Comparative Proteomics Identified EXOSC1 as a Target Protein of Anticancer Peptide LVTX-8 in Nasopharyngeal Carcinoma Cells.

Nasopharyngeal carcinoma (NPC) is a prevalent malignancy that usually occurs among the nose and throat. Due to mild initial symptoms, most patients are diagnosed in the late stage, and the recurrence rate of tumors is high, resulting in many deaths every year. Traditional radiotherapy and chemotherapy are prone to causing drug resistance and significant side effects. Therefore, searching for new bioactive drugs including anticancer peptides is necessary and urgent. LVTX-8 is a peptide toxin synthesized from the cDNA library of the spider Lycosa vittata, which is consisting of 25 amino acids. In this study, a series of in vitro cell experiments such as cell toxicity, colony formation, and cell migration assays were performed to exam the anticancer activity of LVTX-8 in NPC cells (5-8F and CNE-2). The results suggested that LVTX-8 significantly inhibited cell proliferation and migration of NPC cells. To find the potential molecular targets for the anticancer capability of LVTX-8, high-throughput proteomic and bioinformatics analysis were conducted on NPC cells. The results identified EXOSC1 as a potential target protein with significantly differential expression levels under LVTX-8+/LVTX-8- conditions. The results in this research indicate that spider peptide toxin LVTX-8 exhibits significant anticancer activity in NPC, and EXOSC1 may serve as a target protein for its anticancer activity. These findings provide a reference for the development of new therapeutic drugs for NPC and offer new ideas for the discovery of biomarkers related to NPC diagnosis. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (https://proteomecentral.proteomexchange.org) via the iProX partner repository with the data set identifier PXD050542.

Association between lipid accumulation product and psoriasis among adults: a nationally representative cross-sectional study.

BACKGROUND: Lipid accumulation product (LAP) is an accessible and relatively comprehensive assessment of obesity that represents both anatomical and physiological lipid accumulation. Obesity and psoriasis are potentially related, according to previous research. Investigating the relationship between adult psoriasis and the LAP index was the goal of this study. METHODS: This is a cross-sectional study based on data from the National Health and Nutrition Examination Survey (NHANES) 2003-2006 and 2009-2014. The association between LAP and psoriasis was examined using multivariate logistic regression and smoothed curve fitting. To verify whether this relationship was stable across populations, subgroup analyses and interaction tests were performed. RESULTS: The LAP index showed a positive correlation with psoriasis in 9,781 adult participants who were 20 years of age or older. A 27% elevated probability of psoriasis was linked to every unit increase in ln LAP in the fully adjusted model (Model 3: OR 1.27, 95% CI 1.06-1.52). In comparison with participants in the lowest ln LAP quartile, those in the highest quartile had an 83% greater likelihood of psoriasis (Model 3: OR 1.83, 95% CI 1.08-3.11). This positive correlation was more pronounced for young males, participants who had never smoked, non-drinkers, participants who exercised little, as well as non-hypertensive and non-diabetic participants. CONCLUSIONS: This study found that the LAP index and adult psoriasis were positively correlated, especially in young males without comorbidities. Therefore, it is proposed that LAP may serve as a biomarker for early diagnosis of psoriasis and tracking the effectiveness of treatment.

Isothermal nucleic acid amplification technology for rapid detection of virus.

While the research field and industrial market of in vitro diagnosis (IVD) thrived during and post the COVID-19 pandemic, the development of isothermal nucleic acid amplification test (INAAT) based rapid diagnosis was engendered in a global wised large measure as a problem-solving exercise. This review systematically analyzed the recent advances of INAAT strategies with practical case for the real-world scenario virus detection applications. With the qualities that make INAAT systems useful for making diagnosis relevant decisions, the key performance indicators and the cost-effectiveness of enzyme-assisted methods and enzyme-free methods were compared. The modularity of nucleic acid amplification reactions that can lead to thresholding signal amplifications using INAAT reagents and their methodology design were examined, alongside the potential application with rapid test platform/device integration. Given that clinical practitioners are, by and large, unaware of many the isothermal nucleic acid test advances. This review could bridge the arcane research field of different INAAT systems and signal output modalities with end-users in clinic when choosing suitable test kits and/or methods for rapid virus detection.

