miR-181a plays the tumor-suppressor role in chronic myeloid leukemia CD34 + cells partially via SERPINE1.

The formation of the BCR-ABL fusion gene drives human chronic myeloid leukemia (CML). The last 2 decades have witnessed that specific tyrosine kinase inhibitors (TKIs, e.g., imatinib mesylate, IM) against ABL1 improve disease treatment, although some patients still suffer from relapse and TKI resistance. Therefore, a better understanding of the molecular pathology of CML is still urgently needed. miR-181a-5p (miR-181a) acts as a tumor suppressor in CML; however, the molecular mechanism of miR-181a in CML stem/progenitor cells remains elusive. Herein, we showed that miR-181a inhibited the growth of CML CD34+ cells, including the quiescent subset, and sensitized them to IM treatment, while miR-181a inhibition by a sponge sequence collaborated with BCR-ABL to enhance the growth of normal CD34+ cells. Transcriptome data and biochemical analysis revealed that SERPINE1 was a bona fide and critical target of miR-181a, which deepened the understanding of the regulatory mechanism of SERPINE1. Genetic and pharmacological inhibition of SERPINE1 led to apoptosis mainly mediated by caspase-9 activation. The dual inhibition of SERPINE1 and BCR-ABL exhibited a significantly stronger inhibitory effect than a single agent. Taken together, this study demonstrates that a novel miR-181a/SERPINE1 axis modulates CML stem/progenitor cells, which likely provides an important approach to override TKI resistance.

Targeting AXL kinase sensitizes leukemic stem and progenitor cells to venetoclax treatment in acute myeloid leukemia.

The abundance of genetic abnormalities and phenotypic heterogeneities in acute myeloid leukemia (AML) poses significant challenges to the development of improved treatments. Here, we demonstrated that a key growth arrest-specific gene 6/AXL axis is highly activated in cells from patients with AML, particularly in stem/progenitor cells. We developed a potent selective AXL inhibitor that has favorable pharmaceutical properties and efficacy against preclinical patient-derived xenotransplantation (PDX) models of AML. Importantly, inhibition of AXL sensitized AML stem/progenitor cells to venetoclax treatment, with strong synergistic effects in vitro and in PDX models. Mechanistically, single-cell RNA-sequencing and functional validation studies uncovered that AXL inhibition, alone or in combination with venetoclax, potentially targets intrinsic metabolic vulnerabilities of AML stem/progenitor cells and shows a distinct transcriptomic profile and inhibits mitochondrial oxidative phosphorylation. Inhibition of AXL or BCL-2 also differentially targets key signaling proteins to synergize in leukemic cell killing. These findings have a direct translational impact on the treatment of AML and other cancers with high AXL activity.

A conserved ZFX/WNT3 axis modulates the growth and imatinib response of chronic myeloid leukemia stem/progenitor cells.

BACKGROUND: Zinc finger protein X-linked (ZFX) has been shown to promote the growth of tumor cells, including leukemic cells. However, the role of ZFX in the growth and drug response of chronic myeloid leukemia (CML) stem/progenitor cells remains unclear. METHODS: Real-time quantitative PCR (RT-qPCR) and immunofluorescence were used to analyze the expression of ZFX and WNT3 in CML CD34+ cells compared with normal control cells. Short hairpin RNAs (shRNAs) and clustered regularly interspaced short palindromic repeats/dead CRISPR-associated protein 9 (CRISPR/dCas9) technologies were used to study the role of ZFX in growth and drug response of CML cells. Microarray data were generated to compare ZFX-silenced CML CD34+ cells with their controls. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to study the molecular mechanisms of ZFX to regulate WNT3 expression. RT-qPCR and western blotting were used to study the effect of ZFX on ß-catenin signaling. RESULTS: We showed that ZFX expression was significantly higher in CML CD34+ cells than in control cells. Overexpression and gene silencing experiments indicated that ZFX promoted the in vitro growth of CML cells, conferred imatinib mesylate (IM) resistance to these cells, and enhanced BCR/ABL-induced malignant transformation. Microarray data and subsequent validation revealed that WNT3 transcription was conservatively regulated by ZFX. WNT3 was highly expressed in CML CD34+ cells, and WNT3 regulated the growth and IM response of these cells similarly to ZFX. Moreover, WNT3 overexpression partially rescued ZFX silencing-induced growth inhibition and IM hypersensitivity. ZFX silencing decreased WNT3/ß-catenin signaling, including c-MYC and CCND1 expression. CONCLUSION: The present study identified a novel ZFX/WNT3 axis that modulates the growth and IM response of CML stem/progenitor cells.

