Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases.

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy of T cell progenitors, known to be a heterogeneous disease in pediatric and adult patients. Here we attempted to better understand the disease at the molecular level based on the transcriptomic landscape of 707 T-ALL patients (510 pediatric, 190 adult patients, and 7 with unknown age; 599 from published cohorts and 108 newly investigated). Leveraging the information of gene expression enabled us to identify 10 subtypes (G1­G10), including the previously undescribed one characterized by GATA3 mutations, with GATA3R276Q capable of affecting lymphocyte development in zebrafish. Through associating with T cell differentiation stages, we found that high expression of LYL1/LMO2/SPI1/HOXA (G1­G6) might represent the early T cell progenitor, pro/precortical/cortical stage with a relatively high age of disease onset, and lymphoblasts with TLX3/TLX1 high expression (G7­G8) could be blocked at the cortical/postcortical stage, while those with high expression of NKX2-1/TAL1/LMO1 (G9­G10) might correspond to cortical/postcortical/mature stages of T cell development. Notably, adult patients harbored more cooperative mutations among epigenetic regulators, and genes involved in JAK-STAT and RAS signaling pathways, with 44% of patients aged 40 y or above in G1 bearing DNMT3A/IDH2 mutations usually seen in acute myeloid leukemia, suggesting the nature of mixed phenotype acute leukemia.

MFAP2 promotes the progression of oral squamous cell carcinoma by activating the Wnt/ß-catenin signaling pathway through autophagy.

Microfibrillar-associated protein 2 (MFAP2) is a small glycoprotein that is involved in vascular development and metabolic disease. The present study aims to explore the regulatory role of MFAP2 in the development and progression of oral squamous cell carcinoma (OSCC), including the underlying mechanisms. MFAP2 expression and its association with the progression of OSCC are explored using bioinformatics. MFAP2 expression in OSCC tissues is detected by immunohistochemical staining. SCC15 cell migration, invasion, apoptosis, proliferation, and viability are detected by wound healing, Transwell, flow cytometry, colony formation, and cell counting kit-8 assays. An in vivo experiment is used to detect tumor formation. Western blot analysis is used to determine MFAP2's regulatory role in autophagy and the Wnt/ß-catenin signaling pathway. MFAP2 is highly expressed in SCC15 cells and OSCC tissues, which correlates positively with the poor prognosis of patients with OSCCs. Functionally, MFAP2 promotes oncogenic autophagy to increase cell invasion, migration, and proliferation but inhibits apoptosis in SCC15 cells and promotes tumor growth in vivo. Mechanistically, MFAP2 upregulates autophagy and Wnt/ß-catenin signaling to stimulate OSCC development. Intriguingly, regulation of Wnt/ß-catenin signaling dependent on autophagy contributes to the malignant behaviors of SCC15 cells. MFAP2 could serve as a novel biomarker for OSCC and could affect OSCC tumorigenesis and development via autophagic regulation of Wnt/ß-catenin signaling.

Effect of single-port video-assisted thoracoscopy on surgical site wound infection and healing in patients with lung cancer: A meta-analysis.

We performed a meta-analysis to comprehensively assess the effect of single-port video-assisted thoracoscopy on surgical site wound infection and healing in patients with lung cancer. A computerised search for studies on single-port video-assisted thoracoscopy treatment of lung cancer was conducted from the time of database creation through February 2023 using the PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases. Two investigators independently screened the literature, extracted information, and evaluated the quality of studies according to inclusion and exclusion criteria. Either a fixed or random-effects model was used in calculating the relative risk (RR) with 95% confidence intervals (CIs). Meta-analysis was performed using RevMan 5.4 software. The results showed that, compared with multi-port video-assisted thoracoscopy, single-port video-assisted thoracoscopy significantly reduced surgical site wound infection (RR: 0.38, 95% CI: 0.19-0.77, P = .007) and significantly promoted wound healing (RR: 0.37, 95% CI: 0.22-0.64, P < .001). Compared with multi-port video-assisted thoracoscopy, single-port video-assisted thoracoscopy significantly reduced surgical site wound infections and also promoted wound healing. However, because of large variations in study sample sizes, some of the literature reported methods of inferior quality. Additional high-quality studies containing large sample sizes are needed to further validate these results.

