Excess non-COVID-19-related mortality among inflammatory bowel disease decedents during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic disrupted healthcare in the United States. AIM: To investigate COVID-19-related and non-COVID-19-related death and characteristics associated with excess death among inflammatory bowel disease (IBD) decedents. METHODS: We performed a register-based study using data from the National Vital Statistics System, which reports death data from over 99% of the United States population, from January 1, 2006 through December 31, 2021. IBD-related deaths among adults 25 years and older were stratified by age, sex, race/ethnicity, place of death, and primary cause of death. Predicted and actual age-standardized mortality rates (ASMRs) per 100000 persons were compared. RESULTS: 49782 IBD-related deaths occurred during the study period. Non-COVID-19-related deaths increased by 13.14% in 2020 and 18.12% in 2021 [2020 ASMR: 1.55 actual vs 1.37 predicted, 95% confidence interval (CI): 1.26-1.49; 2021 ASMR: 1.63 actual vs 1.38 predicted, 95%CI: 1.26-1.49]. In 2020, non-COVID-19-related mortality increased by 17.65% in ulcerative colitis (UC) patients between the ages of 25 and 65 and 36.36% in non-Hispanic black (NHB) Crohn's disease (CD) patients. During the pandemic, deaths at home or on arrival and at medical facilities as well as deaths due to neoplasms also increased. CONCLUSION: IBD patients suffered excess non-COVID-19-related death during the pandemic. Excess death was associated with younger age among UC patients, and with NHB race among CD patients. Increased death at home or on arrival and due to neoplasms suggests that delayed presentation and difficulty accessing healthcare may have led to increased IBD mortality.

Age and urban-rural disparities in cutaneous melanoma mortality rates in the United States during the COVID-19 pandemic.

Most recent studies on the coronavirus disease 2019 (COVID-19) pandemic and cutaneous melanoma (CM) focused more on delayed diagnosis or advanced presentation. We aimed to ascertain mortality trends of CM between 2012 and 2022, focusing on the effects of the COVID-19 pandemic. In this serial population-based study, the National Vital Statistics System dataset was queried for mortality data. Excess CM-related mortality rates were estimated by calculating the difference between observed and projected mortality rates during the pandemic. Totally there were 108,853 CM-associated deaths in 2012-2022. CM-associated mortality saw a declining trend from 2012 to 2019 overall. However, it increased sharply in 2020 (ASMR 3.73 per 100,000 persons, 5.95% excess mortality), and remained high in 2021 and 2022, with the ASMRs of 3.82 and 3.81, corresponding to 11.17% and 13.20% excess mortality, respectively. The nonmetro areas had the most pronounced rise in mortality with 12.20% excess death in 2020, 15.33% in 2021 and 20.52% in 2022, corresponding to a 4-6 times excess mortality risk compared to large metro areas during the pandemic. The elderly had the most pronounced rise in mortality, but the mortality in the younger population was reduced.

Trends in gynaecologic cancer mortality and the impact of the COVID-19 pandemic in the United States.

OBJECTIVES: Our aim was to assess the trend in gynaecologic cancer (GC) mortality in the period from 2010 to 2022 in the United States, with focus on the impact of the pandemic on increased deaths. METHODS: GC mortality data were extracted from the Center for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) platform. We analysed mortality trends and evaluated observed vs. predicted mortality for the period from 2020 to 2022 with joinpoint regression and prediction modelling analyses. RESULTS: A total of 334,382 deaths among adults aged 25 years and older with gynaecologic cancer were documented from 2010 to 2022. The overall age-standardised mortality rate (ASMR, per 100,000 persons) for ovarian cancer-related death decreased gradually from 7.189 in 2010 to 5.517 in 2019, yielding an APC (annual percentage change) of -2.8%. However, the decrease in ovarian cancer-related mortality slowed down by more than 4-fold during the pandemic. Cervical cancer -related mortality decreased slightly prior to the pandemic and increased during the pandemic with an APC of 0.6%, resulting in excess mortality of 4.92%, 9.73% and 2.03% in 2020, 2021 and 2022, respectively. For uterine corpus cancer, the ASMR increased from 1.905 in 2010 to 2.787 in 2019, and increased sharply to 3.079 in 2021 and 3.211 in 2022. The ASMR rose steadily between 2013 and 2022, yielding an APC of 6.9%. CONCLUSIONS: Overall, we found that GC-related mortality increased during the COVID-19 pandemic, and this increase was not specific to age, race, or ethnicity.

