Properties of Cosmic Deuterons Measured by the Alpha Magnetic Spectrometer.

Precision measurements by the Alpha Magnetic Spectrometer (AMS) on the International Space Station of the deuteron (D) flux are presented. The measurements are based on 21×10^{6} D nuclei in the rigidity range from 1.9 to 21 GV collected from May 2011 to April 2021. We observe that over the entire rigidity range the D flux exhibits nearly identical time variations with the p, ^{3}He, and ^{4}He fluxes. Above 4.5 GV, the D/^{4}He flux ratio is time independent and its rigidity dependence is well described by a single power law ∝R^{Δ} with Δ_{D/^{4}He}=-0.108±0.005. This is in contrast with the ^{3}He/^{4}He flux ratio for which we find Δ_{^{3}He/^{4}He}=-0.289±0.003. Above ∼13 GV we find a nearly identical rigidity dependence of the D and p fluxes with a D/p flux ratio of 0.027±0.001. These unexpected observations indicate that cosmic deuterons have a sizable primarylike component. With a method independent of cosmic ray propagation, we obtain the primary component of the D flux equal to 9.4±0.5% of the ^{4}He flux and the secondary component of the D flux equal to 58±5% of the ^{3}He flux.

[Dislocation into the anterior chamber and spontaneous repositioning of a dexamethasone intravitreal implant: a case report].

A 61-year-old male patient presented with blurred vision in the right eye for 1 day. The patient had previously undergone phacoemulsification with intraocular lens implantation (10 years ago) and intravitreal implantation of dexamethasone (due to uveitis) in the eye. There was edema in the inferior cornea, along with Descemet membrane folds. The rod-shaped dexamethasone implant was visible in the inferior anterior chamber. Without pupil dilation, the patient was asked to keep a supine position and avoid head tilting for 1 day. The implant spontaneously relocated into the vitreous cavity, resulting in a reduction of corneal edema. This suggests that the dislocation of the intravitreal implant into the anterior chamber may be caused by a local zonular abnormality, and the dislocated implant has the potential to reposition itself spontaneously.

Causal associations between serum amino acid levels and osteoarthritis: a Mendelian randomization study.

OBJECTIVE: The association between serum amino acid (AA) levels and osteoarthritis (OA) risk remains unclear. METHOD: We performed a two-sample Mendelian randomization (MR) analysis to analyze the causal effects of serum AA levels on the OA risk by using summary-level genome-wide association study (GWAS) data. Inverse variance weighted (IVW) and Wald ratio were used as the main analysis. We also applied MR-Egger, Weighted median and Robust Adjusted Profile Score (MR.RAPS) methods. Heterogeneity and horizontally pleiotropic outliers were checked. The causal effects of AAs on early-onset all OA were explored. We also performed multivariable MR (MVMR) and conducted the bidirectional MR. RESULTS: The results suggested that genetically predicted alanine (Ala), tyrosine (Tyr) and isoleucine (Ile) levels were significantly associated with OA risk [e.g., association between Ala and hip/knee OA risk: OR = 0.82, 95% confidence interval (CI) = 0.75-0.90, P = 1.54E-05]. The study yielded little evidence of associations between genetically predicted AA levels with early-onset all OA risk. When adjusting the body mass index (BMI) in the MVMR model, suggestive causal effects of Ala and Tyr were also identified, while the effects of Ile substantially attenuated with OA risk. No significant associations between OA and AA levels were observed after testing for bidirectionality. CONCLUSIONS: Some AAs, such as Ala, Tyr and Ile likely affects the OA risk especially at hip or knee joints. The findings highlight the important role that serum AAs might play in the development of OA and provided new treatment approaches to OA.

Properties of Cosmic-Ray Sulfur and Determination of the Composition of Primary Cosmic-Ray Carbon, Neon, Magnesium, and Sulfur: Ten-Year Results from the Alpha Magnetic Spectrometer.

