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.

[Report of six cases with mast cell leukemia and a literature review].

From October 2021 to February 2023, we retrospectively analyzed the clinical and laboratory data of six patients (three male and three female, median age: 54 years, age range: 29-73 years) with mast cell leukemia (MCL) diagnosed in the First Affiliated Hospital of Soochow University (The Mastocytosis Collaborative Network of China). All patients had acute MCL, with at least one C-finding present. The main clinical presentations were hypoalbuminemia (n=4), fatigue (n=3), fever (n=2), abdominal discomfort (n=2), osteolytic lesions (n=2), dizziness (n=1), skin flushing (n=1), and weight loss (n=1). Splenomegaly and lymphadenopathy were noted in six and three patients, respectively. Six patients were strongly positive for CD117, five were positive for CD30 and CD25, and four were positive for CD2. Four patients had a normal karyotype and two patients had an abnormal karyotype. Gene mutations were detected in 4/6 cases. The median serum tryptase level was 24.9 (range: 20.1-171.9) µg/L. Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively. One patient treated with interferon combined with glucocorticoids was lost to follow-up, and one patient abandoned treatment. The follow-up time ranged from 1.1 to 21.7 months. Three patients died and two survived. Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.

[Doublecortin-like kinase 1 activates Hippo pathway to promote migration, invasion and proliferation of pancreatic cancer cells].

Objective: To explore the mechanism of Doublecortin-like kinase 1 (DCLK1) in promoting cell migration, invasion and proliferation in pancreatic cancer. Methods: The correlation between DCLK1 and Hippo pathway was analyzed using TCGA and GTEx databases and confirmed by fluorescence staining of pancreatic cancer tissue microarrays. At the cellular level, immunofluorescence staining of cell crawls and western blot assays were performed to clarify whether DCLK1 regulates yes associated protein1 (YAP1), a downstream effector of the Hippo pathway. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to analyze the expressions of YAP1 binding transcription factor TEA-DNA binding proteins (TEAD) and downstream malignant behavior-promoting molecules CYR61, EDN1, AREG, and CTGF. Transwell test of the DCLK1-overexpressing cells treated with the Hippo pathway inhibitor Verteporfin was used to examine whether the malignant behavior-promoting ability was blocked. Analysis of changes in the proliferation index of experimental cells used real-time label-free cells. Results: TCGA combined with GTEx data analysis showed that the expressions of DCLK1 and YAP1 molecules in pancreatic cancer tissues were significantly higher than those in adjacent tissues (P<0.05). Moreover, DCLK1was positively correlated with the expressions of many effectors in the Hippo pathway, including LATS1 (r=0.53, P<0.001), LATS2 (r=0.34, P<0.001), MOB1B (r=0.40, P<0.001). In addition, the tissue microarray of pancreatic cancer patients was stained with multicolor fluorescence, indicated that the high expression of DCLK1 in pancreatic cancer patients was accompanied by the up-regulated expression of YAP1. The expression of DCLK1 in pancreatic cancer cell lines was analyzed by the CCLE database. The results showed that the expression of DCLK1 in AsPC-1 and PANC-1 cells was low. Thus, we overexpressed DCLK1 in AsPC-1 and PANC-1 cell lines and found that DCLK1 overexpression in pancreatic cancer cell lines promoted YAP1 expression and accessible to the nucleus. In addition, DCLK1 up-regulated the expression of YAP1 binding transcription factor TEAD and increased the mRNA expression levels of downstream malignant behavior-promoting molecules. Finally, Verteporfin, an inhibitor of the Hippo pathway, could antagonize the cell's malignant behavior-promoting ability mediated by high expression of DCLK1. We found that the number of migrated cells with DCLK1 overexpressing AsPC-1 group was 68.33±7.09, which was significantly higher than 22.00±4.58 of DCLK1 overexpressing cells treated with Verteporfin (P<0.05). Similarly, the migration number of PANC-1 cells overexpressing DCLK1 was 65.66±8.73, which was significantly higher than 37.00±6.00 of the control group and 32.33±9.61 of Hippo pathway inhibitor-treated group (P<0.05). Meanwhile, the number of invasive cells in the DCLK1-overexpressed group was significantly higher than that in the DCLK1 wild-type group cells, while the Verteporfin-treated DCLK1-overexpressed cells showed a significant decrease. In addition, we monitored the cell proliferation index using the real-time cellular analysis (RTCA) assay, and the proliferation index of DCLK1-overexpressed AsPC-1 cells was 0.66±0.04, which was significantly higher than 0.38±0.01 of DCLK1 wild-type AsPC-1 cells (P<0.05) as well as 0.05±0.03 of DCLK1-overexpressed AsPC1 cells treated with Verteporfin (P<0.05). PANC-1 cells showed the same pattern, with a proliferation index of 0.77±0.04 for DCLK1-overexpressed PANC-1 cells, significantly higher than DCLK1-overexpressed PANC1 cells after Verteporfin treatment (0.14±0.05, P<0.05). Conclusion: The expression of DCLK1 is remarkably associated with the Hippo pathway, it promotes the migration, invasion, and proliferation of pancreatic cancer cells by activating the Hippo pathway.

