertheless, it remains unclear whether METTL16 mediated m6A modification of lncRNAs can regulate AURKA activation in cancer progression. Here we aimed to investigate the functional links between lncRNAs and the m6A modification in AURKA signaling and HCC progression. Here we show that LncRNA TIALD (transcript that induced AURKA Lysosomal degradation) was down-regulated in HCC tissues by METTL16 mediated m6A methylation to facilitate its RNA degradation, and correlates with poor prognosis. Functional assays reveal that TIALD inhibits HCC metastasis both in vitro and in vivo. Mechanistically, TIALD directly interacts with AURKA and facilitate its degradation through the lysosomal pathway to inhibited EMT and metastasis of HCC. AURKA’s specific inhibitor alisertib exerts effective therapeutic effect on liver cancer with low TIALD expression, which mightprovide a new insight into HCC therapy. Our study uncovers a negative functional loop of METTL16-TIALD-AURKA axis, and identifies a new mechanism for METTL16 mediated m6A-induced decay of TIALD on AURKA signaling in HCC progression, which may provide potential prognostic and therapeutic targets for HCC.

Acute alcoholic liver injury is an important health problem worldwide. Apples are rich in many nutrients and have a variety of biological activities, including antioxidant, anti-inflammatory, and anti-tumor, and therefore have the potential to be a natural protective agent against acute alcoholic liver injury. This study evaluated the protective effect of apples (Malus pumila Mill) on acute alcoholic liver injury in rats. Male Wistar rats were randomly assigned to four groups: a control group (C), a control group that was fed fresh apples (CA), an ethanol-treated group (E), and an ethanol-treated group that was fed fresh apples (EA). Rats were treated with continuous forced gavage with 40° ethanol (4 mL/kg) for one week to simulate human alcoholism. Liver injury was assessed based on changes in the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as histological analysis. The protective effect of apples on alcoholic liver injury was assessed in terms of alcohol metabolism, oxidative stress, inflammation, lipid synthesis, and tissue fibrosis. The results showed that apple consumption protected against alcoholic liver injury, as indicated by the decreased serum ALT and AST levels, reduced liver lipid peroxidation, and improved liver histopathology. Moreover, apple consumption increased antioxidant enzyme activity and reduced inflammatory cytokine levels in the liver. These findings suggest that apple consumption may have a protective effect against acute ethanol-induced liver injury in rats, possibly through its antioxidant and anti-inflammatory properties.

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Purpose:Intratumoral hepatitis B virus (HBV) integrations and mutations are related to hepatocellular carcinoma (HCC) progression. Circulating cell-free DNA (cfDNA) has shown itself as a powerful noninvasive biomarker for cancer. However, the HBV integration and mutation landscape on cfDNA remains unclear.Experimental Design:A cSMART (Circulating Single-Molecule Amplification and Resequencing Technology)-based method (SIM) was developed to simultaneously investigate HBV integration and mutation landscapes on cfDNA with HBV-specific primers covering the whole HBV genome. Patients with HCC (n = 481) and liver cirrhosis (LC; n = 517) were recruited in the study.Results:A total of 6,861 integration breakpoints including TERT and KMT2B were discovered in HCC cfDNA, more than in LC. The concentration of circulating tumor DNA (ctDNA) was positively correlated with the detection rate of these integration hotspots and total HBV integration events in cfDNA. To track the origin of HBV integrations in cfDNA, whole-genome sequencing (WGS) was performed on their paired tumor tissues. The paired comparison of WGS data from tumor tissues and SIM data from cfDNA confirmed most recurrent integration events in cfDNA originated from tumor tissue. The mutational landscape across the whole HBV genome was first generated for both HBV genotype C and B. A region from nt1100 to nt1500 containing multiple HCC risk mutation sites (OR > 1) was identified as a potential HCC-related mutational hot zone.Conclusions:Our study provides an in-depth delineation of HBV integration/mutation landscapes at cfDNA level and did a comparative analysis with their paired tissues. These findings shed light on the possibilities of noninvasive detection of virus insertion/mutation.

