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Isavuconazole is a triazole with broad-spectrum antifungal activity. In this post-hoc analysis of two prospective clinical trials (VITAL and SECURE), the safety and efficacy of isavuconazole in patients aged ≥ 65 years with invasive fungal diseases were evaluated. Patients were divided into two subgroups (≥ 65 and Clinicaltrials.gov identifier NCT00634049 and NCT00412893.

To investigate the impact of an electronic medical record management system (EMRMS) on disease activity and the frequency of outpatient visits among patients with ankylosing spondylitis (AS). We identified 652 patients with AS who were followed up for at least 1 year before and after the first Ankylosing Spondylitis Disease Activity Score (ASDAS) assessment and compared the number of outpatient visits and average visit time within 1 year before and after the initial ASDAS assessment. Finally, we analyzed 201 patients with AS who had complete data and received ≥ 3 continuous ASDAS assessments at an interval of 3 months, and we compared the results of the second and third ASDAS assessments with those of the first. The number of annual outpatient visits increased after ASDAS assessment (4.0 (4.0, 7.0) vs. 4.0 (4.0, 8.0), p p = 0.073), especially among patients whose with an inactive disease activity was p = 0.033; ASDAS erythrocyte sedimentation rate (ESR) 6.4 (8.7, 11.1) vs. 6.1 (8.1, 10.0) min, p = 0.027). Among patients who received at least three ASDAS assessments, the third ASDAS-CRP tended to be lower than the first (1.5 (0.9, 2.1) vs. 1.4 (0.8, 1.9), p = 0.058). The use of an EMRMS increased the frequency of ambulatory visits among AS patients with high and very high disease activity and reduced the visit time among those with an inactive disease. Continual ASDAS assessments may help control the disease activity of patients with AS.

We aim to investigate the alteration in disease activity of ankylosing spondylitis (AS) individuals before, during, and after the COVID-19 wave in Taiwan by using electronic medical-record management system (EMRMS). We identified 126 AS individuals from the single center, and gathered data of the three disease activities (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Ankylosing Spondylitis Disease Activity Score with erythrocyte sedimentation rate [ASDAS-ESR], and Ankylosing Spondylitis Disease Activity Score with C-Reactive Protein [ASDAS-CRP]) by using EMRMS before (7 February to 1 May, 2021), during (2 May to 24 July, 2021), and after the COVID-19 wave (25 July to 16 October, 2021). We compared the disease activity measures of the three phases through a paired t test. Among the 126 individuals, CRP was significantly higher during the COVID-19 wave (0.2 (0.1, 0.5) mg/dl, p = 0.001) than before the wave (0.2 (0.1, 0.4) mg/dl), ESR (8.0 (4.0, 15.0) mm/h, p = 0.003) and ASDAS-ESR (1.4 (1.0, 1.9), p = 0.032) were significantly higher after the wave than during the wave (6.0 (3.0, 12.0) mm/h and 1.2 (0.9, 1.8) mm/h) e. ESR, CRP, ASDAS-ESR and ASDAS-CRP were all significant higher after COVID-19 wave than before. The disease activities of AS individuals in Taiwan worsened after 2021 COVID-19 wave in Taiwan.

This study aims to depict and compare clinical characteristics and risk behavior among groups of individuals using ketamine, polydrugs or smoking cigarette. A total of 185 drug-using participants and 49 smokers participated in this study. A cross-sectional interview was used to collect information on demographics, drug- and sex-related behaviors, HIV serostatus, lower urinary tract symptoms (LUTS), behavioral dispositions. N-back memory test was used to measure short-term memory. Result shows that 10 participants (5.41%) were HIV positive and 14 (7.57%) having LUTS. Individuals with ketamine and polydrugs use have significantly worse drug-related problem than cigarette smokers. Compared to cigarette smokers and ketamine users, individuals with polydrug users scored significantly higher on impulsivity measures. Cigarette smokers performed significantly better than the other two groups on the memory tests. A few patients had been infected with HIV and diagnosed with LUTS. Findings support that memory on short term recalls of patients with ketamine use might be impaired. Study findings warrants the necessarily of further study on influences of using ketamine.