Analysis of Cyclocarya paliurus flavonoids modulation on the physiology and gene expression in Enterococcus faecalis under bile salt stress.

Enterococcus faecalis is one of the probiotic groups in the intestinal tract which has varieties of functional effects in the host, such as a protective barrier, nutritional efficacy and antibacterial effects. Stress conditions such as low pH, bile salts, and hypertonicity are inevitable negative factors for the normal survival of E. faecalis in the gastrointestinal tract. Under the stress and inhibition of bile salt, E. faecalis needs specific adaptation and coping style if it wants to successfully colonize the intestine stably. The appropriate concentration of flavonoids can assist probiotics to serve a beneficial role and help them resist the stress of external irresistible environmental factors. In the present research, RNA-sequence (RNA-seq) technology was employed to investigate the influence of Cyclocarya paliurus flavonoids (CPF) on E. faecalis 131-2 (E. faecalis 131-2) exposed to bile salt stress. Analysis results revealed that under bile salt stress, many genes related to cellular process, catalytic activity and transport activity were significantly differentially expressed (P < 0·05), and some not expected variations of which could be partly alleviated by supplementation of CPF, indicating its capacity to improve the bile salt tolerances of E. faecalis 131-2. Additionally, CPF alleviated the obvious inhibitory effects of bile salt stress on the exponential growth of E. faecalis 131-2. An overall view of the physiological and transcriptomic changes of E. faecalis 131-2 under bile salt stresses with or without CPF will further deepen our understanding of the mechanism by which CPF assists E. faecalis 131-2 to perform beneficial functions in the gastrointestinal environment.

[Willingness of receiving influenza vaccine and its influencing factors among health care workers in Yangtze River Delta region from 2020 to 2021].

Objective: To analyze the willingness of receiving influenza vaccine and its influencing factors among health care workers (HCWs) in Yangtze River Delta region from 2020 to 2021. Methods: Convenient sampling method was adopted. From July 2020 to March 2021, 76 hospitals in Jiangsu, Zhejiang, Anhui and Shanghai provinces were selected according to the hospital level and job position, and a questionnaire survey was conducted on the willingness of receiving influenza vaccination. Logistic regression model was used to analyze the influencing factors of vaccination intention. Results: A total of 1 332 HCWs were investigated, with a ratio of male to female about 1∶3.2, and the length of working years was (15.07±9.75) years. A total of 614 HCWs had received influenza vaccine in 2019, with a vaccination rate of 46.09%. About 63.21% (842/1 332) of HCWs were willing to be vaccinated with influenza vaccine. The results of binary logistic regression analysis showed that the willingness of receiving influenza vaccine among HCWs in primary hospitals was higher than that in secondary hospitals (OR=0.573) and tertiary hospitals (OR=0.357). The willingness of HCWs who had received influenza vaccine in 2019 was higher than that of HCWs who had not received influenza vaccine (OR=0.226) and had unknown history of influenza vaccination (OR=0.228). The willingness of HCWs in departments of prevention, health care and infection was higher than that in departments of pre-examination, outpatient, emergency, pediatrics and respiratory (OR=1.670). Conclusion: The willingness of receiving influenza vaccination among HCWs in Yangtze River Delta region is high, but it is still lower than that in developed countries. It is necessary to strengthen publicity and education to improve the influenza immunization level of HCWs.

[Advances in research of interchangeable immunization with live attenuated Japanese encephalitis vaccines and inactivated vaccines].