Proteomics profiling for the global and acetylated proteins of papillary thyroid cancers.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy cancer among the malignancies of thyroid. Despite of wide usages of proteomics in PTC, the profile of acetylated proteins in PTC remains unsettled, which is helpful for understanding the carcinogenesis mechanism and identifying useful biomarkers for PTC. METHODS: The surgically removed specimens of cancer tissues (Ca-T) and adjacent normal tissues (Ca-N) from 10 female patients pathological diagnosed as PTC (TNM stage III) were enrolled in the study. After preparing the pooled extracts of the whole proteins and the acetylated proteins from 10 cases, TMT labeling and LC/MS/MS methods were applied to the assays of global proteomics and acetylated proteomics separately. Bioinformatics analysis, including KEGG, gene ontology (GO) and hierarchical clustering were performed. Some differentially expressed proteins (DEPs) and differentially expressed acetylated proteins (DEAPs) were validated by individual Western blots. RESULTS: Controlled with the normal tissues adjacent to the lesions, 147 out of 1923 identified proteins in tumor tissues were considered as DEPs in global proteomics, including 78 up-regulated and 69 down-regulated ones, while 57 out of 311 identified acetylated proteins in tumor tissues were DEAPs in acetylated proteomics, including 32 up-regulated and 25 down-regulated, respectively. The top 3 up- and down-regulated DEPs were fibronectin 1, KRT1B protein and chitinase-3-like protein 1, as well as keratin, type I cytoskeletal 16, A-gamma globin Osilo variant and Huntingtin interacting protein-1. The top 3 up- and down-regulated DEAPs were ribosomal protein L18a-like protein, alpha-1-acid glycoprotein 2 and eukaryotic peptide chain release factor GTP-binding subunit ERF3A, as well as trefoil factor 3, thyroglobulin and histone H2B. Functional GO annotation and KEGG pathway analysis based on the DEPs and DEAPs showed completely different changing pictures. Contrary to the top 10 up- and -down regulated DEPs, most of which were addressed in PTC and other types of carcinomas, changes of the majority DEAPs were not mentioned in the literatures. CONCLUSIONS: Taken the profiling of the global and acetylated proteomics together will provide more broad view of protein alterations on the carcinogenesis and new direction for selecting biomarker for diagnosis of PTC.

Analysis of miRNA expression profiles in exosomes of SMB-S15 cells treated with resveratrol.

Exosomes are double-layered vesicle bodies secreted by cells, in which microRNAs (miRNAs) play an important role. In a previous study, we found that treatment of the prion-infected cell line SMB-S15 with resveratrol can effectively inhibit the propagation of PrPSc in vitro and eliminate its infectivity in vivo. In this study, the global expression profiles of miRNAs in extracellular exosomes during resveratrol clearance of PrPSc in SMB-S15 cells were analyzed. Extracted exosomal miRNAs from the prion-infected cell line SMB-S15 (S15) and its normal partner cell line SMB-PS (PS) as well as SMB-S15 cells exposed to resveratrol for 4 days (RES4) and 8 days (RES8) were subjected into deep sequencing. Similarities and differences in the levels of differentially expressed miRNAs as well as the signaling pathways that are potentially involved were comparatively analyzed. The possible influences on the expression of genes affected by changes in exosomal miRNAs in the context of the prion pathway were further analyzed. These alterations in exosomal miRNA levels may help us to understand the functional transmission of intercellular messages and the pathogenesis of prion biology and prion disease.

Diagnostic accuracy of cerebrospinal fluid biomarkers in genetic prion diseases.

