Comparative Proteomics Identified EXOSC1 as a Target Protein of Anticancer Peptide LVTX-8 in Nasopharyngeal Carcinoma Cells.

Nasopharyngeal carcinoma (NPC) is a prevalent malignancy that usually occurs among the nose and throat. Due to mild initial symptoms, most patients are diagnosed in the late stage, and the recurrence rate of tumors is high, resulting in many deaths every year. Traditional radiotherapy and chemotherapy are prone to causing drug resistance and significant side effects. Therefore, searching for new bioactive drugs including anticancer peptides is necessary and urgent. LVTX-8 is a peptide toxin synthesized from the cDNA library of the spider Lycosa vittata, which is consisting of 25 amino acids. In this study, a series of in vitro cell experiments such as cell toxicity, colony formation, and cell migration assays were performed to exam the anticancer activity of LVTX-8 in NPC cells (5-8F and CNE-2). The results suggested that LVTX-8 significantly inhibited cell proliferation and migration of NPC cells. To find the potential molecular targets for the anticancer capability of LVTX-8, high-throughput proteomic and bioinformatics analysis were conducted on NPC cells. The results identified EXOSC1 as a potential target protein with significantly differential expression levels under LVTX-8+/LVTX-8- conditions. The results in this research indicate that spider peptide toxin LVTX-8 exhibits significant anticancer activity in NPC, and EXOSC1 may serve as a target protein for its anticancer activity. These findings provide a reference for the development of new therapeutic drugs for NPC and offer new ideas for the discovery of biomarkers related to NPC diagnosis. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (https://proteomecentral.proteomexchange.org) via the iProX partner repository with the data set identifier PXD050542.

Extent of surgery for unilateral papillary thyroid cancer with nonsuspicious contralateral nodules by ultrasound.

BACKGROUND: The discussion about surgical treatment of patients with papillary thyroid cancer(PTC) has been an ongoing issue, which is mainly focused on characteristics of tumor, but rarely on nonsuspicious contralateral nodules. We aimed to compare recurrence-free survival(RFS)/progression-free survival(PFS) of unilateral PTC patients with nonsuspicious contralateral nodules after different extents of surgery. METHODS: Unilateral PTC patients with nonsuspicious contralateral nodules underwent surgery from 2015 to 2017 were enrolled. The association between surgical extent and RFS/PFS was analyzed by Kaplan-Meier method and Cox proportional hazards model. RESULTS: A total of 1293 PTC patients (595[46.0%]TT,523[40.4%]lobectomy+nodule enucleation(LNE),175[13.5%]lobectomy) were analyzed. Patients with a greater surgical extent were more likely to be older, have a greater multifocality of the tumor and contralateral nodules, larger contralateral nodules and primary tumors, and more micro extrathyroidal extension (P < 0.05). After a median follow-up of 45 months, significant growth(>3 mm) was identified in 24 (4.6%) and 19 (10.9%) patients in the LNE and lobectomy group, 7 (1.2%), 14 (2.7%) and 11 (6.3%) structural recurrences and 7 (1.2%), 11 (2.1%) and 7 (4.0%) progression in disease were identified in the TT, LNE and lobectomy groups, respectively. Unadjusted and adjusted RFS/PFS were significantly worse for patients treated with lobectomy than for those who underwent LNE or TT(3-year RFS, 95.5%, 98.2% vs. 99.0%; 3-year PFS, 97.9%, 98.9% vs. 99.0%, P < 0.05), but difference in PFS between LNE and TT lost statistical significance (unadjusted P = 0.226, adjusted P = 0.150). CONCLUSIONS: Due to subtle changes in nodules and acceptable prognosis, lobectomy is a considerable option for unilateral PTC patients with nonsuspicious nodules, when a similar prognosis to TT is expected, LNE may be an effective alternative to optimize quality of life.

Computational Screening of Promising Deep-Ultraviolet Light Emitters.