Japanese encephalitis (JE) virus is the leading cause of vaccine-preventable encephalitis in Asia and the Western Pacific, which mainly invades central nervous system. Vaccination is the most important strategy to prevent JE. Currently, both live attenuated Japanese encephalitis vaccines (JE-L) and inactivated vaccines (JE-I) are in use. Due to the supply of vaccines and the personal choice of recipients, there will be a demand for interchangeable immunization of these two vaccines. However, relevant research is limited. By reviewing domestic and foreign research evidence, this article summarizes the current situation of the interchangeable use of JE-L and JE-I, and makes recommendations when the interchangeable immunization is in urgent need, so as to provide reference for practical vaccination and policymaking in China.

[Epidemiological characteristics and spatiotemporal clustering of hepatitis A in Zhejiang Province from 2010 to 2019].

Objective: To analyze the epidemiological characteristics and spatiotemporal clustering of hepatitis A in Zhejiang Province from 2010 to 2019. Methods: The data of hepatitis A incidence in Zhejiang Province from 2010 to 2019 were collected from the infectious disease surveillance system of China Information System for Disease Control and Prevention. ArcGIS 10.7 software was used for spatial autocorrelation analysis. SaTScan 9.6 software was used for spatiotemporal scanning analysis. SPSS 25.0 software was used for additional analysis. Results: Zhejiang Province has reported 5 465 cases of hepatitis A in 2010-2019 years, with an average annual incidence rate of 1.00/100 000, and periodicity and seasonality are not obvious. The incidence of male was higher than that of female (P=0.023), and the highest incidence rate was 50-59 years old. Spatial autocorrelation analysis showed that there was a positive spatial correlation between the incidence of hepatitis A in Zhejiang Province from 2010 to 2017, with the weakest correlation in 2010 (Moran's I =0.103, Z=1.769, P=0.049), and the strongest correlation in 2016 (Moran's I=0.328, Z=4.979, P=0.001). Spatiotemporal scanning analysis showed that there was spatial aggregation of hepatitis A in Zhejiang Province from 2010 to 2019, with a total of three aggregation areas identified. Among them, the mostly aggregation area was concentrated in Xiangshan county of Ningbo city, which covered 10 counties (cities and districts), including Ninghai county and Yinzhou district, and appeared from January 1 to June 30, 2012. Conclusion: The incidence level of hepatitis A in Zhejiang Province shows a stable fluctuation trend from 2010 to 2019, and the seasonal regularity is not obvious. The population group aged 50-59 years old is the key population. There is spatial aggregation in the epidemic situation of hepatitis A. Targeted prevention and control measures of hepatitis A should be done based on the law of spatiotemporal aggregation and local incidence.

[The preference for Front-of-Pack Labeling and its association with the understanding of Nutrition Facts Panel among residents aged 18 to 70: results of a survey in 6 provinces of China].

Objective: To investigate the preference for Front-of-Pack Labeling (FOP) and its association with the understanding of the Nutrition Facts Panel among Chinese residents. Methods: A multi-stage sampling strategy was adopted to select 3 002 people aged between 18 and 70 years old from the eastern region of China (Beijing, Jiangsu Province, Guangdong Province), the northeast region (Heilongjiang Province), the central region (Henan Province) and the western region (Sichuan Province) from July 2020 to March 2021. Socio-demographic characteristics of participants and their understanding of the Nutrition Facts Panel and preference for FOP were collected. The χ² test was conducted to compare the preference for FOP in different groups of population, and multivariate logistic regression was used to analyze the association between the preference for FOP and the understanding of the Nutrition Facts Panel. Results: The mean age of 3 002 participants was (42.3±13.4) years, of which 1 914 (63.8%) were females and 69.3% could not understand the Nutrition Facts Panel. About 2 458 respondents (81.9%) suggested that FOP could be promoted. The top three nutrients that should be labeled were sugar (68.4%), salt (68.2%) and total fat (62.4%). The number of participants who believed that the Multiple Traffic Lights (MTL) could be easier to help consumers to quickly choose healthy food, attract attention and provide the most needed information was 1 064 (35.4%), 1 026 (34.2%) and 1 140 (38.0%), respectively. The multivariate logistic regression analysis showed that, compared with the Guideline Daily Amount (GDA) system, participants who could not understand the Nutrition Facts Panel preferred (1) Nutri-Score, Warning labels, and Health logos: Smart Choice in terms of"Which format of FOP could quickly help you choose food more easily?"[OR (95%CI): 2.21 (1.62-3.02), 1.64 (1.22-2.22), 1.79 (1.31-2.45), respectively]; (2) Nutri-Score, Warning labels, and Health logos: Smart Choice in terms of"Which format of FOP could attract your attention the most?"[OR (95%CI): 2.62 (1.92-3.59), 1.96 (1.45-2.66), 2.25 (1.66-3.04), respectively]; and (3) Nutri-Score, Warning labels, and Health logos: Smart Choice in terms of"Which format of FOP could provide you with the most needed information?"[OR (95%CI): 2.33 (1.70-3.21), 2.21 (1.66-2.95), 2.01 (1.50-2.71), respectively]. Conclusion: The residents from six provinces in China have a supportive attitude towards FOP. The interpretive FOP with color information, specific nutrient information and summary indicator can be launched. The nutrition information of sugar, salt and total fat could be prioritized to be labeled on the FOP.

