PolyAtailor: measuring poly(A) tail length from short-read and long-read sequencing data.

The poly(A) tail is a dynamic addition to the eukaryotic mRNA and the change in its length plays an essential role in regulating gene expression through affecting nuclear export, mRNA stability and translation. Only recently high-throughput sequencing strategies began to emerge for transcriptome-wide profiling of poly(A) tail length in diverse developmental stages and organisms. However, there is currently no easy-to-use and universal tool for measuring poly(A) tails in sequencing data from different sequencing protocols. Here we established PolyAtailor, a unified and efficient framework, for identifying and analyzing poly(A) tails from PacBio-based long reads or next generation short reads. PolyAtailor provides two core functions for measuring poly(A) tails, namely Tail_map and Tail_scan, which can be used for profiling tails with or without using a reference genome. Particularly, PolyAtailor can identify all potential tails in a read, providing users with detailed information such as tail position, tail length, tail sequence and tail type. Moreover, PolyAtailor integrates rich functions for poly(A) tail and poly(A) site analyses, such as differential poly(A) length analysis, poly(A) site identification and annotation, and statistics and visualization of base composition in tails. We compared PolyAtailor with three latest methods, FLAMAnalysis, FLEPSeq and PAIsoSeqAnalysis, using data from three sequencing protocols in HeLa samples and Arabidopsis. Results show that PolyAtailor is effective in measuring poly(A) tail length and detecting significance of differential poly(A) length, which achieves much higher sensitivity and accuracy than competing methods. PolyAtailor is available at https://github.com/BMILAB/PolyAtailor.

Coagulation-centered three-step approach for removing by-product organic pollutants from tetrabromobisphenol A industrial wastewater: Experimental and theoretic investigations.

The challenge of meeting discharge standards for tetrabromobisphenol A (TBBPA) production wastewater, characterized by high concentrations of organic by-products, necessitates effective treatment methods. This study identifies 2,4-dibromophenol, 2,6-dibromophenol, 2,4,6-tribromophenol, chlorobenzene, and toluene as the primary organic by-product pollutants. A coagulation-centered three-step approach was established for TBBPA industrial wastewater treatment. The initial step involves acidification treatment to exploit the reduced solubility of 2,4-dibromophenol, 2,6-dibromophenol, and 2,4,6-tribromophenol under acidic conditions, with the optimal pH determined as 2.7-3.1. An acid-activated montmorillonite coagulant (AMC), prepared through roasting and high-pressure acid leaching, exhibits a distinctive "Core-shell" structure, contributing significantly to the combined coagulation and adsorption mechanism. The acid-soluble aluminum salts in AMC form positively charged flocs, electrostatically attracting negatively charged organic compounds in the wastewater. Simultaneously, the porous insoluble silicon framework displays strong adsorption capacity for pollutants. The removal efficiencies for toluene, chlorobenzene, 2,4-dibromophenol, 2,6-dibromophenol, and 2,4,6-tribromophenol reached 88.2%, 89.1%, 88.8%, 87.1%, and 89.4%, respectively. Elemental analysis reveals that the coloration of the wastewater stems from complexation reactions between phenolic compounds and Fe3+, originating from the corrosion of iron or steel reaction vessel. Post-treatment with cation exchange resin resulted in removal efficiencies of 5.2%, 59.1%, 80.2%, 77.9%, and 88.3% for the five substances, respectively. This study outlines a crucial pathway for the effective purification of TBBPA wastewater.

Co-expression of recombinant human collagen α1(III) chain with viral prolyl 4-hydroxylase in Pichia pastoris GS115.