The evolution and inter-sectoral interaction mechanism of China's national medical alliance: An analysis based on complex systems theory.

This work investigates the performance and inter-sectoral interaction mechanism of China's largest vertically integrated care network, the national medical alliance (NMA). The data collected derive from the China Health Statistics Bulletin and the China Health Statistical Yearbook for the period 2009-2018. The data include 64 observation indicators for five medical sectors in the NMA, namely, tertiary hospitals (THS), secondary hospitals (SHS), community health centres (CHCS), township hospitals (TsHS) and professional public health institutions (PPHIS). This research combines complex systems theory with a multilevel structural dynamic factor model, and yields two main results. First, although the trend for the NMA's global factor is increasing, the evolutionary paths for sectoral factors differ substantially. Among the sectoral factors, the sectoral factor of THS continued to decline, and neither the sectoral factor of CHCS nor the sectoral factor of TsHS has significantly improved. Then, the interaction mechanism between the various NMA sectors is investigated. While a close relationship has been formed between THS and CHCS and between SHS and CHCS, there remains no close two-way relationship between either THS and TsHS or THS and SHS. Thus, going forward, to reach the policy expectations, China's NMA implementation must consider the interaction between different constituent sectors.

Analysis of Pedestrian Fractures in Collisions Between Small Cars and Pedestrians Based on Surveillance Videos.

OBJECTIVE: To discuss the collision relationship and the cause of the fracture caused by traffic accidents in which the front of a small car collides with the side of a pedestrian while braking. METHODS: The surveillance videos of 42 traffic accidents involving the front of a small car colliding with the side of a pedestrian while braking were collected. By analyzing the surveillance videos and the paths, the speed of the collision, the relationship between the vehicle and the pedestrian upon collision, and the movement trajectory of the human body were clearly identified. The type and severity of the injuries were also determined through autopsy. The characteristics of the human injuries and vehicle paths were analyzed according to the collision speed (<40 km/h, 40-60 km/h, 60-90 km/h), and the correlations between the fracture and the height of the pedestrian, the height of the hood and the length of the hood were discussed. RESULTS: When a small car hits the side of a pedestrian, the front bumper first hits the lower limbs of the pedestrian, and then, the human body falls to the side of the vehicle, causing a secondary collision with the hood and front windshield; thus, the pedestrian is thrown at a speed similar to the speed of the vehicle, finally falling to the ground and sliding forward a certain distance. (1) When V is less than 40 km/h (n = 10), the pedestrian's head did not collide with the windshield, and the fatal injuries were caused by the individual striking the ground. (2) When V is greater than 40 km/h (n = 32), the majority (97%) of cases showed collision with the windshield. (3) When 40 to 60 km/h (n = 16), the pedestrian's head collided with the windshield, which can cause fatal injuries, and pelvic fractures and rib fractures occurred in 56.25% of patients. (4) When V is less than 60 km/h (n = 26), the ratio of the height of the pedestrian to the height of the hood was significantly smaller in the pelvic fracture group than in the nonpelvic fracture group (P < 0.01). (5) When 60 to 90 km/h (n = 16), there were holes in the windshield, and the pedestrians experienced severe head injuries, with cervical spine fracture occurring in 37.5% of patients, pelvic fractures occurring in 43.75% of patients, and rib fractures occurring in 31.25% of patients. CONCLUSIONS: When V is less than 40 km/h, the vehicle does not cause severe injuries in pedestrians; when V is greater than 40 km/h, the collisions of the pedestrian's head with the windshield lead to severe head injuries and the accident can cause severe pelvic and rib fractures; when V is greater than 60 km/h, the collisions of the pedestrian's head with the windshield can cause cervical spine fracture in addition to head injuries. The occurrence of human injuries is related to not only the vehicle speed but also factors such as the height of the pedestrian, the height of the hood and the length of the hood.

Bioinformatics-Guided Identification of Ethyl Acetate Extract of Citri Reticulatae Pericarpium as a Functional Food Ingredient with Anti-Inflammatory Potential.