Excess psoriasis and psoriatic arthritis mortality during the COVID-19 pandemic in the United States: A nationwide population-based study from 2010 to 2021.

BACKGROUND: Little is known about mortality trends among patients with psoriasis (PsO) and psoriatic arthritis (PsA) in the United States. OBJECTIVES: To ascertain mortality trends of PsO and PsA between 2010 and 2021, focusing on the effects of the COVID-19 pandemic. METHODS: We collected data from the National Vital Statistic System and calculated age-standardized mortality rates (ASMR) and cause-specific mortality for PsO/PsA. We evaluated observed versus predicted mortality for 2020-2021 based on trends from 2010 to 2019 with joinpoint and prediction modelling analysis. RESULTS: Among 5810 and 2150 PsO- and PsA-related deaths between 2010 and 2021, ASMR for PsO dramatically increased between 2010-2019 and 2020-2021 (annual percentage change [APC] 2.07% vs. 15.26%; p < 0.01), leading to a higher observed ASMR (per 100,000 persons) than predicted for 2020 (0.27 vs. 0.22) and 2021 (0.31 vs. 0.23). The excess mortality of PsO was 22.7% and 34.8% higher than that in the general population in 2020 (16.4%, 95% CI: 14.9%-17.9%) and 2021 (19.8%, 95% CI: 18.0%-21.6%) respectively. Notably, the ASMR rise for PsO was most pronounced in the female (APC: 26.86% vs. 12.19% in males) and the middle-aged group (APC: 17.67% vs. 12.47% in the old-age group). ASMR, APC and excess mortality for PsA were similar to PsO. SARS-CoV-2 infection contributed to more than 60% of the excess mortality for PsO and PsA. CONCLUSIONS: Individuals living with PsO and PsA were disproportionately affected during the COVID-19 pandemic. Both ASMRs increased at an alarming rate, with the most pronounced disparities among the female and middle-aged groups.

Comparison of clinical outcomes of conbercept versus ranibizumab treatment for retinopathy of prematurity: a multicentral prospective randomised controlled trial.

PURPOSE: To compare the recurrence rate and surgical complications of retinopathy of prematurity (ROP) between patients treated with intravitreal injection of conbercept (IVC) and intravitreal injection of ranibizumab (IVR) within 6 months. METHODS: A multicentral prospective, randomised controlled trial was applied from May 2017 to February 2019 for the infants diagnosed as aggressive posterior-ROP, zone I or posterior zone II treatment-requiring ROP by binocular indirect ophthalmoscope and RetCam3. These infants were assigned to randomly receive either intravitreal injection of 0.25 mg conbercept or 0.25 mg ranibizumab. The recurrence rate, fundus fluorescence angiography (FFA) and surgical complications were examined during the follow-up period of 6 months. Recurrent eyes were retreated by laser or another intravitreal injection within the 72 hours. RESULTS: A total of 30 infant patients (60 eyes) underwent IVC and 30 patients (60 eyes) underwent IVR. A total of 10 eyes (16.67%) in the IVC group and 14 eyes (23.34%) in the IVR group developed recurrence. There was no significant statistical difference in the recurrence rate between the two groups (χ2=0.83, p=0.36). The postmenstrual age (PMA) at first injection was (34.60±3.47) weeks in IVC and (35.14±1.76) in IVR group. In recurrent cases, the mean PMA at second treatment were (43.31±3.85) and (43.43±3.89) weeks in the IVC and IVR group, respectively. The period between two treatments was (8.71±6.62) for the IVC and (8.29±2.56) weeks for the IVR group. All these results showed no significant statistical difference between these two groups. The fluorescein leakage were observed in the eyes of recurrent infants by FFA. There were no other complications in the two groups except for complicated cataract in three eyes. CONCLUSION: Both IVC and IVR are effective therapies for the treatment of ROP. Conbercept is a new option for treating ROP.

Extracellular matrix stiffness controls VEGF165 secretion and neuroblastoma angiogenesis via the YAP/RUNX2/SRSF1 axis.