The Collagen α1(Ш) chain (COL3A1) is an important structural protein on the surface of human skin. The activity of prolyl 4-hydroxylase (P4H) is crucial to maintaining the stable triple-helix structure and function of human COL3A1. To obtain hydroxylated human COL3A1, virus-derived P4H A085R was co-expressed with human COL3A1 in Pichia pastoris GS115. Colony PCR analysis and sequencing after transfection confirmed that the target gene was successfully inserted. Quantitative reverse transcription PCR (RT-qPCR) indicated that human COL3A1 and P4H A085R were expressed at mRNA levels in the clones. SDS-PAGE and Western blot analysis of supernatant from the recombinant methylotrophic yeast culture showed that recombinant human COL3A1 (rhCOL3A1) was secreted into the culture medium with an apparent molecular mass of approximately 130 kDa. It was observed that the amount of secreted rhCOL3A1 was highest at 120 h after induction. Furthermore, mass spectrometry analysis demonstrated that rhCOL3A1 was successfully expressed in P. pastoris. The His-tagged rhCOL3A1 protein was purified by Ni-affinity column chromatography.

CuO nanosheets incorporated scrap steel slag coupled with persulfate catalysts for high-efficient degradation of sulfonamide from water.

A highly efficient and magnetically recoverable persulfate (PS) catalyst was prepared for the removal of sulfonamide (SMD) from wastewater, which is difficult to be degraded by the conventional biological treatment. In this study, the scrap steel slag (SSS) was used as supporting carrier and the CuO nanosheet was incorporated on the surface of SSS. The optimal conditions were determined as follows: the dosage of CuO/SSS was 1 g L-1, the PS concentration was 4 mM and the optimal initial pH was 6.85. Under the optimal conditions, the maximum SMD removal efficiency of 80.29% was achieved within 30 min by using CuO/SSS + PS. In addition, the CuO/SSS + PS system had a wide pH range (5-9) and more than 60% removal efficiency of SMD could be obtained with the pH between 3 and 11. The mechanism based on the phase transformation of Cu(I/II), Cu(II/III) and Fe(II/III) was elucidated by using different analytical techniques, such as SEM, XRD, XPS, BET, FTIR, VSM characterization and free radical analysis. This study provided a new pathway for the SSS resource utilization and the effective degradation of SMD from the refractory wastewater by using CuO/SSS catalyst coupled with PS system.

Antioxidant Peptides from the Collagen of Antler Ossified Tissue and Their Protective Effects against H2O2-Induced Oxidative Damage toward HaCaT Cells.

Antler ossified tissue has been widely used for the extraction of bioactive peptides. In this study, collagen was prepared from antler ossified tissue via acetic acid and pepsin. Five different proteases were used to hydrolyze the collagen and the hydrolysate treated by neutrase (collagen peptide named ACP) showed the highest DPPH radical clearance rate. The extraction process of ACP was optimized by response surface methodology, and the optimal conditions were as follows: a temperature of 52 °C, a pH of 6.1, and an enzyme concentration of 3200 U/g, which resulted in the maximum DPPH clearance rate of 74.41 ± 0.48%. The peptides (ACP-3) with the strongest antioxidant activity were obtained after isolation and purification, and its DPPH free radical clearance rate was 90.58 ± 1.27%; at the same time, it exhibited good scavenging activity for ABTS, hydroxyl radical, and superoxide anion radical. The study investigated the protective effect of ACP-3 on oxidative damage in HaCaT cells. The findings revealed that all groups that received ACP-3 pretreatment exhibited increased activities of SOD, GSH-Px, and CAT compared to the model group. Furthermore, ACP-3 pretreatment reduced the levels of ROS and MDA in HaCaT cells subjected to H2O2-induced oxidative damage. These results suggest that collagen peptides derived from deer antler ossified tissue can effectively mitigate the oxidative damage caused by H2O2 in HaCaT cells, thereby providing a foundation for the utilization of collagen peptides in pharmaceuticals and cosmetics.

Analysis of the aqueous humor lipid profile in patients with polypoidal choroidal vasculopathy.