Deep-ultraviolet (DUV) light sources are technologically highly important, but DUV light-emitting materials are extremely rare; AlN and its alloys are the only materials known so far, significantly limiting the chemical and structural spaces for materials design. Here, we perform a high-throughput computational search for DUV light emitters based on a set of carefully designed screening criteria relating to the sophisticated electronic structure. In this way, we successfully identify 5 promising material candidates that exhibit comparable or higher radiative recombination coefficients than AlN, including BeGeN2, Mg3NF3, KCaBr3, KHS, and RbHS. Further, we unveil the unique features in the atomic and electronic structures of DUV light emitters and elucidate the fundamental genetic reasons why DUV light emitters are extremely rare. Our study not only guides the design and synthesis of efficient DUV light emitters but also establishes the genetic nature of ultrawide-band-gap semiconductors in general.

A frogspawn inspired twin Mo2C/Ni composite with a conductive fibrous network as a robust bifunctional catalyst for advanced anion exchange membrane electrolyzers.

Anion exchange membrane water electrolysis (AEMWE) is considered one of the most cost-effective methods for producing green hydrogen. However, the performance of AEMWE is still restrained by the slow reaction kinetics and poor ion/electron transport of catalysts. Herein, inspired by frogspawn, Mo2C nanoparticles coupled with Ni were in situ embedded into a N-doped porous carbon nanofiber network (Mo2C/NCNTs@Ni) by chemical crosslinking electrospinning combined with carbonization. The unique bionic structure can guarantee favorable overall structural flexibility and fast ion/electron transport kinetics. As a result of the robust hydrogen binding energy of Mo2C, as well as the synergistic impact between Ni and Mo2C nanoparticles and the conductive network resembling frogspawn, the catalyst developed demonstrates excellent performance in both the HER and OER. When employed as a bifunctional catalyst in water electrolysis, Mo2C/NCNTs@Ni delivers overpotentials of 155 mV and 320 mV at 10 mA cm-2 for the HER and OER, respectively. In addition, the Mo2C/NCNTs@Ni also displays excellent long-term durability during a continuous operation test under different currents for 50 h. The assembled AEMWE electrolyzers with Mo2C/NCNTs@Ni as both the anode and cathode can achieve a current density of 82.5 mA cm-2 at 1.99 V, indicating great potential for industrial water splitting. These results give an insight for the development of advanced bifunctional electrocatalysts for the next generation of green and efficient H2 production by water electrolysis.

Comprehensive analysis of m6 A methylome and transcriptome by Nanopore sequencing in clear cell renal carcinoma.

N6 -methyladenosine (m6 A) is the most prevalent epigenetic modification on eukaryotic messenger RNAs. Recent studies have focused on elucidating the key role of m6 A modification patterns in tumor progression. However, the relationship between m6 A and transcriptional regulation remains elusive. Nanopore technology enables the quantification of m6 A levels at each genomic site. In this study, a pair of tumor tissues and adjacent normal tissues from clear cell renal cell carcinoma (ccRCC) surgical samples were collected for Nanopore direct RNA sequencing. We identified 9644 genes displaying anomalous m6 A modifications, with 5343 genes upregulated and 4301 genes downregulated. Among these, 5224 genes were regarded as dysregulated genes, encompassing abnormal regulation of both m6 A modification and RNA expression. Gene Set Enrichment Analysis revealed an enrichment of these genes in pathways related to renal system progress and fatty acid metabolic progress. Furthermore, the χ2 test demonstrated a significant association between the levels of m6 A in dysregulated genes and their transcriptional expression levels. Additionally, we identified four obesity-associated genes (FTO, LEPR, ADIPOR2, and NPY5R) among the dysregulated genes. Further analyses using public databases revealed that these four genes were all related to the prognosis and diagnosis of ccRCC. This study introduced the novel approach of employing conjoint analysis of m6 A modification and RNA expression based on Nanopore sequencing to explore potential disease-related genes. Our work demonstrates the feasibility of the application of Nanopore sequencing technology in RNA epigenetic regulation research and identifies new potential therapeutic targets for ccRCC.

Rad6, a ubiquitin conjugator required for insect-pathogenic lifestyle, UV damage repair, and genomic expression of Beauveria bassiana.