Citri Reticulatae Pericarpium (CRP) is one of the most commonly used food supplements and folk medicines worldwide, and possesses cardiovascular, digestive, and respiratory protective effects partially through its antioxidant and anti-inflammatory functions. The unique aromatic flavor and mild side effects make CRP a promising candidate for the development of anti-inflammatory functional food. However, recent studies show that the crude alcoholic extract and some isolated compounds of CRP show compromised anti-inflammatory activity, which became the main factor hindering its further development. To identify the bioactive compounds with anti-inflammatory potential, and improve the anti-inflammatory effects of the extract, a bioinformatics-guided extraction protocol was employed in this study. The potential bioactive candidates were identified by combing network pharmacology analysis, molecular docking, principal components analysis, k-means clustering, and in vitro testing of reference compounds. Our results demonstrated that 66 compounds in CRP could be grouped into four clusters according to their docking score profile against 24 receptors, while the cluster containing flavonoids and phenols might possess a more promising anti-inflammatory function. In addition, in vitro anti-inflammatory tests of the seven reference compounds demonstrated that hesperitin, naringenin, and gardenin B, which were grouped into a cluster containing flavonoids and phenols, significantly decreased LPS-induced NO, TNF-α, and IL-6 production of macrophages. While the compounds outside of that cluster, such as neohesperidin, naringin, hesperidin, and sinensetin showed little effect on alleviating LPS-induced NO and proinflammatory cytokine production. Based on the chemical properties of selected compounds, ethyl acetate (EtOAc) was selected as the solvent for extraction, because of its promising solubility of flavonoids and phenols. Furthermore, the ethanol alcoholic extract was used as a reference. The chemical profiling of EtOAc and crude alcoholic extract by HPLC/MS/MS also demonstrated the decreased abundance of flavonoid glycosides in EtOAc extract but increased abundance of phenols, phenolic acid, and aglycones. In accordance with the prediction, the EtOAc extract of CRP, but not the crude alcoholic extract, significantly decreased the NO, IL-6, and TNF-α production. Taken together, the results suggested selective extraction of phenols and flavonoids rich extract was able to increase the anti-inflammatory potential of CRP partially because of the synergistic effects between flavonoids, phenols, and enriched polymethoxyflavones. Our study might pave the road for the development of ethyl acetate extract of CRP as a novel functional food with anti-inflammatory function.

Unraveling SO2-tolerant mechanism over Fe2(SO4)3/TiO2 catalysts for NOx reduction.

Developing low-temperature SO2-tolerant catalysts for the selective catalytic reduction of NOx is still a challenging task. The sulfation of active metal oxides and deposition of ammonium bisulfate deactivate catalysts, due to the difficult decomposition of the as-formed sulfate species at low temperatures (<300 °C). In recent years, metal sulfate catalysts have attracted increasing attention owing to their good catalytic activity and strong SO2 tolerance at higher temperatures (>300°C); however, the SO2-tolerant mechanism of metal sulfate catalysts is still ambiguous. In this study, Fe2(SO4)3/TiO2 and Ce2(SO4)3/TiO2 catalysts were prepared using the corresponding metal sulfate salt as the precursor. These catalysts were tested for their low-temperature activity and SO2 tolerance activity. Compared to Ce2(SO4)3/TiO2, Fe2(SO4)3/TiO2 showed significantly better low-temperature activity and SO2 tolerance. It was demonstrated that less surface sulfate species formed on Fe2(SO4)3/TiO2 and Ce2(SO4)3/TiO2. However, the presence of NO and O2 could assist the decomposition of NH4HSO4 over Fe2(SO4)3/TiO2 at a lower temperature, endowing Fe2(SO4)3/TiO2 with better low-temperature SO2 tolerance than Ce2(SO4)3/TiO2. This study unraveled the SO2-tolerant mechanism of Fe2(SO4)3/TiO2 at lower temperatures (<300 °C), and a potential strategy is proposed for improving the low-temperature SO2-tolerance of catalysts with Fe2(SO4)3 as the main active component or functional promoter.