[Association between the awareness of Nutrition Facts Panel and prepackaged food purchase behavior among residents].

Objective: To explore the association between the cognition of Nutrition Facts Panel and prepackaged food purchase behavior among residents in six provinces in China. Methods: Using a multi-stage sampling method, 3 002 adults aged 18-70 were selected from the western region (Sichuan), eastern region (Guangdong, Jiangsu, Beijing), central region (Henan), and northeastern region (Heilongjiang) of China from July 2020 to March 2021. Socio-demographic characteristics of participants and their cognition of Nutrition Facts Panel and prepackaged food purchase behavior were collected through questionnaire. A multivariate binary logistic regression model was used to analyze the association between cognition of Nutrition Facts Panel and prepackaged food purchase behavior. Results: The age of 3 002 subjects was (42.3±13.4) years, among which 63.8% (1 914) were female, 66.7% knew the Nutrition Facts Panel, 49.8% would read it when purchasing, 30.7% could understand it, and 56.6% (1 699) bought prepackaged food more than once a week. The results of multivariate analysis showed that after adjusting for relevant confounding factors, compared with the participants knowing but not reading the Nutrition Facts Panel, the group knowing and reading was more likely to buy 11 types of prepackaged food at least once a week (all P<0.05). Compared with the participants reading but not understanding the Nutrition Facts Panel, the group reading and understanding was less likely to buy 11 types of prepackaged food at least once a week (all P<0.05). Conclusion: There was a correlation between cognition of Nutrition Facts Panel and prepackaged food purchase behavior among residents.

[The purchase behavior of prepackaged food and its determinants among primary and middle school students in 6 provinces of China].

Objective: To examine the purchase behaviors of prepackaged food and its determinants among primary and middle school students in 6 provinces of China. Methods: A multi-stage sampling strategy was adopted to select 2 499 primary and middle school students and their parents from the eastern region of China(Beijing, Jiangsu Province, Guangdong Province), the northeast region(Heilongjiang Province), the central region(Henan Province) and the western region(Sichuan Province) from July 2020 to March 2021. Socio-demographic characteristics of students and their parents, eating-related behaviors and the purchase behaviors of prepackaged food of students, and parents' attitudes towards students' eating behavior were collected through questionnaire towards students and their parents. The χ² test was conducted to compare the purchase behaviors in different groups of students, and multivariate logistic stepwise regression analysis was used to analyze the determinants among primary and middle school students. Results: The age of 2 499 participants was(12.7±2.5) years. There were 1 272(50.9%) females and 1 279(51.2%) middle school students. About 1 404(56.2%) students bought prepackaged food. The top 6 prepackaged foods bought at least once a week were milk and dairy products(74.6%), baked food(58.7%), beverages(42.8%), puffed food(40.8%), chocolate and candy(39.8%), and nuts and dried fruits(37.5%). The multivariate logistic regression model analysis results showed that compared with primary school students, rural students, non-boarding students, students who did not like snacks and students whose parents paid attention to their children eating snacks, middle school students(OR=3.36, 95%CI:2.73-4.12), urban students(OR=1.33, 95%CI:1.11-1.61), boarding students(OR=2.15, 95%CI:1.66-2.79), students who liked snacks(OR=2.01, 95%CI:1.66-2.43), students whose parents did not pay attention to their children eating snacks(OR=1.27, 95%CI:1.05-1.54) were more likely to buy prepackaged food by themselves. Compared with students whose parents had education level of junior high school and below, students whose parents had education level of undergraduate and above(OR=0.70, 95%CI:0.53-0.92) were less likely to buy prepackaged food by themselves. Compared with students whose family monthly income was less than 5 000 yuan, students whose family monthly income was over 10 000 yuan(OR=0.67, 95%CI:0.52-0.87) were less likely to buy prepackaged food by themselves. Conclusion: Many primary and middle school students buy prepackaged food by themselves in 6 provinces of China. Individual characteristics such as grade, place of residence, boarding status, as well as family environment such as parents' education level, monthly income and concern about children eating snacks are the influencing factors of purchasing prepackaged food.

