UFMylation: a ubiquitin-like modification.

Post-translational modifications (PTMs) add a major degree of complexity to the proteome and are essential controllers of protein homeostasis. Amongst the hundreds of PTMs identified, ubiquitin and ubiquitin-like (UBL) modifications are recognized as key regulators of cellular processes through their ability to affect protein-protein interactions, protein stability, and thus the functions of their protein targets. Here, we focus on the most recently identified UBL, ubiquitin-fold modifier 1 (UFM1), and the machinery responsible for its transfer to substrates (UFMylation) or its removal (deUFMylation). We first highlight the biochemical peculiarities of these processes, then we develop on how UFMylation and its machinery control various intertwined cellular processes and we highlight some of the outstanding research questions in this emerging field.

IRE1 RNase controls CD95-mediated cell death.

Signalling by the Unfolded Protein Response (UPR) or by the Death Receptors (DR) are frequently activated towards pro-tumoral outputs in cancer. Herein, we demonstrate that the UPR sensor IRE1 controls the expression of the DR CD95/Fas, and its cell death-inducing ability. Both genetic and pharmacologic blunting of IRE1 activity increased CD95 expression and exacerbated CD95L-induced cell death in glioblastoma (GB) and Triple-Negative Breast Cancer (TNBC) cell lines. In accordance, CD95 mRNA was identified as a target of Regulated IRE1-Dependent Decay of RNA (RIDD). Whilst CD95 expression is elevated in TNBC and GB human tumours exhibiting low RIDD activity, it is surprisingly lower in XBP1s-low human tumour samples. We show that IRE1 RNase inhibition limited CD95 expression and reduced CD95-mediated hepatic toxicity in mice. In addition, overexpression of XBP1s increased CD95 expression and sensitized GB and TNBC cells to CD95L-induced cell death. Overall, these results demonstrate the tight IRE1-mediated control of CD95-dependent cell death in a dual manner through both RIDD and XBP1s, and they identify a novel link between IRE1 and CD95 signalling.

Membrane-bound CD95 ligand modulates CD19-mediated B cell receptor signaling and EBV activation.

Post-transplant lymphoproliferative disorders (PTLDs) are associated with Epstein-Barr virus (EBV) infection in transplant recipients. Most of lymphoblastoid cell lines (LCLs) derived from EBV-immortalized B cells or PTLDs are sensitive to CD95-mediated apoptosis and cytotoxic T cell (CTL) killing. CD95 ligand (CD95L) exists as a transmembrane ligand (mCD95L) or a soluble form (sCD95L). Using recombinant mCD95L and sCD95L, we observed that sCD95L does not affect LCLs. While high expression of mCD95L in CTLs promotes apoptosis of LCLs, low expression induces clathrin-dependent CD19 internalization, caspase-dependent CD19 cleavage, and proteasomal/lysosomal-dependent CD19 degradation. The CD95L/CD95-mediated CD19 degradation impairs B cell receptor (BCR) signaling and inhibits BCR-mediated EBV activation. Interestingly, although inhibition of the caspase activity restores CD19 expression and CD19-mediated BCR activation, it fails to rescue BCR-mediated EBV lytic gene expression. EBV-specific CTLs engineered to overexpress mCD95L exhibit a stronger killing activity against LCLs. This study highlights that engineering EBV-specific CTLs to express a higher level of mCD95L could represent an attractive therapeutic approach to improve T cell immunotherapy for PTLDs.

Analysis of the Causal Relationship Between Gut Microbiota and Bone Remodeling Growth Factor from the Gene Association.