This study aimed to investigate the lipid profiles of aqueous humor from polypoidal choroidal vasculopathy (PCV) patients and identify potential biomarkers to increase the understanding of PCV pathomechanism. An ultra-high performance liquid chromatography-tandem mass spectrometry based untargeted lipidomic analysis was performed to acquire lipid profiles of aqueous humor of PCV patients and control subjects. Differentially expressed lipids were identified by univariate and multivariate analyses. A receiver operator characteristic curve (ROC) analysis was conducted to confirm the potential of identified lipids as biomarkers. Sixteen PCV patients and twenty-eight control subjects were enrolled in this study. In total, we identified 33 lipid classes and 639 lipid species in aqueous humor using the LipidSearch software. Of them, 50 differential lipids were obtained by combining univariate and multivariate statistical analyses (VIP>1 and P < 0.05), and 19 potential lipid biomarkers were identified by ROC analysis. In addition, significant alterations were found in several metabolic pathways, including glycerophospholipid, glycerolipid, and glycosylphosphatidylinositol-anchor biosynthesis. This study is the first to systematically characterize the alterations in lipid profiles in aqueous humor of PCV patients and screen for the potential lipid biomarkers for PCV diagnosis and treatment intervention. The results of this study are likely to broaden our understanding of the pathogenesis of PCV and contribute to improvements in the diagnosis and treatment of the disease.

Traditional fermented soybean products: processing, flavor formation, nutritional and biological activities.

Traditional fermented soybean food has emerged as an important part of people's dietary structure because of the unique flavors and improved health benefit. During fermentation, the nutrients in soybean undergo a series of biochemical reactions catalyzed naturally by microorganism secreted enzymes. Thereafter, many functional and bioactive substances such as bioactive peptides, unsaturated fatty acids, free soy isoflavones, vitamins and minerals are produced, making fermented soy products more advantageous in nutrition and health. This review comprehensively discusses the historical evolution, distribution, traditional fermentation processing, main sources and characteristics of fermented strains, flavor components, nutritional properties, and biological activities of four traditional fermented soybean foods including douchi, sufu, dajiang, and soy sauce. In the end, we introduce four major challenges encountered by traditional fermented soybean foods including high salt content, formation of biogenic amine, the presence of pathogenic microorganisms and mycotoxins, and quality inconsistency. We conclude that the establishment of scientific quality standard and innovated fermentation processing is the potential solutions to combat the issues and improve the safety of traditional fermented soybean products.

MXene Nanosheets Induce Efficient Iron Selenide Active Sites to Boost the Electrocatalytic Hydrogen Evolution Reaction.

Along with the widespread utilization of hydrogen energy, the rise of highly active hydrogen evolution electrocatalysts with affordable costs presently becomes a substantial crux of this emerging domain. In this work, we demonstrate a feasible and convenient in situ seed-induced growth strategy for the construction of small-sized FeSe2 nanoparticles decorated on two-dimensional (2D) superthin Ti3C2Tx MXene sheets (FeSe2/Ti3C2Tx) through a manipulated bottom-up synthetic procedure. By virtue of the distinctive 0D/2D heterostructures, abundant exposed surface area, well-distributed FeSe2 catalytic centers, strong surface electronic coupling, and high electrical conductivity, the resultant FeSe2/Ti3C2Tx nanoarchitectures are endowed with a superior electrocatalytic hydrogen evolution capacity including a competitive onset potential of 89 mV, a favorable Tafel slope of 78 mV dec-1, and a long-period stability, significantly better than that of the pristine FeSe2 and Ti3C2Tx catalysts.

CspB and CspC are induced upon cold shock in Bacillus cereus strain D2.

Bacillus cereus D2, a psychrotrophic strain, plays an essential role in the restoration of heavy metal-contaminated soils, especially at low temperatures. However, the cold shock response mechanisms of this strain are unclear. In this study, the cold shock response of B. cereus D2 was characterized; as per the Arrhenius curve, 10 °C was chosen as the cold shock temperature. Six cold shock-like proteins were found and temporarily named cold shock protein (Csp)1-6; the respective genes were cloned and identified. Quantitative real-time PCR results showed that csp1, csp2, csp3, and csp6 were overexpressed under cold shock conditions. Interestingly, after cloning the respective encoding genes into the pET-28a (+) vector and their subsequent transformation into E. coli BL21 (DE3), the strains expressing Csp2 and Csp6 grew faster at 10 °C, showing a large number of bacteria. These results suggest that Csp2 and Csp6 are the major cold shock proteins in B. cereus D2. Of note, the comparison of amino acid sequences and structures showed that Csp2 and Csp6 belong to the CspB and CspC families, respectively. Additionally, we show that the number of hydrophobic residues is not a determining feature of major Csps, while, on the other hand, the formation of an α-helix in the context of a leucine residue is the most dominant difference between major and other Bacillus and E. coli Csps.