We report the properties of primary cosmic-ray sulfur (S) in the rigidity range 2.15 GV to 3.0 TV based on 0.38×10^{6} sulfur nuclei collected by the Alpha Magnetic Spectrometer experiment (AMS). We observed that above 90 GV the rigidity dependence of the S flux is identical to the rigidity dependence of Ne-Mg-Si fluxes, which is different from the rigidity dependence of the He-C-O-Fe fluxes. We found that, similar to N, Na, and Al cosmic rays, over the entire rigidity range, the traditional primary cosmic rays S, Ne, Mg, and C all have sizeable secondary components, and the S, Ne, and Mg fluxes are well described by the weighted sum of the primary silicon flux and the secondary fluorine flux, and the C flux is well described by the weighted sum of the primary oxygen flux and the secondary boron flux. The primary and secondary contributions of the traditional primary cosmic-ray fluxes of C, Ne, Mg, and S (even Z elements) are distinctly different from the primary and secondary contributions of the N, Na, and Al (odd Z elements) fluxes. The abundance ratio at the source for S/Si is 0.167±0.006, for Ne/Si is 0.833±0.025, for Mg/Si is 0.994±0.029, and for C/O is 0.836±0.025. These values are determined independent of cosmic-ray propagation.

Temporal Structures in Positron Spectra and Charge-Sign Effects in Galactic Cosmic Rays.

We present the precision measurements of 11 years of daily cosmic positron fluxes in the rigidity range from 1.00 to 41.9 GV based on 3.4×10^{6} positrons collected with the Alpha Magnetic Spectrometer (AMS) aboard the International Space Station. The positron fluxes show distinctly different time variations from the electron fluxes at short and long timescales. A hysteresis between the electron fluxes and the positron fluxes is observed with a significance greater than 5σ at rigidities below 8.5 GV. On the contrary, the positron fluxes and the proton fluxes show similar time variation. Remarkably, we found that positron fluxes are modulated more than proton fluxes with a significance greater than 5σ for rigidities below 7 GV. These continuous daily positron fluxes, together with AMS daily electron, proton, and helium fluxes over an 11-year solar cycle, provide unique input to the understanding of both the charge-sign and mass dependencies of cosmic rays in the heliosphere.

Temporal Structures in Electron Spectra and Charge Sign Effects in Galactic Cosmic Rays.

We present the precision measurements of 11 years of daily cosmic electron fluxes in the rigidity interval from 1.00 to 41.9 GV based on 2.0×10^{8} electrons collected with the Alpha Magnetic Spectrometer (AMS) aboard the International Space Station. The electron fluxes exhibit variations on multiple timescales. Recurrent electron flux variations with periods of 27 days, 13.5 days, and 9 days are observed. We find that the electron fluxes show distinctly different time variations from the proton fluxes. Remarkably, a hysteresis between the electron flux and the proton flux is observed with a significance of greater than 6σ at rigidities below 8.5 GV. Furthermore, significant structures in the electron-proton hysteresis are observed corresponding to sharp structures in both fluxes. This continuous daily electron data provide unique input to the understanding of the charge sign dependence of cosmic rays over an 11-year solar cycle.

Development and validation of risk prediction models for stroke and mortality among patients with type 2 diabetes in northern China.

BACKGROUND: Stroke is one of the leading causes of disability and mortality in patients with type 2 diabetes mellitus (T2DM). Risk models have been developed for predicting stroke and stroke-associated mortality among patients with T2DM. Here, we evaluated risk factors of stroke for individualized prevention measures in patients with T2DM in northern China. METHODS: In the community-based Tianjin Chronic Disease Cohort study, 58,042 patients were enrolled between January 2014 and December 2019. We used multiple imputation (MI) to impute missing variables and univariate and multivariate Cox's proportional hazard regression to screen risk factors of stroke. Furthermore, we established and validated first-ever prediction models for stroke (Model 1 and Model 2) and death from stroke (Model 3) and evaluated their performance. RESULTS: In the derivation and validation groups, the area under the curves (AUCs) of Models 1-3 was better at 5 years than at 8 years. The Harrell's C-index for all models was above 0.7. All models had good calibration, discrimination, and clinical net benefit. Sensitivity analysis using the MI dataset indicated that all models had good and stable prediction performance. CONCLUSION: In this study, we developed and validated first-ever risk prediction models for stroke and death from stroke in patients with T2DM, with good discrimination and calibration observed in all models. Based on lifestyle, demographic characteristics, and laboratory examination, these models could provide multidimensional management and individualized risk assessment. However, the models developed here may only be applicable to Han Chinese.

[The mechanism of S100A7 inducing the migration and invasion in cervical cancer cells].