BACKGROUND: A growing body of evidence indicates a close association between the gut microbiota (GM) and the bone remodeling (BR) process, raising suspicions that the GM may actively participate in BR by modulating the levels of growth factors. However, the precise causal relationship between them remains unclear. Due to many confounding factors, many microorganisms related to BR growth factors have not been identified. We aimed to elucidate the causal relationship between the GM and BR growth factors. METHODS: We evaluated the genome-wide association study (GWAS) summary statistics for GM and five common growth factors associated with BR: namely, bone morphogenetic proteins (BMP), transforming growth factors(TGF), insulin growth factors (IGFs), epidermal growth factors (EGFs), and fibroblast growth factors (FGF). The causal relationship between the GM and BR growth factors was studied by double-sample Mendelian randomized analysis. We used five Mendelian randomization (MR) methods, including inverse variance-weighted (IVW), MR-Egger, simple mode, weighted median, and weighted model methods. RESULTS: Through MR analysis, a total of 56 bacterial genera were co-identified as associated with BMP, TGF, IGF, EGF, and FGF. Among them, eight genera were found to have a causal relationship with multiple growth factors: Marvinbryantia was causally associated with BMP-6 (P = 0.018, OR = 1.355) and TGF-ß2 (P = 0.002, OR = 1.475); Lachnoclostridium, BMP-7 (P = 0.021, OR = 0.73) and IGF-1 (P = 0.046, OR = 0.804); Terrisporobacter, TGF-ß (P = 0.02, OR = 1.726) and FGF-23 levels (P = 0.016, OR = 1.76); Ruminiclostridium5, TGF-ß levels (P = 0.024, OR = 0.525) and FGFR-2 (P = 0.003, OR = 0.681); Erysipelatoclostridium, TGF-ß2 (P = 0.001, OR = 0.739) and EGF and its receptor (EGFR) (P = 0.012, OR = 0.795); Eubacterium_brachy_group, FGFR-2 (P = 0.045, OR = 1.153) and EGF (P = 0.013, OR=0.7); Prevotella9 with EGFR (P = 0.022, OR = 0.818) and FGFR-2 (P = 0.011, OR = 1.233) and Faecalibacterium with FGF-23 (P =0.02, OR = 2.053) and IGF-1 (P = 0.005, OR = 0.843). CONCLUSION: We confirmed the causal relationship between the GM and growth factors related to BR, which provides a new perspective for the study of BR, through targeted regulation of specific bacteria to prevent and treat diseases and growth factor-mediated BR disorders.

A Prediction Model for the Efficacy of Transvaginal Repair in Patients With Cesarean Scar Defect: An Evidence-Based Proposal for Patient Selection.

STUDY OBJECTIVE: To establish a prediction model to help doctors determine which patients with cesarean scar defect are more suitable for transvaginal repair. DESIGN: Retrospective analysis. SETTING: Xinhua Hospital and Shanghai First Maternity & Infant Hospital between June 2014 and May 2021. PATIENTS: 1015 women who underwent transvaginal repair of cesarean scar defect (CSD). INTERVENTIONS: All enrolled patients underwent CSD repair performed by the same gynecologist and his team. And followed up a clinic visit at 6 months to record their menstruation and measure multiple parameters of the CSD by Magnetic Resonance Imaging. MAIN OUTCOMES AND MEASURES: CSD patients are categorized as optimal healing group when the menstruation duration is no more than 7 days, meanwhile the thickness of residual myometrium is no less than 5.39 mm after vaginal repair. The final nomogram is constructed to predict surgical outcomes based on preoperative variables. RESULTS: The key factors that determine optimal healing are the timing of cesarean section (elective or emergency), menstrual cycle, CSD length, width, depth, and the thickness of the lower uterine segment. With the prediction model, scores are given to each parameter according to the statistics. Total scores range from 0 to 25 points, with a cutoff point of 16.5. When a score is greater than 16.5, the transvaginal repair can achieve optimal healing. Uterine position (anteflexion or retroflexion) and preoperative thickness of residual myometrium are the key factors affecting postoperative thickness of residual myometrium. The width of the CSD and the thickness of the lower uterine segment are the key factors affecting abnormal uterine bleeding symptoms (p < 0.01). CONCLUSIONS: For the first time, we established a prediction model system that may predict the repair effect of CSD and can potentially be useful in future clinical trials to determine which patients are more suitable for surgery or other treatment options.

Interruption Value Type and Source Matter in Different Phases of an Interruption Process: Emotional/Cognitive Impact and Neural Evidence.