[Efficacy and safety of neoadjuvant toripalimab combined with nimotuzumab and chemotherapy in patients with unresectable stage â £ squamous cell carcinoma of penis].

Objective: To compare the efficacy and safety of neoadjuvant chemotherapy alone or combined with toripalimab and nimotuzumab in patients with unresectable locally advanced or metastatic squamous cell carcinoma of penis. Methods: A total of 33 patients with unresectable squamous cell carcinoma of penis undergoing neoadjuvant chemotherapy alone or combined with toripalimab and nimotuzumab at Sun Yat-sen University Cancer Center from May 2015 to June 2021 were enrolled retrospectively. All the patients were male, with a median age (M(IQR))of 49.0 (13.5) years (range: 30 to 70 years). According to the therapy protocols, patients were divided into the chemotherapy group (16 cases) and the triple combination group (17 cases). Log-rank test was used to compare the progression-free survival and overall survival. χ2 test or Fisher exact method was used to compare the objective response rate, pathological down-stage rate and adverse events between these two groups. Results: The follow-up time was 28.1(19.2) months (range: 1.5 to 33.4 months). Patients of triple combination group were observed significantly longer progression-free survival (30.0 months vs. 8.2 months, χ²=3.998, P=0.046) than those of chemotherapy group. The median overall survival of the triple combination group and chemotherapy group were not reached and 15.2 months (χ²=3.298, P=0.069), respectively. Although there was no significant difference in the subsequent surgical resection rate between these two groups (12/17 vs.11/16, P=1), the objective response rate and the pathological complete response rate in triple combination group were significantly higher than in chemotherapy group (13/17 vs. 6/16, χ²=5.125, P=0.024; 6/7 vs. 0, P=0.001). The main common grade 1 to 2 adverse events in the triple combination group were alopecia (16 cases), anemia (15 cases), and nausea (14 cases). The main common grade 1 to 2 adverse events in the chemotherapy group were anemia (14 cases), alopecia (12 cases), decreased appetite (12 cases), and nausea (11 cases). The incidence of adverse events ≥grade 3 was similar in the triple combination group and chemotherapy group (8/17 vs. 6/16, χ²=0.308, P=0.579). There was no grade 3 adverse event in both groups. Conclusion: Compared with traditional chemotherapy alone, chemotherapy combined with toripalimab and nimotuzumab provides longer progression-free survival and similar toxicity for unresectable stage Ⅳ squamous cell carcinoma of penis.

[Impact of different obesity patterns on coronary microvascular function in male patients with non-obstructive coronary artery disease].

