Molecular Mechanism of WWOX Inhibiting the Development of Esophageal Cancer by Inhibiting Hippo Signaling Pathway.

With the emergence of combined surgical treatments, complemented by radiotherapy and chemotherapy, survival rates for esophageal cancer patients have improved, but the overall 5-year survival rate remains low. Therefore, there is an urgent need for further research into the pathogenesis of esophageal cancer and the development of effective prevention, diagnosis, and treatment methods. We initially utilized the GeneCards and DisGeNET databases to identify the esophageal cancer-associated gene WWOX (WW domain containing oxidoreductase). Subsequently, we employed RT-qPCR (Reverse transcription-quantitative PCR) and WB (western blot) to investigate the differential expression of WWOX in HEEC (human esophageal endotheliocytes) and various ESCC (esophageal squamous cell carcinoma) cell lines. We further evaluated alterations in cell proliferation, migration and apoptosis via CCK8 (cell counting kit-8) and clonal formation, Transwell assays and flow cytometry. Additionally, we investigated changes in protein expressions related to the Hippo signaling pathway (YAP/TEAD) through RT-qPCR and WB. Lastly, to further elucidate the regulatory mechanism of WWOX in ESCC, we performed exogenous YAP rescue experiments in ESCC cells with WWOX overexpression to investigate the alterations in apoptosis and proliferation. Results indicated that the expression of WWOX in ESCC was significantly downregulated. Subsequently, upon overexpression of WWOX, ESCC cell proliferation and migration decreased, while apoptosis increased. Additionally, the expression of YAP and TEAD were reduced. However, the sustained overexpression of YAP attenuated the inhibitory effects of WWOX on ESCC cell malignancy. In conclusion, WWOX exerts inhibitory effects on the proliferation and migration of ESCC and promotes apoptosis by suppressing the Hippo signaling pathway. These findings highlight the potential of WWOX as a novel target for the diagnosis and treatment of esophageal cancer.

Toward Accurate Human Parsing Through Edge Guided Diffusion.

Existing human parsing frameworks commonly employ joint learning of semantic edge detection and human parsing to facilitate the localization around boundary regions. Nevertheless, the parsing prediction within the interior of the part contour may still exhibit inconsistencies due to the inherent ambiguity of fine-grained semantics. In contrast, binary edge detection does not suffer from such fine-grained semantic ambiguity, leading to a typical failure case where misclassification occurs inner the part contour while the semantic edge is accurately detected. To address these challenges, we develop a novel diffusion scheme that incorporates guidance from the detected semantic edge to mitigate this problem by propagating corrected classified semantics into the misclassified regions. Building upon this diffusion scheme, we present an Edge Guided Diffusion Network (EGDNet) for human parsing, which can progressively refine the parsing predictions to enhance the accuracy and coherence of human parsing results. Moreover, we design a horizontal-vertical aggregation to exploit inherent correlations among body parts along both the horizontal and vertical axes, which aims at enhancing the initial parsing results. Extensive experimental evaluations on various challenging datasets demonstrate the effectiveness of the proposed EGDNet. Remarkably, our EGDNet shows impressive performances on six benchmark datasets, including four human body parsing datasets (LIP, CIHP, ATR, and PASCAL-Person-Part), and two human face parsing datasets (CelebAMask-HQ and LaPa).

Global Research Trends on Infertility and Psychology From the Past Two Decades: A Bibliometric and Visualized Study.