The E2 ubiquitin conjugator Rad6 is required for DNA damage bypass in budding yeast but remain functionally unknown in filamentous fungi. Here, we report pleiotropic effect of Rad6 ortholog in Beauveria bassiana, a wide-spectrum fungal insecticide. Global ubiquitination signal was greatly attenuated in the absence of rad6. The blocked ubiquitination led to severe growth defect, blocked asexual development, and abolished infectivity/insect pathogenicity, which correlated with compromised conidial quality (including viability, hydrophobicity, adherence to insect cuticle, and thermotolerance) and blocked secretion of cuticle-degrading enzymes including Pr1 family proteases. Importantly, Rad6 played much greater role in photoreactivation of UVB-impaired conidia by a 3- or 5-h light plus 9- or 7-h dark incubation than in dark reactivation of those impaired conidia by a 12-h dark incubation. The high activity of Rad6 in photoreactivation in vivo was derived from its link to a protein complex cored by the photolyase regulators WC1 and WC2 via the strong interactions of Rad6 with the E3 partner Rad18 and Rad18 with WC2 revealed in yeast two-hybrid assays. Transcriptomic analysis resulted in identification of 2700 differentially regulated genes involved in various function categories and metabolism pathways, indicating a regulatory role of Rad6-mediated ubiquitination in gene expression networks and genomic stability. Conclusively, Rad6 is required for asexual and insect-pathogenic lifecycles, solar UV damage repair, and genomic expression of B. bassiana. The primary dependence of its strong anti-UV role on photoreactivation in vivo unveils a scenario distinct from the core role of its yeast ortholog in DNA damage bypass.

High photoreactivation activities of Rad2 and Rad14 in recovering insecticidal Beauveria bassiana from solar UV damage.

Anti-ultraviolet (UV) roles of Rad2 and Rad14 depend on nucleotide excision repair (NER) of UV-induced DNA lesions in budding yeast but remain unexplored yet in filamentous fungi. Here, nucleus-specific Rad2 and Rad14 orthologs are shown to recover Beauveria bassiana, a main source of wide-spectrum mycoinsecticides, from solar UV damage through photorepair-depending photoreactivation. As a photorepair index, photoreactivation (germination) rates of lethal UVB dose-irradiated conidia via a 3- or 5-h light plus 9- or 7-h dark incubation at 25 °C were drastically reduced in the Δrad2 and Δrad14 mutants versus a wild-type strain. As an NER index, nighttime-mimicking 12-h dark reactivation rates of low UVB dose-impaired conidia decreased sharply compared to the corresponding photoreactivation rates in the presence or absence of either ortholog, indicating that its extant NER activity was limited to recovering light UVB damage in the field. The high photoreactivation activity of either Rad2 or Rad14 was derived from its tight link to a large protein complex formed by photolyase regulators and other anti-UV proteins through multiple protein-protein interactions revealed by yeast two-hybrid assays. Therefore, Rad2 and Rad14 recover B. bassiana from solar UV damage through photoreactiovation in vivo that depends primarily on photorepair, although they contribute little to the fungal lifecycle-related phenotypes. These findings unveil a novel scenario distinguished from the NER-depending anti-UV roles of Rad2 and Rad14 in the model yeast and broaden a biological basis crucial for rational application of fungal insecticides to improve pest control efficacy via feasible recovery of solar UV damage.

Celastrol inhibits angiogenesis and the biological processes of MDA-MB-231 cells via the DEGS1/S1P signaling pathway.

Celastrol (Cel) shows potent antitumor activity in various experimental models. This study examined the relationship between Cel's antivascular and antitumor effects and sphingolipids. CCK-8 assay, transwell assay, Matrigel, PCR-array/RT-PCR/western blotting/immunohistochemistry assay, ELISA and HE staining were used to detect cell proliferation, migration and invasion, adhesion and angiogenesis, mRNA and protein expression, S1P production and tumor morphology. The results showed that Cel could inhibit proliferation, migration or invasion, adhesion and angiogenesis of human umbilical vein endothelial cells (HUVECs) and MDA-MB-231 cells by downregulating the expression of degenerative spermatocyte homolog 1 (DEGS1). Transfection experiments showed that downregulation of DEGS1 inhibited the above processes and sphingosine-1-phosphate (S1P) production of HUVECs and MDA-MB-231 cells, while upregulation of DEGS1 had the opposite effects. Coculture experiments showed that HUVECs could promote proliferation, migration and invasion of MDA-MB-231 cells through S1P/sphingosine-1-phosphate receptor (S1PR) signaling pathway, while Cel inhibited these processes in MDA-MB-231 cells induced by HUVECs. Animal experiments showed that Cel could inhibit tumor growth in nude mice. Western blotting, immunohistochemistry and ELISA assay showed that Cel downregulated the expression of DEGS1, CD146, S1PR1-3 and S1P production. These data confirm that DEGS1/S1P signaling pathway may be related to the antivascular and antitumor effects of cel.