Women who underwent vaginal pelvic reconstructive surgery with or without mesh consecutively between 2004 and 2018 were retrospectively analyzed to determine the learning curve in vaginal pelvic reconstructive surgery. With cumulative summation (CUSUM) analysis of surgical failure and operation time, we assessed the learning curve of vaginal pelvic reconstructive surgery, including sacrospinous ligament fixation, anterior colporrhaphy, posterior colporrhaphy, and optional vaginal hysterectomy with or without mesh placement. The study is based on two individual surgeons who performed vaginal pelvic reconstructive surgery with or without mesh. Two hundred and sixty-four women with stage III or IV pelvic organ prolapse underwent vaginal pelvic reconstructive surgery by surgeons A or B. The median follow-up time of 44 months ranged from 24 to 120 months. Surgical proficiency was achieved in 32–33 vaginal pelvic reconstructive surgery procedures without mesh and 37–47 procedures in the same surgery with mesh. The total surgical success rates for surgeons A and B were 82.2% and 94.1%, with median follow-up times of 60 and 33 months, respectively. More procedures were needed for the learning curve of vaginal pelvic reconstructive surgery with mesh. Having crossed the proficiency boundary, the surgical success rate and operation time were improved.

Reassessing the continuing need for and choice of antibiotics by using an antibiotic “time out’’ program may reduce unnecessary treatment. This study aimed to explore the effect of an antibiotic stewardship program (ASP) on the antibiotics consumption, incidence of resistant bacterial infections and overall hospital mortality in a tertiary medical center during the study period 2012–2014. An ASP composed of multidisciplinary strategies including pre-prescription approval and post-approval feedback and audit, and a major “time out’’ intervention (shorten the default antibiotic prescription duration) usage was introduced in year 2013. Consumption of antibiotics was quantified by calculating defined daily doses (DDDs). Interrupted time series (ITS) analysis was used to explore the changes of antibiotics consumption before and after intervention, accounting for temporal trends that may be unrelated to intervention. Our results showed that following the intervention, DDDs showed a decreased trend in overall (in particular the major consumed penicillins and cephalosporins), in both intensive care unit (ICU) and non-ICU, and in non-restrictive versus restrictive antibiotics. Importantly, ITS analysis showed a significantly slope change since intervention (slope change p value 0.007), whereas the incidence of carbapenem-resistant and vancomycin-resistant pathogens did not change significantly. Moreover, annual overall mortality rates were 3.0%, 3.1% and 3.1% from 2012 to 2014, respectively. This study indicates that implementing a multi-disciplinary strategy to shorten the default duration of antibiotic prescription can be an effective manner to reduce antibiotic consumption while not compromising resistant infection incidence or mortality rates.

Abnormal accumulation of acrolein, an α, β unsaturated aldehyde has been reported as one pathological cause of the CNS neurodegenerative diseases. In the present study, the neuroprotective effect of selumetinib (a MEK–ERK inhibitor) on acrolein-induced neurotoxicity was investigated in vitro using primary cultured cortical neurons. Incubation of acrolein consistently increased phosphorylated ERK levels. Co-treatment of selumetinib blocked acrolein-induced ERK phosphorylation. Furthermore, selumetinib reduced acrolein-induced increases in heme oxygenase-1 (a redox-regulated chaperone protein) and its transcriptional factor, Nrf-2 as well as FDP-lysine (acrolein-lysine adducts) and α-synuclein aggregation (a pathological biomarker of neurodegeneration). Morphologically, selumetinib attenuated acrolein-induced damage in neurite outgrowth, including neuritic beading and neurite discontinuation. Moreover, selumetinib prevented acrolein-induced programmed cell death via decreasing active caspase 3 (a hallmark of apoptosis) as well as RIP (receptor-interacting protein) 1 and RIP3 (biomarkers for necroptosis). In conclusion, our study showed that selumetinib inhibited acrolein-activated Nrf-2-HO-1 pathway, acrolein-induced protein conjugation and aggregation as well as damage in neurite outgrowth and cell death, suggesting that selumetinib, a MEK–ERK inhibitor, may be a potential neuroprotective agent against acrolein-induced neurotoxicity in the CNS neurodegenerative diseases.