OBJECTIVE: To examine the effect of interruption value type (utilitarian, hedonic) and source (external, internal) in different phases of an interruption process. BACKGROUND: Prior studies on interruption mostly focused on the cognitive outcomes of utilitarian interruptions. Hedonic interruptions are common in life; however, they are not sufficiently explored through research. Hedonic value is closely associated with emotional experiences, and, in turn, influences behaviors. Moreover, the way the effect of values is moderated by interruptions initiated by intrinsic motives is worth exploring. METHOD: A 2 × 2 mixed design experiment was conducted with 48 participants who were asked to respond to instant messages during the writing task. The interruption value was induced by work or non-work tasks. The interruption source was manipulated by providing an alert. Functional near-infrared spectroscopy, behavioral data, and subjective measurements were collected and analyzed. RESULTS: Hedonic interruptions increased emotional valence, while utilitarian interruptions decreased it. These effects were strengthened by internal interruptions. The effect of interruption value type on work exhaustion was also moderated by the source. Interruption value type and source influenced the attention allocation before an interruption occurred. Hedonic interruptions led to longer resumption lags, whereas utilitarian interruptions required longer interruption durations. Internal interruptions led to improved performance in the resumed task. CONCLUSION: Interruption source modulate the effect of interruption value type, especially on emotional experience and attention allocation before an interruption occurs. APPLICATION: Self-initiated hedonic interruptions have emotional benefits, while alerts for utilitarian interruptions will improve attention on the main task before interruptions.

Advances in Transition-Metal-Based Dual-Atom Oxygen Electrocatalysts.

Oxygen electrocatalysis has aroused considerable interest over the past years because of the new energy technologies boom in hydrogen energy and metal-air battery. However, due to the sluggish kinetic of the four-electron transfer process in oxygen reduction reaction and oxygen evolution reaction, the electro-catalysts are urgently needed to accelerate the oxygen electrocatalysis. Benefit from the high atom utilization efficiency, unprecedentedly high catalytic activity, and selectivity, single-atom catalysts (SACs) are considered the most promising candidate to replace the traditional Pt-group-metal catalysts. Compared with SACs, the dual-atom catalysts (DACs) are attracting more attraction including higher metal loading, more versatile active sites, and excellent catalytic activity. Therefore, it is essential to explore the new universal methods approaching to the preparation, characterization, and to elucidate the catalytic mechanisms of the DACs. In this review, several general synthetic strategies and structural characterization methods of DACs are introduced and the involved oxygen catalytic mechanisms are discussed. Moreover, the state-of-the-art electrocatalytic applications including fuel cells, metal-air batteries, and water splitting have been sorted out at present. The authors hope this review has given some insights and inspiration to the researches about DACs in electro-catalysis.

Clinical characterization, treatment, and outcome of nivolumab-induced bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is a serious and rare complication of nivolumab. This study aimed to explore the clinical characteristics of nivolumab-induced BP and provide a reference for prevention and treatment of BP. METHODS: Literature on nivolumab-induced BP was collected for retrospective analysis by searching both Chinese and English databases as of July 31, 2023. RESULTS: Sixty patients were included, with a median age of 71 years (range 30 to 85 years), and they were predominantly male (78.3%). The median time to onset of BP was 31 weeks (range 2.4, 216) after nivolumab administration. Tense bullae (93.3%), pruritus (55.0%), and urticarial plaques (31.7%) were the most common manifestations. Lesions were found on the limbs (50.0%), trunk (38.3%), palms and soles (15.0%). Skin biopsies mainly showed subepidermal bullous/blister (50.0%) and eosinophilic infiltration (46.7%). Direct immunofluorescence showed mainly linear deposition of C3 and IgG (46.7%) at the dermal-epidermal junction. The patients stopped taking nivolumab and received systemic steroids (73.3%), topical steroids (63.3%), monoclonal antibodies (21.7%), doxycycline/minocycline (30.0%) and other treatments. Symptoms improved or were relieved in 88.4% of patients but did not improve in 8.3% of patients. CONCLUSION: Clinicians should closely monitor symptoms of BP in those receiving and discontinuing nivolumab, especially in older men. Early diagnosis and timely initiation of treatment may improve patient outcomes.

Electroactive Microorganisms in Advanced Energy Technologies.