Objectives: The aim of this study was to evaluate the global scientific output of research on infertility and psychology; explore the current status and trends in this field through the cooperation of authors, countries, and institutions; shed light on the direction of clinical infertility research in the future, and provide inspiration for targeted diagnosis and treatment of infertility. Methods: Research publications on infertility and psychology from the past two decades were retrieved from the Web of Science Core Collection (WoSCC). Bibliometric analyses were performed using VOSviewer software and the bibliometrix R package. Network maps were generated to evaluate the collaborations between different authors, countries, institutions, and keywords. Results: A total of 151 articles related to the study of infertility and psychology were identified. We observed a gradual increase in the number of publications from 2001 to 2021, and the trend has been relatively stable in the past eight years. Human Reproduction (England), as the leading journal publishing the most papers (29 articles), was cited in the most journals (1208 times). Boivin J was the most prolific author (16 articles), with the largest number of citations (890 times) and the highest h-index (14) during the past decades. Boivin J was also the leader with the highest publication frequency and more active cooperation with other top authors. The United Kingdom (34 papers) and Cardiff University (25 articles) contributed the most publications and were the leading contributors in this field. Active cooperation between countries and between institutions was observed, and analyses of articles and references were also shown. The main hot topics included matters related to women (39 times), in-vitro salt (31 times), infertility (30 times), couples (25 times), and impact (24 times). Conclusion: Our study results provide a comprehensive overview of the development of scientific literature, allowing relevant authors and research teams to recognize the current research status in this field. At the same time, infertility and psychology may soon become hotspots and should be closely monitored.

Curcumin attenuates inflammation and cell apoptosis through regulating NF-κB and JAK2/STAT3 signaling pathway against acute kidney injury.

Curcumin alleviates septic acute kidney injury (SAKI); however, the underlying mechanism remained unclear. To explore this, SAKI cell model and mice model were conducted by using LPS and cecal ligation and puncture (CLP), respectively. Cell counting kit-8 (CCK-8) and enzyme-linked immunosorbent assay (ELISA) assays indicated that LPS reduced the viability, but upregulated the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6, whereas Curcumin pretreatment had no effect on viability, but reduced the levels of TNF-α and IL-6. Further assays showed that Curcumin partly attenuated the LPS-induced injury as the viability was enhanced, TNF-α and IL-6 expressions and cell apoptosis rates were reduced. Western blot analysis indicated that Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3, p-65-NF-κB and cell apoptosis pathways were activated by LPS but suppressed by Curcumin. Mice SAKI model further indicated that the serum Cystatin C (Cys-C), creatinine (Cr) and blood urea nitrogen (BUN) were increased within 24 h of model construction while those indicators were decreased at 48 h. Pretreated with Curcumin, NF-κB inhibitor (PDTC) or JAK2 inhibitor (AG-490) could weaken the renal histological injury and the increased serum Cys-C, Cr and BUN, IL-6 and TNF-α induced by CLP. Moreover, PDTC, AG-490 and Curcumin all significantly reversed the previously increased expressions of p-JAK2/STAT3, p-p65 and proapoptotic proteins in the mice with AKI. The present study revealed that Curcumin attenuated SAKI through inhibiting NF-κB and JAK2/STAT3 signaling pathways, and proposed that Curcumin could be a potential therapeutic agent for treating SAKI.

Modified Aminoglycosides Bind Nucleic Acids in High-Molecular-Weight Complexes.

Aminoglycosides represent a large group of antibiotics well known for their ability to target the bacterial ribosome. In studying 6"-substituted variants of the aminoglycoside tobramycin, we serendipitously found that compounds with C12 or C14 linear alkyl substituents potently inhibit reverse transcription in vitro. Initial observations suggested specific inhibition of reverse transcriptase. However, further analysis showed that these and related compounds bind nucleic acids with high affinity, forming high-molecular weight complexes. Stable complex formation is observed with DNA or RNA in single- or double-stranded form. Given the amphiphilic nature of these aminoglycoside derivatives, they likely form micelles and/or vesicles with surface-bound nucleic acids. Hence, these compounds may be useful tools to localize nucleic acids to surfaces or deliver nucleic acids to cells or organelles.

Roles of specific aminoglycoside-ribosome interactions in the inhibition of translation.