Background Hepatocellular carcinoma (HCC) generally arises from a background of liver cirrhosis (LC). Patients with cirrhosis and suspected HCC are recommended to undergo serum biomarker tests and imaging diagnostic evaluation. However, the performance of routine diagnostic methods in detecting early HCC remains unpromising. Methods Here, we conducted a large-scale, multicenter study of 1675 participants including 490 healthy controls, 577 LC patients, and 608 HCC patients from nine clinical centers across nine provinces of China, profiled gene mutation signatures of cell-free DNA (cfDNA) using Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) through detecting 931 mutation sites across 21 genes. Results An integrated diagnostic model called “Combined method” was developed by combining three mutation sites and three serum biomarkers. Combined method outperformed AFP in the diagnosis of HCC, especially early HCC, with sensitivities of 81.25% for all stages and 66.67% for early HCC, respectively. Importantly, the integrated model exhibited high accuracy in differentiating AFP-negative, AFP-L3-negative, and PIVKA-II-negative HCCs from LCs.

Background In insects, the chemosensory system is crucial in guiding their behaviors for survival. Plagiodera versicolora (Coleoptera: Chrysomelidae), is a worldwide leaf-eating forest pest in salicaceous trees. There is little known about the chemosensory genes in P. versicolora. Here, we conducted a transcriptome analysis of larvae heads in P. versicolora. Results In this study, 29 odorant binding proteins (OBPs), 6 chemosensory proteins (CSPs), 14 odorant receptors (ORs), 13 gustatory receptors (GRs), 8 ionotropic receptors (IRs) and 4 sensory neuron membrane proteins (SNMPs) were identified by transcriptome analysis. Compared to the previous antennae and foreleg transcriptome data in adults, 12 OBPs, 2 CSPs, 5 ORs, 4 IRs, and 7 GRs were newly identified in the larvae. Phylogenetic analyses were conducted and found a new candidate CO2 receptor (PverGR18) and a new sugar receptor (PverGR23) in the tree of GRs. Subsequently, the dynamic expression profiles of various genes were analyzed by quantitative real-time PCR. The results showed that PverOBP31, OBP34, OBP35, OBP38, and OBP40 were highly expressed in larvae, PverOBP33 and OBP37 were highly expressed in pupae, and PverCSP13 was highly expressed in eggs, respectively. Conclusions We identified a total of 74 putative chemosensory genes based on a transcriptome analysis of larvae heads in P. versicolora. This work provides new information for functional studies on the chemoreception mechanism in P. versicolora.

Two types of high power alternating current (AC) locomotive in China are prone to serious high-order polygonal wear, which has significant negative effects on the operation of locomotives. This study investigates factors influencing polygonal wear in locomotive wheels and determines methods of minimizing operation damage. We designed experiments to analyze the process of polygonization formation of wheels to identify the key influencing factors, finding that natural vibration of wheelsets is the central inherent factor of wheel polygonization and that these vibrations can be easily stimulated by wheel or rail irregularities. We found that poor re-profiling quality is the key external factor in these irregularities. The wheelset bending resonance is activated when the remaining wheel polygonal wear has a wavelength of 200 mm in the 1/3 octave band, in turn leading to significant increases of wheel polygonal wear. In this study, we review a new wheelset design that can mitigate and/or eliminate the polygonal wheel wear due to increased stiffness in wheel bending. We evaluate the potential capacity of the newly designed wheelset and propose two proven effective measures to further improve the wheel re-profiling quality for polygonal wear.

Inactivating mutations in the liver kinase B1 (LKB1) tumor suppressor gene underlie Peutz-Jeghers syndrome (PJS) and occur frequently in various human cancers. We previously showed that LKB1 regulates centrosome duplication via PLK1. Here, we report that LKB1 further helps to maintain genomic stability through negative regulation of survivin, a member of the chromosomal passenger complex (CPC) that mediates CPC targeting to the centromere. We found that loss of LKB1 led to accumulation of misaligned and lagging chromosomes at metaphase and anaphase and increased the appearance of multi- and micro-nucleated cells. Ectopic LKB1 expression reduced these features and improved mitotic fidelity in LKB1-deficient cells. Through pharmacological and genetic manipulations, we showed that LKB1-mediated repression of survivin is independent of AMPK, but requires p53. Consistent with the key influence of LKB1 on survivin expression, immunohistochemical analysis indicated that survivin is highly expressed in intestinal polyps from a PJS patient. Lastly, we reaffirm a potential therapeutic avenue to treat LKB1-mutated tumors by demonstrating the increased sensitivity to survivin inhibitors of LKB1-deficient cells.