Application of Artificial Intelligence to Quantitative Assessment of Fundus Tessellated Density in Young Adults with Different Refractions.

INTRODUCTION: The aim of this study was to quantitatively assess fundus tessellated density (FTD) and associated factors by artificial intelligence (AI) in young adults. METHODS: A total of 1,084 undergraduates (age, 17-23 years old) were enrolled in November 2021. The students were divided into three groups according to axial length (AL): group 1 (AL <24.0 mm, n = 155), group 2 (24 mm ≤ AL <26 mm, n = 578), and group 3 (AL ≥26 mm, n = 269). FTD was calculated by extracting the fundus tessellations as the regions of interest (circle 1, diameter of 3.0 mm; circle 2, diameter of 6.0 mm) and then calculating the average exposed choroid area per unit area of fundus. RESULTS: Among 1,084 students, 1,002 (92.5%) students' FTDs were extracted. The mean FTD was 0.06 ± 0.06 (range, 0-0.40). In multivariate analysis, FTD was significantly associated with male sex, longer AL, thinner subfoveal choroid thickness (SFCT), increased choriocapillaris vessel density (VD), and decreased deeper choroidal VD (all p < 0.05). In circle 1 (diameter of 3.0 mm) and circle 2 (diameter of 6.0 mm), analysis of variance showed that the FTD of the nasal region (p < 0.05) was significantly larger than that of the superior, inferior, and temporal regions. CONCLUSION: AI-based imaging processing could improve the accuracy of fundus tessellation diagnosis. FTD was significantly associated with a longer AL, thinner SFCT, increased choriocapillaris VD, and decreased deeper choroidal VD.

First Report of Pectobacterium brasiliense Causing Bacterial Blackleg and Soft Rot of Potato in Pennsylvania.

