Search

BackgroundPrevious studies showed the conflicting associations between circulating micronutrient levels and systemic lupus erythematosus (SLE). Therefore, we aimed to clarify the causal association between circulating micronutrient levels and the risk of SLE by two-sample Mendelian randomization (MR) analysis.Methods56 single nucleotide polymorphisms (SNPs) significantly associated with 14 circulating micronutrients (vitamin A, B6, B9, B12, C, D and E, phosphorus, calcium, magnesium, copper, iron, zinc, and selenium) in published genome-wide association studies (GWAS) were used as instrumental variables (IVs). And summary statistics related to SLE were obtained from the IEU OpenGWAS database. We used the MR Steiger test to estimate the possible causal direction between circulating micronutrients and SLE. In the MR analysis, inverse variance weighting (IVW) method and the Wald ratio was as the main methods., Moreover, the MR-Pleiotropy residuals and outliers method (MR-PRESSO), Cochrane’s Q-test, MR-Egger intercept method and leave-one-out analyses were applied as sensitivity analyses. Additionally, we conducted a retrospective analysis involving the 20,045 participants from the Third National Health and Nutritional Examination Survey (NHANES III). Weight variables were provided in the NHANES data files. Univariate and multivariate logistic regression analyses were performed to determine the associations between circulating micronutrients and SLE.ResultsThe MR estimates obtained from the IVW method revealed potential negative correlations between circulating calcium (OR: 0.06, 95% CI: 0.01–0.49, P = 0.009), iron levels (OR: 0.63, 95% CI: 0.43–0.92, P = 0.016) and the risk of SLE. The results remained robust, even under various pairs of sensitivity analyses. Our retrospective analysis demonstrated that the levels of vitamin D, serum total calcium, and serum iron were significantly lower in SLE patients (N = 40) when compared to the control group (N = 20,005). Multivariate logistic regression analysis further established that increased levels of vitamin D and serum total calcium served as protective factors against SLE.ConclusionOur results provided genetic evidence supporting the potential protective role of increasing circulating calcium in the risk of SLE. Maintaining adequate levels of calcium may help reduce the risk of SLE.

Abstract Background Staphylococcus aureus and its single or mixed biofilm infections seriously threaten global public health. Phage therapy, which uses active phage particles or phage-derived endolysins, has emerged as a promising alternative strategy to antibiotic treatment. However, high-efficient phage therapeutic regimens have yet to be established. Results In this study, we used an enrichment procedure to isolate phages against methicillin-resistant S. aureus (MRSA) XN108. We characterized phage SYL, a new member of the Kayvirus genus, Herelleviridae family. The phage endolysin LysSYL was expressed. LysSYL demonstrated stability under various conditions and exhibited a broader range of efficacy against staphylococcal strains than its parent phage (100% vs. 41.7%). Moreover, dynamic live/dead bacterial observation demonstrated that LysSYL could completely lyse MRSA USA300 within 10 min. Scan and transmission electron microscopy revealed evident bacterial cell perforation and deformation. In addition, LysSYL displayed strong eradication activity against single- and mixed-species biofilms associated with S. aureus. It also had the ability to kill bacterial persisters, and proved highly effective in eliminating persistent S. aureus when combined with vancomycin. Furthermore, LysSYL protected BALB/c mice from lethal S. aureus infections. A single-dose treatment with 50 mg/kg of LysSYL resulted in a dramatic reduction in bacterial loads in the blood, liver, spleen, lungs, and kidneys of a peritonitis mouse model, which resulted in rescuing 100% of mice challenged with 108 colony forming units of S. aureus USA300. Conclusions Overall, the data provided in this study highlight the strong therapeutic potential of endolysin LysSYL in combating staphylococcal infections, including mono- and mixed-species biofilms related to S. aureus.