As a critical transmitter, the compact 532 nm lasers operating on high repetition and narrow pulse widths have been used widely for airborne or space-borne laser active remote sensing. We developed a free space pumped TEM00 mode sub-nanosecond 532 nm laser that occupied a volume of less than 125 mm × 50 mm × 40 mm (0.25 liters). The fundamental 1064 nm laser consists of a passively Q-switched composite crystal microchip laser and an off-axis, two-pass power amplifier. The pump sources were two single-emitter semiconductor laser diodes (LD) of 808 nm with a maximum continuous wave (CW) power of 10 W each. The average power of fundamental 1064 nm laser was 1.26 W with the laser operating at 16 kHz repetition rates, and 857ps pulse widths. Since the beam distortion would be severe in microchip lasers in terms of the increase in heat load, for obtaining a high beam quality of 532 nm, the beam distortion was compensated by adjusting the distribution of pumping beam in our experiment of fundamental amplification. Furthermore, better than 0.6 W average power, 770 ps, beam quality of M2 ＜1.2, and 16 kHz pulse output at 532 nm was obtained by a Type I LiB3O5 (LBO) crystal in the critical phase matching (CPM) regime for second harmonic generation (SHG).

The femtosecond-pulsed laser processed black silicon (fs-bSi) features high absorptance in a wide spectral range but suffers from high amount of laser induced damage as compared to bSi fabricated by other methods. Here, we aim to minimize the charge carrier recombination in the fs-bSi caused by laser damage as indicated by the sub-bandgap absorption and as quantified by the carrier lifetime, while maintaining high absorption in the above-bandgap. The effect of the laser parameters, including the focal position, the average power, and the scan speed are systematically studied by characterizing the surface morphology, the absorptance spectra, and the minority-carrier recombination lifetime. For the surface passivation of fs-bSi we use the well-established atomic layer deposited (ALD) Al2O3. The results show that with the tailored laser parameters, high average absorptance of about 96% in the visible range and minority carrier lifetime of 54 μs at the injection level of Δn = 1 ∙ 1015 cm−3 can be obtained simultaneously. This work paves the way towards high-performance broadband optoelectronic devices based on surface passivated fs-bSi.

Positive resection margin frequently exists in breast-conserving treatment (BCT) of early-stage breast cancer, and insufficient therapeutic efficacy is common during radiotherapy (RT) in advanced breast cancer patients. Moreover, a multimodal nanotherapy platform is urgently required for precision cancer medicine. Therefore, a biodegradable cyclic RGD pentapeptide/hollow virus-like gadolinium (Gd)-based indocyanine green (RHV-Gd@ICG) nanoprobe is developed to improve fluorescence image-guided surgery and breast cancer RT efficacy. RHV-Gd exhibits remarkably improved aqueous stability, tumor retention, and target specificity of ICG, and achieves outstanding magnetic resonance/second near-infrared (NIR-II) window multimodal imaging in vivo. The nanoprobe-based NIR-II fluorescence image guidance facilitates complete tumor resection, improves the overall mouse survival rate, and effectively discriminates between benign and malignant breast tissues in spontaneous breast cancer transgenic mice (area under the curve = 0.978; 95% confidence interval: 0.952, 1.0). Moreover, introducing the nanoprobe to tumors generated more reactive oxygen species under X-ray irradiation, improved RT sensitivity, and reduced mouse tumor progression. Notably, the nanoprobe is biodegradable in vivo and exhibits accelerated bodily clearance, which is expected to reduce the potential long-term inorganic nanoparticle toxicity. Overall, the nanoprobe provides a basis for developing precision breast cancer treatment strategies.