Potato (Solanum tuberosum) plants showing blackleg and soft rot symptoms were collected at a commercial vegetable farm near Newmanstown, PA in August 2021 (Fig. S1). The incidence of potato blackleg in the unirrigated field was about 5 to 8%, but approximately 30% in the irrigated field. The diseased stems were cut into 5 cm and surface disinfected. The stem segments were placed into a 50-mL tube containing 15 mL of sterile water for 15 min for bacterial release. The bacterial suspension was streaked on crystal violet polypectate (CVP) (Hélias et al. 2012) plates and incubated at 28°C for 48 h. Three single colonies produced pits on CVP were picked and purified. Genomic DNA of all three isolates were extracted using the FastDNA Spin Kit (MP Biomedicals, Santa Ana, CA). Polymerase chain reaction (PCR) was performed using all three extracted DNAs as a template with the primer pairs gapA 7F/938R (Cigna et al. 2017), recA F/R (Waleron et al. 2001), dnaA F/R (Schneider et al. 2011) and dnaX F/R (Slawiak et al. 2009) targeting the gapA, recA, dnaA and dnaX genes, respectively. Isolate 21PA01 was further studied as a representative isolate. PCR amplicons derived from both forward and reverse primers were sequenced and analyzed using the BLAST algorithm against the NCBI database (https://www.ncbi.nlm.nih.gov). The regions of gapA (GenBank accession No. ON989738), recA (ON989739), dnaA (OP121183), and dnaX (OP121184) had 99.86%, 100%, 98.88%, and 100% identities with Pectobacterium brasiliense strains S1.16.01.3M (MN167062.1), BL-2 (MW721598.1), IPO:4132 (CP059956.1), and BL-2 (MW721603.1), respectively. A phylogenetic maximum-likelihood tree of the concatenated genes with the length of 2551 bp was constructed to visualize the relationship among different species of Dickeya and Pectobacterium. As a result, 21PA01 was in a single monophyletic cluster with other Pectobacterium brasiliense reference strains (Fig. S2 C). To confirm the pathogen, Koch's postulates were performed. Seed pieces of potato 'Lamoka' were planted in potting mix in one-gallon plastic pots in a greenhouse. Three weeks after emergence, the stems of three plants were each injected with 10 µL of bacteria suspension of either 21PA01 at 107 CFU/mL, P. parmentieri ME175 in tryptic soy broth (TSB) at 107 CFU/mL or TSB at 2 cm above the soil line. Seven days after inoculation, stems inoculated with 21PA01 and ME175 showed black and rotten symptoms, whereas the TSB-injected control plants remained symptomless. In addition, 'Lamoka' tubers were inoculated by placing 10 µL 21PA01 and ME175 suspensions at 107 CFU/mL, and TSB in a 1-cm-deep hole poked in a tuber separately and then sealed with petroleum gel, followed by incubation in a moist chamber at 22 °C for 4 d. The 21PA01 and ME175 inoculated tubers showed soft rot symptoms, but the TSB treatment had no symptoms. Bacterial colonies were isolated from the infected stems and confirmed by the DNA sequences as described above. PCR result was negative on control plant samples. Both stem and tuber inoculation trials were repeated two times, and the results were consistent. Thus, 21PA01 was identified as Pectobacterium brasiliense. To our knowledge, this is the first report of P. brasiliense infecting potatoes in Pennsylvania, USA, although it has been reported somewhere else (van der Merwe et al. 2010, Zhao et al. 2018). This could be a new species in Northeastern US.

In vivo analysis of ciliary muscle in myopic Chinese young adults using ArcScan Insight® 100.

OBJECTIVE: To analyse the morphological characteristics of the ciliary muscle (CM) and to explore its relationship with different ocular biometric parameters in myopic young Chinese adults. METHODS: This observational, cross-sectional study included 50 right eyes from 50 myopic adults. The CM area (CMA), CM thickness (CMT) and CM length (CML) were measured using the ArcScan Insight® 100. CMT was determined at three points: 1.0 mm (CMT-1), 2.0 mm (CMT-2) and 3.0 mm (CMT-3) posterior to the scleral spur. CML was measured on the scleral (CMLs) and vitreous (CMLv) aspects. The spherical equivalent refraction (SER), axial length (AL) and subfoveal choroidal thickness (SFCT) were examined to determine their associations with CM parameters (CMA, CML and CMT). RESULTS: The mean SER and AL were -4.39 ± 2.29 D and 25.61 ± 1.15 mm, respectively. Compared with the nasal CMA, CML and CMT (CMT-1, CMT-2 and CMT-3) findings, the temporal CM parameters (CMA, CMLs, CMLv, CMT-1, CMT-2 and CMT-3) were found to be significantly thicker (all p < 0.001, except CMLv and CMT-1; p < 0.01). The nasal CMA was associated with the average corneal curvature (r = 0.30, p = 0.03) and SER (r = -0.30, p = 0.04). Nasal and temporal CMT-2 were negatively correlated with SER (r = -0.33 and -0.32, respectively, both p < 0.05). There was no correlation between CM parameters (except nasal CMLs, r = 0.31, p = 0.03) and SFCT, or between CM parameters and either the AL or anterior chamber depth (all p > 0.05). CONCLUSION: These results suggest that there is temporal versus nasal asymmetry of the CM. CMA, CMT or CML did not vary with axial growth of the eye. The CM is not simply stretched as the eye elongates in myopic young adults.

