[The safety and efficacy of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia in children].

To explore the safety and efficacy of blinatumomab in the treatment of CD19 positive (CD19+) B-cell acute lymphoblastic leukemia (B-ALL) in children. A retrospective analysis was conducted on the clinical data of pediatric B-ALL patients who received blinatumomab treatment from Hematology & Blood Diseases Hospital of Chinese Academy of Medical Sciences from August 2021 to October 2023. Based on their disease status, the patients were divided into refractory/relapsed(RR) group, minimal residual disease clearance (MC) group, and chemotherapy intolerance (IC) group. Clinical data of the children were collected to evaluate the adverse drug reactions, therapeutic efficacy and survival of the children. In total, 35 patients were included, with 20 males and 15 females, aged from 0.6 to 16.4 (9.9±4.2) years old. There were 10 cases in the RR group, 20 cases in the MC group and 5 cases in the IC group. A total of 56 cycles of infusion were completed, with one cycle in 24 cases, two cycles in 5 cases, three cycles in 2 cases and four cycles in 4 cases. The median infusion time [M (Q1, Q3)] from the first to the fourth cycle was 14 (14, 28) days, 28 (28, 28) days, 28 (28, 28) days and 28 (26, 28) days, respectively. In terms of adverse reactions, the incidence of grade 1-2 cytokine release syndrome(CRS) was 57.1% (32/56), with grade 1 CRS accounting for 84.4% (27/32). The incidence rate of immune effector cell-associated neurotoxicity syndrome(ICANS) (grade 4) was 1.8% (1/56). In the RR group, 6 cases were treated effectively, and minimal residual disease(MRD) turned negative, before treatment, MRD levels were all less than 20%. Among them, 3 cases had MRD turning positive again 14 to 42 days after discontinuation of Belintoumab. Four cases were treated ineffectively, with MRD >20% before treatment. All MRD positive cases in MC group turned negative and all MRD negative cases in the IC group remained negative after treatment. The median follow-up time of RR group was 5.7 (3.8, 9.4) months, and 1 year median survival rate and event-free survival rate were 40.0%±21.9% and 33.3%±19.2%, respectively. The median follow-up time for MC and IC group patients was 6.7 (5.2, 12.5) months and 7.1 (5.1, 7.6) months, respectively, with an event free survival rate of 100%. The safety and efficacy of using belintoumab in partial RR, MRD clearance, and chemotherapy intolerance are good.

A site-resolved two-dimensional quantum simulator with hundreds of trapped ions.

A large qubit capacity and an individual readout capability are two crucial requirements for large-scale quantum computing and simulation1. As one of the leading physical platforms for quantum information processing, the ion trap has achieved a quantum simulation of tens of ions with site-resolved readout in a one-dimensional Paul trap2-4 and of hundreds of ions with global observables in a two-dimensional (2D) Penning trap5,6. However, integrating these two features into a single system is still very challenging. Here we report the stable trapping of 512 ions in a 2D Wigner crystal and the sideband cooling of their transverse motion. We demonstrate the quantum simulation of long-range quantum Ising models with tunable coupling strengths and patterns, with or without frustration, using 300 ions. Enabled by the site resolution in the single-shot measurement, we observe rich spatial correlation patterns in the quasi-adiabatically prepared ground states, which allows us to verify quantum simulation results by comparing the measured two-spin correlations with the calculated collective phonon modes and with classical simulated annealing. We further probe the quench dynamics of the Ising model in a transverse field to demonstrate quantum sampling tasks. Our work paves the way for simulating classically intractable quantum dynamics and for running noisy intermediate-scale quantum algorithms7,8 using 2D ion trap quantum simulators.

Realizing Synthetic Dimensions and Artificial Magnetic Flux in a Trapped-Ion Quantum Simulator.