Genetic prion diseases are a rare and diverse group of fatal neurodegenerative disorders caused by pathogenic sequence variations in the prion protein gene, PRNP. Data on CSF biomarkers in patients with genetic prion diseases are limited and conflicting results have been reported for unclear reasons. Here, we aimed to analyse the diagnostic accuracy of CSF biomarkers currently used in prion clinical diagnosis in 302 symptomatic genetic prion disease cases from 11 prion diagnostic centres, encompassing a total of 36 different pathogenic sequence variations within the open reading frame of PRNP. CSF samples were assessed for the surrogate markers of neurodegeneration, 14-3-3 protein (14-3-3), total-tau protein (t-tau) and α-synuclein and for prion seeding activity through the real-time quaking-induced conversion assay. Biomarker results were compared with those obtained in healthy and neurological controls. For the most prevalent PRNP pathogenic sequence variations, biomarker accuracy and associations between biomarkers, demographic and genetic determinants were assessed. Additionally, the prognostic value of biomarkers for predicting total disease duration from symptom onset to death was investigated. High sensitivity of the four biomarkers was detected for genetic Creutzfeldt-Jakob disease associated with the E200K and V210I mutations, but low sensitivity was observed for mutations associated with Gerstmann-Sträussler-Scheinker syndrome and fatal familial insomnia. All biomarkers showed good to excellent specificity using the standard cut-offs often used for sporadic Creutzfeldt-Jakob disease. In genetic prion diseases related to octapeptide repeat insertions, the biomarker sensitivity correlated with the number of repeats. New genetic prion disease-specific cut-offs for 14-3-3, t-tau and α-synuclein were calculated. Disease duration in genetic Creutzfeldt-Jakob disease-E200K, Gerstmann-Sträussler-Scheinker-P102L and fatal familial insomnia was highly dependent on PRNP codon 129 MV polymorphism and was significantly associated with biomarker levels. In a large cohort of genetic prion diseases, the simultaneous analysis of CSF prion disease biomarkers allowed the determination of new mutation-specific cut-offs improving the discrimination of genetic prion disease cases and unveiled genetic prion disease-specific associations with disease duration.

Nesting the SIRV model with NAR, LSTM and statistical methods to fit and predict COVID-19 epidemic trend in Africa.

OBJECTIVE: Compared with other regions in the world, the transmission characteristics of the COVID-19 epidemic in Africa are more obvious, has a unique transmission mode in this region; At the same time, the data related to the COVID-19 epidemic in Africa is characterized by low data quality and incomplete data coverage, which makes the prediction method of COVID-19 epidemic suitable for other regions unable to achieve good results in Africa. In order to solve the above problems, this paper proposes a prediction method that nests the in-depth learning method in the mechanism model. From the experimental results, it can better solve the above problems and better adapt to the transmission characteristics of the COVID-19 epidemic in African countries. METHODS: Based on the SIRV model, the COVID-19 transmission rate and trend from September 2021 to January 2022 of the top 15 African countries (South Africa, Morocco, Tunisia, Libya, Egypt, Ethiopia, Kenya, Zambia, Algeria, Botswana, Nigeria, Zimbabwe, Mozambique, Uganda, and Ghana) in the accumulative number of COVID-19 confirmed cases was fitted by using the data from Worldometer. Non-autoregressive (NAR), Long-short term memory (LSTM), Autoregressive integrated moving average (ARIMA) models, Gaussian and polynomial functions were used to predict the transmission rate ß in the next 7, 14, and 21 days. Then, the predicted transmission rate ßs were substituted into the SIRV model to predict the number of the COVID-19 active cases. The error analysis was conducted using root-mean-square error (RMSE) and mean absolute percentage error (MAPE). RESULTS: The fitting curves of the 7, 14, and 21 days were consistent with and higher than the original curves of daily active cases (DAC). The MAPE between the fitted and original 7-day DAC was only 1.15% and increased with the longer of predict days. Both the predicted ß and DAC of the next 7, 14, and 21 days by NAR and LSTM nested models were closer to the real ones than other three ones. The minimum RMSEs for the predicted number of COVID-19 active cases in the next 7, 14, and 21 days were 12,974, 14,152, and 12,211 people, respectively when the order of magnitude for was 106, with the minimum MAPE being 1.79%, 1.97%, and 1.64%, respectively. CONCLUSION: Nesting the SIRV model with NAR, LSTM, ARIMA methods etc. through functionalizing ß respectively could obtain more accurate fitting and predicting results than these models/methods alone for the number of confirmed COVID-19 cases in Africa in which nesting with NAR had the highest accuracy for the 14-day and 21-day predictions. The nested model was of high significance for early understanding of the COVID-19 disease burden and preparedness for the response.