Large-scale production of green and pollution-free materials is crucial for deploying sustainable clean energy. Currently, the fabrication of traditional energy materials involves complex technological conditions and high costs, which significantly limits their broad application in the industry. Microorganisms involved in energy production have the advantages of inexpensive production and safe process and can minimize the problem of chemical reagents in environmental pollution. This paper reviews the mechanisms of electron transport, redox, metabolism, structure, and composition of electroactive microorganisms in synthesizing energy materials. It then discusses and summarizes the applications of microbial energy materials in electrocatalytic systems, sensors, and power generation devices. Lastly, the research progress and existing challenges for electroactive microorganisms in the energy and environment sectors described herein provide a theoretical basis for exploring the future application of electroactive microorganisms in energy materials.

EI24 alleviates renal interstitial fibrosis through inhibition of epithelial-mesenchymal transition and fibroblast activation.

Etoposide-induced 2.4 (EI24) exerts tumor suppressor activity through participating in cell apoptosis, autophagy, and inflammation. However, its role in renal diseases has not been elucidated. This study showed that the EI24 level decreased gradually in the kidneys of mice with unilateral ureteral obstruction (UUO) and in another fibrosis model induced by diabetic kidney disease. The overexpression of EI24 was used to investigate the possible role both in vivo and in vitro. The overexpression 1 day after UUO through tail vein injection alleviated the progression of renal interstitial fibrosis (RIF). EI24 inhibited epithelial-mesenchymal transition, excessive deposition of the extracellular matrix, and activation of fibroblasts. Furthermore, administration of EI24-overexpressing plasmids restrained the phosphorylation of nuclear factor-κB (NF-κB) and c-Jun kinase (JNK) through regulating the proteasome-dependent degradation of TRAF2, and then, inhibited the expression of downstream inflammation-associated cytokines (interleukin-6, tumor necrosis factor-α, and monocyte chemotactic protein-1) and infiltration of macrophages and neutrophils in mouse kidney after UUO. In conclusion, the data indicated that EI24, a novel anti-fibrosis regulator, was important in the progression of RIF.

Tunable type-II lateral MoSi2N4/WSi2N4 heterostructures for photocatalytic applications.

Combining various two-dimensional crystals has emerged as an exciting way to tailor the properties of lateral heterostructures for new-generation optoelectronic devices. Herein, a seamless lateral heterostructure based on MoSi2N4 and MoSi2N4 monolayers along armchair interfaces is predicted, and its electronic and optical properties are investigated by using first principles calculations. Our calculations indicate that the MoSi2N4/WSi2N4 lateral heterostructures (HSs) possess excellent stability due to the very small lattice mismatch. In contrast to their parent monolayers with wide indirect band gaps, all (MoSi2N4)m(WSi2N4)n lateral HSs are direct gap semiconductors, and their direct gap nature is independent of compositions and strains. The band alignment of (MoSi2N4)m(WSi2N4)16-m lateral HSs undergoes a quasi-type-I to type-II to quasi-type-II to quasi-type-I band transition with an increase in m. (MoSi2N4)8(WSi2N4)8 is a type-II semiconductor, and the band arrangement changes from type-II to quasi-type-I upon applying tensile strain. Compared with pristine materials, the band edges of MoSi2N4/WSi2N4 lateral HSs are more favorable for photocatalytic water splitting. Furthermore, MoSi2N4/WSi2N4 lateral HSs exhibit higher visible light absorption. These results greatly expand the optoelectronic applications of Mxenes in the 2D realm.

Rapid detection of carbamate pesticide residues using microchip electrophoresis combining amperometric detection.

The long-term consumption of food with pesticide residues has harmful effects on human health and the demand for pesticide detection technology tends to be miniaturized and instant. To this end, we demonstrated the first application of indirectly detecting two carbamate pesticides, metolcarb and carbaryl, by gold nanoparticle-modified indium tin oxide electrode in dual-channel microchip electrophoresis and amperometric detection (ME-AD) system. m-Cresol and α-naphthol were obtained after pesticide hydrolysis in alkaline solution, and then separated and detected by ME-AD. Parameters including the detection potential and running buffer concentration and pH were optimized to improve the detection sensitivity and separation efficiency. Under the optimal conditions, the two analytes were completely separated within 80 s. m-Cresol and α-naphthol presented a wide linear range from 1 to 100 µM, with limits of detection of 0.16 µM and 0.34 µM, respectively (S/N = 3). Moreover, the reliability of this system was demonstrated by analyzing metolcarb and carbaryl in spiked vegetable samples.