Synthetic dimension is a potent tool in quantum simulation of topological phases of matter. Here we propose and demonstrate a scheme to simulate an anisotropic Harper-Hofstadter model with controllable magnetic flux on a two-leg ladder using the spin and motional states of a single trapped ion. We verify the successful simulation of this model by comparing the measured dynamics with theoretical predictions under various coupling strength and magnetic flux, and we observe the chiral motion of wave packets on the ladder as evidence of the topological chiral edge modes. We develop a quench path to adiabatically prepare the ground states for varying magnetic flux and coupling strength, and we measure the chiral current on the ladder for the prepared ground states, which allows us to probe the quantum phase transition between the Meissner phase and the vortex phase. Our work demonstrates the trapped ion as a powerful quantum simulation platform for topological quantum matter.

Evidence for Chiral Wobbler in Nuclei.

Three ΔI=1 bands with the πg_{9/2}⊗νg_{9/2} configuration have been identified in _{35}^{74}Br_{39}. Angular distribution, linear polarization, and lifetime measurements were performed to determine the multipolarity, type, mixing ratio, and absolute transition probability of the transitions. By comparing these experimental observations with the corresponding fingerprints and the quantum particle rotor model calculations, the second and third lowest bands are, respectively, suggested as the chiral partner and one-phonon wobbling excitation built on the yrast band. The evidence indicates the first chiral wobbler in nuclei.

[Clinical features and prognostic analysis of testicular relapse in pediatric acute lymphoblastic leukemia].

Objective: To investigate the clinical features and prognosis of testicular relapse in pediatric acute lymphoblastic leukemia (ALL). Methods: Clinical data including the age, time from initial diagnosis to recurrence, relapse site, and therapeutic effect of 37 pediatric ALL with testicular relapse and treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between November 2011 and December 2022 were analyzed retrospectively. Patients were grouped according to different clinical data. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis. Results: The age at initial diagnosis of 37 pediatric testicular relapse patients was (5±3) years and the time from initial diagnosis to testicular recurrence was (37±15) months. The follow-up time was 43 (22, 56) months. Twenty-three patients (62%) were isolated testis relapse. The 5-year OS rate and EFS rate of the 37 relapsed children were (60±9) % and (50±9) % respectively. Univariate analysis showed that the 2-year EFS rate in the group of patients with time from initial diagnosis to testicular recurrence >28 months was significantly higher than those ≤28 months ((69±10)% vs. (11±11)%, P<0.05), 2-year EFS rate of the isolated testicular relapse group was significantly higher than combined relapse group ((66±11)% vs. (20±13) %, P<0.05), 2-year EFS rate of chimeric antigen receptor T (CAR-T) cell treatment after relapse group was significantly higher than without CAR-T cell treatment after relapse group ((78±10)% vs. (15±10)%, P<0.05). ETV6-RUNX1 was the most common genetic aberration in testicular relapsed ALL (38%, 14/37). The 4-year OS and EFS rate of patients with ETV6-RUNX1 positive were (80±13) % and (64±15) %, respectively. Multivariate analysis identified relapse occurred≤28 months after first diagnosis (HR=3.09, 95%CI 1.10-8.72), combined relapse (HR=4.26, 95%CI 1.34-13.52) and CAR-T cell therapy after relapse (HR=0.15,95%CI 0.05-0.51) were independent prognostic factors for 2-year EFS rate (all P<0.05). Conclusions: The outcome of testicular relapse in pediatric ALL was poor. They mainly occurred 3 years after initial diagnosis. ETV6-RUNX1 is the most common abnormal gene.Patients with ETV6-RUNX1 positive often have a favorable outcome. Early relapse and combined relapse indicate unfavorable prognosis, while CAR-T cell therapy could significantly improve the survival rate of children with testicular recurrence.

[Clinical and prognostic characteristics of pediatric acute myeloid leukemia with myelodysplasia-related changes under different diagnostic criteria].