Development and validation of a prognostic scoring model for mortality risk stratification in patients with recurrent or metastatic gastric carcinoma.

BACKGROUND: Survival times differ among patients with advanced gastric carcinoma. A precise and universal prognostic evaluation strategy has not yet been established. The current study aimed to construct a prognostic scoring model for mortality risk stratification in patients with advanced gastric carcinoma. METHODS: Patients with advanced gastric carcinoma from two hospitals (development and validation cohort) were included. Cox proportional hazards regression analysis was conducted to identify independent risk factors for survival. A prognostic nomogram model was developed using R statistics and validated both in bootstrap and external cohort. The concordance index and calibration curves were plotted to determine the discrimination and calibration of the model, respectively. The nomogram score and a simplified scoring system were developed to stratify patients in the two cohorts. RESULTS: Development and validation cohort was comprised of 401 and 214 gastric cancer patients, respectively. Mucinous or non-mucinous histology, ECOG score, bone metastasis, ascites, hemoglobin concentration, serum albumin level, lactate dehydrogenase level, carcinoembryonic antigen level, and chemotherapy were finally incorporated into prognostic nomogram. The concordance indices were 0.689 (95% CI: 0.664 ~ 0.714) and 0.673 (95% CI: 0.632 ~ 0.714) for bootstrap and external validation. 100 and 200 were set as the cut-off values of nomogram score, patients in development cohort were stratified into low-, intermediate- and high-risk groups with median overall survival time 15.8 (95% CI: 12.2 ~ 19.5), 8.4 (95% CI: 6.7 ~ 10.2), and 3.9 (95% CI: 2.7 ~ 5.2) months, respectively; the cut-off values also worked well in validation cohort with different survival time in subgroups. A simplified model was also established and showed good consistency with the nomogram scoring model in both of development and validation cohorts. CONCLUSION: The prognostic scoring model and its simplified surrogate can be used as tools for mortality risk stratification in patients with advanced gastric carcinoma.

Alkali-Resistant Catalytic Reduction of NOx via Naturally Coupling Active and Poisoning Sites.

Releasing the poisoning effect of alkali metals over catalysts is still an intractable issue for selective catalytic reduction (SCR) of NOx with ammonia. The presence of K in fly ash always dramatically suppressed catalytic activity by impairing acidity and redox properties, leading to severe reduction of lifetime for SCR catalysts. Herein, alkali-resistant NOx reduction over TiO2-supported Fe2(SO4)3 catalysts was originally demonstrated via naturally coupling active and poisoning sites. Notably, TiO2-supported Fe2(SO4)3 catalysts expressed admirable NOx conversion and K resistance within a quite broad temperature window of 200-500 °C. The catalysts with more conserved sulfate species revealed that sulfate groups preferred to migrate from the bulk phase to surface, thus effectively binding with K poisons to release the damage on iron active sites. Because of protection effects of migrated sulfates and closely coupling effects with Fe active sites, NH3 and NO adsorption amounts and rates were well maintained. In this way, Fe metal sites and sulfate species closely coupled together on a self-preserved TiO2-supported Fe2(SO4)3 catalyst played essential roles as highly active sites and unique poisoning sites. This work paves a new way to design SCR catalysts with superior alkali resistance that are more reliable in practical deNOx application.

An electrographic AV optimization for the maximum integrative atrioventricular and ventricular resynchronization in CRT.