Protective effect of Amauroderma rugosum ethanol extract and its primary bioactive compound, ergosterol, against acute gastric ulcers based on LXR-mediated gastric mucus secretions.

BACKGROUND: Amauroderma rugosum (Blume & T. Nees) Torrend (Ganodermataceae) is an edible mushroom with a wide range of medicinal values. Our previous publication demonstrated the therapeutic effects of the water extract of A. rugosum (WEA) against gastric ulcers. However, the protective effects of the ethanol extract of A. rugosum (EEA) on gastric mucosa and its major active constituents have not yet been elucidated. PURPOSE: This study aims to evaluate the gastroprotective effects and underlying mechanisms of EEA and its fat-soluble constituent, ergosterol, in acute gastric ulcers. STUDY DESIGN AND METHOD: SD rats were pre-treated with EEA (50, 100, and 200 mg/kg) or ergosterol (5, 10, and 20 mg/kg), and acute gastric ulcer models were constructed using ethanol, gastric mucus secretion inhibitor (indomethacin) or pyloric-ligation. The gastric ulcer area, histological structure alterations (H&E staining), and mucus secretion (AB-PAS staining) were recorded. Additionally, Q-PCR, western blotting, immunohistochemistry, ELISA, molecular docking, molecular dynamics simulations, MM-GBSA analysis, and surface plasmon resonance assay (SPR) were used to investigate the underlying mechanisms of the gastroprotective effect. RESULT: Compared with WEA, which primarily exerts its anti-ulcer effects by inhibiting inflammation, EEA containing fat-soluble molecules showed more potent gastroprotective effect through the promotion of gastric mucus secretion, as the anti-ulcer activity was partly blocked by indomethacin. Meanwhile, EEA exhibited anti-inflammatory effects by suppressing the production of IL-6, IL-1ß, TNF-α, and NO, thereby inhibiting the MAPK pathway. Significantly, ergosterol (20 mg/kg), the bioactive water-insoluble compound in EEA, exhibited a gastroprotective effect comparable to that of lansoprazole (30 mg/kg). The promotion of gastric mucus secretion contributed to the effects of ergosterol, as indomethacin can completely block it. The upregulations of COX1-PGE2 and C-fos, an activator protein 1 (AP-1) transcription factor, were observed after the ergosterol treatment. Ergosterol acted as an LXRß agonist via van der Waals binding and stabilizing the LXRß protein without compromising its flexibility, thereby inducing the upregulation of AP-1 and COX-1. CONCLUSION: EEA and its primary bioactive compound, ergosterol, exert anti-ulcer effects by promoting gastric mucus secretion through the LXRß/C-fos/COX-1/PGE2 pathway.

A Chinese longitudinal maternity cohort study (2013-2021) on intrahepatic cholestasis phenotypes: Risk associations from environmental exposure to adverse pregnancy outcomes.

Intrahepatic cholestasis of pregnancy (ICP) is an idiopathic disease that occurs during mid-to-late pregnancy and is associated with various adverse pregnancy outcomes, including intrauterine fetal demise. However, since the underlying cause of ICP remains unclear, there is an ongoing debate on the phenotyping criteria used in the diagnostic process. Here, we identified single- and multi-symptomatic ICP (ICP-S and ICP-M) in 104,221 Chinese females from the ZEBRA maternity cohort, with the objective of exploring the risk implications of the two phenotypes on pregnancy outcomes and from environmental exposures. We employed multivariate binary logistic regression to estimate confounder-adjusted odds ratios and found that ICP-M was more strongly associated with preterm birth and low birth weight compared to ICP-S. Throughout pregnancy, incremental exposure to PM2.5, O3, and greenness could alter ICP risks by 17.3%, 12.5%, and -2.3%, respectively, with more substantial associations observed with ICP-M than with ICP-S. The major scientific advancements lie in the elucidation of synergistic risk interactions between pollutants and the protective antagonistic effects of greenness, as well as highlighting the risk impact of preconceptional environmental exposures. Our study, conducted in the context of the "three-child policy" in China, provides epidemiological evidence for policy-making to safeguard maternal and neonatal health.