Objective: To evaluate the clinical and prognostic differences in acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) children under different diagnostic criteria (World Health Organization (WHO) 2016 and WHO 2022 criteria). Methods: In this retrospective cohort study, clinical characteristics and prognosis information of 260 acute myeloid leukemia (AML) children admitted to Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from August 2017 to August 2021 were analyzed retrospectively. According to WHO 2016 and WHO 2022 diagnostic criteria, patients were divided into AML-MRC group and non-AML-MRC group, the prognostic and genetic differences between two groups were compared respectively. Meanwhile, the characteristics of children with 8 MRC-related genes defined in WHO 2022 diagnostic criteria were described. Mann-Whitney U test, chi-square test were used for comparison between groups. Survival curve was plotted by Kaplan-Meier method, and comparison between groups was performed by Log-Rank method. Results: Among the 260 children, there were 148 males and 112 females. The follow-up time was 26 (16, 38) months. A total of 28 children (10.8%) were diagnosed with AML-MRC according to the WHO 2016 diagnostic criteria. Compared with non-AML-MRC children, the frequency of PTPN11, RUNX11, SH2B3, MPL and STAG2 mutations was higher in AML-MRC children (25.0% (7/28) vs. 4.3% (10/232), 14.3% (4/28) vs. 3.9% (9/232), 10.7% (3/28) vs. 2.2% (5/232), 10.7% (3/28) vs. 2.2% (5/232), 10.7% (3/28) vs. 0.9% (2/232), all P<0.05). The 2-year overall survival (OS) and events free survival (EFS) rate of 28 AML-MRC children under WHO 2016 diagnostic criteria were worse than those of 232 non-AML-MRC children ((62.1±10.8)% vs. (94.5±1.6)%, χ2=22.1,P<0.001;(48.0±10.6)% vs. (70.9±3.2)%, χ2=6.33,P=0.012). Twenty-seven children (10.4%) were eventually diagnosed with AML-MRC according to WHO 2022 criteria, their 2-year OS rate were worse than 233 non-AML-MRC children ((60.8±11.1)% vs. (94.5±1.6)%, χ2=24.49,P<0.001), and there was no statistically significant difference in EFS rate between two groups at 2 years ((55.1±10.8)% vs. (70.1±3.2)%, χ2=2.44, P=0.119). Conclusions: Compared with the 2022 WHO diagnostic criteria, the survival rates of children with AML-MRC under the 2016 WHO diagnostic criteria were worse than that of children without MRC.The new version of the AML-MRC diagnostic criteria emphasizes the importance of genes.

Realization of a crosstalk-avoided quantum network node using dual-type qubits of the same ion species.

Generating ion-photon entanglement is a crucial step for scalable trapped-ion quantum networks. To avoid the crosstalk on memory qubits carrying quantum information, it is common to use a different ion species for ion-photon entanglement generation such that the scattered photons are far off-resonant for the memory qubits. However, such a dual-species scheme can be subject to inefficient sympathetic cooling due to the mass mismatch of the ions. Here we demonstrate a trapped-ion quantum network node in the dual-type qubit scheme where two types of qubits are encoded in the S and F hyperfine structure levels of 171Yb+ ions. We generate ion photon entanglement for the S-qubit in a typical timescale of hundreds of milliseconds, and verify its small crosstalk on a nearby F-qubit with coherence time above seconds. Our work demonstrates an enabling function of the dual-type qubit scheme for scalable quantum networks.

[Analysis of factors affecting the quality of donor corneal endothelial cells].

