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Background: LXYL-P1-2 is the first reported glycoside hydrolase that can catalyze the transformation of 7-β-xylosyl-10-deacetyltaxol (XDT) to 10-deacetyltaxol (DT) by removing the d-xylosyl group at the C-7 position. Successful synthesis of paclitaxel by one-pot method combining the LXYL-P1-2 and 10-deacetylbaccatin III-10-β-O-acetyltransferase (DBAT) using XDT as a precursor, making LXYL-P1-2 a highly promising enzyme for the industrial production of paclitaxel. The aim of this study was to investigate the catalytic potential of LXYL-P1-2 stabilized on magnetic nanoparticles, the surface of which was modified by Ni2+-immobilized cross-linked Fe3O4@Histidine. Results: The diameter of matrix was 20–40 nm. The Km value of the immobilized LXYL-P1-2 catalyzing XDT (0.145 mM) was lower than that of the free enzyme (0.452 mM), and the kcat/Km value of immobilized enzyme (12.952 mM s−1) was higher than the free form (8.622 mM s−1). The immobilized form maintained 50% of its original activity after 15 cycles of reuse. In addition, the stability of immobilized LXYL-P1-2, maintained 84.67% of its initial activity, improved in comparison with free form after 30 d storage at 4°C. Conclusions: This investigation not only provides an effective procedure for biocatalytic production of DT, but also gives an insight into the application of magnetic material immobilization technology. How to cite: Zou S, Chen TJ, Li DY, et al. LXYL-P1-2 immobilized on magnetic nanoparticles and its potential application in paclitaxel production. Electron J Biotechnol 2021;50.https://doi.org/10.1016/j.ejbt.2020.12.005

Abstract This study aims to verify the time-variant feature of American ginseng (AG) continuous cropping obstacles and to explore the factors impeding continuous cropping. We verified the feature with a plant-soil feedback pot experiment and then investigated the factors by comparing the properties of control soils that had not been previously used for growing ginseng (CS) with those of soils with a 10-year-crop-rotation cycle following the growth of AG (RS). It’s found that the survival rate of AG in RS was lower than that in CS. The RS had lower pH, available potassium content, and urease activity. Additionally, p-coumaric, p-hydroxybenzoic, vanillic, caffeic, and cinnamic acid levels were lower in RS than in CS, but salicylic acid levels showed the opposite pattern. RS had higher Rhodanobacter and lower Acidothermus, Sphingomonas relative abundances in bacterial community. It’s also found that many bacteria were substantially correlated with phenolic acids and soil physiochemical properties. Results indicate that even after 10-year crop rotation, the negative effects of prior continuous cropping of AG has not been eliminated. The growth of AG can be affected negatively with deterioration of soil physicochemical properties and with lower levels of phenolic acids which promote pathogen reproduction. Probiotics reduction also weighs. Moreover, biotic factors are interrelated with abiotic ones. Therefore, it can be inferred that the comprehensive change of soil properties is the main obstacle for continuous cropping.

Evidence of active tuberculosis (ATB) in patients with rheumatic diseases are research priorities but limited data from China have been reported. Research targeting patients not taking anti-TNF biologics are especially insufficient. We aimed to investigate the prevalence and risk factors of ATB in this at-risk population. We conducted a tertiary hospital-based, multi-center, cross-sectional study by using stratified multi-stage cluster sampling strategy to screen ATB in patients with rheumatic diseases. We estimated the prevalence of ATB in patients with rheumatic diseases and identified risk factors among those who were not taking anti-TNF biologic. A total of 13,550 eligible patients were enrolled, and the result showed the standardized prevalence of ATB according to the composition ratio of various types of rheumatic disease was 882/100000 (95% confidence interval (CI): 706-1057). Multivariable logistic regression analysis in patients not taking anti-TNF biologics showed that the independent risk factors of ATB were having systemic lupus erythematosus (SLE) (OR=2.722, 95% CI: 1.437-5.159, p=0.002), having Behcet’s disease (BD) (OR= 5.261, 95% CI: 2.071-13.365, p

The Journal of Clinical Medicine retracts the article entitled “Cardiovascular Disease and Exercise: From Molecular Mechanisms to Clinical Applications” [...]