It is difficult to draw conclusions about the effect of resistance exercises on information processing speed and inhibitory control from previous studies due to possible underestimations of maximal strength and the lack of information on the intervention programs. To address this issue, a familiarization of resistance exercise was introduced before the strength test, and the repetition-to-fatigue method was used to calculate the 1RM (one repetition max). A two-arm RCT was conducted to evaluate the cognitive effect of resistance exercise. Male adults aged 50–65 years old performed a single bout of multiple joint, structural barbell resistance exercises (back squat, press, and deadlift) with 75% 1RM * 5 repetitions * 3 sets with 2–3 min rest between sets and exercises or a stretching exercise session (active-control intervention). This type of resistance exercise improved the information processing speed measured by Stroop task reaction time (t(23) = − 2.313, p = .030, M = − 16 ms, 95% CI [− 30, − 2]) and decreased the conflict-related neural activity measured by event-related potential N2b in both congruent (t(20) = 2.674, p = .015, M = 2.290 μv, 95% CI [0.504, 4.075]) and incongruent (t(20) = 2.851, p = .018, M = 2.291 μv, 95% CI [0.439, 4.142]) conditions. Resistance exercise significantly improved information processing speed and decrease conflict-related neural activity, but did not change inhibitory control in older adults compared to active control.Trial registration: NCT04534374 (01/09/2020).

Different functional connectivities in the brain, specifically in the frontoparietal and motor cortex–sensorimotor circuits, have been associated with superior performance in athletes. However, previous electroencephalogram (EEG) studies have only focused on the frontoparietal circuit and have not provided a comprehensive understanding of the cognitive–motor processes underlying superior performance. We used EEG coherence analysis to examine the motor cortex–sensorimotor circuit in golfers of different skill levels. Twenty experts, 18 amateurs, and 21 novices performed 60 putts at individual putting distances (40–60% success rate). The imaginary inter-site phase coherence (imISPC) was used to compute 8–13 Hz coherence that can be used to distinguish expert-novice and expert-amateur differences during motor preparation. We assessed the 8–13 Hz imISPC between the Cz and F3, F4, C3, C4, T3, T4, P3, P4, O1, and O2 regions. (1) Amateurs had lower 8–13 Hz imISPC in the central regions (Cz–C3 and C4) than novices and experts, but experts had lower 8–13 Hz imISPC than novices. (2) Skilled golfers (experts and amateurs) had lower 8–13 Hz imISPC in the central–parietal regions (Cz–P3 and P4) than novices. (3) Experts had lower 8–13 Hz imISPC in the central–left temporal regions (Cz–T7) than amateurs and novices. Our study revealed that refinement of the motor cortex–sensorimotor circuit follows a U-shaped coherence pattern based on the stage of learning. The early learning stage (i.e., novice to amateur) is characterized by lower connectivity between the regions associated with motor control and visuospatial processes, whereas the late learning stage (i.e., amateur to expert) is characterized by lower connectivity in the regions associated with verbal-analytic and motor control processes.

Serum cytokine and chemokine networks may reflect the complex systemic immunological interactions in cancer patients. Studying groups of cytokines and their networks may help to understand their clinical biology. A total of 178 cases of ovarian cancer were analyzed in this study, including 73 high-grade serous (HGSC), 66 clear cell (CCC) and 39 endometrioid carcinomas. Suspension cytokine arrays were performed with the patients’ sera taken before the primary surgery. Associations between each cytokine and clinicopathological factors were analyzed in all patients using multivariate linear regression models, and cluster analyses were performed for each histotype. In the multivariate analyses, twelve of 27 cytokines were correlated with histotypes. Cluster analyses in each histotype revealed 2 cytokine signatures S1 and S2 in HGSC, and similarly C1 and C2 in CCC. Twenty-two of 27 cytokines were commonly clustered in HGSC and CCC. Signature S1 and C1 included IL-2,6,8,15, chemokines and angiogenic factors, whereas signature S2 and C2 included IL-4,5,9,10,13, TNF-α and G-CSF. Four subgroups based on a high or low level for each signature were identified, and this cluster-based classification demonstrated significantly different progression-free and overall survivals for CCC patients (P = 0.00097 and P = 0.017).

The current study examined the effects of acute moderate-intensity aerobic exercise (MAE) on inhibitory control and resting-state heart rate variability (HRV) in children with Attention-Deficit/Hyperactivity Disorder (ADHD). Our data show that acute MAE resulted in higher response accuracy of a modified flanker task regardless of task difficulty for 60 min (p = .001). Aerobic exercise further resulted in more effective conflict detection, as measured by greater amplitude (p = .012) and shorter latency (p = .029) of the N2 component of event-related brain potential, for 60 min regardless of task difficulty. In contrast, acute MAE did not modulate sympathovagal balance signified by HRV at either 30 min or 60 min following exercise cessation. Collectively, our findings suggest that the beneficial effects of acute aerobic exercise on inhibitory control are sustained for 60 min in children with ADHD. However, acute aerobic exercise may not modulate sympathovagal balance during the post-exercise recovery. Overall, we highlight the importance of acute aerobic exercise for children with ADHD as a potential means to facilitate brain health.