Transcriptomics Based Network Analyses and Molecular Docking Highlighted Potentially Therapeutic Biomarkers for Colon Cancer.

In this study, machine learning-based multiple bioinformatics analysis was carried out for the purpose of the deep and efficient mining of high-throughput transcriptomics data from the TCGA database. Compared with normal colon tissue, 2469 genes were significantly differentially expressed in colon cancer tissue. Gene functional annotation and pathway analysis suggested that most DEGs were functionally related to the cell cycle and metabolism. Weighted gene co-expression network analysis revealed a significant module and the enriched genes that were closely related to fatty acid degradation and metabolism. Based on colon cancer progression, the trend analysis highlighted that several gene sets were significantly correlated with disease development. At the same time, the most specific genes were functionally related to cancer cell features such as the high performance of DNA replication and cell division. Moreover, survival analysis and target drug prediction were performed to prioritize reliable biomarkers and potential drugs. In consideration of a combination of different evidence, four genes (ACOX1, CPT2, CDC25C and PKMYT1) were suggested as novel biomarkers in colon cancer. The potential biomarkers and target drugs identified in our study may provide new ideas for colonic-related prevention, diagnosis, and treatment; therefore, our results have high clinical value for colon cancer.

Decursin alleviates LPS-induced lung epithelial cell injury by inhibiting NF-κB pathway activation.

OBJECTIVE: To reveal the possible effects of decursin on viability, oxidative stress, and inflammatory response in lipopolysaccharide (LPS)-treated human bronchial epithelial cells-2B (BEAS-2B) and human pulmonary artery endothelial cells (HPAEC) cells, and revealed the potential mechanisms. METHODS: LPS was used to induce acute lung injury (ALI) in normal human lung epithelial cells, including BEAS-2B and HPAEC cells. Cell viability and apoptosis in response to LPS and decursin in BEAS-2B and HPAEC cells were, respectively, evaluated by MTT colorimetric and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. The oxidative stress and inflammatory response in LPS-treated BEAS-2B and HPAEC cells were detected by enzyme-linked-immunosorbent serologic assay. In addition, the role of decursin in nuclear -factor-kappa B (NF-κB) activation was analyzed by immunoblot and immunofluorescence assays. RESULTS: Our data revealed that decursin could alleviate the viability of LPS-induced BEAS-2B and HPAEC cells. Decursin could also reduce LPS-induced oxidative stress in BEAS-2B and HPAEC cells. In addition, it could reduce LPS-induced inflammation in BEAS-2B and HPAEC cells. Mechanically, decursin suppressed the activation of NF-κB pathway. CONCLUSION: Decursin suppressed NF-κB pathway, and therefore alleviated ALI.

Small Open Reading Frame-Encoded Micro-Peptides: An Emerging Protein World.

Small open reading frames (sORFs) are often overlooked features in genomes. In the past, they were labeled as noncoding or "transcriptional noise". However, accumulating evidence from recent years suggests that sORFs may be transcribed and translated to produce sORF-encoded polypeptides (SEPs) with less than 100 amino acids. The vigorous development of computational algorithms, ribosome profiling, and peptidome has facilitated the prediction and identification of many new SEPs. These SEPs were revealed to be involved in a wide range of basic biological processes, such as gene expression regulation, embryonic development, cellular metabolism, inflammation, and even carcinogenesis. To effectively understand the potential biological functions of SEPs, we discuss the history and development of the newly emerging research on sORFs and SEPs. In particular, we review a range of recently discovered bioinformatics tools for identifying, predicting, and validating SEPs as well as a variety of biochemical experiments for characterizing SEP functions. Lastly, this review underlines the challenges and future directions in identifying and validating sORFs and their encoded micropeptides, providing a significant reference for upcoming research on sORF-encoded peptides.

