ARRDC5 deficiency impairs spermatogenesis by affecting SUN5 and NDC1.

Sperm with normal morphology and motility are essential for successful fertilization, and the strong attachment of the sperm head-tail coupling apparatus to the nuclear envelope during spermatogenesis is required to ensure the integrity of sperm for capacitation and fertilization. Here, we report that Arrdc5 is associated with spermatogenesis. The Arrdc5 knockout mouse model showed male infertility characterized by a high bent-head rate and reduced motility in sperm, which led to capacitation defects and subsequent fertilization failure. Through mass spectrometry, we found that ARRDC5 affects spermatogenesis by affecting NDC1 and SUN5. We further found that ARRDC5 might affect the vesicle-trafficking protein SEC22A-mediated transport and localization of NDC1, SUN5 and other head-tail coupling apparatus-related proteins that are responsible for initiating the attachment of the sperm head and tail. We finally performed intracytoplasmic sperm injection as a way to explore therapeutic strategies. Our findings demonstrate the essential role and the underlying molecular mechanism of ARRDC5 in anchoring the sperm head to the tail during spermatogenesis.

Bi-allelic variants in ASTL cause abnormal fertilization or oocyte maturation defects.

Fertilization is a fundamental process of development, and the blocking mechanisms act at the zona pellucida (ZP) and plasma membrane of the egg to prevent any additional sperm from binding, permeating and fusing after fertilization. In clinical practice, some couples undergoing recurrent IVF failures that mature oocytes had abnormal fertilization for unknown reason. Ovastacin encoded by ASTL cleave the ZP protein ZP2 and play a key role in preventing polyspermy. Here, we identified bi-allelic variants in ASTL that are mainly characterized by fertilization problems in humans. All four independent affected individuals had bi-allelic frameshift variants or predicted damaging missense variants, which follow a Mendelian recessive inheritance pattern. The frameshift variants significantly decreased the quantity of ASTL protein in vitro. And all missense variants affected the enzymatic activity that cleaves ZP2 in mouse egg in vitro. Three knock-in female mice (corresponding to three missense variants in patients) all show subfertility due to low embryo developmental potential. This work presents strong evidence that pathogenic variants in ASTL cause female infertility and provides a new genetic marker for the diagnosis of fertilization problems.

CCDC28A deficiency causes sperm head defects, reduced sperm motility and male infertility in mice.

Mature spermatozoa with normal morphology and motility are essential for male reproduction. The epididymis has an important role in the proper maturation and function of spermatozoa for fertilization. However, factors related to the processes involved in spermatozoa modifications are still unclear. Here we demonstrated that CCDC28A, a member of the CCDC family proteins, is highly expressed in testes and the CCDC28A deletion leads to male infertility. We found CCDC28A deletion had a mild effect on spermatogenesis. And epididymal sperm collected from Ccdc28a-/- mice showed bent sperm heads, acrosomal defects, reduced motility and decreased in vitro fertilization competence whereas their axoneme, outer dense fibers, and fibrous sheath were all normal. Furthermore, we found that CCDC28A interacted with sperm acrosome membrane-associated protein 1 (SPACA1) and glycogen synthase kinase 3a (GSK3A), and deficiencies in both proteins in mice led to bent heads and abnormal acrosomes, respectively. Altogether, our results reveal the essential role of CCDC28A in regulating sperm morphology and motility and suggesting a potential marker for male infertility.

A plant-specific SWR1 chromatin-remodeling complex couples histone H2A.Z deposition with nucleosome sliding.