Abstract Polyphenol oxidases (PPOs) are type-3 copper enzymes and are involved in many biological processes. However, the potential functions of PPOs in pollination are not fully understood. In this work, we have screened 13 PPO members in Nicotiana. tabacum (named NtPPO1-13, NtPPOs) to explore their characteristics and functions in pollination. The results show that NtPPOs are closely related to PPOs in Solanaceae and share conserved domains except NtPPO4. Generally, NtPPOs are diversely expressed in different tissues and are distributed in pistil and male gametes. Specifically, NtPPO9 and NtPPO10 are highly expressed in the pistil and mature anther. In addition, the expression levels and enzyme activities of NtPPOs are increased after N. tabacum self-pollination. Knockdown of NtPPOs would affect pollen growth after pollination, and the purines and flavonoid compounds are accumulated in self-pollinated pistil. Altogether, our findings demonstrate that NtPPOs potentially play a role in the pollen tube growth after pollination through purines and flavonoid compounds, and will provide new insights into the role of PPOs in plant reproduction.

Summary: MicroRNA (miRNA) sponges synergistically modulate physiological and pathological processes in the form of modules or clusters. Here, we present a protocol for inferring and analyzing miRNA sponge modules in heterogeneous data using the R package miRSM 2.0. We describe steps for identifying gene modules, inferring miRNA sponge modules at multi-sample and single-sample levels, and performing modular analysis. From the perspective of computational biology, miRSM 2.0 has the potential to advance our understanding of the role of miRNA sponges in diseases.For complete details on the use and execution of this protocol, please refer to Zhang et al.1,2,3 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

In the early stage of pipeline network reform in China, it is still controversial to formulate an appropriate pipeline freight pricing strategy. Focusing on this issue, this paper puts forward an integrated framework to analyze the impact of different pipeline pricing strategies on the economic-environmental benefits of China’s oil product logistics. A basic mathematical programming model is developed to simulate the planning of nationwide oil product logistics at the tactical level. On this basis, five pipeline pricing strategies are customized for comparative analysis, including pricing as usual (PAU), pricing by benchmarking railway (PBR), pricing by discounting on excess (PDE), tiered pricing by mileage (TPM), and tiered pricing by volume (TPV). Then, the basic logistics optimization model is upgraded accordingly. The real-world case study in China in 2019 is carried out in detail and the results demonstrate that (i) Except for TPM, the other pricing strategies can achieve coordination between oil shippers and pipeline carriers compared with PAU; (ii) Ranked by economic performance as follows: PDE >PBT>TPV> PAU>TPM; (iii) As for PDE, it also helps to reduce carbon emissions by 0.5% annually. The proposed method can be a theoretical guide for oil and gas logistics managers and decision-makers within and beyond China.

Abstract Limited studies have been conducted on Chinese women's willingness to donate milk following perinatal loss. In this study, we explore the relationship among childbirth trauma, willingness to donate milk, and resilience in women following perinatal loss, and the mediating effect of resilience between childbirth trauma and willingness to donate milk. A cross‐sectional study was carried out throughout 4 months. We used convenience sampling methods and recruited 241 women following a perinatal loss from eight tertiary hospitals in Sichuan Province, China. Participants completed four questionnaires during a face‐to‐face individual interview: the general information questionnaire, the Willingness to Donate Milk Scale (WMDS), the City Birth Trauma Scale, and the Brief Resilience Scale. SPSS 20.0 was used to analyze the collected data. In our study, childbirth trauma was negatively correlated with the total and each dimension score of WMDS (p

ObjectiveTo assess whether the administration of Zishen Yutai Pill (ZYP) could improve the pregnancy outcomes in different subgroups of women undergoing fresh embryo transfer cycles.Materials and methodsThis is a post hoc analysis of a large scale, placebo-controlled, double blind, randomized clinical trial (RCT) regarding the use of ZYP during assisted reproductive technology (ART) treatment. The RCT was conducted at 19 in vitro fertilization (IVF) centers between April 2014 and June 2017. A total of 2265 women undergoing fresh embryo transfer cycles were randomly assigned in a 1:1 ratio to receive ZYP (n = 1131) or placebo (n = 1134). Post hoc logistic regression analyses were applied in this study to examine the between-group differences of ZYP and placebo on clinical pregnancy rate among different subgroups. Detailed analyses, both in intention-to-treat (ITT) and per-protocol population, were also conducted in specific subgroups with regards to rates of implantation, biochemical pregnancy, clinical pregnancy, live birth, pregnancy loss, as well as other neonatal indices.ResultsZYP showed a significantly higher clinical pregnancy rates than placebo in the ITT population. Detailed subgroup analyses were conducted in subgroup in advanced maternal age (AMA, ≥ 35 years old) and overweight/obese patients (BMI > 24), due to the clinical importance and statistical results. In these subgroups, baseline characteristics were similar between two arms (all P > 0.05). Significantly elevated clinical pregnancy rates were observed in ZYP cohort (both P < 0.05) compared with the placebo group. Results also showed that ZYP treatment resulted in significantly higher rates of implantation, biochemical pregnancy in AMA or overweight/obese patients in ITT analysis (all P < 0.05).ConclusionsThe current post hoc subgroup analysis suggested that AMA and overweight/obese women could experience clinical benefits when treated with ZYP in their fresh embryo transfer cycles. The study provides references for the use of ZYP in ART practices. However, further studies in specific subgroups should be examined in more rigorous clinical trial settings.Clinical trial registrationChictr.org.cn, ChictrTRC-14004494.