MAPK-like protein 1 positively regulates maize seedling drought sensitivity by suppressing ABA biosynthesis.

Mitogen-activated protein kinase (MAPK) cascades play vital roles in regulating plant growth, development, and stress responses. MAPK-like (MPKL) proteins are a group of kinases containing the MAPK signature TxY motif and showing sequence similarity to MAPKs. However, the functions of plant MPKL proteins are currently unknown. The maize (Zea mays) genome contains four genes encoding MPKL proteins, here named ZmMPKL1 to ZmMPKL4. In this study, we show that ZmMPKL1 possesses kinase activity and that drought-induced ZmMPKL1 expression, ZmMPKL1 overexpression and knockout maize seedlings exhibited no visible morphological difference from wild-type B73 seedlings when grown under normal conditions. By contrast, under drought conditions, ZmMPKL1-overexpressing seedlings showed increased stomatal aperture, water loss, and leaf wilting and knockout seedlings showed the opposite phenotypes. Moreover, these drought-sensitive phenotypes in ZmMPKL1-overexpressing seedlings were restored by exogenous abscisic acid (ABA). ZmMPKL1 overexpression reduced drought-induced ABA production in seedlings and the knockout showed enhanced ABA production. Drought-induced transcription of ABA biosynthetic genes were suppressed and ABA catabolic genes were enhanced in ZmMPKL1-overexpressing seedlings, while their transcription were reversely regulated in knockout seedlings. These results suggest that ZmMPKL1 positively regulates seedlings drought sensitivity by altering the transcription of ABA biosynthetic and catabolic genes, and ABA homeostasis.

Choroidal changes in lens-induced myopia in guinea pigs.

INTRODUCTION: This study aimed to determine the role of the choroid in lens-induced myopia (LIM) in guinea pigs. METHODS: Guinea pigs were randomly divided into two groups: a normal control (NC) group and a LIM group. Refraction and axial length (AL) were measured by streak retinoscopy and A-scan ultrasonography. The choroidal thickness (ChT), vessel density of the choriocapillaris (VDCC) and vessel density of the choroidal layer (VDCL) were assessed by Spectral-domain Optical Coherence Tomography Angiography (SD-OCT). In addition, the choroidal expression of nitric oxide synthase (NOS) enzymes at the mRNA and protein levels was analyzed by real-time fluorescence quantitative PCR, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. RESULTS: In the LIM group, refraction and AL were increased significantly compared with those in the NC group at 2 weeks (refraction: LIM vs. NC, -4.23 ± 0.43 D vs. 2.20 ± 0.48 D; AL: LIM vs. NC, 8.36 ± 0.05 mm vs. 8.22 ± 0.03 mm) and 4 weeks (refraction: LIM vs. NC, -5.88 ± 0.49 D vs. 1.63 ± 0.41 D; AL: 8.57 ± 0.06 mm vs. 8.40 ± 0.04 mm). The ChT and VDCC were decreased significantly compared with those in the NC group at 2 weeks (ChT: LIM vs. NC, 60.92 ± 8.15 µm vs. 79.11 ± 7.47 µm; VDCC: LIM vs. NC, 23.43 ± 3.85% vs. 28.74 ± 4.11%) and 4 weeks (ChT: LIM vs. NC, 48.43 ± 6.85 µm vs. 76.38 ± 7.84 µm; VDCC: LIM vs. NC, 21.29 ± 2.17% vs. 27.64 ± 2.91%). The VDCL was also decreased compared with that in the NC group at 2 weeks and 4 weeks (NC vs. LIM, 24.87 ± 5.16% vs. 22.45 ± 3.26%; 23.37 ± 5.85% vs. 21.39 ± 2.62%; all P > 0.05). Moreover, the ChT was positively correlated with the VDCC and VDCL. The mRNA and protein expression of NOS enzymes (eNOS and nNOS) was increased. CONCLUSIONS: During the development of myopia, the ChT, VDCC and VDCL were decreased, while NOS expression in the choroid was increased. The expression of NOS was negatively correlated with the ChT, VDCC and VDCL. NO may play an important role in regulating the choroid during myopia development.