Quantitative proteomic analysis of hepatic tissue in allotetraploid hybridized from red crucian carp and common carp identified crucial proteins and pathways associated with metabolism and growth rate.

Allotetraploid is a new species produced by distant hybridization between red crucian carp (Carassius auratus red var., abbreviated as RCC) and common carp (Cyprinus carpio L., abbreviated as CC). There is a significant difference in growth rate between allotetraploid and its parents. However, the underlying molecular mechanism is largely unknown. In this study, to find direct evidence associated with metabolism and growth rate in protein level, we performed quantitative proteomics analysis on liver tissues between allotetraploid and its parents. A total of 2502 unique proteins were identified and quantified by SWATH-MS in our proteomics profiling. Subsequently, comprehensive bioinformatics analyses including gene ontology enrichment analysis, pathway and network analysis, and protein-protein interaction analysis (PPI) were conducted based on differentially expressed proteins (DEPs) between allotetraploid and its parents. The results revealed several significant DEPs involved in metabolism pathways in liver. More specifically, the integrative analysis highlighted that the DEPs ACSBG1, OAT, and LDHBA play vital roles in metabolism pathways including "pentose phosphate pathway," "TCA cycle," and "glycolysis and gluconeogenesis." These could directly affect the growth rate in fresh water fishes by regulating the metabolism, utilization, and exchange of substance and energy. Since the liver is the central place for metabolism activity in animals, we firstly established the comprehensive and quantitative proteomics knowledge base for liver tissue from freshwater fishes, our study may serve as an irreplaceable reference for further studies regarding fishes' culture and growth.

Risk Factors for Death Among the First 80 543 Coronavirus Disease 2019 (COVID-19) Cases in China: Relationships Between Age, Underlying Disease, Case Severity, and Region.

BACKGROUND: Knowledge of COVID-19 epidemiology remains incomplete and crucial questions persist. We aimed to examine risk factors for COVID-19 death. METHODS: A total of 80 543 COVID-19 cases reported in China, nationwide, through 8 April 2020 were included. Risk factors for death were investigated by Cox proportional hazards regression and stratified analyses. RESULTS: Overall national case-fatality ratio (CFR) was 5.64%. Risk factors for death were older age (≥80: adjusted hazard ratio, 12.58; 95% confidence interval, 6.78-23.33), presence of underlying disease (1.33; 1.19-1.49), worse case severity (severe: 3.86; 3.15-4.73; critical: 11.34; 9.22-13.95), and near-epicenter region (Hubei: 2.64; 2.11-3.30; Wuhan: 6.35; 5.04-8.00). CFR increased from 0.35% (30-39 years) to 18.21% (≥70 years) without underlying disease. Regardless of age, CFR increased from 2.50% for no underlying disease to 7.72% for 1, 13.99% for 2, and 21.99% for ≥3 underlying diseases. CFR increased with worse case severity from 2.80% (mild) to 12.51% (severe) and 48.60% (critical), regardless of region. Compared with other regions, CFR was much higher in Wuhan regardless of case severity (mild: 3.83% vs 0.14% in Hubei and 0.03% elsewhere; moderate: 4.60% vs 0.21% and 0.06%; severe: 15.92% vs 5.84% and 1.86%; and critical: 58.57% vs 49.80% and 18.39%). CONCLUSIONS: Older patients regardless of underlying disease and patients with underlying disease regardless of age were at elevated risk of death. Higher death rates near the outbreak epicenter and during the surge of cases reflect the deleterious effects of allowing health systems to become overwhelmed.