Objective: To explore the factors influencing the quality of donor corneal endothelium. Methods: A retrospective case series study was conducted. Data from 568 donor corneas obtained from the Shandong Eye Bank between July 1, 2020, and June 30, 2021, were collected for analysis. The corneal endothelium of the donor corneas was observed using corneal endothelial microscopy to assess corneal endothelial cell density (ECD), coefficient of variation, and hexagonal cell ratio (HEX). Relevant factors of corneal donors were collected, including gender, age, cause of death, season of death, time from death to corneal retrieval, and methods of corpse preservation, to investigate their impact on the quality of donor corneal endothelium. The age factor was divided into five age groups: 0-20 years, 21-40 years, 41-60 years, 61-80 years, and >80 years. The time of corneal retrieval was divided into three periods based on the time elapsed since the donor's death: <6 hours, 6-12 hours, and >12 hours. The relationship between these factors and corneal endothelial conditions was analyzed. Results: The 568 donor corneas were obtained from 288 donors, including 225 males (78.13%) and 63 females (21.87%). The mean age was 51.77±18.48 years. The causes of death among donors were as follows: cardiovascular diseases 54.58% (275 individuals), cancer 17.96% (74 individuals), organ failure 14.26% (49 individuals), and accidents 13.20% (64 individuals). The mean time of corneal retrieval after donor death was 140 (76, 400) minutes (ranging from 30 minutes to 45 hours). Among the 145 corneas (25.53%) that had their initial corneal endothelial microscopy examination, the images were not clear, and after thorough rewarming, 106 corneas (18.7%) still had unclear images and could not be analyzed. Among the 462 corneas (81.3%) with clear images, the ECD was (2 602.23±318.40) cells/mm², the coefficient of variation was 36.61%±4.81%, and the HEX was 52.73%±7.15%. The ECD of corneas from older donors was lower compared to younger donors, and the differences between age groups were statistically significant (P<0.001). Corneas from donors who died due to accidents had a higher ECD [(2 829.88±313.90) cells/mm²] compared to those who died from cancer, cardiovascular diseases, and organ failure, and the differences were statistically significant (P<0.001). The ECD was highest when corneas were retrieved within 6 hours after death, and the difference was statistically significant (P<0.001). Older donors had higher coefficients of variation but lower HEX values (both P<0.05). Corneas retrieved after a longer time from death had higher coefficients of variation, and the difference was statistically significant (P<0.05), but there was no statistically significant difference in HEX (P>0.05). Organ failure, cryopreservation, and corneal retrieval time >12 hours were risk factors for unclear corneal endothelial imaging (all P<0.001). Among the 136 corneal endothelial images (23.94%), circular, oval, or band-shaped dark areas were observed, and corneas with dark areas had lower ECD (P<0.05). The longer the time elapsed from death to corneal retrieval, the more dark areas were observed (P<0.001). The presence of dark areas did not affect the coefficient of variation and HEX (P>0.05). Conclusion: Advanced donor age, death due to chronic diseases, longer time elapsed from death to corneal retrieval, and cryopreservation of the body lead to a decrease in the quality of donor corneal endothelium.

[Management of liver transplantation perioperative period in acute-on-chronic liver failure].

Acute-on-chronic liver failure (ACLF) is a potentially reversible entity that occurs in patients with chronic liver disease accompanied with or without cirrhosis and is characterized by extrahepatic organ failure and high short-term mortality. Currently, the most effective treatment method for patients with ACLF is liver transplantation; therefore, admission timing and contraindications must be emphasized. The function of vital organs such as the heart, brain, lungs, and kidneys should be actively supported and protected during the liver transplantation perioperative period in patients with ACLF. Focusing on the anesthesia management level during anesthesia selection, intraoperative monitoring, three-stage management, prevention and treatment of post-perfusion syndrome, monitoring and management of coagulation function, volume monitoring and management, and body temperature monitoring management for liver transplantation should strengthen anesthesia management. Additionally, standard postoperative intensive care treatment should be recommended, and grafts and other vital organ functions should be monitored throughout the perioperative period to promote early postoperative recovery in patients with ACLF.

[Genomics of next generation sequencing in pediatric B-acute lymphoblastic leukemia and its impact on minimal residual disease].