In this paper, a comparative study of the very-high-cycle fatigue (VHCF) behavior of railway wheel steel under axial loading and rolling contact loading was conducted. Fatigue tests were performed with an ultrasonic fatigue test machine under axial loading, and the fracture surfaces from the fatigue tests and shattered rims taken from the failed railway wheels were observed. The wheel steel under axial loading presents a VHCF behavior with Mode I crack, and that under rolling contact loading is a VHCF behavior with mix Mode II-III crack. For the VHCF behavior with Mode I crack ,surface and interior crack initiation occurred with equal probability at both low and high stress levels and produced a dual linear S-N curve since the value of fatigue limits for the surface and interior crack initiation are close. For the VHCF behavior with mix Mode II-III crack, cracks were initiated from the interior Al O inclusion and the fatigue life was beyond 10 cycles. Fatigue bands were observed on the fracture surface under rolling contact loading. The ferrite nanograins formed due to the stress state of shear plastic strain with a large compressive stress. The formed nanograins were softer than the matrix caused by the redistribution of the carbon.

This study aimed to explore predictors of bone metastasis (BM) of esophageal carcinoma (EC) and factors affecting the prognosis of EC with BM (ECBM).We retrospectively studied the data of EC patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. Logistic regression analysis was used to analyze the risk factors of BM. Cox regression and Fine and Gray's competing risk regression were performed to identify prognostic factors associated with all-cause and cancer-specific death, respectively. The Kaplan-Meier method was used to assess survival.After exclusion, 8,916 patients were eligible, of whom 462 (5.2%) had ECBM. Independent risk factors of BM were age65 years, male sex, stage T1, advanced N stage, and non-bone organ metastases. For EC, the median survival time (MST) was 17 months, and the 3- and 5-year survival rates were 31.6% and 23.3%, respectively; meanwhile, for BM, the MST was 5 months, and the 3- and 5-year survival rates were 2% and 1%, respectively. Adenocarcinoma, stage T2, the absence of non-bone organ metastases, and combined radiotherapy and chemotherapy were associated with a reduced risk of all-cause death in ECBM patients. Stage T2, the absence of non-bone organ metastases, and combined radiotherapy and chemotherapy were associated with a decreased risk of cancer-specific death in ECBM patients.Although rare, BM severely impairs the prognosis of EC. BM predictors and factors influencing the prognosis of ECBM may help distinguish high-risk patients with BM and assess survival in ECBM patients.

BACKGROUND Oesophagogastric anastomosis is mainly complicated by its tediousness. We hope to modify an oesophagogastric anastomotic technique that simplifies anastomosis. METHODS We conducted a retrospective analysis of 57 cases executed using reverse-puncture anastomotic (RPA) technique and 64 cases of manual purse anastomosis (MPA) technique for robot-assisted minimally invasive oesophagectomy (RAMIE). Baseline characteristics and perioperative outcomes were analysed. RESULTS There were no significant differences between the 2 groups with regards to demographic data and clinical features. All patients had R0 resection. Relative to MPA, RPA group experienced significantly shorter operation times (232.5 ± 33.84 min vs. 262.3 ± 83.94 min, p = 0.038).RPA group patients had shorter anastomotic times relative to MPA group patients (10.5 ± 3.4 min vs. 18.3 ± 4.1 min, p = 0.014). No adverse events were observed. CONCLUSIONS Reverse-puncture anastomosis is safe, feasible in RAMIE. This approach has the potential to efficiently shorten the anastomotic time and ensure safe operation.

BackgroundClinical staging is essential for clinical decisions but remains imprecise. We purposed to construct a novel survival prediction model for improving clinical staging system (cTNM) for patients with esophageal adenocarcioma (EAC).MethodsA total of 4180 patients diagnosed with EAC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and included as the training cohort. Significant prognostic variables were identified for nomogram model development using multivariable Cox regression. The model was validated internally by bootstrap resampling, and then subjected to external validation with a separate cohort of 886 patients from 2 institutions in China. The prognostic performance was measured by concordance index (C-index), Akaike information criterion (AIC) and calibration plots. Different risk groups were stratified by the nomogram scores.ResultsA total of six variables were determined related with survival and entered into the nomogram construction. The calibration curves showed satisfied agreement between nomogram-predicted survival and actual observed survival for 1-, 3-, and 5-year overall survival. By calculating the AIC and C-index values, our nomogram presented superior discriminative and risk-stratifying ability than current TNM staging system. Significant distinctions in survival curves were observed between different risk subgroups stratified by nomogram scores.ConclusionThe established and validated nomogram presented better risk-stratifying ability than current clinical staging system, and could provide a convenient and reliable tool for individual survival prediction and treatment strategy making.