BACKGROUND: Atrioventricular (AV) delay could affect AV and ventricular synchrony in cardiac resynchronization therapy (CRT). Strategies to optimize AV delay according to optimal AV synchrony (AVopt-AV) or ventricular synchrony (AVopt-V) would potentially be discordant. This study aimed to explore a new AV delay optimization algorithm guided by electrograms to obtain the maximum integrative effects of AV and ventricular resynchronization (opt-AV). METHODS: Forty-nine patients with CRT were enrolled. AVopt-AV was measured through the Ritter method. AVopt-V was obtained by yielding the narrowest QRS. The opt-AV was considered to be AVopt-AV or AVopt-V when their difference was < 20 ms, and to be the AV delay with the maximal aortic velocity-time integral between AVopt-AV and AVopt-V when their difference was > 20 ms. RESULTS: The results showed that sensing/pacing AVopt-AV (SAVopt-AV/PAVopt-AV) were correlated with atrial activation time (Pend-As/Pend-Ap) (P < 0.05). Sensing/pacing AVopt-V (SAVopt-V/PAVopt-V) was correlated with the intrinsic AV conduction time (As-Vs/Ap-Vs) (P < 0.01). The percentages of patients with more than 20 ms differences between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were 62.9% and 57.1%, respectively. Among them, opt-AV was linearly correlated with SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The sensing opt-AV (opt-SAV) = 0.1 × SAVopt-AV + 0.4 × SAVopt-V + 70 ms (R2 = 0.665, P < 0.01) and the pacing opt-AV (opt-PAV) = 0.25 × PAVopt-AV + 0.5 × PAVopt-V + 30 ms (R2 = 0.560, P < 0.01). CONCLUSION: The SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were correlated with the atrial activation time and the intrinsic AV conduction interval respectively. Almost half of the patients had a > 20 ms difference between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The opt-AV could be estimated based on electrogram parameters.

Electrophysiological characteristics of epicardial to endocardial breakthrough in intractable cavotricuspid isthmus-dependent atrial flutter.

BACKGROUND: Epicardial to endocardial breakthrough (EEB) exists widely in atrial arrhythmia and is a cause for intractable cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL). This study aimed to investigate the electrophysiological features of EEB in EEB-related CTI dependent AFL. METHODS: Six patients with EEB-related CTI-dependent AFL were identified among 142 consecutive patients who underwent CTI-dependent AFL catheter ablation with an ultra-high-density, high-resolution mapping system in three institutions. Activation maps and ablation procedure were analyzed. RESULTS: A total of seven EEBs were found in six patients. Four EEBs (including three at the right atrial septum and one in paraseptal isthmus) were recorded in three patients during tachycardia. The other three EEBs were identified at the inferolateral right atrium (RA) during pacing from the coronary sinus. The conduction characteristics through the EEB-mediated structures were evaluated in three patients. Two patients only showed unidirectional conduction. Activation maps indicated that CTI-dependent AFL with EEB at the atrial septum was actually bi-atrial macro-reentrant atrial tachycardia (BiAT). Intensive ablation at the central isthmus could block CTI bidirectionally in four cases. However, ablation targeted at the inferolateral RA EEB was required in two cases. Meanwhile, local potentials at the EEB location gradually split into two components with a change in activation sequence. CONCLUSIONS: EEB is an underlying cause for intractable CTI-dependent AFL. EEB-mediated structure might show unidirectional conduction. CTI-dependent AFL with EEB at the atrial septum may represent BiAT. Intensive ablation targeting the central isthmus or EEB at the inferolateral RA could block the CTI bidirectionally.

Sex hormone-binding globulin regulates the activity of the ERK pathway in the placentas of patients with gestational diabetes mellitus.

The sex hormone-binding globulin (SHBG) is involved in the onset and progression of insulin resistance and metabolic syndromes, with its expression downregulated in the placental tissues of patients with gestational diabetes mellitus (GDM). However, the underlying mechanisms for these effects remain unclear. In this study, we enrolled an equal number (30) of GDM and non-GDM puerperae who underwent cesarean section at Shengjing Hospital. After due approval by the ethics committee, the expression levels of SHBG and extracellular-signal-regulated kinase (ERK) pathway markers in the placental tissues of these individuals were measured via reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assays. The correlation analysis of these genes revealed that the expression of SHBG in placental tissues was downregulated and negatively correlated with the expression of ERK pathway markers, which were upregulated in placental tissues. Further investigations using the HTR-8/SVneo trophoblast cell line revealed that the trophoblasts with small interfering RNA (siRNA)-silenced SHBG expression displayed increased mRNA and protein expression levels of ERK pathway markers, as well as reduced apoptosis and enhanced proliferation. In contrast, trophoblasts with high SHBG expression showed a downregulated expression of ERK pathway markers, increased apoptosis, reduced proliferation, and a shorter S phase. Therefore, we believe that SHBG may participate in the onset of insulin resistance and GDM by regulating the activity of the ERK pathway.