Objective: To describe the gene mutation profile of newly diagnosed pediatric B-acute lymphoblastic leukemia (B-ALL) and analyze its effect on minimal residual disease (MRD). Methods: A total of 506 newly diagnosed B-ALL children treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from September 2018 to July 2021 were enrolled in this retrospective cohort study. The enrolled children were divided into MRD ≥1.00% group and <1.00% group according to MRD results on the 19th day since chemotherapy, and MRD ≥0.01% group and <0.01% group according to MRD results on the 46th day. Clinical characteristics and gene mutations of two groups were compared. Comparisons between groups were performed with chi-square test or Fisher's exact test. Independent risk factors of MRD results on the 19th day and the 46th day were analyzed by Logistic regression model. Results: Among all 506 patients, there were 318 males and 188 females. On the 19th day, there were 114 patients in the MRD ≥1.00% group and 392 patients in the MRD <1.00% group. On the 46th day, there were 76 patients in the MRD ≥0.01% group and 430 patients in the MRD <0.01% group. A total of 187 gene mutations were detected in 487 (96.2%) of 506 children. The most common gene mutations were signal transduction-related KRAS gene mutations in 111 cases (22.8%) and NRAS gene mutations in 99 cases (20.3%). Multivariate analysis showed that PTPN11 (OR=1.92, 95%CI 1.00-3.63), KMT2A (OR=3.51, 95%CI 1.07-11.50) gene mutations and TEL-AML1 (OR=0.48, 95%CI 0.27-0.87), BCR-ABL1 (OR=0.27, 95%CI 0.08-0.92) fusion genes and age >10 years (OR=1.91, 95%CI 1.12-3.24) were independent influencing factors for MRD ≥1.00% on the 19th day. BCORL1 (OR=2.96, 95%CI 1.18-7.44), JAK2 (OR=2.99, 95%CI 1.07-8.42) and JAK3 (OR=4.83, 95%CI 1.50-15.60) gene mutations and TEL-AML1 (OR=0.43, 95%CI 0.21-0.87) fusion gene were independent influencing factors for MRD ≥0.01% on the 46th day. Conclusions: Children with B-ALL are prone to genetic mutations, with abnormalities in the RAS signaling pathway being the most common. Signal transduction related PTPN11, JAK2 and JAK3 gene mutations, epigenetic related KMT2A gene mutation and transcription factor related BCORL1 gene mutation are independent risk factors for MRD.

Probing Complex-Energy Topology via Non-Hermitian Absorption Spectroscopy in a Trapped Ion Simulator.

Non-Hermitian systems generically have complex energies, which may host topological structures, such as links or knots. While there has been great progress in experimentally engineering non-Hermitian models in quantum simulators, it remains a significant challenge to experimentally probe complex energies in these systems, thereby making it difficult to directly diagnose complex-energy topology. Here, we experimentally realize a two-band non-Hermitian model with a single trapped ion whose complex eigenenergies exhibit the unlink, unknot, or Hopf link topological structures. Based on non-Hermitian absorption spectroscopy, we couple one system level to an auxiliary level through a laser beam and then experimentally measure the population of the ion on the auxiliary level after a long period of time. Complex eigenenergies are then extracted, illustrating the unlink, unknot, or Hopf link topological structure. Our work demonstrates that complex energies can be experimentally measured in quantum simulators via non-Hermitian absorption spectroscopy, thereby opening the door for exploring various complex-energy properties in non-Hermitian quantum systems, such as trapped ions, cold atoms, superconducting circuits, or solid-state spin systems.

Next-generation gene panel testing in adolescents and adults in a medical neuropsychiatric genetics clinic.

Intellectual disability (ID) encompasses a clinically and genetically heterogeneous group of neurodevelopmental disorders that may present with psychiatric illness in up to 40% of cases. Despite the evidence for clinical utility of genetic panels in pediatrics, there are no published studies in adolescents/adults with ID or autism spectrum disorder (ASD). This study was approved by our institutional research ethics board. We retrospectively reviewed the medical charts of all patients evaluated between January 2017 and December 2019 in our adult neuropsychiatric genetics clinic at the McGill University Health Centre (MUHC), who had undergone a comprehensive ID/ASD gene panel. Thirty-four patients aged > 16 years, affected by ID/ASD and/or other neuropsychiatric/behavioral disorders, were identified. Pathogenic or likely pathogenic variants were identified in one-third of our cohort (32%): 8 single-nucleotide variants in 8 genes (CASK, SHANK3, IQSEC2, CHD2, ZBTB20, TREX1, SON, and TUBB2A) and 3 copy number variants (17p13.3, 16p13.12p13.11, and 9p24.3p24.1). The presence of psychiatric/behavioral disorders, regardless of the co-occurrence of ID, and, at a borderline level, the presence of ID alone were associated with positive genetic findings (p = 0.024 and p = 0.054, respectively). Moreover, seizures were associated with positive genetic results (p = 0.024). One-third of individuals presenting with psychiatric illness who met our red flags for Mendelian diseases have pathogenic or likely pathogenic variants which can be identified using a comprehensive ID/ASD gene panel (~ 2500 genes) performed on an exome backbone.