Two new compounds 6,7-dimethoxy-2-[2-(2′-hydroxyphenyl)ethyl]chromone (1) and 6,7-dimethoxy-2-[2-(4′-hydroxyphenyl)ethenyl]chromone (2), together with ten known 2-(2-phenylethyl)chromones (3–12) were isolated from the resinous wood of Aquilaria sinensis (Lour.) Gilg. Their structures were elucidated by detailed IR, MS, NMR spectroscopic analyses, and comparison with reported. The absolute configuration of 3 was confirmed by Cu Kα X-ray crystallographic experiment, and the X-ray crystallographic data of 3 were firstly reported. Compounds 2, 8, 10, and 11 exhibited strong ABTS•+ radical scavenging activity, with IC50 values of 12.3, 16.5, 12.1, and 34.7 μM, respectively.

Background and Objectives: Postoperative major complications after esophageal cancer resection vary and may significantly impact long-term outcomes. This study aimed to build an individualized nomogram to predict post-esophagectomy major morbidity. Methods: This retrospective study included 599 consecutive patients treated at a single center between January 2017 and April 2019. Of them, 420 and 179 were assigned to the model development and validation cohorts, respectively. Major morbidity predictors were identified using multiple logistic regression. Model discrimination and calibration were evaluated by validation. Regarding clinical usefulness, we examined the net benefit using decision curve analysis. Results: The mean age was 64 years; 79% of the patients were male. The most common comorbidities were hypertension, diabetes mellitus, and stroke history. The 30-day postoperative major morbidity rate was 24%. Multivariate logistic regression analysis showed that age, smoking history, coronary heart disease, dysphagia, body mass index, operation time, and tumor size were independent risk factors for surgery-associated major morbidity. Areas under the receiver-operating characteristic curves of the development and validation groups were 0.775 (95% confidence interval, 0.721–0.829) and 0.792 (95% confidence interval, 0.709–0.874), respectively. In the validation cohort, the nomogram showed good calibration. Decision curve analysis demonstrated that the prediction nomogram was clinically useful. Conclusion: Morbidity models and nomograms incorporating clinical and surgical data can be used to predict operative risk for esophagectomy and provide appropriate resources for the postoperative management of high-risk patients.

Funding Information: This work is supported by the National Natural Science Foundation of China under grant no. 6207030573 , the National Basic Research Program of China (973 Program) under grant no. 2012CB934200 , and the Specialized Research Fund for the Doctoral Program of Higher Education under grant no. 20130071110018 . Publisher Copyright: © 2021 Elsevier B.V. Copyright: Copyright 2021 Elsevier B.V., All rights reserved. The NO2 sensing performance of a special lateral photovoltaic self-powered gas sensor based on the N-hyperdoped microstructured silicon (N-Si) is systematically studied under the different light illumination. The dependence of sensing characteristics on light intensity and wavelength is obtained, respectively. Results show that the sensing properties can be changed effectively by the different intensities and wavelengths, suggesting that a multidimensional regulation/optimization for the sensing characteristics is possible by light. More interestingly, the light with wavelength of 940 nm and intensity of ∼18 μW/cm2 could bring a comprehensive optimization for gas sensing, under which the N-Si sensor exhibits the excellent overall performance with simultaneously the low light power needed, good gas response, high sensitivity, wide detectable range and short response time at room temperature.

The near-infrared fluorescence imaging has been integrated into the operating room to guide tumor resection, potentially reducing the positive margin rates in breast-conserving surgery (BCS). Relative to the widely used first near-infrared fluorescence imaging, imaging in the second near-infrared (NIR-II) region possesses higher contrast and deeper tissue penetration, particularly in the NIR-IIb window, offering many new opportunities for imaging-guided BCS. Here, we fabricated the c(RGDfC) functionalized erbium-based rare-earth nanoparticles (ErNPs@cRGD) with superior optical property in NIR-IIb region. Owing to deeper tissue penetration and efficient tumor targeting, ErNPs@cRGD-based NIR-IIb fluorescence imaging achieved enhanced signal-to-background ratios in tumor visualization, which was able to guide more complete tumor resection, identify multiple microtumors and distinguish malignant lesions from normal tissues in various mice models. Based on these, this NIR-IIb imaging strategy for surgical navigation can significantly reduce positive margin rates and improve prognosis, laying a foundation for the clinical resection of breast cancer.