Objective: To investigate the mechanism of S100A7 inducing the migration and invasion in cervical cancers. Methods: Tissue samples of 5 cases of cervical squamous cell carcinoma and 3 cases of adenocarcinoma were collected from May 2007 to December 2007 in the Department of Gynecology of the Affiliated Hospital of Qingdao University. Immunohistochemistry was performed to evaluate the expression of S100A7 in cervical carcinoma tissues. S100A7-overexpressing HeLa and C33A cells were established with lentiviral systems as the experimental group. Immunofluorescence assay was performed to observe the cell morphology. Transwell assay was taken to detect the effect of S100A7-overexpression on the migration and invasion of cervical cancer cells. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to examine the mRNA expressions of E-cadherin, N-cadherin, vimentin and fibronectin. The expression of extracellular S100A7 in conditioned medium of cervical cancer cell was detected by western blot. Conditioned medium was added into Transwell lower compartment to detect cell motility. Exosomes were isolated and extracted from the culture supernatant of cervical cancer cell, the expressions of S100A7, CD81 and TSG101 were detected by western blot. Transwell assay was taken to detect the effect of exosomes on the migration and invasion of cervical cancer cells. Results: S100A7 expression was positively expressed in cervical squamous carcinoma and negative expression in adenocarcinoma. Stable S100A7-overexpressing HeLa and C33A cells were successfully constructed. C33A cells in the experimental group were spindle shaped while those in the control group tended to be polygonal epithelioid cells. The number of S100A7-overexpressed HeLa cells passing through the Transwell membrane assay was increased significantly in migration and invasion assay (152.00±39.22 vs 105.13±15.75, P<0.05; 115.38±34.57 vs 79.50±13.68, P<0.05). RT-qPCR indicated that the mRNA expressions of E-cadherin in S100A7-overexpressed HeLa and C33A cells decreased (P<0.05) while the mRNA expressions of N-cadherin and fibronectin in HeLa cells and fibronectin in C33A cells increased (P<0.05). Western blot showed that extracellular S100A7 was detected in culture supernatant of cervical cancer cells. HeLa cells of the experimental group passing through transwell membrane in migration and invasion assays were increased significantly (192.60±24.41 vs 98.80±47.24, P<0.05; 105.40±27.38 vs 84.50±13.51, P<0.05) when the conditional medium was added into the lower compartment of Transwell. Exosomes from C33A cell culture supernatant were extracted successfully, and S100A7 expression was positive. The number of transmembrane C33A cells incubated with exosomes extracted from cells of the experimental group was increased significantly (251.00±49.82 vs 143.00±30.85, P<0.05; 524.60±52.74 vs 389.00±63.23, P<0.05). Conclusion: S100A7 may promote the migration and invasion of cervical cancer cells by epithelial-mesenchymal transition and exosome secretion.

[Effect and mechanism of 1, 25(OH)2D3 on myocardial inflammation induced by Coxsackie virus B3 in mice].