Deposition of H2A.Z in chromatin is known to be mediated by a conserved SWR1 chromatin-remodeling complex in eukaryotes. However, little is known about whether and how the SWR1 complex cooperates with other chromatin regulators. Using immunoprecipitation followed by mass spectrometry, we found all known components of the Arabidopsis thaliana SWR1 complex and additionally identified the following three classes of previously uncharacterized plant-specific SWR1 components: MBD9, a methyl-CpG-binding domain-containing protein; CHR11 and CHR17 (CHR11/17), ISWI chromatin remodelers responsible for nucleosome sliding; and TRA1a and TRA1b, accessory subunits of the conserved NuA4 histone acetyltransferase complex. MBD9 directly interacts with CHR11/17 and the SWR1 catalytic subunit PIE1, and is responsible for the association of CHR11/17 with the SWR1 complex. MBD9, TRA1a, and TRA1b function as canonical components of the SWR1 complex to mediate H2A.Z deposition. CHR11/17 are not only responsible for nucleosome sliding but also involved in H2A.Z deposition. These results indicate that the association of the SWR1 complex with CHR11/17 may facilitate the coupling of H2A.Z deposition with nucleosome sliding, thereby co-regulating gene expression, development, and flowering time.

Acupuncture plus topiramate placebo versus topiramate plus sham acupuncture for the preventive treatment of chronic migraine: A single-blind, double-dummy, randomized controlled trial.

BACKGROUND: Acupuncture has been used for the treatment of chronic migraine, but high-quality evidence is scarce. We aimed to evaluate acupuncture's efficacy and safety compared to topiramate for chronic migraine. METHODS: This double-dummy randomized controlled trial included participants aged 18-65 years diagnosed with chronic migraine. They were randomly assigned (1:1) to receive acupuncture (three sessions/week) plus topiramate placebo (acupuncture group) or topiramate (50-100 mg/day) plus sham acupuncture (topiramate group) over 12 weeks, with the primary outcome being the mean change in monthly migraine days during weeks 1-12. RESULTS: Of 123 screened patients, 60 (mean age 45.8, 81.7% female) were randomly assigned to acupuncture or topiramate groups. Acupuncture demonstrated significantly greater reductions in monthly migraine days than topiramate (weeks 1-12: -2.79 [95% CI: -4.65 to -0.94, p = 0.004]; weeks 13-24: -3.25 [95% CI: -5.57 to -0.92, p = 0.007]). No severe adverse events were reported. CONCLUSIONS: Acupuncture may be safe and effective for treating chronic migraine. The efficacy of 12 weeks of acupuncture was sustained for 24 weeks and superior to that of topiramate. Acupuncture can be used as an optional preventive therapy for chronic migraine. TRIAL REGISTRATION: ISRCTN.org Identifier 13563102.

Meiotic defects in human oocytes: Potential causes and clinical implications.

Meiotic defects cause abnormal chromosome segregation leading to aneuploidy in mammalian oocytes. Chromosome segregation is particularly error-prone in human oocytes, but the mechanisms behind such errors remain unclear. To explain the frequent chromosome segregation errors, recent investigations have identified multiple meiotic defects and explained how these defects occur in female meiosis. In particular, we review the causes of cohesin exhaustion, leaky spindle assembly checkpoint (SAC), inherently unstable meiotic spindle, fragmented kinetochores or centromeres, abnormal aurora kinases (AURK), and clinical genetic variants in human oocytes. We mainly focus on meiotic defects in human oocytes, but also refer to the potential defects of female meiosis in mouse models.

Changes in the cortical network during sleep stage transitions.

Sleep state transitions are closely related to insomnia, drowsiness, and sleep maintenance. However, how the cortical network varies during such a transition process remains unclear. Changes in the cortical interaction during the short-term process of sleep stage transitions were investigated. In all, 40 healthy young participants underwent overnight polysomnography. The phase transfer entropy of six frequency bands was obtained from 16 electroencephalography channels to assess the strength and direction of information flow between the cortical regions. Differences in the cortical network between the first and the last 10 s in a 40-s transition period across wakefulness, N1, N2, N3, and rapid eye movement were, respectively, studied. Various frequency bands exhibited different patterns during the sleep stage transitions. It was found that the mutual transitions between the sleep stages were not necessarily the opposite. More significant changes were observed in the sleep deepening process than in the process of sleep awakening. During sleep stage transitions, changes in the inflow and outflow strength of various cortical regions led to regional differences, but for the entire sleep progress, such an imbalance did not intensify, and a dynamic balance was instead observed. The detailed findings of variations in cortical interactions during sleep stage transition promote understanding of sleep mechanism, sleep process, and sleep function. Additionally, it is expected to provide helpful clues for sleep improvement, like reducing the time required to fall asleep and maintaining sleep depth.