The wide Mg alloy sheets produced by hot extrusion usually can easily form an inhomogeneous texture, resulting in anisotropic mechanical properties and poor formability. However, few studies have been carried out on the bulk texture investigation at different areas of as-extruded Mg alloy sheets, especially the Mg alloys with different alloying elements. In this work, the effect of Al on the bulk texture and mechanical properties at different areas for three wide Mg-Al-Zn alloy sheets with different Al contents (Mg-3Al-0.5Zn, Mg-8Al-0.5Zn and Mg-9Al-0.5Zn) are mainly investigated by neutron diffraction. The results showed that a strong and uneven basal texture was formed in the Mg-3Al-0.5Zn sheet. Meanwhile, the intensity of the basal texture was significantly weakened due to the numerous fine precipitates of Mg17Al12 particles, with the Al content increasing, which hinder the grain growth during extrusion, while fine recrystallized grains have a more random orientation. The enhanced tensile properties in Mg-8Al-0.5Zn and Mg-9Al-0.5Zn alloy sheets are ascribed to the cooperation effect of a refined microstructure, precipitates and weakened basal texture. Among the three Mg alloy sheets, the Mg-8Al-0.5Zn alloy sheet has a yield strength of about 270 MPa, an ultimate tensile strength of about 330 MPa and ultimate elongation of about 16% in the extrusion direction, which possesses the most excellent comprehensive mechanical properties.

Background. Q-1 is a novel compound extracted from the Miao medicine Tiekuaizi. Although Q-1 is known to be a coumarin derivative, its structure has not been deposited in the ACX library. Our previous study showed that Q-1 inhibits the activity of inflammatory cells. This study explores the efficacy of Q-1 in regulating rheumatoid arthritis (RA). The findings show that Q-1 acts through the NF-κB signaling pathway. Methods. The effects of Q-1 were explored using a bovine type II collagen-induced arthritis (CIA) rat model. The CIA rats were intragastrically administered with high (30 mg·kg−1) or low (15 mg·kg−1) doses of Q-1. The control group was administered with an equal volume of drinking water, while the positive control group was administered with Tripterygium glycoside (9.45 mg·kg−1) for 28 consecutive days. The arthritis indices and ankle joint swelling rates were determined. The levels of IL-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1) in serum and sialic acid (SA) in liver homogenate were determined by enzyme-linked immunosorbent assay (ELISA). The pathological features of the ankle joint were analyzed by hematoxylin and eosin (HE) staining. The IκB, P-IκB, P65, and P-P65 protein levels in synovial tissue were assayed by western blotting. Results. The arthritis index, ankle joint swelling rate, IL-1β, IL-6, and MCP-1 levels in serum, SA level in liver tissue, and IκB, P-IκB, P65, and P-P65 protein levels in synovial tissues were significantly higher ( P < 0.01 ) in the CIA model compared to the control group. RA was successfully replicated by the CIA model, as shown by the joint swelling results and histopathological sections of the ankle. Notably, all the above indicators decreased significantly ( P < 0.01 ) after treatment with Q-1 compared to the model. In addition, animals treated with Q-1 showed lower inflammation in the ankle joints than the model rats. Conclusion. The findings indicate that Q-1 effectively inhibited RA in rats by downregulating IκB, P-IκB, P65, and P-P65, inhibiting the excessive release of inflammatory factors, and inhibiting the overactivation of the NF-κB signaling pathway.