Objective: To explore the effect and mechanism of 1, 25(OH)2D3 on myocardial inflammation induced by Coxsackie virus B3 (CVB3) in mice. Methods: Wild type (WT) and 1α-hydroxylase knockout [1(OH)ase-/-] male mice were divided into four groups: WT group, WT+CVB3 group, 1(OH)ase-/-+CVB3 group and 1(OH)ase-/-+CVB3+VD3 group, with 8 mice in each group. The indicators for evaluating myocardial cell injury were examined by different methods. The mRNA levels of pro-inflammatory cytokines [interlenkin (IL)-1ß, IL-6, interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α)] were determined by quantitative real-time PCR. Hematoxylin-eosin (HE) staining was used to observe the myocardial histopathological changes. The apoptosis of myocardial cells was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and flow cytometry. Fluo-4/AM fluorescence probe was used to detect intracellular calcium ion content. Meanwhile, the expression levels of Ca2+/Calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) protein as well as endoplasmic reticulum stress-related proteins like glucose-related protein 78 (GRP78) and C/EBP homologous protein (CHOP) in the myocardial tissues were detected by Western blot. Results: Compared with WT group, the mRNA levels of pro-inflammatory factors increased in the cardiomyocytes of mice in WT+CVB3 group, including IL-1ß (14.88±3.32 vs 1.03±0.02, P=0.009), IL-6 (7.00±1.09 vs 1.81±0.18, P=0.005), IFN-γ (4.70±1.11 vs 1.34±0.34, P=0.006) and TNF-α (17.20±3.22 vs 1.02±0.12, P<0.001). Similarly, the infiltration of inflammatory cells, and the apoptosis rate of cardiomyocytes elevated (16.66%±1.09% vs 7.85%±1.12%, P=0.012). The level of calcium ions in myocardial cytoplasm was significantly higher in WT+CVB3 group than that in the WT group (2.98±1.05 vs 0.96±0.10, P=0.006). Likewise, the expression levels of pCaMKⅡ(1.97±0.34 vs 1.00±0, P<0.001), GRP78 (1.78±0.19 vs 1.00±0, P=0.005) and CHOP (1.62±0.09 vs 1.00±0, P=0.002) in WT+CVB3 group up-regulated. The above myocardial cell injury markers were more significant in the 1(OH)ase-/-+CVB3 group. In the 1(OH)ase-/-+CVB3+VD3 group, 1, 25(OH)2D3 supplementation significantly improved myocardial cell injury indicators. Meanwhile, the specific inhibitors of CaMKⅡ can also reduce the myocardial injury and apoptosis rate of CVB3-infected mice. Conclusion: 1, 25(OH)2D3 deficiency can aggravate myocardial inflammation through over activation of CaMKⅡ.

[Drug resistance and genomic characteristics of a strain of O139 Vibrio cholerae isolated from human bloodstream infection].

Objective: To analyze the drug resistance and genomic characteristics of a strain of serogroup O139 Vibrio cholerae producing cholera toxin isolated from the bloodstream of a person with bacteremia. Methods: The broth dilution method and automatic drug sensitivity analyzer were used to determine the antibiotic sensitivity of the strain. The complete genome sequence of the strain was obtained by using second-generation gene sequencing and nanopore sequencing. BLAST software was used for comparison and analysis with CARD, Resfinder, ISfinder, VFDB, and other databases. The drug-resistant genes, insertion sequences and virulence genes carried by the strain were identified. MEGA 5.1 software was used to construct a genetic phylogenetic tree based on the core genomic single nucleotide polymorphisms. Results: V. cholerae SH400, as the toxigenic strain, carried multiple virulence-related genes and four virulence islands. The strain was resistant to streptomycin, tetracycline and cotrimoxazole, carrying corresponding drug-resistant genes. The strain also carried IncA/C plasmid with the size of 172914 bp and contained 10 drug-resistant genes. Combined with the genomic evolutionary relationship, this study found that the drug-resistant genes and drug-resistant plasmids carried among strains showed certain aggregation. The traditional ST type of strain SH400 was ST69, and the cgMLST type was a new type highly similar to cgST-252. Conclusion: This strain of serogroup O139 V. cholerae carries the ctxAB gene, multiple drug-resistant genes and IncA/C plasmid, and there are multiple drug-resistant islands.

Properties of Daily Helium Fluxes.

We present the precision measurement of 2824 daily helium fluxes in cosmic rays from May 20, 2011 to October 29, 2019 in the rigidity interval from 1.71 to 100 GV based on 7.6×10^{8} helium nuclei collected with the Alpha Magnetic Spectrometer (AMS) aboard the International Space Station. The helium flux and the helium to proton flux ratio exhibit variations on multiple timescales. In nearly all the time intervals from 2014 to 2018, we observed recurrent helium flux variations with a period of 27 days. Shorter periods of 9 days and 13.5 days are observed in 2016. The strength of all three periodicities changes with time and rigidity. In the entire time period, we found that below ∼7 GV the helium flux exhibits larger time variations than the proton flux, and above ∼7 GV the helium to proton flux ratio is time independent. Remarkably, below 2.4 GV a hysteresis between the helium to proton flux ratio and the helium flux was observed at greater than the 7σ level. This shows that at low rigidity the modulation of the helium to proton flux ratio is different before and after the solar maximum in 2014.

What is an appropriate caesarean delivery rate for China: a multicentre survey.