Heterozygous loss-of-function variants in LHX8 cause female infertility characterized by oocyte maturation arrest.

PURPOSE: The genetic causes of oocyte maturation arrest leading to female infertility are largely unknown, and no population-based genetic analysis has been applied in cohorts of patients with infertility. We aimed to identify novel pathogenic genes causing oocyte maturation arrest by using a gene-based burden test. METHODS: Through comparison of exome sequencing data from 716 females with infertility characterized by oocyte maturation arrest and 3539 controls, we performed a gene-based burden test and identified a novel pathogenic gene LHX8. Splicing event was evaluated using a minigene assay, expression of LHX8 protein was assessed in HeLa cells, and nuclear subcellular localization was determined in both HeLa cells and mouse oocytes. RESULTS: A total of 5 heterozygous loss-of-function LHX8 variants were identified from 6 independent families (c.389+1G>T, c.412C>T [p.Arg138∗], c.282C>A [p.Cys94∗]; c.257dup [p.Tyr86∗]; and c.180del, [p.Ser61Profs∗30]). All the identified variants in LHX8 produced truncated LHX8 protein and resulted in loss of LHX8 nuclear localization in both HeLa cells and mouse oocytes. CONCLUSION: By combining genetic evidence and functional evaluations, we identified a novel pathogenic gene LHX8 and established the causative relationship between LHX8 haploinsufficiency and female infertility characterized by oocyte maturation arrest.

Effect of EGFR amplification on the prognosis of EGFR-mutated advanced non-small-cell lung cancer patients: a prospective observational study.

BACKGROUND: Epidermal growth factor receptor (EGFR) amplification refers to the copy number increase of EGFR gene, and is often identified as a "bypass" way of Epidermal growth factor receptor Tyrosine kinase inhibitors (EGFR-TKI) resistance. We aimed to explore the effect of EGFR amplification on EGFR mutation treatment-naive advanced non-squamous non-small cell lung cancer (NSCLC) patients. METHODS: We conducted a prospective observational study in single center, enrolling advanced non-squamous NSCLC patients receiving Tyrosine kinase inhibitors (TKIs) between March 3, 2019, and February 1, 2022. Next-generation sequencing (NGS) was used to detect genetic alterations in tumor tissue samples. Progression-free survival (PFS) curves were performed using the Kaplan-Meier method. Univariate and multivariate analyses were used to evaluate factors affecting the efficacy of TKIs. RESULTS: A total of 117 treatment-naive advanced NSCLC patients were identified in this study. EGFR amplification was found in 22 of 117 (18.8%) patients with EGFR mutations. Of 22 patients with EGFR amplification, 10 patients harbored EGFR 19 del, 11 patients with 21-L858R. The median follow-up time was 22.47 months. The median PFS of the patients with or without EGFR amplification was 8.25 months and 10.67 months, respectively (log-rank test, P = 0.63). In multivariate analysis, EGFR amplification was not an independent prognosis factor for the patients receiving first-line TKIs [HR = 1.38, 95%CI (0.73-2.58), P = 0.321]. Subgroup analysis revealed that EGFR amplification is a risk factor for progression in the brain metastasis population. [HR = 2.28, 95%CI (1.01, 5.14), P = 0.047]. CONCLUSION: EGFR amplification is not an independent prognosis factor for PFS in advanced non-squamous NSCLC patients receiving first-line TKIs. However, it is an independent risk factor for PFS in the brain metastasis population.

Interactions of central and autonomic nervous systems in patients with sleep apnea-hypopnea syndrome during sleep.