Aminoglycosides containing a 2-deoxystreptamine core (AGs) represent a large family of antibiotics that target the ribosome. These compounds promote miscoding, inhibit translocation, and inhibit ribosome recycling. AG binding to helix h44 of the small subunit induces rearrangement of A-site nucleotides A1492 and A1493, which promotes a key open-to-closed conformational change of the subunit and thereby increases miscoding. Mechanisms by which AGs inhibit translocation and recycling remain less clear. Structural studies have revealed a secondary AG binding site in H69 of the large subunit, and it has been proposed that interaction at this site is crucial for inhibition of translocation and recycling. Here, we analyze ribosomes with mutations targeting either or both AG binding sites. Assaying translocation, we find that ablation of the h44 site increases the IC50 values for AGs dramatically, while removal of the H69 site increases these values modestly. This suggests that the AG-h44 interaction is primarily responsible for inhibition, with H69 playing a minor role. Assaying recycling, we find that mutation of h44 has no effect on AG inhibition, consistent with a primary role for AG-H69 interaction. Collectively, these findings help clarify the roles of the two AG binding sites in mechanisms of inhibition by these compounds.

Tobramycin Variants with Enhanced Ribosome-Targeting Activity.

With the increased evolution of aminoglycoside (AG)-resistant bacterial strains, the need to develop AGs with 1) enhanced antimicrobial activity, 2) the ability to evade resistance mechanisms, and 3) the capability of targeting the ribosome with higher efficiency is more and more pressing. The chemical derivatization of the naturally occurring tobramycin (TOB) by attachment of 37 different thioether groups at the 6''-position led to the identification of generally poorer substrates of TOB-targeting AG-modifying enzymes (AMEs). Thirteen of these displayed better antibacterial activity than the parent TOB while retaining ribosome-targeting specificity. Analysis of these compounds in vitro shed light on the mechanism by which they act and revealed three with clearly enhanced ribosome-targeting activity.

[Determination of patulin in juice by ultra performance liquid chromatography-tandem mass spectrometry].

A method was developed for the simultaneous determination of patulin in juice by solid phase extraction (SPE)-ultra performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). The cloudy juice was hydrolyzed by enzyme and extracted by ethyl acetate. The extract of cloudy juice was then enriched and purified by an HLB SPE cartridge. If the juice was clear it was directly treated by the cartridge as above. The separation was performed on a C18 column with the gradient elution of acetonitrile and water. The patulin was detected by MS with electrospray negative ionization (ESI-) in the mode of multiple reaction monitoring (MRM). The good linearity was observed in the range of 1.0 - 500 microg/L with the correlation coefficient of 0. 999 and the limit of quantitation of 5.0 microg/kg. The recoveries were in the range of 80. 6% -91. 8% at three spiked levels of 5.0, 25.0 and 100.0 microg/kg with the relative standard deviations of 1.5% -7.3%. It was proved to be a simple, reliable and accurate method which can fully meet the requirements of patulin detection in juice samples according to most domestic and international legislations.

Candida cellulosicola sp. nov., a xylose-utilizing anamorphic yeast from rotten wood.

Two xylose-utilizing yeast strains isolated from rotten wood collected in the rainforest in different mountains of Hainan province, southern China, were studied. Sequence analysis of the large subunit rDNA D1/D2 domain and internal transcribed spacer region revealed that the strains represent a novel anamorphic yeast species, for which the name Candida cellulosicola sp. nov. is proposed; the type strain is HNX16-2(T) (=CGMCC 2.3503(T)=CBS 11952(T)). Phylogenetically, the novel species was closely related to a xylose-utilizing teleomorphic ascomycetous yeast species Spencermartinsiella europaea in the family Trichomonascaceae, but differed from the latter by 3.0% mismatches in the D1/D2 domain.

[Determination of 153 pesticide residues in tea using on-line gel permeation chromatography-gas chromatography/mass spectrometry].

A method was developed for the determination of 153 pesticide residues in tea using on-line gel permeation chromatography-gas chromatography/mass spectrometry (GPC-GC/ MS). The pesticide residues were extracted with acetonitrile under ultrasonic operation, and the extract was first cleaned up with an ENVI-carb solid phase extraction column and then separated and detected with the on-line GPC-GC/MS system. The recoveries of the method ranged from 73.32% to 117.05% with the relative standard deviations (RSDs) from 0.76% to 13.18%. The limits of detection and the limits of quantification were 0.0003-0.006 mg/kg and 0.001-0.02 mg/kg, respectively. This method is simple, rapid and characterized with acceptable sensitivity and accuracy to meet the requirements for the analysis of multiple pesticide residues in tea.