Only one of three hydrophobins (Hyd1-3) contributes to conidial hydrophobicity and insect pathogenicity of Metarhizium robertsii.

Class I/II hydrophobins constitute a family of small amphiphilic proteins that mediate cell hydrophobicity and adhesion to host or substrata and have pleiotropic effects in filamentous fungi. Here we report that only class I Hyd1 is essential for conidial hydrophobicity and insect pathogenicity among three hydrophobins (Hyd1-3) characterized in Metarhizium robertsii, an insect-pathogenic fungus. Aerial conidiation levels of three Δhyd1 mutants were much more reduced in 5-day-old cultures than in 7-day-old cultures, which were wettable (hydrophilic), but restored to a wild-type level in 15-day-old cultures. The Δhyd1 mutants were compromised in conidial quality, including significant decreases in hydrophobicity (58%), adhesion to insect cuticle (36%), insect pathogenicity via normal cuticle infection (37%), UVB resistance (20%), and heat tolerance (10%). In contrast, none of all examined phenotypes were affected in the null mutants of hyd2 and hyd3. Intriguingly, micromorphology and integrity of hydrophobin rodlet bundles on conidial coat were not affected in all mutant and wild-type strains, but the rodlet bundles were disordered in the absence of hyd1, suggesting a link of the disorder to the decreased hydrophobicity. Therefore, Hyd1 mediates the fungal hydrophobicity and plays an important role in conidial quality control and insect-pathogenic lifecycle. Class I Hyd2 and class II Hyd3 seem functionally redundant in M. robertsii.

Cascade NH3 Oxidation and N2O Decomposition via Bifunctional Co and Cu Catalysts.

The selective catalytic oxidation of NH3 (NH3-SCO) to N2 is an important reaction for the treatment of diesel engine exhaust. Co3O4 has the highest activity among non-noble metals but suffers from N2O release. Such N2O emissions have recently been regulated due to having a 300× higher greenhouse gas effect than CO2. Here, we design CuO-supported Co3O4 as a cascade catalyst for the selective oxidation of NH3 to N2. The NH3-SCO reaction on CuO-Co3O4 follows a de-N2O pathway. Co3O4 activates gaseous oxygen to form N2O. The high redox property of the CuO-Co3O4 interface promotes the breaking of the N-O bond in N2O to form N2. The addition of CuO-Co3O4 to the Pt-Al2O3 catalyst reduces the full NH3 conversion temperature by 50 K and improves the N2 selectivity by 20%. These findings provide a promising strategy for reducing N2O emissions and will contribute to the rational design and development of non-noble metal catalysts.

Association between surgical extent and recurrence in unilateral intermediate- to high-risk papillary thyroid cancer.

BACKGROUND: Guidelines recommend total thyroidectomy (TT) to facilitate radioactive ablation and serological follow-up for intermediate- to high-risk papillary thyroid carcinoma (PTC). However, the association between surgical extent and tumor recurrence in these patients has not been well validated. We aimed to examine the association between the extent of surgery and recurrence in patients with completely resected unilateral intermediate- to high-risk PTC. METHODS: Patients with completely resected unilateral PTC from 2000 to 2017 in a single institute were reviewed. Those who had extrathyroidal extension (ETE) or lymph node metastasis (LNM, cN1 or pN1 > 5 lymph nodes involved) were included for analysis. Cox proportional hazards models were applied to measure the association between surgical extent and recurrence-free survival (RFS) while adjusting for patient demographic, clinicopathological and treatment variables. RESULTS: A total of 4550 patients (mean[SD] age, 43.0[11.7] years; 3379 women[74.3%]) were included. Of these patients, 2262(49.7%), 656(14.4%), 1032(22.7%), and 600 (13.2%) underwent lobectomy, TT, lobectomy + neck dissection (ND) and TT + ND, respectively. With a median follow-up period of 68 months, after multivariate adjustment, lobectomy was associated with a compromised RFS compared with other surgical extents (HR[95%CI], TT 0.537[0.333-0.866], P = 0.011, lobectomy + ND 0.531[0.392-0.720] P < 0.0001, TT + ND 0.446[0.286-0.697] P < 0.0001). RFS was similar between the two extents with ND (lobectomy + ND, HR [95%CI], 1.196 [0.759-1.885], P = 0.440). CONCLUSION: Lobectomy alone is associated with an elevated recurrence risk in patients with unilateral intermediate- to high-risk PTC compared with larger surgical extents. However, lobectomy and ND may provide similar tumor control compared with the conventional approach of TT and ND.