Non-coding RNAs (ncRNAs) act as important modulators of gene expression and they have been confirmed to play critical roles in the physiology and development of malignant tumors. Understanding the synergism of multiple ncRNAs in competing endogenous RNA (ceRNA) regulation can provide important insights into the mechanisms of malignant tumors caused by ncRNA regulation. In this work, we present a framework, SCOM, for identifying ncRNA synergistic competition. We systematically construct the landscape of ncRNA synergistic competition across 31 malignant tumors, and reveal that malignant tumors tend to share hub ncRNAs rather than the ncRNA interactions involved in the synergistic competition. In addition, the synergistic competition ncRNAs (i.e. ncRNAs involved in the synergistic competition) are likely to be involved in drug resistance, contribute to distinguishing molecular subtypes of malignant tumors, and participate in immune regulation. Furthermore, SCOM can help to infer ncRNA synergistic competition across malignant tumors and uncover potential diagnostic and prognostic biomarkers of malignant tumors. Altogether, the SCOM framework (https://github.com/zhangjunpeng411/SCOM/) and the resulting web-based database SCOMdb (https://comblab.cn/SCOMdb/) serve as a useful resource for exploring ncRNA regulation and to accelerate the identification of carcinogenic biomarkers.

Abstract Background The CRISPR-Cas13 system is an RNA-guided RNA-targeting system and has been widely used in transcriptome engineering with potentially important clinical applications. However, it is still controversial whether Cas13 exhibits collateral activity in mammalian cells. Results Here, we find that knocking down gene expression using RfxCas13d in the adult brain neurons caused death of mice, which may result from the collateral activity of RfxCas13d rather than the loss of target gene function or off-target effects. Mechanistically, we show that RfxCas13d exhibits collateral activity in mammalian cells, which is positively correlated with the abundance of target RNA. The collateral activity of RfxCas13d could cleave 28s rRNA into two fragments, leading to translation attenuation and activation of the ZAKα-JNK/p38-immediate early gene pathway. Conclusions These findings provide new mechanistic insights into the collateral activity of RfxCas13d in mammalian cells and warn that the biosafety of the CRISPR-Cas13 system needs further evaluation before application to clinical treatments.

In this paper, we study a free boundary problem for vascularized tumor growth with a time delay in the process of tumor regulating apoptosis. The characteristic of this model is that both vascularization and apoptosis regulation is considered. In mathematical form, this model is expressed as a free boundary problem with Robin boundary. We prove the existence and uniqueness of the global solution and their asymptotic behavior. The effects of vascularization parameters and apoptosis regulation parameters on tumor are discussed. Depending on the importance of regulating the apoptosis rate, the tumor will tend to the unique steady state or eventually disappear. For some parameter values, the final results show that the dynamic behavior of the solutions of our model is analogous to the quasi-stationary solutions. Our results are also verified by numerical simulation.

The citrate industry has a wide range of applications in food, pharmaceutical, and other fields. As a common class of food additives and functional supplements with tremendous development potential and strong core competitiveness, particles with good powder characteristics and functionalization are becoming one of the primary directions in the evolution of citrate into the high-end market. This article reviews the primary citrate crystallization techniques and examines the fundamental citrate crystallization mechanisms by describing citrate nucleation and growth during the industrial crystallization process. A variety of citrate hydrates are also summarized. The primary control conditions of the three essential product indices of purity, particle size, and grain shape are established. The need to take into account the density, fluidity, caking resistance, dissolution rate, suspension, bioavailability, and other indices of products is highlighted, along with applications for products that meet the purity and particle size requirements. While summarizing industrial citrate crystallization equipment, this paper also discusses the beneficial effect of continuous crystallization in achieving industrialization. Finally, the future development of citrate crystals is anticipated, and it is suggested that the combination of basic research and application research should be strengthened to explore the new application field of citrate crystals, and the automation and intelligence of the crystal preparation process should be realized as far as possible.