OBJECTIVE: To assess the current status of caesarean delivery (CD) in China, propose reference CD rates for China overall, and by regions, investigate the main indications for CDs and identify possible areas for safe reduction. DESIGN: A multicentre cross-sectional study. SETTING: A total of 94 hospitals across 23 provinces in China. POPULATION: A total of 73 977 randomly selected deliveries. METHODS: We used a modified Robson classification to characterise CDs in subgroups and by regions, and the World Health Organization (WHO) C-Model to calculate reference CD rates. MAIN OUTCOME MEASURES: CD rates in China. RESULTS: In 2015-2016, the overall CD rate in China was 38.9% (95% CI 38.6-39.3%). Considering the obstetric characteristics of the population, the multivariable model-based reference CD rate was estimated at 28.5% (95% CI 28.3-28.8%). Accordingly, an absolute reduction of 10.4% (or 26.7% relative reduction) may be considered. The CD rate varied substantially by region. Previous CD was the most common indication in all regions, accounting for 38.2% of all CDs, followed by maternal request (9.8%), labour dystocia (8.3%), fetal distress (7.7%) and malpresentation (7.6%). Overall, 12.7% of women had prelabour CDs, contributing to 32.8% of the total CDs. CONCLUSIONS: Nearly 39% of births were delivered by caesarean in China but a reduction of this rate by a quarter may be considered attainable. Repeat CD contributed more than one-third of the total CDs. Given the large variation in maternal characteristics, region-specific or even hospital-specific reference CD rates are needed for precision management of CD. TWEETABLE ABSTRACT: The caesarean rate in 2015-2016 in China was 38.9%, whereas the reference rate was 28.5%.

Mechanistic Study of Macranthoside B Effects on Apoptotic Cell Death in Human Cervical Adenocarcinoma Cells.

Macranthoside B (MB) is a triterpenoid saponin extracted from Lonicera macranthoides, a traditional Chinese medicine. In the current study, we investigated the anticancer potential of MB in various cancer cells and elucidated its underlying mechanisms. MB exposure inhibited cell proliferation, induced mitochondrial membrane potential (MMP) loss, increased sub-G1 accumulation, and resulted in cleavage of caspase-3 and PARP, which are reflective of apoptosis. In HeLa cells, MB induced down-regulation of SOD2 and GPx1, phosphorylation of Akt and PDK1, and thus promoted ROS-mediated apoptosis. This was further supported by the protection of sub-G1 accumulation, MMP loss, cleavage of caspase-3 and PARP in the presence of N-acetylcysteine (NAC). Additionally, MB induced cell death via down-regulation of ubiquitin-like with PHD and ringfinger domains 1 (UHRF1) and Bcl-xL. Taken together, this study provides a new insight into the apoptosis- inducing potential of MB, and its molecular mechanisms are associated with an increase in oxidative stress and inhibition of the PDK1/Akt pathway.

Efficacy and safety of FiLaC™ for perianal fistulizing Crohn's disease: a systematic review and meta-analysis.

BACKGROUND: Most patients with perianal fistulizing Crohn's disease (pfCD) present with complex types of perianal fistulas and need repetitive repair operations, resulting in a high risk of sphincter injury. Fistula-tract Laser Closure (FiLaC™) is a novel sphincter-saving technique that obliterates the fistula tract with a photothermal effect. The aim of the present systematic review and meta-analysis was to evaluate the efficacy and safety of FiLaC in pfCD. METHODS: This study was conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Electronic databases, including PubMed, Embase, Cochrane Library and Wanfang Data were searched for published articles from January 2000 to June 2021. The clinicaltrials.gov website was searched for completed or ongoing trials on pfCD and FiLaC™. The references of each article were also searched for eligible data. The main outcome was the primary healing rate of the FiLaC™ procedure. Additionally, fecal incontinence was analyzed as the secondary outcome to evaluate the safety of FiLaC™. RESULTS: Six studies met the eligibility criteria and were included in the final analysis. All studies were published within the past 6 years and came from European countries. There were 50 pfCD patients recruited, and 31 patients' fistulas were healed after FiLaC™. The pooled primary healing rate was 68% (95% CI 53.0-84.0%, I2 = 27%, p = 0.23). There was no major fecal incontinence after surgery. CONCLUSIONS: These data suggest that FiLaC™ may be an effective and safe procedure for pfCD patients. However, the evidence is poor and there is a need for more high-quality prospective controlled studies with long-term follow-up before this minimally invasive technique is recommended for surgical treatment of pfCD.