A nomogram for predicting lateral lymph node metastasis in cN0 unifocal papillary thyroid microcarcinoma.

BACKGROUND: Identifying risk factors for occult lateral lymph node metastasis (LLNM) in papillary thyroid microcarcinoma (PTMC) can provide valuable insights into the necessity of lateral neck dissection (LND). The objective of this study was to develop a nomogram for predicting the probability of LLNM in patients with cN0 unifocal PTMC. METHODS: We conducted a retrospective analyzed a total of 4872 patients with cN0 unifocal PTMC who were treated at our center from January 2013 to June 2018. Logistic regression analysis was used to determine the risk factors for LLNM, and a nomogram was constructed based on these risk factors. RESULTS: The rate of LLNM was 3.2%. Tumors located in the upper lobe(odds ratio [OR] = 2.56, 95% confidence interval [CI] 1.80-3.62; p < 0.001) and size greater than 7 mm (OR = 2.59, 95% CI 1.85-3.62; p < 0.001) had a significantly higher risk of LLNM compared to tumors in the lower or middle lobe and size less than or equal to 7 mm. Tumors with extrathyroidal extension (ETE) had a significantly higher risk of LLNM (OR = 1.41, 95% CI 1.01-1.99; p = 0.044). The presence of three or more central lymph node metastases (CLNMs) (OR = 5.84, 95% CI 3.83-8.93; p < 0.001) or one or two CLNMs (OR = 2.91, 95% CI 1.93-4.42; p < 0.001) also increased the risk of LLNM compared to having no CLNMs. A nomogram incorporating these risk factors was developed, and the receiver operating characteristic (ROC) curve demonstrated an area under the curve (AUC) of 0.777, indicating a high degree of predictive accuracy. CONCLUSION: Tumor location in the upper lobe, greater than 7 mm in size, ETE, and CLNMs, especially three or more, were independent risk factors for LLNM in cN0 unifocal PTMC. The nomogram based on these factors exhibited favorable predictive value and consistency.

Hashimoto's thyroiditis is negatively associated with lymph node metastasis in PTMC.

PURPOSE: The association between Hashimoto's thyroiditis (HT) and lymph node metastasis (LNM) of papillary thyroid microcarcinoma (PTMC) remains poorly understood. We aimed to elucidate the impact of HT on PTMC and its association with LNM. METHODS: A retrospective cohort study was conducted at a single cancer referral center. Patients diagnosed with PTMC and complete clinicopathological results between January 2013 and June 2018 were included. Propensity score matching (PSM) and logistic regression analysis were performed to evaluate the difference in LNM characteristics between patients with and without HT. RESULTS: Among the 9929 PTMC patients, 2389 (24.1%) were pathologically diagnosed with HT. After PSM using variables including age, sex, primary tumor size, central neck dissection, extrathyroidal extension (ETE), gross ETE, multifocality and bilaterality, we identified 2324 pairs of patients for analysis. Patients with HT had a significantly lower incidence of LNM in the central neck (40.9% vs 56.2%, P < 0.001) and lateral neck (11.6% vs 14.2%, P = 0.016), a lower incidence of extranodal extension (ENE) (10.1% vs 17.0%, P < 0.001), fewer positive lymph nodes (median [IQR], 0 [0 to 2] vs 1 [0 to 3], P < 0.001), and a lower lymph node ratio (median [IQR], 0.00 [0.00 to 0.15] vs 0.12 [0.00 to 0.33], P < 0.001) than those without HT. Logistic regression analysis indicated that patients with HT had a significantly reduced risk of CLNM and LLNM compared to those without HT. CONCLUSIONS: Our study indicated a negative association between HT and LNM in PTMC.

Anti-lipid accumulation effects and mechanism of the extract and isolated compounds from Potentilla longifolia.