Yellowgenes are thought to be involved in the melanin biosynthetic pathway and play a crucial role in pigmentation reactions in insects. However, little research has been done onyellowgenes in lepidopteran pests. To clarify the function of one of theyellowgenes (yellow-y) inSpodoptera litura, we cloned the full-length ofyellow-y, and investigated its spatial and temporal expression profiles by quantitative real-time PCR (qPCR). It revealed thatyellow-ywas highly expressed in larva of fourth, fifth, and sixth instars, as well as in epidermis (Ep), fat bodies (FB), Malpighian tubes (MT), and midguts (MG) of the larvae; whereas it was expressed in very low levels in different tissues of adults, and was almost undetected in pupa. This expression profile suggests an important role ofyellow-yin larvae, minor role in adults, and no role in pupae. To confirm this, we disruptedyellow-yusing the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system, and obtained G0 insects with mutation inyellow-y. The mutation inyellow-yclearly rendered the larvae body, a color yellower than that of wide type insects, and in addition, the mutation resulted in abnormal segmentation and molting for older larvae. The mutation ofyellow-yalso made various adult tissues (antennae, proboscis, legs, and wings) yellowish. However, the mutation had no effect on pigmentation of the pupal cuticle. Taken together, our study clearly demonstrated the role ofyellow-ynot only in the body pigmentation of larvae and adults, and but also in segmentation and molting of larvae, providing new insights into the physiology of larval development, as well as a useful marker gene for genome editing based studies.

Background Q-1 is a novel compound extracted from the Miao medicine Tiekuaizi. Although Q-1 is known to be a coumarin derivative, its structure has not been deposited in the ACX library. Our previous study showed that Q-1 inhibits the activity of inflammatory cells. This study explores the efficacy of Q-1 in regulating rheumatoid arthritis (RA). The findings show that Q-1 acts through the NF-κB signaling pathway. Methods The effects of Q-1 were explored using a bovine type II collagen-induced arthritis (CIA) rat model. The CIA rats were intragastrically administered with high (30 mg·kg−1) or low (15 mg·kg−1) doses of Q-1. The control group was administered with an equal volume of drinking water, while the positive control group was administered with Tripterygium glycoside (9.45 mg·kg−1) for 28 consecutive days. The arthritis indices and ankle joint swelling rates were determined. The levels of IL-1β, IL-6, monocyte chemoattractant protein-1 (MCP-1) in serum and sialic acid (SA) in liver homogenate were determined by enzyme-linked immunosorbent assay (ELISA). The pathological features of the ankle joint were analyzed by hematoxylin and eosin (HE) staining. The IκB, P-IκB, P65, and P-P65 protein levels in synovial tissue were assayed by western blotting. Results The arthritis index, ankle joint swelling rate, IL-1β, IL-6, and MCP-1 levels in serum, SA level in liver tissue, and IκB, P-IκB, P65, and P-P65 protein levels in synovial tissues were significantly higher (P < 0.01) in the CIA model compared to the control group. RA was successfully replicated by the CIA model, as shown by the joint swelling results and histopathological sections of the ankle. Notably, all the above indicators decreased significantly (P < 0.01) after treatment with Q-1 compared to the model. In addition, animals treated with Q-1 showed lower inflammation in the ankle joints than the model rats. Conclusion The findings indicate that Q-1 effectively inhibited RA in rats by downregulating IκB, P-IκB, P65, and P-P65, inhibiting the excessive release of inflammatory factors, and inhibiting the overactivation of the NF-κB signaling pathway.

Background Current preoperative staging for lymph nodal status remains inaccurate. The purpose of this study was to build an artificial neural network (ANN) model to predict pathologic nodal involvement in clinical stage I-II esophageal squamous cell carcinoma (ESCC) patients and then validated the performance of the model. Methods A total of 523 patients (training set: 350; test set: 173) with clinical staging I-II ESCC who underwent esophagectomy and reconstruction were enrolled in this study. Their post-surgical pathological results were assessed and analysed. An ANN model was established for predicting pathologic nodal positive patients in the training set, which was validated in the test set. A receiver operating characteristic (ROC) curve was also created to illustrate the performance of the predictive model. Results Of the enrolled 523 patients with ESCC, 41.3% of the patients were confirmed pathologic nodal positive (216/523). The ANN staging system identified the tumour invasion depth, tumour length, dysphagia, tumour differentiation and lymphovascular invasion (LVI) as predictors for pathologic lymph node metastases. The C-index for the ANN model verified in the test set was 0.852, which demonstrated that the ANN model had a good predictive performance. Conclusions The ANN model presented good performance for predicting pathologic lymph node metastasis and added indicators not included in current staging criteria and might help improve the staging strategies.