Aberrant variations in angiogenesis have been observed in tumor tissues with abnormal stiffness of extracellular matrix (ECM). However, it remains largely unclear how ECM stiffness influences tumor angiogenesis. Numerous studies have reported that vascular endothelial growth factor-A (VEGF-A) released from tumor cells plays crucial roles in angiogenesis. Hence, we demonstrated the role of ECM stiffness in VEGF-A release from neuroblastoma (NB) cells and the underlying mechanisms. Based on 17 NB clinical samples, a negative correlation was observed between the length of blood vessels and stiffness of NB tissues. In vitro, an ECM stiffness of 30 kPa repressed the secretion of VEGF165 from NB cells which subsequently inhibited the tube formation of human umbilical vein endothelial cells (HUVECs). Knocked down VEGF165 in NB cells or blocked VEGF165 with neutralizing antibodies both repressed the tube formation of HUVECs. Specifically, 30 kPa ECM stiffness repressed the expression and nuclear accumulation of Yes-associated protein (YAP) to regulate the expression of Serine/Arginine Splicing Factor 1 (SRSF1) via Runt-related transcription factor 2 (RUNX2), which may then subsequently induce the expression and secretion of VEGF165 in NB tumor cells. Through implantation of 3D col-Tgels with different stiffness into nude mice, the inhibitory effect of 30 kPa on NB angiogenesis was confirmed in vivo. Furthermore, we found that the inhibitory effect of 30 kPa stiffness on NB angiogenesis was reversed by YAP overexpression, suggesting the important role of YAP in NB angiogenesis regulated by ECM stiffness. Overall, our work not only showed a regulatory effect of ECM stiffness on NB angiogenesis, but also revealed a new signaling axis, YAP-RUNX2-SRSF1, that mediates angiogenesis by regulating the expression and secretion of VEGF165 from NB cells. ECM stiffness and the potential molecules revealed in the present study may be new therapeutic targets for NB angiogenesis.

Cr-Doped Pd Metallene Endows a Practical Formaldehyde Sensor New Limit and High Selectivity.

Electrochemical sensors for detecting micromolecule organics are desirable for improving the perception of environmental quality and human health. However, currently, the electrochemical sensors for formaldehyde are substantially limited on the market due to the long-term unsolved problems of the low electrooxidation efficiency and CO poisoning issue of commercial Pd catalysts. Here, a 2D Cr-doped Pd metallene (Cr-Pdene) with few atomic layers is shown as an advanced catalyst for ultrasensitive and selective sensing of formaldehyde via a highly efficient formaldehyde electrooxidation. It is found that the doping of Cr into Pd metallene can efficiently optimize the electronic structure of Pd and weaken the interaction between Pd and CO, providing an anti-poisoning means to favor CO2 production and suppress CO adsorption. The Cr-Pdene-based electrochemical sensor exhibits one order of magnitude higher detection range and, especially, much higher anti-interference for formaldehyde than that of the conventional sensors. Most importantly, it is demonstrated that the Cr-Pdene can be integrated into commercializable wireless sensor networks or handheld instruments for promising applications relating to the environment, health, and food.

A Unique Gas-Migration, Trapping, and Emitting Strategy for High-Loading Single Atomic Cd Sites for Carbon Dioxide Electroreduction.

Single-atom catalysts (SACs) exhibit great potential in heterogeneous catalysis. However, the achievement of obtaining high-loading SACs remains a bottleneck. Herein, we first demonstrate a unique gas-migration, trapping, and emitting strategy for building a kind of Cd-based SAC for CO2 reduction (CO2RR). The gas-migration and trapping processes (≤750 °C) endows the material with an ultrahigh Cd loading amount of 30.3 wt %, while the emitting process can facilely modulate the loading amount from 30.3 to 1.4 wt %. For the CO2RR, the Cd-NC SACs with a loading amount of 18.4 wt % exhibits the maximum Faraday efficiency of 91.4% for CO at -0.728 V. The operando infrared spectroscopy studies prove the presence of main intermediates *COO-, *COOH, and *CO on Cd-NC-5M SACs during the catalytic process, indicating that the CO2RR follows the proton-decoupled electron-transfer mechanism. Density functional theory simulations reveal that the Cd-N4 structure reduces the Gibbs free energy of the rate-determining step (the hydrogenation step of *COOH).

A Glycosylated Covalent Organic Framework Equipped with BODIPY and CaCO3 for Synergistic Tumor Therapy.