Sofosbuvir-based therapy for late pregnant women and infants with severe chronic hepatitis C: A case series study.

Data on sofosbuvir-based therapy for pregnant women and infants with severe chronic hepatitis C (CHC) are lacking. Two late pregnant women and one female infant with severe CHC were enrolled for treatment. Pregnant Women 1 and 2 and Infant 3 were 30, 33, and 1.2 years old, respectively; the gestational ages of pregnant Women 1 and 2 were 31 and 26 weeks, respectively. Notably, pregnant Women 1 and 2 and Infant 3 had hepatitis C virus (HCV) RNA levels of 139 000, 198 000, and 8 450 000 IU/ml; alanine aminotransferase levels of 420, 781, and 220 U/L; and received sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and sofosbuvir/ledipasvir for 12 weeks, respectively. All three patients were safely cured with favorable tolerance, and two newborns were both breastfeeding and were consistently negative for the anti-HCV antibody during the 1-year follow-up after birth. Additionally, two newborns and Infant 3 had normal growth parameters during the follow-up year one. In conclusion, this case series study found that sofosbuvir-based therapy for pregnant women and infants with severe CHC is safe and effective. The data may fill the gap and provide evidence of the use of sofosbuvir-based therapy as a reference when similar severe CHC situations are encountered during clinical practice.

Unveiling the Mechanism of Frictional Catalysis in Water by Bi12TiO20: A Charge Transfer and Contaminant Decomposition Path Study.

Tribocatalysis, as a new approach in environmental purification, has drawn increasing attention in the past few years. In this work, we successfully convert mechanical energy to chemical energy by Bi12TiO20, which was synthesized by a hydrothermal method. Under magnetic stirring, electrons transfer from the surface of Bi12TiO20 to the polytetrafluoroethylene-sealed magnetic bar due to their friction. Moreover, the holes that remain on Bi12TiO20 provide oxidation properties in the process for organic matter degradation. According to a series of tests, it is noticed that the shape of the stirring bar and the material of the reaction vessel have a remarkable influence on the removal efficiency of contaminants. Simultaneously, multiple tests reveal the high stability of Bi12TiO20. A great potential for Bi12TiO20 to control water pollutants under dark conditions during collection of ambient mechanical energy was clearly demonstrated in this study.

Self-collected versus medic-collected sampling for human papillomavirus testing among women in Lagos, Nigeria: a comparative study.

OBJECTIVE: To evaluate the feasibility and performance of self-collected vaginal swab samples for HPV screening among women in Lagos, Nigeria. METHODS: A cross-sectional study was implemented from March to August 2020 among sexually active women. Study participants provided same-day paired vaginal swab samples. Medic-sampling and poster-directed self-sampling methods were used to collect the two samples per participant. A real-time PCR assay detected HPV 16, HPV 18, other-high-risk (OHR) HPV, and the human ß-globin gene. The self-collected samples' sensitivity, specificity, and accuracy were determined against the medic-collected samples using the MedCalc Online Diagnostic Calculator. RESULTS: Of the 213 women aged 16 ~ 63-year-old recruited, 187 (88%) participants had concordant results, while 26 (12%) participants had discordant results. Among the 187 concordant results, 35 (19%) were HPV positive, 150 (80%) participants were HPV negative, and two (1%) were invalid. 18 (69%) out of the 26 discordant samples were invalid. The self-collected sample was invalid for 14 (54%) participants. Two (8%) medic-collected samples were invalid. Compared to the medic-collected sample, the self-collected sample was 89.80% (95% CI: 77.77 ~ 96.60%) sensitive and 98.21% (95% CI: 94.87 ~ 99.63%) specific, with an accuracy of 96.31% (95% CI: 92.87 ~ 98.40%). The mean age for HPV positive and negative participants were 39 and 40, respectively, with an ANOVA p-value of 0.3932. The stratification of HPV infection by the age group was not statistically significant (P > 0.05). CONCLUSIONS: With high accuracy of 96%, self-collected sampling is adequate when tested with real-time PCR and may increase the uptake of HPV testing. Though more self-collected samples were invalid than medic-collected samples, most likely due to poor collection, they could be identified for repeat testing. Future implementation can avoid this error with improved guidance and awareness.