[Effect evaluation of "Smoking cessation: Doctor first"program in China].

Objective: To evaluate the effect of "Smoking cessation: Doctor first" program on smoking medical staff. Methods: From December 2016 to September 2019, 1 747 smoking medical staff from 54 units of China Tobacco Cessation Alliance were enrolled into"Smoking cessation: Doctor first"program. Demographic characteristics, smoking characteristics, degree of tobacco dependence, willingness to quit smoking and other related factors were collected during the baseline survey. Multivariate logistic regression model was used to analyze the related factors of willingness to quit. The subjects were given intensive smoking cessation intervention from October 2017 to September 2019, including education on the hazards of smoking, methods of smoking cessation and giving smoking cessation drugs. After intervention, the subjects were investigated about their smoking cessation progress and the effect of the project was evaluated. Results: The subjects were (41±11) years old, 91.9% (1 609/1 747) were male and 62.2% (1 086/1 747) were daily smokers. The main reasons for smoking included the influence of friends [697 (39.9%)], the need for social entertainment [629 (36.0%)], the relief of mental stress [589 (33.7%)] and the refreshment [459 (26.3%)]. At baseline, 52.9% (885/1 672) and 43.2% (755/1 747) smokers had intention to quit smoking and had planned to quit within one year, respectively. Multivariate logistic regression model analysis showed that: low education level [OR (95%CI) of high school and junior high school and below were 2.42 (1.61, 3.63) and 1.57 (1.18, 2.11)], daily smoking [OR (95%CI): 1.38 (1.06, 1.78)], thinking quitting smoking is not important [OR (95%CI): 4.15 (3.33, 5.18)] and having no quitting experience [OR (95%CI): 3.21 (2.53, 4.05)] were associated with no intention to quit smoking. After intensive smoking cessation intervention, 81.0% (1 415/1 747) smokers started to quit and 36.6% (518/1 415) quit smoking with drugs, both higher than the baseline level (all P values<0.001). By the end of the program, 60.2% (852/1 415) of the medical staff had quit smoking successfully. Conclusion: "Smoking cessation: Doctor first"program can improve the willingness to quit and the proportion of using smoking cessation drugs of medical staff.

[Preliminary effects of toripalimab combined with axitinib in the treatment of advanced renal cell carcinoma].

Objective: To analyze the efficacy and safety of toripalimab combined with axitinib in the treatment of advanced renal cell carcinoma. Methods: Clinical data of 50 patients with advanced renal cell carcinoma who received axitinib combined with toripalimab were retrospectively collected from the database of Peking University Cancer Hospital. ORR, DCR, PFS, and OS were analyzed. Results: Among the 50 patients, 37 were males; median age was 56 (22-73) years; 38 were pathologically diagnosed as clear cell renal cell carcinoma and 12 were non-clear cell carcinoma. Common metastatic sites included lung, bone, lymph node, liver, and so on. 90% of the patients had received at least one-line of systemic therapy. With a median follow-up time of 11.9 months (0.8-24), 27 of the 50 patients are still on treatment, ORR was 34%, DCR was 86%, median PFS was 13.1 months (95%CI 5.8-20.4), and median OS has not yet reached. One-year OS rate was 84.6%. Common adverse reactions were proteinuria, diarrhea, hypertension, abnormal thyroid function, elevated transaminase, and hand-foot syndrome. Most adverse events were grade 1-2. Conclusion: Toripalimab combined with axitinib was efficient in the treatment of advanced renal cell carcinoma, and had manageable adverse reactions.

[Application and reflection of laboratory-based monitoring in early warning of infectious diseases].