Objective: This study sought to investigate the impact of different obesity patterns on coronary microvascular function in male patients with non-obstructive coronary artery disease. Methods: We retrospectively analyzed clinical data of male patients diagnosed with suspected coronary microvascular dysfunction (CMD) in the First Hospital of Shanxi Medical University between December 2015 and August 2021. All patients underwent the one-day rest and stress 13N-ammonia positron emission tomography myocardial perfusion imaging. Overall obesity was defined by body mass index (BMI) ≥28 kg/m2 and abdominal obesity was defined by waist circumference ≥90 cm. Hyperemic myocardial blood flow (MBF)<2.3 ml·min-1·g-1 or coronary flow reserve (CFR)<2.5 were referred as CMD. All patients were grouped based on their BMI and waist circumference. MBF, CFR, the incidence of CMD, hemodynamic parameters, and cardiac function were compared among the groups. Results: A total of 136 patients were included. According to BMI and waist circumference, patients were categorized into 3 groups: control group (n=45), simple abdominal obesity group (n=53) and compound obesity group (n=38). Resting MBF did not differ between groups (F=0.02,P=0.994). Compared with the control group, hyperemic MBF was significantly lower in the simple abdominal obesity and compound obesity groups ((2.82±0.64) ml·min-1·g-1, (2.44±0.85) ml·min-1·g-1 and (2.49±0.71) ml·min-1·g-1, both P<0.05, respectively). Hyperemic MBF was comparable among the groups of patients with obesity (P=0.772). CFR was significantly lower in the simle abdominal obesity group compared with the control group (2.87±0.99 vs. 3.32±0.62,P=0.012). Compared with the control group, CFR tended to be lower in the compound obesity group (3.02±0.91 vs. 3.32±0.62,P=0.117). The incidence of CMD was significantly higher in both the simple abdominal obesity and compound obesity groups than in the control group (62.3%, 52.6% vs. 22.2%, both P<0.01, respectively). Waist circumference was an independent risk factor for male CMD (OR=1.057, 95%CI: 1.013-1.103, P=0.011). Conclusions: In male patients with non-obstructive coronary artery disease, abdominal obesity is associated with decreased coronary microvascular function. Male patients with simple abdominal obesity face the highest risk of CMD.

High MEK/ERK signalling is a key regulator of diapause maintenance in the cotton bollworm, Helicoverpa armigera.

MEK/ERK signalling has been identified as a key factor that terminates diapause in Sarcophaga crassipalpis and Bombyx mori. Paradoxically, high p-MEK/p-ERK signalling induces diapause in pupae of the moth Helicoverpa armigera; however, the regulatory mechanism is unknown. In the present study, we show that p-MEK and p-ERK are elevated in the brain of diapause-destined pupae and suppression of MEK/ERK activity terminates diapause progress. Reactive oxygen species (ROS) activate MEK/ERK signalling, causing large-scale phosphorylation of downstream proteins. The levels of ubiquitin-conjugated proteins are also significantly reduced when ROS or p-ERK level decreased. Moreover, terminated diapause progress by 20-hydroxyecdysone injection significantly decreases p-MEK, p-ERK and phospho-ribosomal S6 kinase levels, while phospho-MAPK substrates and ubiquitin-conjugated protein levels increase. Our data demonstrate that high MEK/ERK signalling mediated by ROS promotes diapause maintenance via increasing phosphorylation and degradation of downstream substrates. The results of this study may provide important information for understanding the regulatory mechanisms during insect diapause.

The biological characters of Bmelav-like genes in the development of Bombyx mori.

The ELAV/Hu family is a conserved multigene family of pan-neuronal RNA-binding protein involved in post-transcriptional regulation in metazoans. In Drosophila, three members of this family, ELAV, RBP9 and FNE, are involved in neuronal differentiation, gene expression regulation and so on. This family is less well characterized in Bombyx mori. Two orthologs BmELAV-like-1 (BmEL-1) and BmELAV-like-2 (BmEL-2) share 55%-71% and 47%-62% identity with that of in Drosophila and humans, respectively. Bmel-1 is ubiquitously expressed while Bmel-2 is expressed in the head and ovaries specifically. Proteins encoded by both genes are localized in nuclear and cytoplasm. The weight of body, cocoon, pupae and cocoon shell are differently affected in Bmel-1- /-2- mutants created using CRISPR/Cas9 technology. Mutations of both genes increase the expression of four silk protein genes, Fib-L, Fib-H, P25 and Ser-1. In addition, the oviposition ability of Bmel-2- females is decreased. This study not only provides valuable insights into the functional roles of Bmelav-like genes in the growth, cocoon characters and regulation of silk protein genes expression, but also provides useful information for silkworm variety breeding.

Sex ratio effects on reproductive success of male and female Daphnia.

The intensity of mating competition and the opportunity for sexual selection are thought to depend on the operational sex ratio, the ratio of sexually active males to fertilizable females. Cyclic parthenogens, organisms that alternate between sexual reproduction and female-only parthenogenesis, show particularly high variation in sex ratios in natural populations but the effects of this variation on mating competition and reproductive success of each sex are poorly understood. In a series of experiments with Daphnia magna, we experimentally imposed five sex ratio categories, varying from one male per 81 females to an even sex ratio. We found that, in males, reproductive success strongly and monotonically decreased with decreasing number of females per male. In females, in contrast, mating success and reproductive success were reduced only at the most female-biased sex ratio (1:81), when many females remained unmated and unfertilized, and then again at equal sex ratios, probably due to negative effects of high density or stress induced by numerous males. Our results suggest that females experienced male limitation at heavily female-biased sex ratios below one male to about 50 females. As this is well within the sex ratio variation observed in natural Daphnia populations, we conclude that mating competition and the opportunity for sexual selection may exist not only in males but, at least periodically, also in females.