TET3 overexpression facilitates DNA reprogramming and early development of bovine SCNT embryos.

Somatic cell nuclear transfer (SCNT) has been successfully used for cloning in a variety of mammalian species. However, SCNT reprogramming efficiency is relatively low, in part, due to incomplete DNA methylation reprogramming of donor cell nuclei. We previously showed that ten-eleven translocation 3 (TET3) is responsible for active DNA demethylation during preimplantation embryonic development in bovines. In this study, we constructed TET3-overexpressing cell lines in vitro and observed that the use of these fibroblasts as donor cells increased the blastocyst rate by approximately 18 percentage points compared to SCNT. The overexpression of TET3 in bovine SCNT embryos caused a decrease in the global DNA methylation level of the pluripotency genes Nanog and Oct-4, ultimately resulting in an increase in the transcriptional activity of these pluripotency genes. Moreover, the quality of bovine TET3-NT embryos at the blastocyst stage was significantly improved, and bovine TET3-NT blastocysts possessed more total number of cells and fewer apoptotic cells than the SCNT blastocysts, similar to in vitro fertilization (IVF) embryos. Nevertheless, DNA methylation of the imprinting control region (ICR) for the imprinted genes H19-IGF2 in SCNT embryos remained unaffected by TET3 overexpression, maintaining parent-specific activity for further development. Thus, the results of our study provide a promising approach to rectify incomplete epigenetic reprogramming and achieve higher cloning efficiency.

Toward Understanding the Enhanced Pseudocapacitive Storage in 3D SnS/MXene Architectures Enabled by Engineered Surface Reactions.

The optimization of three-dimensional (3D) MXene-based electrodes with desired electrochemical performances is highly demanded. Here, a precursor-guided strategy is reported for fabricating the 3D SnS/MXene architecture with tiny SnS nanocrystals (≈5 nm in size) covalently decorated on the wrinkled Ti3 C2 Tx nanosheets through Ti-S bonds (denoted as SnS/Ti3 C2 Tx -O). The formation of Ti-S bonds between SnS and Ti3 C2 Tx was confirmed by extended X-ray absorption fine structure (EXAFS). Rather than bulky SnS plates decorated on Ti3 C2 Tx (SnS/Ti3 C2 Tx -H) by one-step hydrothermal sulfidation followed by post annealing, this SnS/Ti3 C2 Tx -O presents size-dependent structural and dynamic properties. The as-formed 3D hierarchical structure can provide short ion-diffusion pathways and electron transport distances because of the more accessible surface sites. In addition, benefiting from the tiny SnS nanocrystals that can effectively improve Na+ diffusion and suppress structural variation upon charge/discharge processes, the as-obtained SnS/Ti3 C2 Tx -O can generate pseudocapacitance-dominated storage behavior enabled by engineered surface reactions. As predicted, this electrode exhibits an enhanced Na storage capacity of 565 mAh g-1 at 0.1 A g-1 after 75 cycles, outperforming SnS/Ti3 C2 Tx -H (336 mAh g-1 ), SnS (212 mAh g-1 ), and Ti3 C2 Tx (104 mAh g-1 ) electrodes.

Pituitary miRNAs target GHRHR splice variants to regulate GH synthesis by mediating different intracellular signalling pathways.