Yellow genes are thought to be involved in the melanin biosynthetic pathway and play a crucial role in pigmentation reactions in insects. However, little research has been done on yellow genes in lepidopteran pests. To clarify the function of one of the yellow genes (yellow-y) in Spodoptera litura, we cloned the full-length of yellow-y, and investigated its spatial and temporal expression profiles by quantitative real-time PCR (qPCR). It revealed that yellow-y was highly expressed in larva of fourth, fifth, and sixth instars, as well as in epidermis (Ep), fat bodies (FB), Malpighian tubes (MT), and midguts (MG) of the larvae; whereas it was expressed in very low levels in different tissues of adults, and was almost undetected in pupa. This expression profile suggests an important role of yellow-y in larvae, minor role in adults, and no role in pupae. To confirm this, we disrupted yellow-y using the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system, and obtained G0 insects with mutation in yellow-y. The mutation in yellow-y clearly rendered the larvae body, a color yellower than that of wide type insects, and in addition, the mutation resulted in abnormal segmentation and molting for older larvae. The mutation of yellow-y also made various adult tissues (antennae, proboscis, legs, and wings) yellowish. However, the mutation had no effect on pigmentation of the pupal cuticle. Taken together, our study clearly demonstrated the role of yellow-y not only in the body pigmentation of larvae and adults, and but also in segmentation and molting of larvae, providing new insights into the physiology of larval development, as well as a useful marker gene for genome editing based studies.

Silicon has been studied as a room-temperature material for electrical-based gas sensing but the sensing performance after surface passivation or natural aging is unacceptable. In the present work, we report that for a gas sensor based on the femtosecond-laser structured silicon hyperdoped with sulfur, the gas sensing performance after long-term aging can be significantly enhanced by using a photovoltaic sensing mechanism. After sensor aging, the recorded response/recovery time is 478/2550 s in response to 50 ppm NH3. In comparison, by using the new mechanism, the response/recovery time is much decreased and the shortest is recorded as 292/930 s. Moreover, the relative gas response could be increased by nearly 2 orders of magnitude. Even at a dryer environment where the gas adsorption/desorption process could take hours long, a much enhanced and rapid response is available in the same way. The enhanced sensing performance could be controlled by the bias voltage or by the light density. The results show that for the aged silicon surface, it can also be a potential gas sensing material through different working principles.

Summary Glucosinolates (GSs) are sulfur-containing secondary metabolites characteristic of cruciferous plants [ 1 , 2 ]. Their breakdown products, isothiocyanates (ITCs), are released following tissue disruption by insect feeding or other mechanical damages [ 3 , 4 ]. ITCs repel and are toxic to generalist herbivores, while specialist herbivores utilize the volatile ITCs as key signals for localizing host plants [ 5 , 6 ]. However, the molecular mechanisms underlying detection of ITCs remain open. Here, we report that in the diamondback moth Plutella xylostella, a crucifer specialist, ITCs indeed drive the host preference for Arabidopsis thaliana, and the two olfactory receptors Or35 and Or49 are essential for this behavior. By performing gene expression analyses, we identified 12 (out of 59 in total) female-biased Ors, suggesting their possible involvement in oviposition choice. By ectopically expressing these Ors in Xenopus oocytes and screening their responses with 49 odors (including 13 ITCs, 25 general plant volatiles, and 11 sex pheromone components), we found that Or35 and Or49 responded specifically to three ITCs (iberverin, 4-pentenyl ITC, and phenylethyl ITC). The same ITCs also exhibited highest activity in electroantennogram recordings with female antennae and were the strongest oviposition stimulants. Knocking out either Or35 or Or49 via CRISPR-Cas9 resulted in a reduced oviposition preference for the ITCs, while double Or knockout females lost their ITC preference completely and were unable to choose between wild-type A. thaliana and a conspecific ITC knockout plant. We hence conclude that the ITC-based oviposition preference of the diamondback moth for its host A. thaliana is governed by the cooperation of two highly specific olfactory receptors.