Evaluation of uterine scar healing by transvaginal ultrasound in 607 nonpregnant women with a history of cesarean section.

BACKGROUND: Caesarean scar defect (CSD) seriously affects female reproductive health. In this study, we aim to evaluate uterine scar healing by transvaginal ultrasound (TVS) in nonpregnant women with cesarean section (CS) history and to build a predictive model for cesarean scar defects is very necessary. METHODS: A total of 607 nonpregnant women with previous CS who have transvaginal ultrasound measurements of the thickness of the lower uterine segment. The related clinical data were recorded and analyzed. RESULTS: All patients were divided into two groups according to their clinical symptoms: Group A (N = 405) who had no cesarean scar symptoms, and Group B (N = 141) who had cesarean scar symptoms. The difference in frequency of CS, uterine position, detection rate of CSD and the residual muscular layer (TRM) of the CSD were statistically significant between groups; the TRM measurements of the two groups were (mm) 5.39 ± 3.34 versus 3.22 ± 2.33, P < 0.05. All patients were divided into two groups according to whether they had CSDs: Group C (N = 337) who had no CSDs, Group D (N = 209) who had CSDs on ultrasound examination. The differences in frequency of CS, uterine position, TRM between groups were statistically significant (P < 0.05). In the model predicting CSDs by TRM with TVS, the area under the ROC curve was 0.771, the cut-off value was 4.15 mm. The sensitivity and specificity were 87.8% and 71.3%, respectively. CONCLUSIONS: Patients with no clinical symptoms had a mean TRM on transvaginal ultrasonography of 5.39 ± 3.34 mm, which could be used as a good reference to predict the recovery of patients with CSDs after repair surgery.

Two Factors in Face Recognition: Whether You Know the Person's Face and Whether You Share the Person's Race.

One of the best-known phenomena in face recognition is the other-race effect, the observation that own-race faces are better remembered than other-race faces. However, previous studies have not put the magnitude of other-race effect in the context of other influences on face recognition. Here, we compared the effects of (a) a race manipulation (own-race/other-race face) and (b) a familiarity manipulation (familiar/unfamiliar face) in a 2 × 2 factorial design. We found that the familiarity effect was several times larger than the race effect in all performance measures. However, participants expected race to have a larger effect on others than it actually did. Face recognition accuracy depends much more on whether you know the person's face than whether you share the same race.

Cognitive Behavioral Therapy-Based Short-Term Abstinence Intervention for Problematic Social Media Use: Improved Well-Being and Underlying Mechanisms.

Problematic social media use is detrimental to users' subjective well-being. Based on cognitive behavioral therapy (CBT), we proposed a short-term abstinence intervention to treat this problem. A mixed method study with 65 participants was conducted to examine the effectiveness of this intervention and to reveal the underlying mechanisms of how the intervention influences participants. While the experimental group (N = 33) took eight 2.5-h breaks from social media over two weeks and had daily dairies, the control group (N = 32) used social media as usual and had daily diaries. The results demonstrated that the intervention has a positive effect on life satisfaction. The effect varied with the time users conducted abstinence (work hours vs. off hours) and the level of social media addiction (heavy users vs. normal users). Qualitative findings from dairies and interviews unveiled associations among users' behaviors, feelings, and cognitions during and after abstinence. These results extend the understanding of the CBT-based short-term abstinence intervention and suggest opportunities to alleviate problematic social media use.

Effect of diabetes mellitus on short-term prognosis of 227 pyogenic liver abscess patients after hospitalization.