PURPOSE: Sleep apnea-hypopnea syndrome (SAHS) is an independent risk factor for various cardiovascular and cerebrovascular diseases, but the underlying relationship of its physiological subsystems remains unclear. Thus, we aimed to investigate the effect of SAHS on central and autonomic nervous system (CNS-ANS) interactions during sleep. METHODS: Thirty-five patients with SAHS and 19 healthy age-matched controls underwent overnight polysomnography. The absolute spectral powers of five frequency bands from six EEG channels and ECG morphological features (HR, PR interval, QT interval) were calculated. Multivariable transfer entropy was applied to analyze the differences of the CNS-ANS network interactions between patients with SAHS of different severities and healthy controls during deep, light, and rapid eye movement sleep. RESULTS: The CNS-ANS network interacted bidirectionally in all researched groups, with the cardiac information modulating the brain activity. The information strength from QT to most EEG components and PR to some EEG components was significantly affected by SAHS severity during light sleep, which indicates the coupling features of QT-brain nodes are important indicators. The driver effects from the ß-band significantly increased in patients with SAHS. CONCLUSIONS: Respiratory events may be the main reason for the CNS-ANS interaction changes in SAHS. These findings help explain the physiological regulation process of SAHS and provide valuable information for analysis of the development of SAHS-related cardiovascular and chronic diseases.

Sesquiterpenes from Fissistigma glaucescens inhibiting the proliferation of synoviocytes.

Two new sesquiterpenes, litseachrandaevanes C and D (1 and 2), together with five known sesquiterpenes (3 - 7), were isolated from the stems of Fissistigma glaucescens (Hance) Merr. Their structures were elucidated using comprehensive spectroscopic methods. The inhibitory effect of all compounds on the proliferation of primary synovial cells was evaluated. Compound 3 showed inhibitory effect on the proliferation of synoviocytes, with an IC50 value of 12.5 µM.

Effects of vegetation succession on soil organic carbon fractions and stability in a karst valley area, Southwest China.

A series of complex organic fractions with different physical and chemical properties make up soil organic carbon (SOC), which plays a vital role in climate change and the global carbon cycle. Different SOC fractions have different stability and respond differently to vegetation succession. This research was carried out to assess the impacts of vegetation succession on SOC dynamics in the Qingmuguan karst valley area, southwest China. Soil samples were collected from four typical vegetation succession stages, including farmland, grassland, shrubland, and forest. The total SOC content and four oxidizable SOC fractions were measured. Results showed that the total SOC content and storage under farmland were highest, followed by forest and shrubland, and the grassland had the lowest total SOC content and storage. The SOC sequestration potential under different vegetation types in the study area was grassland (26.32 Mg C ha-1) > shrubland (9.64 Mg C ha-1). All SOC content, storage, and fractions showed a decrease with the increase of soil depth over the 0-50 cm in the study area. The four SOC fractions under forest at topsoil (0-10 cm) were higher than that under the other vegetation types. Compared with the other land uses, the farmland had the highest stable oxidizable SOC fractions (F3 and F4) at the 10-50-cm depth, while the shrubland had the highest active oxidizable SOC fractions (F1 and F2). In terms of the lability index of SOC, shrubland was the largest, followed by grassland and forest, and farmland was the smallest. These results provide essential information about SOC fractions and stability changes resulting from changes of vegetation types in a karst valley area of southwest China. It also supplements our understanding of soil carbon sequestration in vegetation succession.

Characterization of specific spatial functional connectivity difference in depression during sleep.