Ca2+ , a ubiquitous but nuanced modulator of cellular physiology, is meticulously controlled intracellularly. However, intracellular Ca2+ regulation, such as mitochondrial Ca2+ buffering capacity, can be disrupted by 1 O2 . Thus, the intracellular Ca2+ overload, which is recognized as one of the important cell pro-death factors, can be logically achieved by the synergism of 1 O2 with exogenous Ca2+ delivery. Reported herein is a nanoscale covalent organic framework (NCOF)-based nanoagent, namely CaCO3 @COF-BODIPY-2I@GAG (4), which is embedded with CaCO3 nanoparticle (NP) and surface-decorated with BODIPY-2I as photosensitizer (PS) and glycosaminoglycan (GAG) targeting agent for CD44 receptors on digestive tract tumor cells. Under illumination, the light-triggered 1 O2 not only kills the tumor cells directly, but also leads to their mitochondrial dysfunction and Ca2+ overload. An enhanced antitumor efficiency is achieved via photodynamic therapy (PDT) and Ca2+ overload synergistic therapy.

MYT1 attenuates neuroblastoma cell differentiation by interacting with the LSD1/CoREST complex.

Impaired neuronal differentiation is a feature of neuroblastoma tumorigenesis, and the differentiation grade of neuroblastoma tumors is associated with patient prognosis. Detailed understanding of the molecular mechanisms underlying neuroblastoma differentiation will facilitate the development of effective treatment strategies. Recent studies have shown that myelin transcription factor 1 (MYT1) promotes vertebrate neurogenesis by regulating gene expression. We performed quantitative analysis of neuroblastoma samples, which revealed that MYT1 was differentially expressed among neuroblastoma patients with different pathological diagnoses. Analysis of clinical data showed that MYT1 overexpression was associated with a significantly shorter 3-year overall survival rate and poor differentiation in neuroblastoma specimens. MYT1 knockdown inhibited proliferation and promoted the expression of multiple differentiation-associated proteins. Integrated omics data indicated that many genes involved in neuro-differentiation were regulated by MYT1. Interestingly, many of these genes are targets of the REST complex; therefore, we further identified the physical interaction of MYT1 with LSD1/CoREST. Depletion of LSD1 or inhibition of LSD1 by ORY-1001 decreased MYT1 expression, providing an alternative approach to target MYT1. Taken together, our results indicate that MYT1 significantly attenuates cell differentiation by interacting with the LSD1/CoREST complex. MYT1 is, therefore, a promising therapeutic target for enhancing the neurite-inducing effect of retinoic acid and for inhibiting the growth of neuroblastoma.

Near-infrared and metal-free tetra(butylamino)phthalocyanine nanoparticles for dual modal cancer phototherapy.

Synergistic phototherapy combining photodynamic therapy (PDT) and photothermal therapy (PTT) based on near-infrared (NIR) dyes using a single light source offers the opportunity to treat diseases at deep locations. In this study, we reported human serum albumin (HSA)-involving tetra(butylamino)phthalocyanine (Pc)-based nanomaterials of HSA-α-Pc and HSA-ß-Pc as highly efficient dual-phototherapy agents, namely 1(4),8(11),15(18),22(25)-tetra(butylamino)phthalocyanine (α-Pc) and 2(3),9(10),16(17),23(24)-tetra(butylamino)phthalocyanine (ß-Pc). Both HSA-α-Pc and HSA-ß-Pc showed excellent photothermal effects under a single NIR (808 nm) laser irradiation due to the S 1 fluorescence emission quenching of Pcs. Compared to HSA-ß-Pc, HSA-α-Pc exhibited better singlet oxygen generation ability and its highly efficient PDT/PTT dual-phototherapy was also well evidenced via in vitro and vivo experiments under a single 808 nm laser irradiation. Overall, this approach would be viable for the fabrication of more new Pc-based metal-free nano agents for PDT/PTT synergistic phototherapy upon a single NIR light source.

Pd@Au Bimetallic Nanoplates Decorated Mesoporous MnO2 for Synergistic Nucleus-Targeted NIR-II Photothermal and Hypoxia-Relieved Photodynamic Therapy.