A Three-Dimensional Melamine Sponge Modified with MnOx Mixed Graphitic Carbon Nitride for Photothermal Catalysis of Formaldehyde.

Much attention has been paid to developing effective visible light catalytic technologies for VOC oxidation without requiring extra energy. In this paper, a series of sponge-based catalysts with rich three-dimensional porosity are synthesized by combining MnOx and graphitic carbon nitride (GCN) with commercial melamine sponges (MS) coated with polydopamine (PDA), demonstrating excellent photothermal catalytic performance for formaldehyde (HCHO). The three-dimensional porous framework of MS can provide a good surface for material modification and a reliable interface for gas-solid interaction. The grown layer of PDA framework not only increases the near-infrared wavelength absorption for improving the light-to-heat conversion of catalysts, but also brings excellent adhesion for the subsequent addition of MnOX and GCN. The efficient formaldehyde oxidation is attributed to the sufficient oxygen vacancies generated by co-loaded MnOX and GCN, which is conducive to the activation of more O2- in the oxidation process. As the surface temperature of catalyst rapidly increases to its maximum value at ca. 115 °C under visible light irradiation, the HCHO concentration drops from 160 ppm to 46 ppm within 20 min. The reaction mechanism is certified as a classical Mars-van Krevelen mechanism based on the photo-induced thermal catalysis process.

One Hundred Days of Coronavirus Disease 2019 Prevention and Control in China.

The epidemic of novel coronavirus disease was first reported in China in late December 2019 and was brought under control after some 2 months in China. However, it has become a global pandemic, and the number of cases and deaths continues to increase outside of China. We describe the emergence of the pandemic, detail the first 100 days of China's response as a phase 1 containment strategy followed by phase 2 containment, and briefly highlight areas of focus for the future. Specific, simple, and pragmatic strategies used in China for risk assessment, prioritization, and deployment of resources are described. Details of implementation, at different risk levels, of the traditional public health interventions are shared. Involvement of society in mounting a whole country response and challenges experienced with logistics and supply chains are described. Finally, the methods China is employing to cautiously restart social life and economic activity are outlined.

MicroRNA-29b regulates the radiosensitivity of esophageal squamous cell carcinoma by regulating the BTG2-mediated cell cycle.

BACKGROUND: Many patients with esophageal squamous cell carcinoma (ESCC) are inoperable due to old age or advanced stage; thus, radio- and chemotherapy are considered the standard treatments for these patients. However, due to the radiation resistance of tumor cells that may arise during radiotherapy, results are still not satisfactory. The authors' previous studies found that microRNA can affect radiosensitivity, and further microRNA research was conducted to improve the radiosensitivity of ESCC. METHODS: Cells were treated with silent miR-29b (si-miR-29b). Thereafter,proliferation, colony formation, cell cycle, and apoptosis were determined. The luciferase reporting assay was used to confirm the direct interaction between miR-29b and BTG2. Serum samples and clinical follow-up data of 75 elderly or advanced ESCC patients who could not tolerate surgery were collected. RESULTS: The expression level of miR-29 in ESCC serum was closely correlated to radiosensitivity (χ2 =8.36, p < 0.05) and correlated with overall survival (OS; hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.24-0.90). Function assays demonstrated that the number of cell clones increased after radiometry radiation, and the cell cycle was blocked in the G0/G1 phase (from 37.2 to 56.9%) in the si-miR-29b transfection group. Expression of BTG2 was upregulated and expression of cyclin D1 was downregulated (p < 0.05). Transfection of si-BTG2 can reverse this result and restore the expression level of cyclin D1 (p < 0.05). The target gene BTG2 of miR-29b was predicted using a bioinformatics tool and confirmed by dual-luciferase reporter assay. CONCLUSION: Silencing of miR-29b in ESCC cells can increase expression of BTG2 and decrease the level of intracellular cyclin D1, resulting in cell cycle arrest and accumulation in the G0/G1 phase. Because G0/G1-phase cells are insensitive to radiotherapy, the sensitivity of radiotherapy is reduced.