Growth hormone (GH), whose synthesis and release are mainly regulated by intracellular signals mediated by growth hormone-releasing hormone receptor (GHRHR), is one of the major pituitary hormones and critical regulators of organism growth, metabolism, and immunoregulation. Pig GHRHR splice variants (SVs) may activate different signalling pathways via the variable C-terminal by alternative splicing, and SVs have the potential to change microRNA (miRNA) binding sites. In this study, we first confirmed the existence of pig GHRHR SVs (i.e., GHRHR, GHRHR SV1 and SV2) and demonstrated the inhibitory effects of critical pituitary miRNAs (i.e., let-7e and miR-328-5p) on GH synthesis and cell proliferation of primary pituitary cells. The SVs of GHRHR targeted by let-7e and miR-328-5p were predicted via bioinformatics analysis and verified by performing dual-luciferase reporter assays and detecting the expression of target transcripts. The differential responses of let-7e, and miR-328-5p to GH-releasing hormone and the changes in signalling pathways mediated by GHRHR suggested that let-7e and miR-328-5p were involved in GH synthesis mediated by GHRHR SVs, indicating that the two miRNAs played different roles by different ways. Finally, results showed that the protein coded by the GHRHR transcript regulated GH through the NO/NOS signalling pathway, whereas that coded by SV1 and SV2 regulated GH through the PKA/CREB signalling pathway, which was confirmed by the changes in signalling pathways after transfecting the expression vectors of GHRHR SVs to GH3 cells. To the best of our knowledge, this paper is the first to report pituitary miRNAs regulate GH synthesis by targeting the different SVs of GHRHR.

Cutibacterium acnes Type II strains are associated with acne in Chinese patients.

Acne is a common inflammatory skin disease, especially in adolescents. Certain Cutibacterium acnes subtypes are associated with acne, although more than one subtype of C. acnes strains may simultaneously reside on the surface of the skin of an individual. To better understand the relationship between the genomic characteristics of C. acnes subtypes and acnes, we collected 50 C. acnes strains from the facial skin of 10 people (5 healthy individuals, 5 patients with acne) in Liaoning, China and performed whole genome sequencing of all strains. We demonstrated that the six potential pathogenic C. acnes strains were all Type II subtype, and discovered 90 unique genes of the six strains related to acne using pan-genome analysis. The distribution of 2 of the 90 genes was identified by PCR in bacterial cultures collected from the facial skin of 171 individuals (55 healthy individuals, 52 patients with mild acne and 64 patients with moderate to severe acne). Both the genes were significantly associated with acne (Chi square test, P < 0.01). We conclude that Type II strains are associated with acne in Chinese patients.

Association of SNPs in GnRH gene with sperm quality traits of Chinese water buffalo.

Hypothalamic gonadotropin-releasing hormone (GnRH) controls the activity of hypothalamic-pituitary-gonadal axis and plays a key role in the reproductive performance of animals. In this study, five single nucleotide polymorphisms (SNPs), namely g.991T > C, g.1041T > C g.3424T > C, g.3462C > A and g.3463Inde A, were detected in the GnRH gene of 162 water buffaloes by Sanger sequencing. Each SNP was associated with more than two sperm quality traits of ejaculate volume, sperm concentration, post-thaw sperm motility and sperm abnormality. g.3424T > C and g.3462C > A were related to these four traits and had a remarkable effect on ejaculate volume. The three other SNPs were related to sperm concentration, post-thaw sperm motility and sperm abnormality. Moreover, six haplotypes (H1: TCCAI, H2: CTTC-, H3: TCCCI, H4: CTTA-, H5: CCTA- and H6: CTCC-) composed of five SNPs comprising seven different combined genotypes were generated by linkage disequilibrium analysis. Statistics followed by one-way ANOVA indicated that water buffaloes with the haplotype combination H1H1 had the highest genotypic frequency, and those with the H4H4 haplotype combination had the highest ejaculate volume. The sperm concentration of those with haplotype combination H1H5 was higher than that of the other genotypes. In summary, our study showed a remarkable association between the SNPs of GnRH and sperm quality traits of Chinese water buffalo.

MicroRNA 322 Aggravates Dexamethasone-Induced Muscle Atrophy by Targeting IGF1R and INSR.