Identification and molecular analysis of cashmere goat lncRNAs reveal their integrated regulatory network and potential roles in secondary hair follicle.

Long non-coding RNAs (lncRNAs) is a class of eukaryotic transcripts with length of more than 200 bp. They contribute to the regulation of gene expressions involved in multiple processes including the skin cell proliferation, differentiation, and reconstruction of the secondary hair follicles (SHFs). In this study, firstly, we identified 16 putative lncRNAs from SHFs of cashmere goat based on the EST sequences from NCBI database. Secondly, we investigated their transcriptional pattern in SHFs of cashmere goat, and constructed their ceRNA regulatory networks. The RT-qPCR results showed four lncRNAs (lncRNA-475074, -052149, -052140, and -051789) were significantly up-regulated, and nine lncRNAs (lncRNA-711032, -475083, -475070, -052139, -052127, -052037, -051903, -051847, and -051804) were significantly down-regulatd in anagen SHFs of cashmere goat. CeRNA networks analysis revealed complex interactional relationship among lncRNAs, miRNAs and mRNAs. Further, the KEGG pathway enrichment was performed for the potential target genes of the identified lncRNAs based on bioinformatics technique, and the results indicated that differentially expressed lncRNAs directly or indirectly might regulate potential target genes. Our results from this study will provide a significant information for further exploring the functions and possible mechanisms of the identified lncRNAs in SHFs of cashmere goat.

[Establishment of reference interval of vitamin A for Chinese children and adolescents based on expectation-maximization algorithm].

Objective: To establish the reference interval of vitamin A for Chinese children and adolescents by indirect approach. Method: The serum retinol samples from 28 provinces, autonomous regions and municipalities in China between January 2016 and June 2019 were examined by high performance liquid chromatography in third-party clinical laboratory institutions. Using a cross-sectional study, descriptive statistics of serum vitamin A levels in children and adolescents aged 0-18 years were carried out in population, region and season. The distribution parameters of vitamin A levels were calculated iteratively by the expectation-maximization (EM) algorithm, and the reference interval was established. Results: A total of 1 096 597 cases were included in the analysis, including 631 017 males and 465 580 females, with a median age of 3(1, 6) years. Before the age of 4 years, the median serum vitamin A level increased with age [median level and its quartiles was 0.15 (0.11, 0.18) mg/L for neonates, 0.23 (0.18, 0.29) mg/L for infants aged below 1 year, and 0.27 (0.20, 0.34) mg/L for kids aged 1-<4 years]. The median serum vitamin A level was stable at the age of 4-8 years (median level ranged from 0.27 to 0.29 mg/L). Afterwards, the median serum vitamin A level reached 0.30 mg/L at the age of 9 years, and then an increasing trend with age was observed till 18 years. The median serum vitamin A level was higher in south area (male:0.33 mg/L; female:0.34 mg/L), compared with other areas (0.24-0.30 mg/L). The variation of the median serum vitamin A level among seasons was within 0.03 mg/L. Based on EM algorithm using indirect approach, the reference intervals of vitamin A for Chinese children and adolescents were as follows: newborn, 0.27-0.47 mg/L; infants aged below 1 year, 0.36-0.56 mg/L; children aged 1-<7 years, 0.35-0.54 mg/L; children aged 7-<16 years, 0.46-0.60 mg/L; and teenagers aged over 16 years, 0.38-0.59 mg/L. Conclusion: The EM algorithm can provide a basis for the establishment of vitamin A reference interval for Chinese children and adolescents, and the established reference interval needs to be further verified by direct method.

[Immunogenicity and safety of concomitant inoculation of Measles and rubella combined live vaccine and Japanese encephalitis attenuated live vaccine].