Effects of Orthokeratology on Axial Length Elongation in Anisometropes.

INTRODUCTION: This study aimed to investigate the therapeutic effects of overnight orthokeratology (OK) lenses on anisometropes. METHODS: We enrolled 178 anisometropes from August 2015 to August 2017. We then divided these patients into 2 parts depending on them wearing either monocular or binocular OK lenses. In part one, 47 monocular myopic subjects (25 males and 22 females) were treated with OK lenses in the myopic eyes only. We also labeled the myopic eyes as the OK group and the contralateral nonmyopic eyes as the control group. The initial average wearing age of the subjects was 12.35 ± 2.37 years (8-16 years). The mean follow-up duration was 15.43 ± 4.88 months (7-25 months). The average spherical equivalent refraction (SER) was -2.31 ± 1.16 diopter (D) in the OK group and 0.15 ± 0.49 D in the control group (p < 0.001). In part 2, 131 binocular myopic anisometropes (56 males and 75 females) were involved in the study. The eyes with more severe myopia were assigned to the G group and the contralateral eyes to the L group. The initial average wearing age of the subjects was 12.92 ± 2.60 years ( 8-16 years). The mean follow-up duration was 17.83 ± 5.02 months (7-26 months). The average SER was -4.79 ± 1.90 D in the G group and -3.14 ± 1.88 D in the L group (p < 0.001). We calculated the axial length (AL) difference and AL elongation as our primary outcome measures. RESULTS: In part one, the AL elongation in the OK group (0.21 ± 0.09 mm) was significantly lower than that in the control group (0.70 ± 0.17 mm) at 24 months (p < 0.001). Meanwhile, the AL difference exhibited a decrease of 0.50 ± 0.29 mm from a baseline of 1.08 ± 0.35 to 0.58 ± 0.25 mm at 24 months (F = 24.539, p < 0.001). In part 2, the AL had increased by 0.17 ± 0.13 mm in the G group and 0.24 ± 0.18 mm in the L group after 24-month follow-up, respectively (p < 0.001). While the AL difference decreased from 0.55 ± 0.11 mm at the baseline, to 0.48 ± 0.08 mm at 24 months, eliciting a decrement in AL difference of 0.07 ± 0.09 mm (F = 3.884, p = 0.030). CONCLUSIONS: OK lenses can slow down AL growth in anisometropes and has a greater effect on reducing AL elongation in the more severely affected myopic eyes of anisometropic patients.

Oncogenic heterogeneous nuclear ribonucleoprotein D-like promotes the growth of human colon cancer SW620 cells via its regulation of cell-cycle.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) represent a large family of RNA-binding proteins. Heterogeneous nuclear ribonucleoprotein D-like (HNRPDL) is a member of this family. Though aberrant expression of HNRPDL has been reported in a few cancers, whether HNRPDL is deregulated in colon cancer patients and what role this protein plays in these cells are not known yet. In this study, we found that HNRPDL was significantly up-regulated in colon cancer specimens than control. We also demonstrated that HNRPDL silencing inhibited the growth of SW620 cells both in vitro and in vivo. Conversely, we constructed a retroviral vector to deliver HNRPDL into non-malignant NIH-3T3 cells and injected these cells into nude mice. HNRPDL-overexpressing NIH-3T3 cells generated tumors in nude mice but not the control cells. Mechanistically, HNRPDL promoted cell-cycle progression associated with enhanced expressions of cyclin D3 and Ki-67 but decreased expressions of p53 and p21. Taken together, our data demonstrate that HNRPDL is aberrantly expressed in colon cancer cells, which promotes the growth of these cells by activating cell-cycle progression.