Nanozymes are nanomaterials with enzyme-like activity, possessing the unique properties of nanomaterials and natural enzyme-like catalytic functions. Nanozymes are catalytically active, stable, tunable, recyclable, and versatile. Therefore, increasing attention has been paid in the fields of environmental science and life sciences. In this review, we focused on the most recent applications of nanozymes for environmental monitoring, environmental management, and environmental protection. We firstly introduce the tuning catalytic activity of nanozymes according to some crucial factors such as size and shape, composition and doping, and surface coating. Then, the application of nanozymes in environmental fields are introduced in detail. Nanozymes can not only be used to detect inorganic ions, molecules, organics, and foodborne pathogenic bacteria but are also involved in the degradation of phenolic compounds, dyes, and antibiotics. The capability of nanozymes was also reported for assisting air purification, constructing biofuel cells, and application in marine antibacterial fouling removal. Finally, the current challenges and future trends of nanozymes toward environmental fields are proposed and discussed.

Strain preservation to maintain stable vitality and the recombinant enzyme activity plays a crucial role in industrial fermentation. A Pichia pastoris strain is routinely stored at −80 °C in a glycerol vial and activated on an antibiotic-containing YPD agar plate before being used for fermentation. Alternatively, the activated strain should be preserved in the agar slant at 2~4 °C (low-temperature storage) for a short period before use. To maximize the utilization of the low-temperature storage for fermentation, we evaluated this method by observing the capacity of both the vitality and the recombinant enzyme activity of the strain at different preservation durations. We found that engineered yeast could be preserved by low-temperature storage for at least 30 months without losing its vitality and biomass enzyme activity by the end of fermentation and could be directly used for the seed cultivation of fermentation, which is more time-saving than strain recovery from −80 °C in a glycerol vial. Moreover, the antibiotic added to the agar slant could be omitted if the heterologous gene was integrated into the host chromosome. Our approach may greatly elevate the production efficiency of the strain.

The stability of diamond/aluminum composite is of significant importance for its extensive application. In this paper, the interface of diamond/aluminum composite was modified by adding nanoscale W coating on diamond surface. We evaluated the corrosion rate of nanoscale W-coated and uncoated diamond/aluminum composite by a full immersion test and polarization curve test and clarified the corrosion products and corrosion mechanism of the composite. The introduction of W nanoscale coating effectively reduces the corrosion rate of the diamond/aluminum composite. After corrosion, the bending strength and thermal conductivity of the nanoscale W-coated diamond/aluminum composite are considerably higher than those of the uncoated diamond/aluminum composite. The corrosion loss of the material is mainly related to the hydrolysis of the interface product Al4C3, accompanied by the corrosion of the matrix aluminum. Our work provides guidance for improving the life of electronic devices in corrosive environments.

A field experiment lasting 37 years was conducted to evaluate the applications of different rates of pig manure and mineral fertilisers alone or in combination impacts on total phosphorus (Ptotal) and Olsen phosphorus (POlsen) contents and phosphorus activity coefficient (PAC, percentage of POlsen to Ptotal) within soil water-stable aggregates (WSA) in a Mollisol of Northeast China. The contents of Ptotal and POlsen associated with different size classes of WSA significantly (P < 0.05) increased with an increasing rate of applied P. The application of manure alone or combined with mineral fertilisers significantly increased PAC value associated with different size classes of WSA. There were positive correlations between Ptotal and POlsen contents with soil organic carbon (SOC) content within soil WSA. As SOC content increased 1 g/kg, Ptotal and POlsen contents increased 0.06-0.10 g/kg and 7.69-22.2 mg/kg, respectively, and the increase was larger in smaller size classes of WSA. The results suggested that a high manure rate combined with mineral fertilisers is more beneficial for increasing soil phosphorus content and availability. SOC is a vital factor controlling phosphorus content and availability within soil WSA.

Abstract No current in vitro tumor model replicates a tumor’s in vivo microenvironment. A culturing technique that better preserves a tumor’s pathophysiological conditions is needed for some important clinical applications, including personalized drug-sensitivity/resistance assays. In this study, we utilized autologous serum or body fluid to build a 3D scaffold and grow a patient’s tumor. We named this technique “3D-ACM” (autologous culture method). Forty-five clinical samples from biopsies, surgically removed tumor tissues and malignant body fluids were cultured with 3D-ACM. Traditional 3D-FBS (fetal bovine serum) cultures were performed side-by-side for comparison. The results were that cells cultured in 3D-ACM rebuilt tissue-like structures, and retained their immuno-phenotypes and cytokine productions. In contrast, the 3D-FBS method promoted mesenchymal cell proliferation. In preliminary chemo drug-sensitivity assays, significantly higher mortality was always associated with FBS-cultured cells. Accordingly, 3D-ACM appears to more reliably preserve a tumor’s biological characteristics, which might improve the accuracy of drug-testing for personalized cancer treatment.