SO2-Tolerant NOx Reduction by Marvelously Suppressing SO2 Adsorption over FeδCe1-δVO4 Catalysts.

SO2-tolerant selective catalytic reduction (SCR) of NOx at low temperature is still challenging. Traditional metal oxide catalysts are prone to be sulfated and the as-formed sulfates are difficult to decompose. In this study, we discovered that SO2 adsorption could be largely restrained over FeδCe1-δVO4 catalysts, which effectively restrained the deposition of sulfate species and endowed catalysts with strong SO2 tolerance at an extremely low temperature of 240 °C. The increasing oxygen vacancies, enhanced redox properties, and improved acidity contributed to the SCR activity of the FeδCe1-δVO4 catalyst. The reaction pathway changed from the reaction between bidentate nitrate and the NH3 species over CeVO4 catalysts via the Langmuir-Hinshelwood mechanism to that between gaseous NOx and the NH4+/NH3 species over FeδCe1-δVO4 catalysts via the Eley-Rideal mechanism. The effective suppression of SO2 adsorption allowed FeδCe1-δVO4 catalysts to maintain the Eley-Rideal pathways on account of the reduced formation of sulfate species. This work demonstrated an effective route to improve SO2 tolerance via modulating SO2 adsorption on Ce-based vanadate catalysts, which presented a new point for the development of high-performance SO2-tolerant SCR catalysts.

Alkali and Phosphorus Resistant Zeolite-like Catalysts for NOx Reduction by NH3.

At present, the deactivation of selective catalytic reduction (SCR) catalysts caused by the coexistence of alkali metal and phosphorus (P) remains an urgent problem and lacks corresponding strategies against catalyst poisoning. Herein, a novel zeolite-like Ce-Si5Al2Ox catalyst derived from an ultrasmall nanozeolite EMT precursor was synthesized without organic templates at ambient temperature. This catalyst was able to maintain above 95% NOx conversion in the 270-540 °C temperature range. Moreover, 1 wt % potassium (K) and 5 wt % P loading had no influence on the SCR performance of the Ce-Si5Al2Ox catalyst at 300-480 °C. It was demonstrated that cerium (Ce) was highly dispersed in the amorphous aluminum (Al) silicate derived from EMT zeolites and expressed high catalytic performance. Besides, a large number of acid sites were reserved to absorb ammonia allowing effective participation in the SCR reaction and capturing alkali metals, thus improving the SCR performance and K resistance. Additionally, the strong interaction between Ce and aluminosilicate decreased cerium phosphate production, preventing deactivation of the catalysts. Thus, this novel low-cost zeolite-like Ce-Si5Al2Ox catalyst with a highly active ion-exchanged metal phase and abundant surface acid sites paves a way for designing new efficient and poisoning-resistant SCR catalysts for practical applications.

AEG-1 promotes angiogenesis and may be a novel treatment target for tongue squamous cell carcinoma.

BACKGROUND: The study explored the potential function of astrocyte elevated gene-1 (AEG-1) on angiogenesis in tongue squamous cell carcinoma (TSCC) in TSCC cell lines. METHODS: The different degrees of angiogenesis were detected in TSCC cell lines expressing different levels of AEG-1 by chick chorioallantoic membrane (CAM) experimental model. Next, we established xenografts of different TSCC cell lines with different expression levels of AEG-1 in nude mice and conducted immunohistochemistry to evaluate the expression of the angiogenesis-associated factor, that is, vascular endothelial growth receptor factor 2 (VEGFR-2) and microvessel density (MVD). Vascular endothelial growth factor (VEGF) was detected by ELISA. RESULTS: CAM assay showed that the number of vessels was significantly reduced in AEG-1-down um1 cell line (p < .05), whereas the number was significantly increased in AEG-1-over um2 cell line (p < .05). Moreover, up-regulated AEG-1 expression level was associated with higher tumor angiogenesis, which was reflected by augmented expression levels of VEGF (p < .01), VEGFR-2 (p < .05), and MVD counting (p < .01). CONCLUSIONS: This study demonstrated that AEG-1 can promote tumor angiogenesis in TSCC and inhibition of tumor angiogenesis by repressing the expression of AEG-1 may be a novel potential treatment approach for TSCC.