Selection of non-Saccharomyces yeasts for orange wine fermentation based on their enological traits and volatile compounds formation.

In order to select the non-Saccharomyces yeasts for orange wine fermentation, the enological traits and volatile compounds formation of ten non-Saccharomyces yeast strains were evaluated through physicochemical methods and solid-phase microextraction coupled to GC-MS, respectively. The results indicated that non-Saccharomyces yeast fermentation had lower maximum populations (7.8-8.0 Log cfu/mL), longer fermentation period (7-10 days), lower ethanol (4.13-7.79%), lower total acids (7.48-8.51 g/L) and higher volatile acids concentrations (0.08-0.23 g/L) when compared with those of Saccharomyces cerevisiae fermentation. Hanseniaspora uvarum, Hanseniaspora opuntiae, Hanseniaspora occidentalis, Pichia kudriavzevii and Torulaspora delbrueckii were selected as candidates for orange wine fermentation with higher volatile compounds concentration, odor active values and sensory evaluation scores. This study will provide a valuable selection method of non-Saccharomyces yeasts for orange wine fermentation, and an approach to improve the flavor of orange wine or other fruit wine.

Velocity measurement based on multiple self-mixing interference.

This study proposes a novel algorithm based on the multiple self-mixing interference (MSMI) theory to measure the velocity of a remote target without contact. The principle of MSMI is presented and the corresponding formulas for velocity measurement are derived. Fast Fourier transform is applied to detect signal frequency and calculate velocity values. A low-cost, compact, and easy-to-operate experimental setup is also constructed. Experiments are conducted to validate the correctness of our algorithm. This algorithm can improve resolution more easily than conventional self-mixing interference methods.

SATB1 overexpression promotes malignant T-cell proliferation in cutaneous CD30+ lymphoproliferative disease by repressing p21.

Cutaneous CD30(+) lymphoproliferative disease (CD30(+)LPD), characterized by the presence of CD30(+) anaplastic large T cells, comprises the second most common group of cutaneous T-cell lymphoma (CTCL). However, little is known about the pathobiology of the CD30(+) lymphoma cells, as well as the mechanisms of disease progression. Here we report that Special AT-rich region binding protein 1 (SATB1), a thymocyte specific chromatin organizer, is over-expressed in CD30(+) lymphoma cells in most CD30(+)LPDs, and its expression is upregulated during disease progression. Our findings show that SATB1 silencing in CD30(+)LPD cells leads to G1 cell cycle arrest mediated by p21 activation. Using chromatin immunoprecipitation, luciferase assays, and mutational analysis, we demonstrate that SATB1 directly regulates the transcription of p21 in a p53-independent manner. Moreover, DNA demethylation on a specific CpG-rich region of the SATB1 promoter is associated with the upregulation of SATB1 during disease progression. These experiments define a novel SATB1-p21 pathway in malignant CD30(+) T lymphocytes, which provides novel molecular insights into the pathogenesis of CD30(+)LPDs and possibly leads to new therapies.

ZFX modulates the growth of human leukemic cells via B4GALT1.

Zinc finger protein X-linked (ZFX) is a key regulator of both embryonic stem cells (ESCs) and hematopoietic stem cells (HSCs), which is required for both Notch intracellular domain (NotchIC)-induced acute T-cell leukemia and MLL-AF9-induced myeloid leukemia in mouse models. However, the role of ZFX and its underlying mechanism in human leukemic cells remain unclear yet, though accumulating data have demonstrated that ZFX is aberrantly expressed in various human tumors and plays an important role. Herein, we found that ZFX was aberrantly expressed in various human leukemic cell lines and primary cells from leukemia patients compared with control cells. The silence of ZFX led to the growth suppression through either the deregulated cell cycle or the induction of apoptosis in various cells including K562, Jurkat, Namalwa, and THP-1 cells. The gene expression analysis revealed that UDP-Gal:ßGlcNAc ß 1,4-galactosyltransferase, polypeptide 1 (B4GALT1) was significantly down-regulated upon ZFX silencing, which is implicated in the response of K562 cells to the treatment of imatinib mesylate (IM). In addition, lectin blot assay showed that the galactosylation of glycoproteins in K562 cells was suppressed upon ZFX silencing. Interestingly, overexpression of B4GALT1 restored the growth and conferred drug resistance to ZFX-silenced cells. Taken together, we have demonstrated that ZFX is aberrantly expressed in multiple human leukemic cells and it modulates the growth and drug response of leukemic cells partially via B4GALT1, which suggests that ZFX is a new regulator of leukemic cells and warrants intensive investigations on this 'stemness' regulator in these deadly diseases.