Dexamethasone (Dex) has been widely used as a potent anti-inflammatory, antishock, and immunosuppressive agent. However, high dose or long-term use of Dex is accompanied by side effects including skeletal muscle atrophy, whose underlying mechanisms remain incompletely understood. A number of microRNAs (miRNAs) have been shown to play key roles in skeletal muscle atrophy. Previous studies showed significantly increased miR-322 expression in Dex-treated C2C12 myotubes. In our study, the glucocorticoid receptor (GR) was required for Dex to increase miR-322 expression in C2C12 myotubes. miR-322 mimic or miR-322 inhibitor was used for regulating the expression of miR-322. Insulin-like growth factor 1 receptor (IGF1R) and insulin receptor (INSR) were identified as target genes of miR-322 using luciferase reporter assays and played key roles in Dex-induced muscle atrophy. miR-322 overexpression promoted atrophy in Dex-treated C2C12 myotubes and the gastrocnemius muscles of mice. Conversely, miR-322 inhibition showed the opposite effects. These data suggested that miR-322 contributes to Dex-induced muscle atrophy via targeting of IGF1R and INSR. Furthermore, miR-322 might be a potential target to counter Dex-induced muscle atrophy. miR-322 inhibition might also represent a therapeutic approach for Dex-induced muscle atrophy.

miR-140 inhibits porcine fetal fibroblasts proliferation by directly targeting type 1 insulin-like growth factor receptor and indirectly inhibiting type 1 insulin-like growth factor receptor expression via SRY-box 4.

OBJECTIVE: This study aimed to elucidate the effect of miR-140 on the proliferation of porcine fetal fibroblasts (PFFs) and identify the target genes of miR-140 in PFFs. METHODS: In this study, bioinformatics software was used to predict and verify target genes of miR-140. Quantitative polymerase chain reaction and western blot were used to detect the relationship between miR-140 and its target genes in PFFs. Dual luciferase reporter gene assays were performed to assess the interactions among miR-140, type 1 insulinlike growth factor receptor (IGF1R), and SRY-box 4 (SOX4). The effect of miR-140 on the proliferation of PFFs was measured by CCK-8 when PFFs were transfected with a miR-140 mimic or inhibitor. The transcription factor SOX4 binding to promoter of IGF1R was detected by chromatin immunoprecipitation assay (ChIP). RESULTS: miR-140 directly targeted IGF1R and inhibited proliferation of PFFs. Meanwhile, miR-140 targeted transcription factor SOX4 that binds to promoter of porcine IGF1R to indirectly inhibit the expression of IGF1R. In addition, miR-140 inhibitor promoted PFFs proliferation, which is abrogated by SOX4 or IGF1R knockdown. CONCLUSION: miR-140 inhibited PFFs proliferation by directly targeting IGF1R and indirectly inhibiting IGF1R expression via SOX4, which play an important role in the development of porcine fetal.

Ipatasertib sensitizes colon cancer cells to TRAIL-induced apoptosis through ROS-mediated caspase activation.

Due to TRAIL's explicit cancer cell-selectivity, the current study aimed to explore novel agents that sensitized cancer cell for TRAIL-induced apoptosis while sparing normal cell. In this study, we found that TRAIL could induce PARP-1 cleavage and apoptosis in colon cancer HCT116 cell, but HT-29 cell was not sensitive to TRAIL. However, non-cytotoxic doses of ipatasertib in conjunction with TRAIL could induce apoptosis in HT-29 cell. Mechanism studies showed that intracellular ROS level was significant increased during ipatasertib treatment. Excessive cellular levels of ROS further induced DNA damage and subsequently activated apoptotic signaling pathways in TRAIL-resistant HT-29 cells. Combined treatment with sub-toxic doses of ipatasertib and TRAIL leads to caspase activation and PARP-1 cleavage in HT-29 cells. Pretreated with NAC, an antioxidant, could inhibit ROS production and PARP-1 cleavage as well as prevent cell apoptotic death induced by combination therapy with TRAIL and ipatasertib. In addition, NAC can block the up-regulation of p53/PUMA induced by combined treatment with ipatasertib and TRAIL. Transfection with p53 or Puma siRNA for 48 h can reverse ipatasertib-mediated TRAIL sensitization. In conclusion, p53 and PUMA may play a pivotal role in sensitizing colon cancer cell to TRAIL-induced apoptosis by sub-toxic doses of ipatasertib treatment.