BACKGROUND: Pyogenic liver abscess (PLA) is an inflammatory disease with increasing incidence. When it occurs with diabetes mellitus (DM), the risk of recurrence and mortality may increase. However, the effect of DM on the short-term prognosis of PLA patients after hospitalization remained unknown. METHODS: Two hundred twenty-seven PLA patients who received treatment at the First Affiliated Hospital of Xi'an Jiaotong University from January 2011 to January 2018 were retrospectively enrolled. They were divided into two groups as the DM group (n = 61) and the Non-DM group (n = 166). In the DM group, HbA1C level < 7% was considered to be good-control of glycaemia (n = 23). The clinical characteristics and overall short-term survival were analyzed. RESULTS: The proportion of PLA patients with DM was 26.87%. In the DM group, there was a higher incidence of hypertension and Candida spp. infection. Conservative administration and percutaneous drainage were mainly used in patients with good- (60.87%) and poor-control (60.53%) of glycaemia, respectively. During follow-up, 24 (10.57%) died due to uncontrolled systemic infections and other serious complications. Compared with PLA patients without DM, patients in the DM group had significantly increased 6-month mortality rate after discharge (Log-Rank test, P = 0.021). Poor-control of glycaemia did not reduce the six-month survival, while the recurrence rate of PLA within 3 months showed an almost 3-fold increase (13.16% vs. 4.35%). Further multivariate analyses found that DM was the only independent risk factor for the PLA six-month survival (odds ratio [OR]: 3.019, 95% confidence interval [CI]: 1.138-8.010, P = 0.026). However, the blood glucose level had no significant effect on the short-term survival of PLA patients with DM (Log-Rank test, P = 0.218). CONCLUSIONS: In PLA patients, DM aggravated short-term mortality and blood glucose levels should be well controlled.

Treatment and posttreatment effects of a novel magnetic palatal expansion appliance with reactivation system in dogs.

INTRODUCTION: This study aimed to compare the effects of a novel magnetic palatal expansion appliance (MPEA) during the expansion and maintenance period with that of a screw expansion appliance. METHODS: Based on previous research, the MPEA had a reactivation system that was modified for a broader working range and more stable expansion. Thirty-six male beagle dogs were assigned to a magnetic expansion (ME; n = 12), screwed expansion (SE; n = 12) or control (n = 12) group. Half of the dogs from each group were evaluated only during 5 weeks of activation, whereas the rest were evaluated for 5 weeks of activation and 8 additional weeks of retention. Nonmagnetic metal marking implants were implanted on both sides of the midpalatal suture of all dogs. Three-dimensional assessment of treatment and posttreatment dental and skeletal effects were conducted using cone-beam computed tomography. The width of the midpalatal suture, mineralization and deposition rate of bone, and fluorescence integral optical density were calculated during the expansion and retention periods using tetracycline fluorescence labeling. RESULTS: There were increases in the value of all cone-beam computed tomography parameters in the SE and ME groups during the expansion period, and the increase was significantly greater than that of the control group (P <0.01). However, there was no significant difference in the values of any parameters during the retention period. The width of the midline sutures, mineralization and deposition rate of bone, and integral optical density in the 2 experimental groups were significantly higher than those of the control group (P <0.01), and there was no significant difference between the SE and ME groups. After the retention period, the values of all tetracycline fluorescence evaluation parameters of the experimental groups decreased significantly. CONCLUSIONS: The novel MPEA with a reactivation system was able to expand the midpalatal suture effectively. Dental and skeletal expansion effects are similar to those of the screw expansion appliance. Wearing the appliance as a retainer can effectively maintain the expansion effect. The new bone formation rate was accelerated during the expansion process and decreased to normal levels during the retention period.

Regulation of gammaherpesvirus lytic replication by endoplasmic reticulum stress-induced transcription factors ATF4 and CHOP.