Potentilla longifolia is effective in the treatment of hepatitis as a Chinese herb. We firstly evaluated the effect of water extract of P. longifolia (WEPL) on mice with nonalcoholic fatty liver disease (NAFLD) induced by high-fat (HF) diet. The results showed that WEPL reduced HF-induced increases of the serum ALT, AST, TG and TC, and reduced lipid drops of liver tissues to a different extent compared with HF group; WEPL dose-dependently promoted the phosphorylation degrees of AMPK and ACC; WEPL decreased significantly genes expressions of SREBP1α, FAS and SCD1 and increased PPARα and CD36. Then three new (1-3) and 13 known compounds (4-16) were firstly-isolated from the 95% ethanol extract of this plant. Further experiments showed that a new compound (ganyearmcaooside C) showed the best inhibitory effect on lipid accumulation in 3 T3-L1 cells such as reducing the accumulation of oil droplets and triglyceride level, showing new drug potential for related diseases.

High-flux wavelength tunable XUV source in the 12-40.8†eV photon energy range with adjustable energy and time resolution for Tr-ARPES applications.

High-order harmonic generation (HHG) has a broad spectrum covering vacuum ultraviolet to extreme ultraviolet (XUV) bands, which is useful for applications involving material analyses at different information depths. Such an HHG light source is perfect for time- and angle-resolved photoemission spectroscopy. Here, we demonstrate a high-photon flux HHG source driven by a two-color field. Applying a fused silica compression stage to reduce the driving pulse width, we obtained a high XUV photon flux of 2 × 1012 phs/s @21.6 eV on target. We designed a classical diffraction mounted (CDM) grating monochromator that can achieve a wide range of photon energy from 12 to 40.8 eV, while the time resolution is improved by reducing the pulse front tilt after the harmonic selection. We designed a spatial filtering method to adjust the time resolution using the CDM monochromator and significantly reduced the pulse front tilt of the XUV pulses. We also demonstrate a detailed prediction of the energy resolution broadening which is caused by the space charge effect.

Nonspecific interaction and overlap concentration influence macromolecular crowding effect on glucose oxidase activity.

Macromolecular crowding can change kinetics of enzyme catalysis. How interaction between enzymes and neighboring macromolecules contributes to the crowding effect on enzyme catalysis has not been quantitatively revealed. In this study, crowding effects of dextran and poly(ethylene glycol) (PEG) on glucose oxidase (GOx) are studied. Fluorescence resonance energy transfer experiments show the high transfer efficiency and stable interaction between the dextran and GOx. Further fluorescence quenching analysis also proves that the association of the dextran-GOx pair can become stronger than that of the PEG-GOx pair. Dextrans with concentrations above or below their chain overlap concentrations (c*) reduce Michaelis constants (Km) of GOx catalysis by 90 % or 45 %, respectively, through volume exclusion mechanism, and in the meantime elevate the enzymatic efficiency (kcat/Km) by 8-fold or by 3-fold, respectively, which is more dramatic than that found in other enzymes before. Strong association between the enzyme and the dextran results in slow turnover rates (kcat). Intermediate crowding with weak to moderate affinity to the enzyme below the c* can tune the kcat higher than in the free state. Catalysis under crowded conditions is a joint effect of the enzyme-crowder nonspecific interaction, volume exclusion and overlap condition of the crowders.

Prognostic Value of Lymphovascular Invasion in Patients With Pyriform Sinus Carcinoma Treated With Surgery Plus Adjuvant Chemo-/Radiotherapy.

OBJECTIVE: We aimed to determine the prognostic value of lymphovascular invasion (LVI) in pyriform sinus carcinoma (PSC) after primary surgery with adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). METHODS: Patients who underwent primary surgery at our institution between 2000 and 2018 were included in this study and retrospectively analyzed. The endpoints were locoregional recurrence (LRR), distant metastasis (DM), and disease-specific survival (DSS). RESULTS: We reviewed 117 patients with PSC. LVI was identified in 29 patients (24.8%). The 5-year LRR rate, DM rate, and DSS rate were 29.4%, 31.7%, and 45.9%, respectively. Tumors with LVI were associated with a significantly higher LRR (P = 0.002, HR 3.678, 95% CI 1.646-8.218) and DM (P = 0.003, HR 3.666, 95% CI 1.543-8.709) and a lower DSS (P = 0.001, HR 2.814, 95% CI 1.519-5.213) in multivariate analysis. CONCLUSION: LVI is a significant predictor of poor prognosis in patients with PSC treated with surgery plus adjuvant RT/CCRT.