Depression is a common mental illness and a large number of researchers have been still devoted to exploring effective biomarkers for the identification of depression. Few researches have been conducted on functional connectivity (FC) during sleep in depression. In this paper, a novel depression characterization is proposed using specific spatial FC features of sleep electroencephalography (EEG). Overnight polysomnography recordings were obtained from 26 healthy individuals and 25 patients with depression. The weighted phase lag indexes (WPLIs) of four frequency bands and five sleep periods were obtained from 16 EEG channels. The high discriminative connections extracted via feature evaluation and the cross-within variation (CW)-the spatial feature constructed to characterize the different performances in inter- and intra-hemispheric FC based on WPLIs, were utilized to classify patients and normal controls. The results showed that enhanced average FC and spatial differences, higher inter-hemispheric FC and lower intra-hemispheric FC, were found in patients. Furthermore, abnormalities in the inter-hemispheric connections of the temporal lobe in the theta band should be important indicators of depression. Finally, both CW and high discriminative WPLI features performed well in depression screening and CW was more specific for characterizing abnormal cortical EEG performance of depression. Our work investigated and characterized the abnormalities in sleep cortical activity in patients with depression, and may provide potential biomarkers for assisting with depression identification and new insights into the understanding of pathological mechanisms in depression.

Efficacy and acquired resistance for EGFR-TKI plus thoracic SBRT in patients with advanced EGFR-mutant non-small-cell lung cancer: a propensity-matched retrospective study.

BACKGROUND: This retrospective study aimed to evaluate the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) with stereotactic body radiation therapy (SBRT) and to elucidate potential mechanisms of acquired resistance. METHODS: Patients with advanced NSCLC harboring positive EGFR mutations after initial TKI therapy for at least 8 weeks were eligible for SBRT between August 2016 and August 2019. Eligible patients were treated with thoracic SBRT, and TKI was continued after SBRT until it was considered ineffective. The control group was treated with TKIs monotherapy. Propensity score matching (PSM, ratio of 1:2) was used to account for differences in baseline characteristics. Overall survival (OS), progression-free survival (PFS), treatment safety and resistance mechanisms were evaluated. RESULTS: Three hundred eight patients were included in the study population. Among them, 262 patients received TKIs alone, and 46 patients received TKIs with SBRT. Baseline characteristics were not significantly different between the two cohorts after PSM. The median PFS was 19.4 months in the TKIs +SBRT group compared to 13.7 months in the TKIs group (p = 0.034). An influence on OS has not yet been shown (p = 0.557). Of the 135 patients evaluated after PSM, 28 and 71 patients in the TKIs and TKIs +SBRT cohorts, respectively, had plasma cell-free DNA (cfDNA) next-generation sequencing (NGS) performed at baseline and disease progression. In the TKIs +SBRT cohort, the NGS results showed that T790M mutations were detected in 64.3% (18/28) of patients. Patients in the TKIs cohort exhibited fewer T790M-positive mutations (40.8%, p = 0.035) compared to patients in the TKIs +SBRT cohort. CONCLUSION: Real world data prove that TKIs plus thoracic SBRT significantly extend PFS with tolerable toxicity. The mutation ratio of T790M was increased in the TKIs +SBRT group compared to the TKIs only group. Further randomized studies are warranted.

Outcomes from Osteochondral Autograft Transplant or Mosaicplasty in 26 Patients with Type V Osteochondral Lesions of the Talus.