Objective: To evaluate the immunogenicity and safety of concomitant inoculation of Measles and Rubella Combined Live-attenuated Japanese encephalitis vaccine. Methods: Healthy children aged 8 months in selected cities in Zhejiang Province were randomly assigned to the MR and JVE-L combined vaccination group (the experimental group), and the MR single vaccination group (the control group) was taken before the exemption and 6 weeks after the exemption. Peripheral venous blood 1 ml was used as serum antibody test for measles and rubella, and the levels of measles and rubella antibodies before and after vaccination were evaluated. The safety of combined vaccination was evaluated. Measles and rubella IgG antibodies were detected by enzyme-linked immunosorbent assay (ELISA). Data were double-entry with Epidata and statistical analysis was performed using Epi Info epidemiological statistical analysis software. Results: The results showed that no severe adverse event occurred in two groups, clinical reactions in each inoculation group were mild.The seroconversion rate of measles antibody and rubella antibody were 96.43% and 88.49% in the experimental group after vaccination, the geometrical mean concentrations(GMC) of measles antibody was 1 526.45 mIU/ml and the GMC of rubella antibody was 47.70 mIU/ml after concomitant inoculation; the seroconversion rate of measles antibody and rubella antibody were 97.62% and 86.11% in the control group, the GMC of Measles antibody was 1 392.28 mIU/ml and the GMC of Rubella antibody was 45.72 mIU/ml after MV inoculation. No difference were detected in two groups of seroconversion rate of measles antibody and rubella antibody and GMC after vaccination. Conclusion: The immunogenicity and safety is equivalent when MR and JVE-L were simultaneous inoculation.

Transcriptome changes in reciprocal grafts involving watermelon and bottle gourd reveal molecular mechanisms involved in increase of the fruit size, rind toughness and soluble solids.

KEY MESSAGE: Transcriptome landscape reveals the molecular mechanisms involved in the improvement of fruit traits by the grafting of watermelon and bottle gourd. Grafting has been used as a sustainable alternative for watermelon breeding to control soil-borne pathogens and to increase tolerance to various abiotic stresses. However, some reports have shown that grafting can negatively affect the quality of fruits. Despite several field studies on the effects of grafting on fruit quality, the regulation of this process at the molecular level has not been revealed. The aim of this study was to elucidate various molecular mechanisms involved in different tissues of heterografted watermelon and bottle gourd plants. Grafting with bottle gourd rootstock increased the size and rind thickness of watermelon fruits, whereas that with watermelon rootstock produced bottle gourd fruits with higher total soluble solid content and thinner rinds. Correspondingly, genes related to ripening, softening, cell wall strengthening, stress response and disease resistance were differentially expressed in watermelon fruits. Moreover, genes associated mainly with sugar metabolism were differentially expressed in bottle gourd fruits. RNA-seq revealed more than 400 mobile transcripts across the heterografted sets. More than half of these were validated from PlaMoM, a database for plant mobile macromolecules. In addition, some of these mobile transcripts contained a transfer RNA-like structure. Other RNA motifs were also enriched in these transcripts, most with a biological role based on GO analysis. This transcriptome study provided a comprehensive understanding of various molecular mechanisms underlying grafted tissues in watermelon.

Effect of polymer and glass physicochemical properties on MS2 recovery from food contact surfaces.

Viruses are transmissible via their interaction with contact surfaces of food containers or tools. This study evaluated the recoveries of MS2 coliphage, a virus surrogate, from polypropylene (PP), polyvinyl chloride (PVC), polyethylene (PE), and glass (borosilicate and soda lime), as influenced by the surface chemistry and topography. MS2 (5-6 logs) in PBS with 1% TSB was inoculated onto each of 9 different surfaces, 24-h cold-incubated, and recovery was quantified by infectivity. The order of MS2 recovery efficiency from smooth surfaces was PP > PE ≥ soda lime glass, which classified into 3 ANOVA groups, p = 0.05. The MS2 recovery ratios of smooth vs. rough surfaces were 1.4-1.5. Atomic force microscopy revealed 21-nm diam pinholes (<28-nm of MS2 size) in the borosilicate glass. The lowest and highest MS2 recoveries among the 9 surfaces were demonstrated by the hole-bearing borosilicate glass (34 ±â€¯8%) and smooth PP (69 ±â€¯14%) respectively. Generally greater MS2 recovery was obtained from smooth PP and PE surfaces compared to glass, but topographic alterations (pinholes or increased roughness) decreased recovery possibly by trapping the viruses.