BackgroundThis study aimed to present the psychometric properties (dimensionality, reliability, and invariance) of the Chinese 14-Item Resilience Scale (RS-14) within Chinese register nurses (RNs) with less than 3 years work experiences. And we aimed to compare the fit of a unidimensional model and a bifactor model.Materials and methodsThis multicenter cross-sectional survey was conducted from August to September in 2019. A total of 7,231 registered nurses from 90 hospitals were recruited. Data was anonymously obtained through online questionnaires. Both reliability and validity of Chinese RS-14 were assessed. The confirmatory factor analyses (CFA) were used to compare the fit of two different factor structures of the RS-14 (unidimensional model vs. a bifactor model). Moreover, multigroup CFA (MGCFA) were applied to evaluate the measurement invariance (MI) across sociodemographic parameters (gender, educational level, marital status, and et al.).DesignCross-sectional quantitative analyses.ResultsOur study confirmed that the bifactor model presented the best fit within Chinese nurses (CFI = 0.924, TLI = 0.909, RMSEA = 0.095, SRMR = 0.043), and found strong factorial invariance across gender, marital status, and status of receiving standardized training. The reliability of RS-14 was high with a Cronbach’s alpha coefficient of 0.939. Moreover, RS-14 was positively correlated with the social support and was negatively correlated with workplace bullying.ConclusionThis is the first study to explore the latent factor structure for the RS-14 among Chinese RNs and evaluated MI across a series of sociodemographic variables. Based on our findings, the Chinese version RS-14 is both valid and reliable.

Cardiac pressure overload is a crucial risk factor for cardiac hypertrophy and heart failure. Our previous study showed that depletion of the β3-adrenergic receptor (ADRB3) induced left ventricular diastolic dysfunction via potential regulation of energy metabolism and cardiac contraction. However, the effects of ADRB3 on pressure overload-induced heart failure remain unclear. In the present study, systemic ADRB3-knockout mice suffering from transverse aortic constriction (TAC) surgery were used to identify the effects of ADRB3 on pressure overload-induced heart failure. Compared to wild-type mice, ADRB3 depletion significantly improved the left ventricular ejection fraction, reduced left ventricular posterior wall thickness and interventricular septum thickness, and decreased the area of cardiomyocytes after TAC. RNA sequencing and bioinformatics analysis showed that ADRB3 depletion up-regulated 275 mRNAs and down-regulated 105 mRNAs in mice suffering TAC surgery. GO analysis, GO-tree analysis, and GSEA showed that ADRB3 depletion mainly enhanced the innate immune response of hearts in cardiac pressure overload mice. In addition, pathway analysis and Pathway-Act analysis presented that innate immune response-related pathways, including RIG-I-like receptor signaling pathway, antigen processing and presentation, Toll-like receptor signaling pathway, and cell adhesion molecules, were significantly enriched in ADRB3-KO-TAC mice. Ten hub genes were identified using protein-protein interaction network, MCODE, and cytoHubba analysis. Furthermore, the depletion and activation of ADRB3 validated the effects of ADRB3 on the innate immune response of hearts after TAC. In conclusion, ADRB3 depletion relieves pressure overload-induced cardiac hypertrophy and heart failure, and these effects could be explained by the enhancement of innate immune response.