GAS2-Calpain2 axis contributes to the growth of leukemic cells.

Growth arrest specific 2 (GAS2) modulates cell cycle, apoptosis, and Calpain activity. GAS2-Calpain2 axis is required for the growth of BCR-ABL(+) hematopoietic cells and chronic myeloid leukemia cells. However, the expression of GAS2 in acute leukemia patients remains unclear and what role GAS2-Calpain2 axis plays in these leukemic cells is not known yet. In this study, GAS2 was found to have significantly higher expression in 16 various leukemic cell lines than in control cells. Using THP-1 cells (from acute myeloid leukemia patient, AML) and Jurkat cells (from acute lymphoid leukemia patient, ALL) as models, we found that GAS2 silence led to elevated Calpain activity, decreased cellular growth, and inhibition of colony-forming cell (CFC) production; and these effects could be rescued by GAS2 re-expression. Moreover, GAS2 silence prevented tumor formation of THP-1 cells in nude mice. In both THP-1 and Jurkat cells, GAS2 interacted with Calpain2 rather than Calpain1. The dominant negative form of GAS2 (GAS2DN, GAS2Δ171-313) had similar effects on leukemic cells through the activation of Calpain. Importantly, Calpain2 silence abolished the proliferation inhibition induced by GAS2 targeting. We also found that GAS2 was aberrantly expressed and Calpain activity was decreased in clinical isolates from acute leukemia patients. Taken together, our results demonstrated the deregulation of GAS2 in both AML and ALL and the requirement of GAS2-Calpain2 axis for the growth of leukemic cells, which will help to understand the molecular pathogenesis of hematological malignancies and possibly to develop novel approaches to treat these deadly diseases.

Functional, transcriptomic, and lipidomic studies of the choC gene encoding a phospholipid methyltransferase in Aspergillus fumigatus.

IMPORTANCE: This study explored the phospholipid metabolic pathway in A. fumigatus and its relationship with fungal growth, metabolism, and pathogenicity. ChoC, based on its critical roles in many aspects of the fungus and relatively conserved characteristics in filamentous fungi with low similarity with mammalian ones, can be a novel target of new antifungal drugs.

Widespread Involvement of Acetylation in the Retinal Metabolism of Form-Deprivation Myopia in Guinea Pigs.

Myopia has become the major cause of visual impairment worldwide. Although the pathogenesis of myopia remains controversial, proteomic studies suggest that dysregulation of retinal metabolism is potentially involved in the pathology of myopia. Lysine acetylation of proteins plays a key role in regulating cellular metabolism, but little is known about its role in the form-deprived myopic retina. Hence, a comprehensive analysis of proteomic and acetylomic changes in the retinas of guinea pigs with form-deprivation myopia was performed. In total, 85 significantly differential proteins and 314 significantly differentially acetylated proteins were identified. Notably, the differentially acetylated proteins were markedly enriched in metabolic pathways such as glycolysis/gluconeogenesis, the pentose phosphate pathway, retinol metabolism, and the HIF-1 signaling pathway. HK2, HKDC1, PKM, LDH, GAPDH, and ENO1 were the key enzymes in these metabolic pathways with decreased acetylation levels in the form-deprivation myopia group. Altered lysine acetylation of key enzymes in the form-deprived myopic retina might affect the dynamic balance of metabolism in the retinal microenvironment by altering their activity. In conclusion, as the first report on the myopic retinal acetylome, this study provides a reliable basis for further studies on myopic retinal acetylation.