Bimetallic nanoparticles have received considerable attention owing to synergistic effect and their multifunctionality. Herein, new multifunctional Pd@Au bimetallic nanoplates decorated hollow mesoporous MnO2 nanoplates (H-MnO2 ) are demonstrated for achieving not only nucleus-targeted NIR-II photothermal therapy (PTT), but also tumor microenvironment (TME) hypoxia relief enhanced photodynamic therapy (PDT). The Pd@Au nanoplates present a photothermal conversion efficiency (PTCE) as high as 56.9%, superior to those PTAs activated in the NIR-II region such as Cu9 S5 nanoparticles (37%), Cu3 BiS3 nanorods (40.7%), and Au/Cu2-x S nanocrystals (43.2%). They further functionalize with transactivator of transcription (TAT) moiety for cell nuclear-targeting and biodegradable hollow mesoporous MnO2 (≈100 nm) loaded with photosensitizer Ce6 (TAT-Pd@Au/Ce6/PAH/H-MnO2 ) to construct a hierarchical targeting nanoplatform. The as-made TAT-Pd@Au/Ce6/PAH/H-MnO2 demonstrates good premature renal clearance escape ability and increased tumor tissue accumulation. It can be degraded in acidic TME and generate O2 by reacting to endogenous H2 O2 to relieve the hypoxia for enhanced PDT, while the released small TAT-Pd@Au nanoplates can effectively enter into the nucleus to mediate PTT. As a result, a remarkable therapeutic effect is achieved owing to the synergistic PTT/PDT therapy. This hierarchical targeting, TME-responsive, cytoplasm hypoxia relief PDT, and nuclear NIR-II PTT synergistic therapy can pave a new avenue for nanomaterials-based cancer therapy.

Follow-Up Report of Laparoscopic Fundoplication in Different Types of Esophageal Hiatal Hernia in Children.

Background: Esophageal hiatal hernia can be classified into four types. It has been reported that most complications occurred in type II-IV hernia patients compared with type I hernia. This study aimed to investigate and compare the efficacy, complications, and long-time outcomes after laparoscopic fundoplication between type I and type II-IV hernia patients. Materials and Methods: Medical records of 110 children who underwent laparoscopic fundoplication during 2008-2017 in our institution were retrospectively analyzed. Information of postoperative symptoms, complications, and quality of life (QOL) were compared between different types. Results: All 110 children underwent laparoscopic fundoplication, and none converted to open surgery. Type I and type II-IV each accounted for 50.9% and 42.8%. There was no significant difference in the perioperative data between type I and type II-IV esophageal hiatal hernia. The follow-up information of 81 children was obtained. The scores of postoperative symptoms were comparable between type I and type II-IV group, except the severity score of reflux symptom was higher in type I hernia patients (P = .032). The difference in the incidence of postoperative complications and recurrence after laparoscopic fundoplication between type I and type II-IV hernia was not significant. The QOL in three aspects improved significantly after laparoscopic fundoplication in all types of esophageal hiatal hernia. Conclusions: Laparoscopic fundoplication was an effective approach for all types of esophageal hiatal hernia. Type II-IV hernia could obtain a comparable therapeutic effect and long-time outcome compared with type I hernia despite its increased complexity of the anatomy and the required laparoscopic repair procedure.

The deubiquitinating enzyme UCHL1 is a favorable prognostic marker in neuroblastoma as it promotes neuronal differentiation.

BACKGROUND: Neuroblastoma (NB) is the most common pediatric solid tumor that originates from neural crest-derived sympathoadrenal precursor cells that are committed to development of sympathetic nervous system. The well differentiated histological phenotype of NB tumor cells has been reportedly associated with favorable patient outcome. Retinoic acid (RA) can effectively induce NB cell differentiation, thereby being used in the clinic as a treatment agent for inducing the differentiation of high-risk NB. However, the underlying molecular mechanisms of regulating differentiation remain elusive. METHODS: The correlation between clinical characteristics, survival and the deubiquitinating enzyme ubiquitin C-terminal hydrolase 1 (UCHL1) expression were assessed using a neuroblastic tumor tissue microarray, and then validated in three independent patient datasets. The different expression of UCHL1 in ganglioneuroblastoma, ganglioneuroma and NB was detected by immunohistochemistry, mass spectra and immunoblotting analysis, and the correlation between UCHL1 expression and the differentiated histology was analyzed, which was also validated in three independent patient datasets. Furthermore, the roles of UCHL1 in NB cell differentiation and proliferation and the underlying mechanisms were studied by using short hairpin RNA and its inhibitor LDN57444 in vitro. RESULTS: Based on our neuroblastic tumor tissue microarrays and three independent validation datasets (Oberthuer, Versteeg and Seeger), we identified that UCHL1 served as a prognostic marker for better clinical outcome in NB. We further demonstrated that high UCHL1 expression was associated with NB differentiation, indicated by higher UCHL1 expression in ganglioneuroblastomas/ganglioneuromas and well-differentiated NB than poorly differentiated NB, and the positive correlation between UCHL1 and differentiation markers. As expected, inhibiting UCHL1 by knockdown or LDN57444 could significantly inhibit RA-induced neural differentiation of NB tumor cells, characterized by decreased neurite outgrowth and neural differentiation markers. This effect of UCHL1 was associated with positively regulating RA-induced AKT and ERK1/2 signaling activation. What's more, knockdown of UCHL1 conferred resistance to RA-induced growth arrest. CONCLUSION: Our findings identify a pivotal role of UCHL1 in NB cell differentiation and as a prognostic marker for survival in patients with NB, potentially providing a novel therapeutic target for NB.