For figuring out the stress interference of multiphase fracture combinations and its effect on the fracture initiation pressure of subsequent hydraulic fracturing, a calculation model for the coupled stress field with multiple induced fractures preexisted was established based on the calculation model for the stress field with single induced fracture preexisted, and the change laws of circumferential stress field around the wellbore under the effect of induced stress were analyzed. Then, the fracture initiation pressure of subsequent hydraulic fracturing was calculated according to the fracturing mechanics criterion. Finally, the effects of the length, phase, horizontal principal stress difference coefficient and quantity of preexisting fractures on its initiation pressure were analyzed. And the following research results were obtained. First, the circumferential stress difference in the area near the fractures behind the preexisting fractures increase greatly and even the horizontal principal stress is reversed. Second, as the length of new preexisting fractures increases, the initiation pressure of initial preexisting fractures rises first and then drops. And when the length of new preexisting fractures is equal to that of the initial preexisting fractures, the initiation pressure of initial preexisting fractures drops quickly first and then slowly. Third, the initiation pressure of high phase fractures is lower than that of low phase fractures. Fourth, with the increase of fracture quantity, the initiation pressure of new preexisting fractures drops gradually, but the decline trend of initiation pressure difference is not obvious. Fifth, the stress interference of multiphase fractures influences the fracture initiation pressure, and high-phase long fractures and low-phase short fractures are both favorable for the simultaneous initiation of multiphase fractures. Sixth, synchronous propagation of multiple fractures can generate more complicated stress interference and excite the evolution of hydraulic fracture network, so as to realize uniform fracturing stimulation. In conclusion, the research results can provide a theoretical guidance for the design of fracturing operation, e.g. perforation phase of blasting induced fracturing, scale of induced fractures, and pump pressure of subsequent hydraulic fracturing. Keywords: High horizontal ground stress difference, Blasting induced hydraulic fracturing, Distribution of induced stress, Initiation pressure of multi-fractures, Complex fracture network, Design of fracturing operation

The complexity of metabolites in traditional Chinese medicine (TCM) hinders the comprehensive profiling and accurate identification of metabolites. In this study, an approach that integrates enhanced column separation, mass spectrometry post-processing and result verification was proposed and applied in the identification of flavonoids in Dalbergia odorifera. Firstly, column chromatography fractionation, followed by liquid chromatography–tandem mass spectrometry was used for systematic separation and detection. Secondly, a three-level data post-processing method was applied to the identification of flavonoids. Finally, fragmentation rules were used to verify the flavonoid compounds. As a result, a total of 197 flavonoids were characterized in D. odorifera, among which seven compounds were unambiguously identified in level 1, 80 compounds were tentatively identified by MS-DIAL and Compound Discoverer in level 2a, 95 compounds were annotated by Compound discoverer and Peogenesis QI in level 2b, and 15 compounds were exclusively annotated by using SIRIUS software in level 3. This study provides an approach for the rapid and efficient identification of the majority of components in herbal medicines.

Clay minerals are usually regarded as an important factor affecting the results of low salinity water (LSW) flooding. However, experiments on clay minerals are mainly in qualitative stage, the mechanism of clay minerals has not been studied completely. In this paper, Zeta potential of four kinds of clay minerals (montmorillonite; chlorite; illite; kaolinite) in different brine was measured, microscopic models of these clay minerals were made to measured wetting angle in different brine, and montmorillonite and kaolinite were chosen to conduct microscopic displacement experiments through customized micro-glass etching models. From experiment results, the following conclusions can be get: 1). With the decrease of salinity of injected water, the negative zeta potential of clay minerals increases and the wetting angle decreases. 2). Clay minerals are more sensitive to monovalent Na+ than bivalent Ca2+. 3). The results of microscopic experiments show that LSW can effectively improve oil recovery, whether kaolinite or montmorillonite. The recovery of montmorillonite is better with a relatively high salinity of LSW and kaolinite is better with a relatively low salinity of LSW. The mechanism of LSW improves kaolinite recovery factor is the change of wettability while that of montmorillonite is the increase of water phase wettability. However, a lot of droplet-like residual oil cannot be displaced in the montmorillonite throat. In filed production, both kaolinite-rich and montmorillonite-rich reservoirs are suitable for LSW flooding to improve oil recovery. However, for kaolinite reservoirs, a lower salinity of injected water would produce a better result, while for montmorillonite reservoirs, residual oil droplets in the throat are noteworthy.