BACKGROUND Mosaicplasty osteochondral transplantation (MOT) has been proved a feasible choice for the treatment of talus osteochondral injury. It can reduce ankle pain and allow performance of daily living activities and elementary sports. However, there are very little data on the restoration of normal life with large lesions. Our investigation focused on assessing outcomes in patients with large lesions. MATERIAL AND METHODS The MOT operation was used, and the donor site was located at the lateral condyle of the femur. Clinical evaluation included the Berndt and Harty outcome question, Visual Analog Scale (VAS) pain score (during rest, walking and running), American Orthopedic Foot and ankle Association (AOFAS) score, International Knee Documentation Committee (IKDC) subjective knee evaluation form, and the Short Form 36 (SF-36). Twenty-four months after surgery, the graft binding was assessed by MRI using the magnetic resonance observation of cartilage repair tissue (MOCART) score. RESULTS We assessed 26 patients, including 14 males and 12 females. The average follow-up time was 33.9±5.2 months. The average lesion size was 173.1±23.5 mm². The average VAS score during rest improved from 4.62±0.85 preoperatively to 1.08±0.27 postoperatively (P<0.05), the score during walking improved from 5.19±0.63 preoperatively to 1.15±0.37 postoperatively (P<0.05), and the score during running improved from 6.08±0.74 preoperatively to 1.39±0.57 postoperatively (P<0.05). The average postoperative AOFAS ankle score improved to 91.5±2.6 (range, 88 to 96), compared with preoperative 75.0±2.8 (range, 70 to 79) (P<0.05). Two patients developed pain in the donor site of the knee joint, and both of them had 2 or more osteochondral plugs harvested. The postoperative SF-36 score increased to 92.2±2.4 (P<0.05). In the last follow-up, 18 patients answered the Berndt and Harty outcome question, all with "good" as the result. CONCLUSIONS MOT is a feasible choice for patients with larger lesions. It can improve the VAS/AOFAS/IKDC/SF-36 scores, and has high patient satisfaction. Graft incorporation helps improve patient quality of life. Our results indicate that a larger osteochondral plug area increases the risk of developing knee donor site pain.

Joint Green Marketing Decision-Making of Green Supply Chain Considering Power Structure and Corporate Social Responsibility.

In order to explore the impact of a manufacturer's or retailer's undertaking corporate social responsibility (CSR) and different power structures on their joint green marketing decisions and profits in the green supply chain, this paper establishes green supply chain optimization models under six different decision-making scenarios according to two different CSR bearers and three different power structures. Based on the main assumptions of a linear product demand function and CSR measured by consumer surplus, this paper solves the equilibrium solutions of the manufacturer and the retailer through game theory. The results show that: First, the difference in the degree of CSR undertaken by manufacturers and retailers leads to a difference in the ranking of optimal strategies of both parties under the three power structures. Second, under the same power structure, compared with undertaking CSR by oneself, when the other party undertakes CSR, the level of the product's green degree, the level of green promotion, the party's own profit, and the profit of the other party are all higher. Third, regardless of the power structure, manufacturers and retailers undertaking CSR is conducive to improving the level of product greenness, increasing green promotion, lowering the retail price, increasing consumers' willingness to buy green products, and ultimately helping to increase the profits of manufacturers and retailers.

Amorphous/Crystalline Hetero-Phase TiO2 -Coated α-Fe2 O3 Core-Shell Nanospindles: A High-Performance Artificial Nitrogen Fixation Electrocatalyst.

Electrochemical nitrogen fixation techniques have emerged as a promisingly sustainable approach to face the challenge associated with nitrogen activation of ammonia synthesis by the Haber-Bosch process under ambient conditions. Herein, the performance of electrocatalytic nitrogen reduction for the production of α-Fe2 O3 nanospindles coated with mesoporous TiO2 with different crystallinity [denoted as α-Fe2 O3 @mTiO2 -X (X=300, 400, and 500 °C)] were investigated. The as-prepared α-Fe2 O3 @mTiO2 -400 composite exhibits a large NH3 yield (27.2 µg h-1 mgcat. -1 ) at -0. 5 V vs. the reversible hydrogen electrode and a high Faradaic efficiency (13.3 %) in 0.1 m Na2 SO4 , with excellent electrochemical durability. This work presents a novel avenue for the rational design of efficient unique hetero-phase nanocatalysts toward sustainable electrocatalytic N2 fixation.

Cytoplasm lipids can be modulated through hormone-sensitive lipase and are related to mitochondrial function in porcine IVM oocytes.