Measurement of Structural Parameters of the Lamina Cribrosa in Primary Open-Angle Glaucoma and Chronic Primary Angle-Closure Glaucoma by Optical Coherence Tomography and Its Correlations with Ocular Parameters.

PURPOSE: To measure lamina cribrosa thickness (LCT) and anterior lamina cribrosa surface depth (ALCSD) in primary open-angle glaucoma (POAG), chronic primary angle-closure glaucoma (CPACG), and control patients using spectral-domain optical coherence tomography (SD-OCT) and examine its association with relevant ocular parameters. METHODS: In this cross-sectional study, 61 healthy volunteers (61 eyes), 65 POAG patients (65 eyes), and 55 CPACG patients (55 eyes) were recruited to obtain radial B-scans of the optic nerve head by way of enhanced depth imaging using Heidelberg SD-OCT. The obtained LCT and ALCSD were compared among the control, POAG, and CPACG groups. In addition, we evaluated the relationships of mean lamina cribrosa (LC) parameters with visual field (VF) mean deviation (MD), retinal nerve fiber layer (RNFL) thickness, intraocular pressure (IOP), and axial length. RESULTS: The mean LCT of CPACG eyes was greater than that of POAG eyes (p = 0.003), but less than that of normal eyes (p < 0.001). The mean ALCSD of POAG and CPACG eyes was greater than that of normal control eyes (both p < 0.001). However, the mean ALCSD showed no significant difference between the POAG and CPACG groups (p = 0.073). Among all eyes, lower MD and thinner RNFL thickness were associated with a deeper and thinner LC (all p < 0.001). CONCLUSION: LCT is thinner in POAG compared to CPACG eyes. This is compatible with less deformation and compression of the LC in CPACG eyes, implying that the mechanisms of glaucomatous damage are different between POAG and CPACG eyes. Furthermore, VF MD and RNFL thickness were related to LCT and ALCSD in all patients.

Insulin-like growth factor 2 mRNA binding protein 2 promotes aerobic glycolysis and cell proliferation in pancreatic ductal adenocarcinoma via stabilizing GLUT1 mRNA.

Insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) is a member of the IGF2BP protein family consisting of IGF2BP1~3 with the capacity of binding to many transcripts and regulating RNA stability, localization, and translation. In this study, we discovered that expression of IGF2BP2 was upregulated and led to a poor prognosis in pancreatic ductal adenocarcinoma (PDAC). IGF2BP2 protein was gradually elevated from normal pancreas, pancreatic intraepithelial neoplasia to PDAC in an LSL-KrasG12D/+;LSL-Trp53R172H/+;Pdx1-Cre mouse model. Furthermore, we demonstrated that IGF2BP2 promoted aerobic glycolysis and PDAC cell proliferation through directly binding to and stabilizing GLUT1 mRNA. In summary, our study unveiled an important role of IGF2BP2 in PDAC development by modulating aerobic glycolysis and as a potential therapeutic target for PDAC treatment.

Systematic review on the efficacy and safety of immune checkpoint inhibition in renal cell carcinoma.

To perform a systematic review of the relevant literature about clinical trials on efficacy and safety of immune checkpoint inhibition, whether it is used alone, in combination or with other targeted therapies in patients with advanced and metastatic renal cell carcinoma (RCC), two team members reviewed the abstracts and selected pertinent articles from the relevant databases. A narrative review of randomized controlled trials was performed and seven randomized controlled trials were identified in this systematic review. In treatment of RCC, nivolumab has superior efficacy and safety compared with second-line everolimus. Combination strategies, especially those combined with anti-VEGF agents presents better efficacy but worse outcomes in term of safety than monotherapy and conventional treatment and might guide treatment choice for patients with RCC.