AP1G mediates vacuolar acidification during synergid-controlled pollen tube reception.

Double fertilization in angiosperms requires the delivery of immotile sperm through pollen tubes, which enter embryo sacs to initiate synergid degeneration and to discharge. This fascinating process, called pollen tube reception, involves extensive communications between pollen tubes and synergids, within which few intracellular regulators involved have been revealed. Here, we report that vacuolar acidification in synergids mediated by AP1G and V-ATPases might be critical for pollen tube reception. Functional loss of AP1G or VHA-A, encoding the γ subunit of adaptor protein 1 or the shared component of two endomembrane V-ATPases, respectively, impaired synergid-controlled pollen tube reception and caused partial female sterility. AP1G works in parallel to the plasma membrane-associated receptor FERONIA in synergids, suggesting that synergid-mediated pollen tube reception requires proper sorting of vacuolar cargos by AP1G. Although AP1G did not mediate the targeting of V-ATPases, AP1G loss of function or the expression of AP1G-RNAi compromised vacuolar acidification mediated by V-ATPases, implying their genetic interaction. We propose that vacuolar acidification might represent a distinct cell-death mechanism specifically adopted by the plant phylum, which is critical for synergid degeneration during pollen tube reception.

Sex hormone-binding globulin regulates glucose metabolism in human placental trophoblasts via cAMP/PKA/CREB1.

AIM: This study was conducted to investigate the effects of sex hormone-binding globulin (SHBG) on glucose metabolism and insulin resistance in human placental trophoblasts and involvement of the cAMP/PKA/CREB1 signaling pathway in these effects. METHODS: An insulin resistance cell model of human trophoblasts was established. An SHBG-overexpression plasmid was transfected into these cells, and the expression of glucose transporter 1 (GLUT1), CREB and p-CREB was detected and analyzed in normal cells, model cells and all groups of transfected cells by real-time PCR and western blotting; cAMP, PKA, glucose consumption and pyruvic acid levels were also detected. RESULTS: Among the four groups, there was no significant difference in the expression of CREB mRNA or GLUT1 mRNA (P > 0.05); however, CREB, p-CREB, GLUT1 protein, cAMP and PKA showed low expression (P < 0.05) and cell glucose consumption and pyruvate production were decreased (P < 0.05) in the model group, compared to the normal group. SHBG overexpression in insulin-resistant cells partially increased the levels of p-CREB, GLUT1, cAMP and PKA (P < 0.05). Intracellular glucose consumption and pyruvate production were nearly restored to the levels observed in cells from the normal group. CONCLUSION: Sex hormone-binding globulin regulates GLUT1 expression via the cAMP/PKA/CREB1 pathway and affects glucose transport in the placenta, which can induce insulin resistance and gestational diabetes.

Effectiveness of remineralizing agents in the prevention and reversal of orthodontically induced white spot lesions: a systematic review and network meta-analysis.

OBJECTIVES: To compare the effectiveness of remineralizing agents in the prevention and reversal of white spot lesions (WSLs), which occur during fixed orthodontic treatment, through a systematic review and network meta-analysis. MATERIALS AND METHODS: We reviewed controlled randomized clinical trial (RCT) data querying nine databases combined with a manual search (last search date: March 10, 2020). Of 2273 identified studies, 36 RCTs were finally included. After study selection and data extraction, pair-wise and network meta-analyses were performed to analyze the effectiveness of remineralizing agents in the prevention and reversal of WSLs in the short term (≤ 3 months) and long term (> 3 months). The risk of bias was assessed based on the Cochrane guidelines. Statistical heterogeneity, inconsistencies, and cumulative ranking were also evaluated. RESULTS: In terms of WSL prevention, sodium fluoride (NaF) varnish had the highest cumulative ranking for the short-term decalcification index (99.3%); acidulated phosphate fluoride (APF) foam ranked first for long-term incidence (96.9%), followed by difluorosilane (Dfs) varnish and high-concentration fluoride toothpaste (HFT) (79.4% and 77.4%, respectively). In the reversal of WSLs, no significant difference was found among different agents or their combinations for the two available outcomes (short-term integrated fluorescence loss and short-term percentage of fluorescence loss). CONCLUSIONS: In the prevention of WSLs, APF foam showed the best remineralizing effectiveness in the long term (after debonding), followed by Dfs varnish and HFT. It is unclear whether remineralizing agents can effectively reverse WSLs based on the existing evidence. CLINICAL RELEVANCE: APF foam may be recommended as a remineralizing agent for preventing orthodontically induced WSLs. PROSPERO REGISTRATION NUMBER: CRD42019116852.