The important role of TFEB in autophagy-lysosomal pathway and autophagy-related diseases: a systematic review.

Autophagy is a main metabolic process in which eukaryotic cells use lysosomes to eliminate abnormal proteins and damaged organelles to maintain cell homeostasis. Studies have revealed that neurodegenerative diseases, tumor, hepatic diseases, etc. are related to abnormal autophagy processes in recent years. Recent studies have shown that TFEB is a major transcription regulator of autophagy-lysosomal pathway (ALP) transcriptional regulation, which positively regulates the expression of autophagy and lysosomal biogenesis-related genes, thereby promoting autophagosome formation, autophagosome-lysosome fusion, and degradation of autophagy substrates. It has also been found that TFEB promotes clearance of intracellular substrates through lysosomal exocytosis. Therefore, the study of biological functions and related regulatory mechanisms of TFEB will provide important clues and theoretical basis for further explaining its physiological pathogenesis and the treatment of related diseases.

Annealing studies combined with low temperature emission Mössbauer spectroscopy of short-lived parent isotopes: Determination of local Debye-Waller factors.

An extension of the online implantation chamber used for emission Mössbauer Spectroscopy (eMS) at ISOLDE/CERN that allows for quick removal of samples for offline low temperature studies is briefly described. We demonstrate how online eMS data obtained during implantation at temperatures between 300 K and 650 K of short-lived parent isotopes combined with rapid cooling and offline eMS measurements during the decay of the parent isotope can give detailed information on the binding properties of the Mössbauer probe in the lattice. This approach has been applied to study the properties of Sn impurities in ZnO following implantation of 119In (T½ = 2.4 min). Sn in the 4+ and 2+ charge states is observed. Above T > 600 K, Sn2+ is observed and is ascribed to Sn on regular Zn sites, while Sn2+ detected at T < 600 K is due to Sn in local amorphous regions. A new annealing stage is reported at T ≈ 550 K, characterized by changes in the Sn4+ emission profile, and is attributed to the annihilation of close Frenkel pairs.

Effects of miR-18a on proliferation and apoptosis of gastric cancer cells by regulating RUNX1.

OBJECTIVE: The aim of this study was to explore the effects of micro ribonucleic acid (miR)-18a on the proliferation and apoptosis of gastric cancer (GC) cells, and to elucidate the possible underlying mechanism. PATIENTS AND METHODS: In this study, the expression of miR-18a in GC tissues and para-cancer tissues was verified by in situ hybridization (ISH) of GC tissue microarray (TMA). Meanwhile, the effect of miR-18a expression on the prognosis of GC patients was evaluated. GC AGS cell line was selected and transfected with miR-18a mimic and mimic control (NC) to up-regulate miR-18a expression in vitro. Thereafter, changes in cell proliferation, apoptosis and migration after transfection were detected by biological functional assays. Luciferase reporter gene assay was carried out to verify the target gene Runt-related transcription factor 1 (RUNX1) modulated by miR-18a. Finally, the Spearman's grade correlation coefficient was calculated to explore the correlation between the expressions of miR-18a and RUNX1. RESULTS: ISH results of TMA showed that overexpression of miR-18a in GC tissues was significantly associated with low survival rate of patients (p<0.001). High expression of miR-18a remarkably enhanced the proliferation, migration and invasion of GC cells (p<0.05). Besides, it has been predicted in biology that RUNX1 is one of the target genes of miR-18a. Luciferase reporter gene assay showed that Luciferase activity in cells transfected with wild-type (WT) RUNX1 3' untranslated region (3'UTR) was significantly reduced (p<0.05). Moreover, the protein expression of RUNX1 decreased remarkably in GC cells with over-expression of miR-18a (p<0.05). All these findings indicated that the expression of miR-18a was negatively correlated with RUNX1 in GC cells (p<0.001, r=0.86). CONCLUSIONS: MiR-18a exerts a high predictive value for the prognosis of GC patients by directly targeting the transcription factor RUNX1. All our findings may provide therapeutic candidates for GC identification.