Prospective investigation of folic acid supplements before and during early pregnancy and paediatric and adult cancers in the Chinese children and families cohort: a pilot study in a sample of rural and urban families.

OBJECTIVE: To determine the feasibility of long-term prospective follow-up and ascertainment of cancer in offspring and mothers from the 1993-1995 Chinese Community Intervention Program that provided folic acid supplements before and during early pregnancy to reduce neural tube defects. DESIGN: Feasibility pilot study for a prospective cohort study. SETTING: Families residing during 2012-2013 in one rural and one urban county from 21 counties in 3 provinces in China included in the Community Intervention Program campaign. PARTICIPANTS: The feasibility study targeted 560 families, including 280 from the rural and 280 from the urban county included in the large original study; about half of mothers in each group had taken and half had not taken folic acid supplements. INTERVENTION: The planned new study is observational. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary: incidence of paediatric cancers in offspring; secondary: other chronic diseases in offspring and chronic diseases in mothers RESULTS: Only 3.4% of pilot study families could not be found, 3.9% had moved out of the study area and 8.8% refused to participate. Interviews were completed by 82% of mothers, 79% of fathers and 83% of offspring in the 560 families. Almost all mothers and offspring who were interviewed also participated in anthropometric measurements. We found notable urban-rural differences in sociodemographic and lifestyle characteristics of the parents, but fewer differences among the offspring. In eight catchment area hospitals, we identified a broad range of paediatric cancers diagnosed during 1994-2013, although paediatric brain tumours, lymphomas and rarer cancers were likely under-represented. CONCLUSIONS: Overall, 20 years after the original Community Intervention Program, the pilot study achieved high levels of follow-up and family member interview participation, and identified substantial numbers of paediatric malignancies during 1994-2013 in catchment area hospitals. Next steps and strategies for overcoming limitations are described.

15, 16-Dihydrotanshinone I Inhibits Hemangiomas through Inducing Pro-apoptotic and Anti-angiogenic Mechanisms in Vitro and in Vivo.

Infantile hemangioma (IH) is a common and benign vascular neoplasms, which has a high incidence in children. Although IH is benign, some patients experience complications such as pain, functional impairment, and permanent disfigurement. Treatment options for IH include corticosteroids, surgery, vincristine, interferon or cyclophosphamide. However, none of these modalities are ideal due to restrictions or potential serious side effects. There is thus a great need to explore novel treatments for IH with less side effects. Angiogenesis, vasculogenesis and tumorigenesis are the main features of IH. Tanshen is mostly used in Chinese traditional medicine to treat hematological abnormalities. Therefore, the aim of our study was to evaluate anti-proliferation and anti-angiogenesis effects on hemangiomas cells by extracted Tanshen compounds compared with propranolol, the first-line treatment for IH currently, both in vitro and in vivo. Cell viability, apoptosis, protein expression and anti-angiogenesis were analyzed by CCK8, Annexin V staining, Western blot and tube formation, respectively. The anti-tumor activity in vivo was evaluated using a mouse xenograft model. Fourteen major compounds extracting from Tanshen were screened for their ability to inhibit hemangiomas cells. Of the 14 compounds investigated, 15,16-Dihydrotanshinone I (DHTS) was the most potent modulator of EOMA cell biology. DHTS could significantly decrease EOMA cells proliferation by inducing cell apoptosis, which is much more efficient than propranolol in vitro. DHTS increased the expression of several apoptosis-related proteins, including caspase9, caspase3, PARP, AIF, BAX, cytochrome c, caspase8 and FADD and significantly inhibited angiogenesis, as indicated by reduced tube formation and diminished expression of vascular endothelial cell growth factor receptor 2 and matrix metalloproteinase 9. In nude mice xenograft experiment, DHTS (10 mg/kg) could significantly inhibit the tumor growth of EOMA cells as well as propranolol (40 mg/kg). Our study showed that DHTS was much more effective than propranolol in inhibiting hemangiomas proliferation and angiogenesis in vitro and in vivo, which could have potential therapeutic applications for treatment of IH.