Calmodulin level is significantly increased in the cerebrospinal fluid of patients with sporadic Creutzfeldt-Jakob disease.

BACKGROUND AND PURPOSE: Human prion diseases (PrDs) are a group of fatal and transmissible neurodegenerative disorders that are diagnosed definitively in post mortem brains. Calmodulin (CaM) is a ubiquitous calcium-binding protein. Increased brain CaM level has been reported in prion-infected rodent models and some scrapie-infected cells. However, the putative alteration of CaM in cerebrospinal fluid (CSF) of human PrDs is uncertain. Here, we try to figure out the profiles of CSF CaM in sporadic Creutzfeldt-Jacob disease. METHODS: Cerebrospinal fluid samples of 40 Chinese patients with probable sporadic Creutzfeldt-Jacob disease (sCJD) and 40 cases without sCJD (non-PrDs) were recruited in this study. The presence of CaM in the CSF was assessed by Western blot, while total tau levels were measured using an enzyme-linked immunosorbent assay kit. In addition, the presence of CaM in another CSF panel consisting of 30 definite sCJD cases and 30 non-PrD cases was evaluated using CaM-specific Western blot analysis. RESULTS: Cerebrospinal fluid CaM positivity was observed in 28/40 cases of probable sCJD and in 9/40 non-PrD cases. The CSF tau levels in the probable sCJD cases were markedly higher than those in the non-PrD cases. Logistic regression established a significant correlation between CSF CaM signal and total CSF tau level. Similar results were observed in the panel of cases with definite sCJD: the rates of CSF CaM positivity in the definite sCJD cases and the non-PrD cases were 22/30 and 6/30, respectively. CONCLUSIONS: Although CSF CaM positivity might not be a sCJD-specific phenomenon, a significantly high rate of CaM-positive CSF in sCJD cases, especially in those with high CSF tau levels, rendered it a valuable diagnostic biomarker for sCJD.

Upregulation of TDRD1 Promotes the Sexual Maturation in Allotetraploids Hybridized from Red Crucian Carp (Carassius auratus Red var) (♀) and Common Carp (Cyprinus carpio L) (♂).

Allotetraploid hybrids of Red Crucian Carp (Carassius auratus red var, abbreviated as RCC) (♀) and common Carp (Cyprinus carpio L, abbreviated as CC) (♂) is a species produced by distant hybridization. In this study, SWATH mass spectrometry (SWATH-MS) was applied for quantitative proteomics profiling of gonad tissues of allotetraploids and their parents RCC (♀) and CC (♂). A total of 2338 unique proteins were identified in our proteomic profiling by SWATH-MS. Gene enrichment and network analysis based on differentially expressed proteins revealed some metabolic enzymes involved in gonad growth and development of allotetraploids. Especially, the upregulated gene TDRD1 (ratio = 2.59, p = 0.02) in allotetraploids plays a significant role in spermatogenesis, which could speed up the sexual maturation during the process of gonad growth and development. Protein-protein interaction and pathway analysis further suggested that TDRD1 served as a hub protein in metabolic-related pathways and networks. It could regulate gonad development via regulating metabolic pathways in a synergistic way with surrounding regulatory factors including CS, GPIA, PGK1, and IDH2. In addition, TDRD1 could directly regulate spermatogenesis in conjunction with PIWIL1, PIWIL2, and VASA. Quantitative proteomics integrated with network analysis explored the molecular mechanism in that TDRD1 regulated sexual maturation, development, and growth of allotetraploids in a synergetic way with metabolic genes and pathways.