The stress-induced unfolded protein response (UPR) in the endoplasmic reticulum (ER) involves various signaling cross-talks and controls cell fate. B-cell receptor (BCR) signaling, which can trigger UPR, induces gammaherpesvirus lytic replication and serves as a physiological mechanism for gammaherpesvirus reactivation in vivo However, how the UPR regulates BCR-mediated gammaherpesvirus infection is unknown. Here, we demonstrate that the ER stressors tunicamycin and thapsigargin inhibit BCR-mediated murine gammaherpesvirus 68 (MHV68) lytic replication by inducing expression of the UPR mediator Bip and blocking activation of Akt, ERK, and JNK. Both Bip and the downstream transcription factor ATF4 inhibited BCR-mediated MHV68 lytic gene expression, whereas UPR-induced C/EBP homologous protein (CHOP) was required for and promoted BCR-mediated MHV68 lytic replication by suppressing upstream Bip and ATF4 expression. Bip knockout was sufficient to rescue BCR-mediated MHV68 lytic gene expression in CHOP knockout cells, and this rescue was blocked by ectopic ATF4 expression. Furthermore, ATF4 directly inhibited promoter activity of the MHV68 lytic switch transactivator RTA. Altogether, we show that ER stress-induced CHOP inhibits Bip and ATF4 expression and that ATF4, in turn, plays a critical role in CHOP-mediated regulation of BCR-controlled MHV68 lytic replication. We conclude that ER stress-mediated UPR and BCR signaling pathways are interconnected and form a complex network to regulate the gammaherpesvirus infection cycle.

Jagged1 is Clinically Prognostic and Promotes Invasion of Glioma-Initiating Cells by Activating NF-κB(p65) Signaling.

BACKGROUND/AIMS: Jagged1 is the ligands of the Notch signaling and has been shown to promote glioma-initiating cells (GICs) in glioblastoma. The role of Jagged1 in GICs invasion and underlying molecular mechanisms remain unclear. METHODS: Survival data from R2 genomics analysis, the Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA) and visualization platform database were used to evaluate the effects of Jagged1 on overall patient survival. we investigated Jagged1 induced the GICs cells' invasion by matrix degradation assays and Transwell cell invasion assays in vitro, then we further explored the underlying molecular mechanisms using Co-immunoprecipitation (co-IP) analysis. RESULTS: High expression of Jagged1 in human glioma was associated with poor survival. Clinical data analysis showed that the Jagged1 was positively correlated with NF-κB(p65). Jagged1-induced invasion of GICs cells through activation of NF-κB(p65) pathway. In vivo, knockdown of Jagged1 could suppress the tumorigenicity of GICs cells through NF-κB(p65) signaling. CONCLUSION: Insights gained from these findings suggest that Jagged1 plays an important oncogenic role in GICs malignancy by activation of NF-κB(p65) signaling, and Jagged1 could be employed as an effective therapeutic target for GICs.

Obstetrical outcomes after vaginal repair of caesarean scar diverticula in reproductive-aged women.

BACKGROUND: Although vaginal repair has been conducted to manage caesarean scar diverticula, most studies evaluated only the gynaecological outcomes post-surgery, and their obstetrical outcomes were unknown. This study aimed to evaluate the obstetrical outcomes in vaginal repair-treated caesarean scar diverticula patients. METHODS: A series of 51 symptomatic women with caesarean scar defects or a thickness of the remaining muscular layer of less than 3 mm according to transvaginal ultrasound were included. We retrospectively evaluated the gynaecological and obstetrical outcomes after vaginal repair and histologically analysed the defect. RESULTS: Transvaginal ultrasound revealed that the thickness of the remaining muscular layer significantly increased from 2.24 ± 0.81 mm to 6.10 ± 1.43 mm 3 months after vaginal repair. The duration of menstruation significantly decreased from 14.29 ± 3.13 days to 8.31 ± 2.14 days post-vaginal repair. Notably, 26 of the 51 (50.98%) women who were followed for more than 15.04 months post-surgery achieved pregnancy. A total of 6 of the 26 pregnancies (23.08%) resulted in miscarriages, including 5 early miscarriages and 1 late miscarriage. Among the 20 women who achieved pregnancy without miscarriage, 18 had term deliveries, 2 had preterm birth, and none reported uterine rupture. Histological analysis was performed in all 51 cases. Muscle fibre density was significantly lower in the scar than in the myometrium adjacent to the scar and collagen expression was markedly increased in the scar tissue. CONCLUSION: Satisfactory gynaecological and subsequent obstetrical outcomes can be achieved in vaginal repair-treated caesarean scar diverticula patients.