Single incision laparoscopic surgery (SILS) has emerged as least invasive interventions for gynecologic disease. However, SILS is slow to gain in popularity due to difficulties in triangulation and instrument crowding. Besides, the costly instruments may influence patients’ will to have this procedure, and limit other medical expense as well. To optimize outcome and reduce cost, the objective of this study is to evaluate the feasibility and safety for patients undergoing adnexal surgeries using conventional laparoscopic instruments with SILS (SILS-C), and to compare with those of patients subject to TP using conventional laparoscopic instruments (TP-C). This is a retrospective case–control study. The data dated from April 2011 to April 2018. Patients who received concomitant multiple surgeries, were diagnosed with suspected advanced stage ovarian malignancy, or required frozen sections for intraoperative pathologic diagnosis were excluded. Demographic data, including the age, body weight, height, previous abdominal surgery were obtained. The surgical outcomes were compared using conventional statistical methods. 259 patients received SILS-C. The operating time was 63.83 ± 25.31 min. Blood loss was 2.38 ± 6.09 c.c. 58 patients (24.38%) needed addition of port to complete surgery. 384 patients received TP-C. Compared with SILS-C, the operating time was shorter (57.32 ± 26.38 min, OR = 0.984, CI = 0.975–0.992). The patients were further divided into unilateral or bilateral adnexectomy, and unilateral or bilateral cystectomy. Other than the operating time in unilateral cystectomy (66.12 ± 19.5 vs. 58.27 ± 23.92 min, p = .002), no statistical differences were observed in the subgroup analysis. Single incision laparoscopic surgery using conventional laparoscopic instruments is feasible and safe as initial approach to adnexal lesions. In complex setting as unilateral cystectomy or pelvic adhesions, two-port access may be considered.

The regeneration capacity of knee cartilage can be enhanced by applying periosteal grafts, but this effect varies depending on the different sources of the periosteal grafts applied for cartilage formation. Tibia periosteum can be used to enhance cartilage repair. However, long-term analysis has not been conducted. The endochondral ossification capacity of tibia periosteum during cartilage repair also needs to be investigated. In this study, both vascularized and non-vascularized tibia periosteum grafts were studied to understand the relationship between tissue perfusion of the periosteum graft and the effects on cartilage regeneration and bone formation. Furthermore, anti-ossification reagents were added to evaluate the efficacy of the prevention of bone formation along with cartilage regeneration. A critical-size cartilage defect (4 × 4 mm) was created and was covered with an autologous tibia vascularized periosteal flap or with a non-vascularized tibia periosteum patch on the knee in the rabbit model. A portion of the vascularized periosteum group was also treated with the anti-osteogenic reagents Fulvestrant and IL1β to inhibit unwanted bone formation. Our results indicated that the vascularized periosteum significantly enhanced cartilage regeneration in the cartilage defect region in long-term treatment compared to the non-vascularized group. Furthermore, the addition of anti-osteogenic reagents to the vascularized periosteum group suppressed bone formation but also reduced the cartilage regeneration rate. Our study using vascularized autologous tissue to repair cartilage defects of the knee may lead to the modification of current treatment in regard to osteoarthritis knee repair.

Sacrospinous ligament fixation (SSLF) is one of the most utilized surgeries in the management of pelvic organ prolapse (POP). We conducted a large-series study of SSLF in a tertiary center by an experienced urogynecologic team. The 453 women with POP who underwent SSLF at National Taiwan University Hospital in the period from 2002 to 2015 are reviewed. All patients received unilateral SSLF with Veronikis ligature carrier. Concomitant anterior colporrhaphy was performed in 75.3% of the cases and posterior colporrhaphy in 78.6%. The mean operation time was 92.3 ± 31.5 minutes. The intraoperative blood loss was 92.3 ± 91.4 ml. The objective cure rate was 82.5%, and 79 (17.5%) patients recurred. The Kaplan-Meier recurrence-free analysis showed a steep decline during the first postoperative year, and the yearly number of recurrent patients decreased as the follow-up period proceeded. A comparison of the site of recurrence found that anterior compartment prolapse was the most common with 57 cases (12.6%). Paravaginal repair is frequently implemented in the management of recurrent anterior prolapse. In conclusion, SSLF provides excellent support to the apex compartment, and our long-term results show that the anterior compartment is the most commonly encountered type of POP recurrence.