[A special on epidemic prevention and control: analysis on expression of 2019-nCoV related ACE2 and TMPRSS2 in eye tissues].

This article was published ahead of print on the official website of Chinese Journal of Ophthalmolog on Apirl 22,2020. Objective: Angiotensin converting enzyme 2 (ACE2) and Transmembrane serine protease 2 (TMPRSS2) are the key proteins for 2019-nCoV entry into host cells. To evaluate the potential infection risk of 2019-nCoV on ocular surface, we compared ACE2 and TMPRSS2 expression among different eye tissues. Methods: Experimental study. Thirty mice were assigned to male, female, aged, diabetic and non-diabetic groups, with 6 mice in each group. Real-time PCR was performed to quantify ACE2 and TMPRSS2 gene expression in conjunctiva, cornea, lacrimal gland, iris, lens, retina, lung, heart, kidney, and liver from male mice. Immunohistochemistry staining was applied to visualize the distribution of the two proteins in different mice tissues, and in human corneal and conjunctival sections. Published transcriptome datasets were extracted to generate the expression comparasion of ACE2 and TMPRSS2 between human conjunctival and corneal tissues, and results were analyzed using Mann-Whitney U test. Female mice, aged mice, STZ-induced diabetic mice, diabetic group control mice were also subjected to ACE2 expression analysis. Results were analyzed using Student's t-test. Results: The expression of ACE2 and TMPRSS2 genes were the highest in conjunctiva among all the six mice eye tissues explored. The expression of these two genes in conjunctiva were lower than that in kidney and lung. ACE2 and TMPRSS2 shared similar expression pattern with the staining concentrated in corneal epithelium, conjunctival epithelium and lacrimal gland serous cells. The expression levels of ACE2 showed gender difference. Female mice had lower ACE2 in conjunctiva and cornea than male mice, with the expression levels being only 43% (t=3.269, P=0.031) and 63% (t=4.080, P=0.015) of that in the male conjunctiva and cornea, respectively. Diabetic mice expressed more ACE2 in conjunctiva (1.21-fold, P>0.05) and lacrimal gland (1.10-fold, P>0.05) compared with the control group. No significant difference on ACE2 expression was found between the aged and young adult mice. The expression level of human conjunctiva ACE2 and TMPRSS2 were significantly higher than that in the cornea (P=0.007), with 5.74-fold and 12.84-fold higher in the conjunctiva than in the corneal epithelium cells, which resembled the situation in mice. Conclusion: The observation of high-level ACE2 and TMPRSS2 expression in conjunctiva among the 6 eye tissues examined suggests that conjunctiva serves as an infection target tissue of 2019-nCoV. (Chin J Ophthalmol, 2020, 56:438-446).

Suppressions of vibration in the Tip-Tilt mirror control system by add-on controller.

Tip-Tilt mirrors play an important role in astronomical telescopes requiring the tracking performance at the level of microradian or sub-microradian. However, the closed-loop performance suffers a lot from the low-sample rate and time delay of image sensors. Especially, this issue is under the condition of vibrations, because dynamic behaviors are complex and the models are difficult to be obtained accurately. Another challenging issue comes from the measurement of vibrations and its extraction for the closed-loop control. This paper proposes a new method based on an add-on controller of the Tip-Tilt mirror to mitigate telescope vibrations. The proposed method only uses Tip-Tilt errors from an image sensor to implement a disturbance observer, which is not being restricted by an accurate model. As a result, the closed-loop performance can be optimized by designing of a proper Q-filter. To suppress the low-frequency and high-frequency vibrations, a novel Q-filter combining a lowpass filter and a bandpass filter is proposed here. The improved control method is validated by both simulation and experiment in the tip-tilt mirror control system under the condition of vibrations.