Overdrive pacing mapping: An alternative approach used in scar associated localized atrial tachycardia.

BACKGROUND: Mapping and ablation of localized reentry atrial tachycardia (AT) can be challenging, especially in those with varying cycle length (CL). OBJECTIVE: We attempted to use the traditional maneuver of overdrive pacing to facilitate AT mapping. METHODS: Data were collected from 12 patients with localized ATs. All patients had prior cardiac surgery or prior atrial fibrillation ablation. Overdrive pacing mapping (ODPM) was performed to find independent local activity (ILA) and compared with conventional activation mapping (CAM) during ongoing AT to determine its accuracy and efficacy. Patients with macro-reentry AT around the tricuspid or mitral annulus were excluded. RESULTS: Twelve patients with 14 localized ATs were included. All 14 ATs including 4 (29%) with varying CL successfully completed ODPM and had the ILA, although two ATs terminated during ODP and required repeated mapping. Radiofrequency ablation focused on critical sites with ILA was successful in all 12 patients. Using CAM, however, 6 of 14 ATs (43%) mapping attempts were aborted due to AT termination (2 ATs) or varying CL (4 ATs), and only 5 of 8 (63%) located "critical sites" were ultimately confirmed by entrainment and ablation results. After 25 ± 9 months of follow-up, no patient had AT recurrence. CONCLUSION: Our preliminary results demonstrated that ODPM is superior to CAM in ATs that were poorly sustained or with varying CL and is a useful supplement to CAM.

Electrophysiological characteristics of the earliest activation site in idiopathic right ventricular outflow tract arrhythmias under mini-electrode mapping.

INTRODUCTION: Right ventricular outflow tract ventricular arrhythmias (RVOT VAs) often originate in the voltage-transitional zone. The target electrogram could be compromised by the architecture of the roving catheter. Mini-electrodes could improve the mapping resolution, especially in low-voltage areas. The aim was to assess the electrophysiological characteristics of the earliest activation site (EAS) of RVOT VAs during mapping using mini-electrodes. METHODS AND RESULTS: Twenty-seven patients with RVOT-type VAs were mapped using Orion mini-electrodes and the Rhythmia mapping system. Bipolar and unipolar electrograms were analyzed and compared with conventional ablation catheter recordings. Twenty-five patients (25 of 27) were successfully mapped and ablated at the RVOT. At the EAS, all 25 (100%) patients exhibited local sharp potentials (spiky potential) at the VAs, and 88% (22 of 25) individuals showed reverse late potentials in adjacent sinus beats on the bipolar mini-electrode recordings. Related unipolar electrograms manifested 20% "q-plateau-QS," 76% "gross QS," and 4% "late QS" patterns related to spiky potential voltages and advanced times. Compared with electrograms recorded by ablation catheter, bipolar mini-electrode recordings exhibited significantly shorter spiky potential durations (P = 0.001) and a significantly increased incidence of the reverse late potentials (P = 0.041). Unipolar mini-electrode recordings had a lower incidence ratio of "late QS" patterns (P = 0.039). CONCLUSION: Compared with ablation catheter mapping, mini-electrodes improved the mapping resolution of the EAS of RVOT VAs and exhibited shorter spiky potential durations and reduced incidence of "later QS" unipolar patterns.