Quantization of Optic Disc Characteristics in Young Adults Based on Artificial Intelligence.

PURPOSE: This study aimed to automatically and quantitatively analyse the characteristics of the optic disc by applying artificial intelligence (AI) to fundus images. METHODS: A total of 1084 undergraduates were recruited in this cross-sectional study. The optic disc area, cup-to-disc ratio (C/D), optic disc tilt, and the area, width, and height of peripapillary atrophy (PPA) were automatically and quantitatively detected using AI. Based on axial length (AL), participants were divided into five groups: Group 1 (AL ≤ 23 mm); Group 2 (23 mm < AL≤ 24 mm); Group 3 (24 mm < AL≤ 25 mm); Group 4 (25 mm < AL< 26 mm) and Group 5 (AL ≥ 26 mm). Relationships between ocular parameters and optic disc characteristics were analysed. RESULT: A total of 999 undergraduates were included in the analysis. The prevalence of optic disc tilting and PPA were 47.1% and 92.5%, respectively, and increased with the severity of myopia. The mean optic disc area, PPA area, C/D, and optic disc tilt ratio were 1.97 ± 0.46 mm2, 0.84 ± 0.59 mm2, 0.18 ± 0.07, and 0.81 ± 0.08, respectively. In Group 5, the average optic disc area (1.84 ± 0.41 mm2) and optic disc tilt ratio (0.79 ± 0.08) were significantly smaller and the PPA area (1.12 ± 0.61 mm2) was significantly larger than those in the other groups. AL was negatively correlated with optic disc area and optic disc tilt ratio (r=-0.271, -0.219; both p < 0.001) and positively correlated with PPA area, width, and height (r = 0.421, 0.426, 0.345; all p < 0.01). A greater AL (ß = 0.284, p < 0.01) and a smaller optic disc tilt ratio (ß=-0.516, p < 0.01) were related to a larger PPA area. CONCLUSION: The characteristics of the optic disc can be feasibly and efficiently extracted using AI. The quantization of the optic disc might provide new indicators for clinicians to evaluate the degree of myopia.

Effects of Mixed Adding Crude Extracts of ß-Glucosidases from Three Different Non-Saccharomyces Yeast Strains on the Quality of Cabernet Sauvignon Wines.

The aim of this study was to investigate the effects of crude extracts of ß-glucosidase from Issatchenkia terricola SLY-4, Pichia kudriavzevii F2-24 and Metschnikowia pulcherrima HX-13 (termed as SLY-4E, F2-24E and HX-13E) on the flavor complexity and typicality of Cabernet Sauvignon wines. The grape must was fermented using Saccharomyces cerevisiae with single or mixed SLY-4E, F2-24E and HX-13E. The physicochemical characteristics, volatile aroma compounds, total anthocyanins and sensory attributes of the wines were determined. Adding SLY-4E, F2-24E and HX-13E in wines resulted in a decrease in the anthocyanin content, total acids and volatile acids in wines but an increase in the content of terpenes, benzene derivatives, higher alcohols and esters, which may enhance wine sensory qualities and result in loss of wine color. Different adding strategies of ß-glucosidase led to a variety of effects on wine aroma. S/H/F-Ew significantly increased the content of benzene derivatives, higher alcohols and long-chain fatty acid esters, which enhanced the fruity and floral flavor of wines. F2-24E significantly increased the content of short- and medium-chain fatty acid esters, acetate esters and carbonyl compounds. The results indicated that the mixed addition of non-Saccharomyces crude extracts and co-fermentation with S. cerevisiae could further improve wine flavor quality.