Clay minerals are regarded as an important factor affecting the results of low salinity water (LSW) flooding. However, most researchers put great attention on their microscopic properties, only few of them investigated the influence of clay minerals by the sand pack flooding experiments. This paper quantifies the effects of clay minerals on LSW flooding with artificial sand pack samples. We used three kinds of sand pack samples (100% quartz sand; 90%/10% quartz sand/kaolinite or montmorillonite) and heavy oil in the LSW flooding experiments. For the samples made of montmorillonite, results show that there exists an optimal salinity range for the LSW flooding. The best salinity range of Na+ is between 1,000 mg/L and 5,000 mg/L, and Ca2+ is between 500 mg/L and 1,000 mg/L. As for kaolinite, a better result will be produced with lower salinity. In addition, using CaCl solution floods samples made of montmorillonite has a better result. A similar phenomenon was also observed when NaCl solution was used to flood kaolinite samples. Respect of flooding modes, the continuous injection of high-low salinity water is more effective, but the LSW flooding method is better considering the economy and time cost.

Ramsay Hunt syndrome involving the vagus nerve is very rare. We herein describe a 53-year-old man who developed severe pharyngeal pain after alcohol intoxication. Antibiotic treatment was ineffective. Laryngoscopy showed an ulcer on the right side of the epiglottis. As the condition progressed, the patient developed hoarseness. He then gradually developed multiple herpes lesions on the right side of the head, face, and neck along with right peripheral facial paralysis. Corticosteroid, analgesic, antiviral, and nutritional nerve therapy resulted in disappearance of the herpes lesions, epiglottis ulcer, pharyngeal pain, and right head and face pain. The facial paralysis slightly improved, but the hoarseness did not improve. The patient was discharged with an unsatisfactory outcome, and he attempted treatment with acupuncture. After 6 months, the right facial paralysis and hoarseness disappeared. Our case emphasizes the importance of early diagnosis and treatment of atypical Ramsay Hunt syndrome as well as timely communication, enhancement of trust, and reduction of disputes between doctors and patients.

Objective Bronchiectasis is a common chronic airway disease. We investigated the economic burden and associated factors of bronchiectasis in China. Methods In this multicenter retrospective cohort study, we reviewed medical records of patients admitted to 18 tertiary hospitals during 2010 to 2014 with a bronchiectasis-related diagnosis. Results A total 5469 patients with bronchiectasis were admitted, accounting for 3.13% ± 1.80% of all discharged patients with any diagnosis during the same period; 13 patients died upon discharge. The median hospitalization cost was RMB 8421.52 (RMB 5849.88–12,294.47). Risk factors associated with hospitalization costs included age at admission (>70 vs. 80 vs. 15 packs/year vs. non-smokers, OR = 1.127, 95% CI = 1.062–1.228), length of hospitalization (OR = 1.05, 95% CI = 1.046–1.054), combination antibiotic treatment (OR = 1.089, 95% CI = 1.033–1.148), cough (OR = 0.851, 95% CI = 0.751–0.965), dyspnea (OR = 0.93, 95% CI = 0.878–0.984), chronic obstructive pulmonary disease (OR = 0.935, 95% CI = 0.878–0.996), respiratory failure (OR = 0.923, 95% CI = 0.862–0.989), cor pulmonale (OR = 0.919, 95% CI = 0.859–0.982), and death (OR = 1.816, 95% CI = 1.113–2.838). Conclusions Age, smoking status, symptoms, and respiratory comorbidities were associated with hospitalization costs of bronchiectasis.

Background: China is experiencing severe ambient air pollution. However, few studies anywhere have examined the health effects of PM1 (particulate matter with aerodynamic diameter

In this paper, we study a time-delayed free boundary of tumor growth with Gibbs-Thomson relation in the presence of inhibitors. The model consists of two reaction diffusion equations and an ordinary differential equation. The reaction diffusion equations describe the nutrient and inhibitor diffusion within tumors and take into account the Gibbs-Thomson relation at the outer boundary of the tumor. The tumor radius evolution is described by the ordinary differential equation. It is assumed that the regulatory apoptosis process takes longer than the natural apoptosis and proliferation processes. We first show the existence and uniqueness of the solution to the model. Next, we further demonstrate the existence of the stationary solutions and the asymptotic behavior of the stationary solutions when the blood vessel density is a constant. Finally, we further demonstrate the existence of the stationary solutions and the asymptotic behavior of the stationary solutions when the blood vessel density is bounded. The result implies that, under certain conditions, the tumor will probably become dormant or will finally disappear. The conclusions are illustrated by numerical computations. [ABSTRACT FROM AUTHOR]