Despite the fact that our cognition towards infectious disease prevention, the advanced technology and the economic status of the whole society has made a great progress in the last decade, the outbreak of COVID-19 pneumonia has again enabled the public to acquire more about super-challenges of infectious diseases, epidemics and the relevant preventive measurements. In order to identify the epidemic signals in early stage or even before the onset of epidemic, the data research and utilization of a series of factors related to the occurrence and transmission of infectious diseases have played a significant role in research of prevention and control during the whole period of surveillance and early warning. Laboratory-based monitoring for the etiology has always been an important part of infectious disease warning system due to pathogens as the direct cause of such diseases. China has initially established a laboratory-based monitoring and early warning system for bacterial infectious diseases based on the Chinese Pathogen Identification Network with an aim to identify pathogens, outbreaks and sources. This network has played an essential role in early detection, tracking and precise prevention and control of bacterial infectious diseases, such as plague, cholera, and epidemic cerebrospinal meningitis. This issue focuses on the function of laboratory-based monitoring during the period of early warning, prevention, and control of bacterial infectious diseases, and conducted a wide range of researches based on the analysis of the epidemic and outbreak isolates, together with field epidemiological studies and normal monitoring systems. All of these could illustrate the effect of laboratory surveillance in the infectious disease risk assessment and epidemic investigation. At the same time, we have put forward our review and expectation of scenarios about laboratory-based monitoring and early warning technologies to provide innovative thoughts for promoting a leapfrog development of infectious disease monitoring and early warning system in China.

[Effects of p16/pRb and JNK signaling pathways in hydroquinone-induced malignant transformation of TK6 cells].

Objective: To investigate the cell cycle and apoptosis in hydroquinone (HQ) -induced malignant transformation of TK6 cells and its related regulatory mechanisms. Methods: TK6 cells were exposed to 20 µmol/L HQ, 24 h/time, once a week, for 19 weeks as experimental group and TK6 cells treated with phosphate buffer (PBS) for 19 weeks was used as control group from March 2014. In regulatory mechanism research, the cells were divided into four groups: control group, experimental group, control inhibitor group and experimental inhibitor group (inhibitor groups were added 10 µmol/L P600125) . Cell cycle and apoptosis were detected by flow cytometry. The protein expression of cell cycle-related proteins and JNK signaling pathway proteins were detected by Western blot. Results: Flow cytometry showed that compared with control group, the ratio of cells in the G0/G1 phase of the experimental group was significantly decreased (P=0.001) , and the ratio of cells in the S phase was significantly increased (P=0.002) . Western blotting demonstrated that the protein expressions of p-Rb (Ser780) , E2F1, Cyclin D1, p-p16 (Ser152) , JNK1, p-JNK1 (Thr183/Tyr185) , c-jun, p-c-jun (Ser63) (P=0.015, 0.021, 0.001, 0.001, 0.005, 0.001, 0.039, 0.003) were up-regulated, while the protein expressions of Rb (P=0.048) and p16 (P=0.002) were significantly down-regulated. After exposed to SP600125, compared with experimental group, there were no significant changes in cell cycle distribution (P=0.946) and apoptosis rate (P=0.923) in experimental inhibitor group. The expression of c-jun (P=0.040) protein was down-regulated, while the expression of Rb (P=0.027) protein was up-regulated in experimental inhibitor group. Conclusion: In HQ-induced TK6 cells malignant transformation, the cell cycle is arrested in the S phase, and the p16/pRb signaling pathway is inhibited, while the JNK signaling pathway is activated. However, the activated JNK signaling pathway may not be involved in the regulation of cell cycle.

Identification and characterization of enzymes involved in the biosynthesis of pyrimidine nucleoside antibiotics.

Covering: up to September 2020 Hundreds of nucleoside-based natural products have been isolated from various microorganisms, several of which have been utilized in agriculture as pesticides and herbicides, in medicine as therapeutics for cancer and infectious disease, and as molecular probes to study biological processes. Natural products consisting of structural modifications of each of the canonical nucleosides have been discovered, ranging from simple modifications such as single-step alkylations or acylations to highly elaborate modifications that dramatically alter the nucleoside scaffold and require multiple enzyme-catalyzed reactions. A vast amount of genomic information has been uncovered the past two decades, which has subsequently allowed the first opportunity to interrogate the chemically intriguing enzymatic transformations for the latter type of modifications. This review highlights (i) the discovery and potential applications of structurally complex pyrimidine nucleoside antibiotics for which genetic information is known, (ii) the established reactions that convert the canonical pyrimidine into a new nucleoside scaffold, and (iii) the important tailoring reactions that impart further structural complexity to these molecules.

Erratum: Properties of a New Group of Cosmic Nuclei: Results from the Alpha Magnetic Spectrometer on Sodium, Aluminum, and Nitrogen [Phys. Rev. Lett. 127, 021101 (2021)].

This corrects the article DOI: 10.1103/PhysRevLett.127.021101.