Intracellular lipids provide energy for oocyte maturation and development. Triglycerides are the main components of cytoplasm lipid droplets, and hydrolysis of triglycerides requires several lipase-mediated steps. The aim of this study was to determine the effects of the ß-adrenoceptor agonist isoproterenol (ISO) and the hormone-sensitive lipase (HSL) inhibitor CAY10499 on the IVM of porcine oocytes. ISO (5mg L-1) and CAY10499 (20mg L-1) had positive and negative effects respectively on invitro oocyte maturation and subsequent embryo development. The rates of polar body extrusion, cleavage and blastocyst formation were significantly higher in the ISO-treated group than the control and CAY10499-treated groups. ISO treatment also upregulated intracellular cAMP levels in comparison with the control group, while CAY10499 significantly increased the triglyceride content of matured oocytes when compared with other groups, consistent with the observed decrease in LIPE (HSL) mRNA levels. Furthermore, the inhibitory effects of CAY10499 included decreases in mitochondrial membrane potential and mitochondrial temperature. These results indicate that ISO has a positive effect on the IVM of porcine oocytes, and that intracellular lipid metabolism can be modulated by CAY10499 through inhibition of HSL and is closely related to mitochondrial function.

Systematic profiling identifies PDLIM2 as a novel prognostic predictor for oesophageal squamous cell carcinoma (ESCC).

Till now, no appropriate biomarkers for high-risk population screening and prognosis prediction have been identified for patients with oesophageal squamous cell carcinoma (ESCC). In this study, by the combined use of data from the Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA)-oesophageal carcinoma (ESCA), we aimed to screen dysregulated genes with prognostic value in ESCC and the genetic and epigenetic alterations underlying the dysregulation. About 222 genes that had at least fourfold change in ESCC compared with adjacent normal tissues were identified using the microarray data in GDS3838. Among these genes, only PDLIM2 was associated with nodal invasion and overall survival (OS) at the same time. The high PDLIM2 expression group had significantly longer OS and its expression was independently associated with better OS (HR: 0.64, 95% CI: 0.43-0.95, P = 0.03), after adjustment for gender and pathologic stages. The expression of its exon 7/8/9/10 had the highest AUC value (0.724) and better prognostic value (HR: 0.43, 95% CI: 0.22-0.83, P = 0.01) than total PDLIM2 expression. PDLIM2 DNA copy deletion was common in ESCC and was associated with decreased gene expression. The methylation status of two CpG sites (cg23696886 and cg20449614) in the proximal promoter region of PDLIM2 showed a moderate negative correlation with the gene expression in PDLIM2 copy neutral/amplification group. In conclusion, we infer that PDLIM2 expression might be a novel prognostic indicator for ESCC patients. Its exon 7/8/9/10 expression had the best prognostic value. Its down-regulation might be associated with gene-level copy deletion and promoter hypermethylation.

The SUMO E3 Ligase-Like Proteins PIAL1 and PIAL2 Interact with MOM1 and Form a Novel Complex Required for Transcriptional Silencing.

The mechanism by which MORPHEUS' MOLECULE1 (MOM1) contributes to transcriptional gene silencing has remained elusive since the gene was first identified and characterized. Here, we report that two Arabidopsis thaliana PIAS (PROTEIN INHIBITOR OF ACTIVATED STAT)-type SUMO E3 ligase-like proteins, PIAL1 and PIAL2, function redundantly to mediate transcriptional silencing at MOM1 target loci. PIAL1 and PIAL2 physically interact with each other and with MOM1 to form a high molecular mass complex. In the absence of either PIAL2 or MOM1, the formation of the high molecular mass complex is disrupted. We identified a previously uncharacterized IND (interacting domain) in PIAL1 and PIAL2 and demonstrated that IND directly interacts with MOM1. The CMM2 (conserved MOM1 motif 2) domain of MOM1 was previously shown to be required for the dimerization of MOM1. We demonstrated that the CMM2 domain is also required for the interaction of MOM1 with PIAL1 and PIAL2. We found that although PIAL2 has SUMO E3 ligase activity, the activity is dispensable for PIAL2's function in transcriptional silencing. This study suggests that PIAL1 and PIAl2 act as components of the MOM1-containing complex to mediate transcriptional silencing at heterochromatin regions.