Aberrant activation of epithelial to mesenchymal transition (EMT) associated factors were highly correlated with increased mortality in cancer patients. SNAIL family of transcriptional repressors comprised of three members, each of which were essentially associated with gastrulation and neural crest formation. Among which, SNAI1 and SNAI2 were efficiently induced during EMT and their expressions were correlated with poor clinical outcome in patients with breast, colon and ovarian carcinoma. In an ovarian cancer cell lines panel, we identified that SNAI1 and SNAI2 expressions were mutually exclusive, where SNAI1 predominantly represses SNAI2 expression. Detailed analysis of SNAI2 promoter region revealed that SNAI1 binds to two E-box sequences that mediated transcriptional repression. Through epigenetic inhibitor treatments, we identified that inhibition of histone deacetylase (HDAC) activity in SNAI1 overexpressing cells partially rescued SNAI2 expression. Importantly, we demonstrated a significant deacetylation of histone H3 and significant enrichments of HDAC1 and HDAC2 corepressors in both E-box regions of SNAI2 promoter. Our results suggested that SNAI1 repression on SNAI2 expression was predominantly mediated through the recruitment of the histone deacetylation machinery. Utilization of HDAC inhibitors would require additional profiling of SNAI1 activity and combined targeting of SNAI1 and HDACs might render efficient cancer treatment.

Upper lip scars are at risk of hypertrophy. Our center therefore uses microporous tape and silicone sheeting for postoperative scar care following cleft lip repair. However, some babies have previously ingested their silicone sheeting, which has the potential for respiratory compromise or gastrointestinal obstruction. Self-dry silicone gel is reportedly also effective for preventing hypertrophic scars. Hence, we sought to test whether silicone gel, which cannot be ingested whole, might be non-inferior to silicone sheeting for controlling against upper lip scar hypertrophy. This was a mixed prospective and retrospective case-controlled clinical trial involving patients undergoing unilateral cleft lip repair, 29 of whom received standard postoperative silicone sheeting (control group) and another 33 age-matched consecutive patients who received self-dry silicone instead. The Vancouver scar scale, visual analogue scale and photographically assessed scar width assessments were the same in both groups at six months after surgery. In conclusion, silicone gel appears to be non-inferior to silicone sheeting for postoperative care of upper lip scars as judged by scar quality at six months, but silicone sheeting has the safety disadvantage that it can be swallowed whole by babies. It is thus recommended that silicone gel be used for upper lip scar management in babies.

Clinical studies report significant increases in acrolein (an α,β-unsaturated aldehyde) in the substantia nigra (SN) of patients with Parkinson’s disease (PD). In the present study, acrolein-induced neurotoxicity in the nigrostriatal dopaminergic system was investigated by local infusion of acrolein (15, 50, 150 nmoles/0.5 μl) in the SN of Sprague-Dawley rats. Acrolein-induced neurodegeneration of nigrostriatal dopaminergic system was delineated by reductions in tyrosine hydroxylase (TH) levels, dopamine transporter levels and TH-positive neurons in the infused SN as well as in striatal dopamine content. At the same time, apomorphine-induced turning behavior was evident in rats subjected to a unilateral infusion of acrolein in SN. Acrolein was pro-oxidative by increasing 4-hydroxy-2-nonenal and heme oxygenase-1 levels. Furthermore, acrolein conjugated with proteins at lysine residue and induced α-synuclein aggregation in the infused SN. Acrolein was pro-inflammatory by activating astrocytes and microglia. In addition, acrolein activated caspase 1 in the infused SN, suggesting acrolein-induced inflammasome formation. The neurotoxic mechanisms underlying acrolein-induced neurotoxicity involved programmed cell death, including apoptosis and necroptosis. Compared with well-known Parkinsonian neurotoxins, including 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and rotenone which do not exist in the SN of PD patients, our in vivo study shows that acrolein acts as a Parkinsonian neurotoxin in the nigrostriatal dopaminergic system of rat brain.