Recent progress in two-dimensional inorganic quantum dots.

The development of two-dimensional (2D) inorganic materials-based quantum dots (QDs) is still in its infancy but is triggering immense enthusiasm due to their high chemical stability, good aqueous dispersibility, excellent optical property, good biocompatibility and easy functionalization. This review covers almost all the extant 2D-QDs based on graphene, phosphorene, silicene, carbides, nitrides, transition metal dichalcogenide, transition metal oxides and MXenes, etc. Their categories, synthetic routes, properties, functionalization and applications are critically highlighted. In the application section, special emphasis is placed on the progress in bioimaging, cancer therapy, fluorescent sensing and optoelectronics. Meanwhile, the latest advances in 2D QDs-based catalysis and energy since 2015 are addressed. Moreover, 2D nanoclusters, in particular 2D-QDs, are also included. This review provides guidance for 2D-QDs studies to meet the increasing demands in the many diverse applications.

Microbacterium zeae sp. nov., an endophytic bacterium isolated from maize stem.

A novel Gram-stain positive, aerobic, non-motile, non-spore-forming and rod-shaped strain designated 1204T was isolated from surface-sterilised stem tissue of maize planted in Fangshan District of Beijing, People's Republic of China. A polyphasic taxonomic study was performed on the new isolate. On the basis of 16S rRNA gene sequence similarity studies, this isolate belongs to the genus Microbacterium. High levels of 16S rRNA gene sequence similarity were found between strain 1204T and Microbacterium enclense NIO-1002T (98.8%) and Microbacterium proteolyticum RZ36T (98.4%) respectively. However, the DNA-DNA hybridization values between strain 1204T and its closely related species M. proteolyticum DSM 27100T and M. enclense DSM 25125T were 53.9 ± 1.6 and 20.9 ± 1.5% respectively. The DNA G+C content of strain 1204T was determined to be 68.0 mol%. The major fatty acids were found to consist of anteiso-C15:0 (37.6%), iso-C16:0 (28.6%) and anteiso-C17:0 (16.6%). The predominant menaquinone was MK-11 and the polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, an unidentified glycolipid and an unidentified lipid. The results of physiological and biochemical tests and minor differences in the fatty acid profiles allowed a clear phenotypic differentiation of strain 1204T from the closely related species in the genus Microbacterium. Thus, it was concluded that strain 1204T represents a novel species within the genus Microbacterium, for which the name Microbacterium zeae sp. nov. is proposed, with the type strain 1204T (= CGMCC 1.15289 = DSM 100750).

Phosphoproteomics reveals ALK promote cell progress via RAS/ JNK pathway in neuroblastoma.

Emerging evidence suggests receptor tyrosine kinase ALK as a promising therapeutic target in neuroblastoma. However, clinical trials reveal that a limited proportion of ALK-positive neuroblastoma patients experience clinical benefits from Crizotinib, a clinically approved specific inhibitor of ALK. The precise molecular mechanisms of aberrant ALK activity in neuroblastoma remain elusive, limiting the clinical application of ALK as a therapeutic target in neuroblastoma. Here, we describe a deep quantitative phosphoproteomic approach in which Crizotinib-treated neuroblastoma cell lines bearing aberrant ALK are used to investigate downstream regulated phosphoproteins. We identified more than 19,500-and quantitatively analyzed approximately 10,000-phosphorylation sites from each cell line, ultimately detecting 450-790 significantly-regulated phosphorylation sites. Multiple layers of bioinformatic analysis of the significantly-regulated phosphoproteins identified RAS/JNK as a downstream signaling pathway of ALK, independent of the ALK variant present. Further experiments demonstrated that ALK/JNK signaling could be inactivated by either ALK- or JNK-specific inhibitors, resulting in cell growth inhibition by induction of cell cycle arrest and cell apoptosis. Our study broadly defines the phosphoproteome in response to ALK inhibition and provides a resource for further clinical investigation of ALK as therapeutic target for the treatment of neuroblastoma.