Local increase of the Curie temperature in Mn/Fe implanted Y3Fe5O12 (YIG).

The change in the Curie temperature of single crystalline garnet Y3Fe5O12 (YIG) sample due to lattice damage induced by ion implantation has been investigated in 57Fe emission Mössbauer Spectroscopy (eMS) following implantation of 57Mn (T½ = 1.5 min). The Mössbauer spectra analysis reveal high spin Fe3+ ions substituted on both the octahedral and the tetrahedral sites. Measurements in the temperature range 298 K-798 K show that average values of the magnetic hyperfine field are decreased by the implantation-induced damage on the local lattice structure of the YIG. The Curie temperature, however, is determined to be 651 ± 5 K, considerably higher than the value of bulk YIG (559 K). This is most likely due to lattice damage-induced changes on the spin configurations of YIG through a FeA-O-FeD distortion scheme.

miR-137 alleviates focal cerebral ischemic injury in rats by regulating JAK1/STAT1 signaling pathway.

The repairing effect and potential mechanism of miR-137 on cerebral ischemic injury in rats was investigated. The volume of cerebral infarction and calculated brain water content was detected by triphenyltetrazolium chloride staining. The expression of inflammatory factors was detected by enzyme-linked immunosorbent assay. The pathological damage of brain tissue was analyzed by hematoxylin and eosin and Nissl staining. The apoptosis in ischemic brain tissue was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling. The levels of STAT1 and JAK1 proteins were analyzed by Western blot. The expression of miR-137 in primary hippocampal neurons was detected by reverse transcription polymerase chain reaction. miR-137 overexpression significantly improved brain damage in rats. miR-137 overexpression can reduce the expression of TNF-α, IL-1ß, and IL-6. miR-137 overexpression can reduce the degree of brain tissue damage and inhibit the expression of JAK1 and STAT1 proteins. miR-137 overexpression can reduce oxygen-glucose deprivation (OGD)/R-induced cell damage, improve cell proliferation, and reduce apoptotic rate. JAK1 and STAT1 protein expression was inhibited in hippocampal neurons after OGD/R treatment after transfection with miR-137 mimic. After the addition of the Filgotinib inhibitor, the levels of JAK1 and STAT1 proteins were significantly reduced. The results suggested that miR-137 overexpression can effectively improve ischemic injury after focal cerebral ischemia and protect against by inhibiting JAK1/STAT1 pathway.

Effects of propofol on proliferation and apoptosis of cardia cancer cells via MAPK/ERK signaling pathway.

OBJECTIVE: To explore the influences of propofol on the proliferation and apoptosis of cardia cancer cells via mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. PATIENTS AND METHODS: A total of 65 surgical resection specimens of cardia cancer were selected as research objects and divided into control group and with low (12.5 µmol/L), medium (25 µmol/L), and high (50 µmol/L) propofol concentration groups. The apoptosis of cancer cells, ERK1/2 phosphorylation level, expressions of Caspase-3, B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X protein (Bax) in each group were detected. RESULTS: Propofol in different concentrations could all effectively inhibit the proliferation of cardia cancer cells in a dose-dependent manner. Different concentrations of propofol promoted the apoptosis of cardia cancer cells, and the apoptosis rate constantly increased with the rising concentration of propofol (p<0.05). Propofol could repress the expression of Bcl-2 and up-regulate the expression levels of Caspase-3, Bax, and phosphorylated ERK1/2. CONCLUSIONS: Propofol can inhibit the proliferation and induce the apoptosis of cardia cancer cells, and the action mechanism may be correlated with the inhibition on the MAPK/ERK signaling pathway.