Constitutive functional HIF-2α was recently identified in cancer and stem cell lines under normoxia. In this study, BEAS-2B, a bronchial epithelial cell line, was shown to constitutively express active HIF-2α under normoxia and exhibit markers of pluripotency including Oct-4, Nanog and sphere formation. Oct-4 expression was reduced after knockdown of HIF-2α under normoxia. Global enrichment analysis of HIF-2α demonstrated the diverse functions of HIF-2α under normoxia. Bioinformatics analysis of the enriched loci revealed an enhancer role of HIF-2α binding sites, involvement of HIF-2α interacting proteins and enriched de novo motifs which suggest the diverse role of HIF-2α in pseudohypoxia. The low ratio of the discovered loci overlapping with those revealed in cancer cell lines 786-O (16.1%) and MCF-7 (15.9%) under hypoxia indicated a prevailing non-canonical mechanism. Hypoxia had positive, marginal or adverse effects on the enrichment of the selected loci in ChIP-PCR assays. Deletion of the N-terminal activation domain (N-TAD) of HIF-2α disrupted the reporting activity of two of the loci annotated to ELN and ANKRD31. Hypoxia incurring abundance variation of HIF-2α may misrepresent the N-TAD functions as canonical hypoxia inducible features via C-TAD activation. Elucidation of the pseudohypoxia functions of constitutive HIF-2α is useful for resolving its role in malignancy and pluripotency.

Trehalose is a natural disaccharide that is found in a diverse range of organisms but not in mammals. Autophagy is a process which mediates the sequestration, lysosomal delivery and degradation of proteins and organelles. Studies have shown that trehalose exerts beneficial effects through inducing autophagy in mammalian cells. However, whether trehalose or other saccharides can activate autophagy in keratinocytes is unknown. Here, we found that trehalose treatment increased the LC3-I to LC3-II conversion, acridine orange-stained vacuoles and GFP-LC3B (LC3B protein tagged with green fluorescent protein) puncta in the HaCaT human keratinocyte cell line, indicating autophagy induction. Trehalose-induced autophagy was also observed in primary keratinocytes and the A431 epidermal cancer cell line. mTOR signalling was not affected by trehalose treatment, suggesting that trehalose induced autophagy through an mTOR-independent pathway. mTOR-independent autophagy induction was also observed in HaCaT and HeLa cells treated with sucrose or raffinose but not in glucose, maltose or sorbitol treated HaCaT cells, indicating that autophagy induction was not a general property of saccharides. Finally, although trehalose treatment had an inhibitory effect on cell proliferation, it had a cytoprotective effect on cells exposed to UVB radiation. Our study provides new insight into the saccharide-mediated regulation of autophagy in keratinocytes.

Epithelial-mesenchymal transition (EMT), a biological process by which polarized epithelial cells convert into a mesenchymal phenotype, has been implicated to contribute to the molecular heterogeneity of epithelial ovarian cancer (EOC). Here we report that a transcription factor—Grainyhead-like 2 (GRHL2) maintains the epithelial phenotype. EOC tumours with lower GRHL2 levels are associated with the Mes/Mesenchymal molecular subtype and a poorer overall survival. shRNA-mediated knockdown of GRHL2 in EOC cells with an epithelial phenotype results in EMT changes, with increased cell migration, invasion and motility. By ChIP-sequencing and gene expression microarray, microRNA-200b/a is identified as the direct transcriptional target of GRHL2 and regulates the epithelial status of EOC through ZEB1 and E-cadherin. Our study demonstrates that loss of GRHL2 increases the levels of histone mark H3K27me3 on promoters and GRHL2-binding sites at miR-200b/a and E-cadherin genes. These findings support GRHL2 as a pivotal gatekeeper of EMT in EOC via miR-200-ZEB1.

H3K9 methylation is an important histone modification that is correlated with gene transcription repression. The asymmetric H3K9 dimethylation (H3K9me2) pattern between paternal and maternal genomes is generated soon after fertilization. In the present study, we carefully determined the dynamics of H3K9me2 changes in mouse zygotes and investigated the regulatory mechanisms. The results indicated that histone methyltransferase G9a, but not GLP, was involved in the regulation of asymmetric H3K9me2 and G9a was the methyltransferase that induced the appearance of H3K9me2 in the male pronucleus of the zygote treated with cycloheximide. We found that there were two distinct mechanisms that regulate H3K9me2 in the male pronucleus. Before 8 h of in vitro fertilization (IVF), a mechanism exists that inhibits the association of G9a with the H3K9 sites. After 10 h of IVF the inhibition of G9a activity depends on yet unknown novel protein(s) synthesis. The two mechanisms of transfer take place between 8–10 h of IVF and the novel protein failed to inhibit G9a activity in time, resulting in the appearance of a low level de novo H3K9me2 in the male pronucleus.