Abstract Background One-stop occlusion, which is defined as the combination of atrial septal defect [ASD] or patent foramen ovale [PFO] occlusion and left atrial appendage [LAA] closure, in patients with ASD/PFO and atrial fibrillation (AF) has not yet been investigated systematically. This study aimed to evaluate the safety and efficacy of one-stop occlusion in the treatment of adult patients with ASD/PFO and AF. Methods Inpatients with AF and ASD/PFO were recruited between August 2014 and April 2019. Preoperatively, transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) were conducted to identify the ASD/PFO size and margin, presence of thrombus in the LAA, and LAA orifice width and depth at 0°, 45°, 90°, and 135°. After confirmation of the indications of LAA closure (LAAC) and ASD/PFO occlusion, the procedures were performed simultaneously under general anesthesia. Oral anticoagulants were administered for 45–60 days, followed with regular evaluation of TTE and TEE. Results Forty-nine patients (age, 65.6 ± 9.6 years) were recruited in this study, including 24 patients with ASD and 25 patients with PFO. They were treated with LAAC and ASD/PFO occlusion successfully. The mean ASD size and mean diameter of the ASD occluders were 14.2 ± 7.7 and 25.4 ± 8.5 mm, respectively. The mean PFO size was 3.5 ± 0.4 mm. The mean maximal LAA orifice width and depth were 20.5 ± 3.4 and 28.3 ± 3.6 mm, respectively. All patients were implanted with a Watchman device (diameter, 27.1 ± 2.9 mm). Postoperatively, all patients took anticoagulants orally for 45–60 days, and their mean postoperative follow-up duration was 29.0 ± 12.1 months. Postoperative TEE showed that all had normal positioning of the LAA and ASD/PFO occluders. At 45–60 days after operation, TEE showed that the LAA and ASD/PFO occluder were in the normal position; however, two patients who took warfarin and novel oral anticoagulants, respectively, have developed occluder thrombosis. After adjusted anticoagulant therapy, TEE showed that the thrombus disappeared at 6 months after operation. Conclusion One-stop occlusion is safe and effective for the treatment of adult patients with ASD/PFO and AF. It is also feasible to administer warfarin or novel oral anticoagulants after operation.

Mitochondria are well known as the centre of energy metabolism in eukaryotic cells. However, they can not only generate ATP through the tricarboxylic acid cycle and oxidative phosphorylation but also control the mode of cell death through various mechanisms, especially regulated cell death (RCD), such as apoptosis, mitophagy, NETosis, pyroptosis, necroptosis, entosis, parthanatos, ferroptosis, alkaliptosis, autosis, clockophagy and oxeiptosis. These mitochondria-associated modes of cell death can lead to a variety of diseases. During cell growth, these modes of cell death are programmed, meaning that they can be induced or predicted. Mitochondria-based treatments have been shown to be effective in many trials. Therefore, mitochondria have great potential for the treatment of many diseases. In this review, we discuss how mitochondria are involved in modes of cell death, as well as basic research and the latest clinical progress in related fields. We also detail a variety of organ system diseases related to mitochondria, including nervous system diseases, cardiovascular diseases, digestive system diseases, respiratory diseases, endocrine diseases, urinary system diseases and cancer. We highlight the role that mitochondria play in these diseases and suggest possible therapeutic directions as well as pressing issues that need to be addressed today. Because of the key role of mitochondria in cell death, a comprehensive understanding of mitochondria can help provide more effective strategies for clinical treatment.

BackgroundIntrauterine devices (IUDs) are commonly used as a contraceptive method. IUD migration and colon perforation are rare but serious complications occurring sometimes years after insertion.CaseA 42-year-old woman with complaints of slight abdominal pain underwent a colonoscopy. Colonoscopy showed that a “nail” had penetrated the ascending colon wall and that an arm of the “nail” was embedded in the colon wall. We did not remove the “nail” rashly under colonoscopy. Considering the safety and effectiveness of the patient's operation, we were able to remove the “nail” easily by performing laparoscopic-endoscopic cooperative surgery (LECS) combined with hysteroscopy at the same time.ConclusionWe report a case of successful removal of a colonic perforation device by colonoscopy, laparoscopy, and hysteroscopy, which is the first method used.

Hematopoietic stem cells (HSC) give rise to the cells of the blood system over the whole lifespan. N6-methyladenosine (m6A), the most prevalent RNA modification, modulates gene expression via the processes of “writing” and “reading”. Recent studies showed that m6A “writer” genes (Mettl3 and Mettl14) play an essential role in HSC. However, which reader deciphers the m6A modification to modulate HSC remains unknown. In this study, we observed that dysfunction of Ythdf3 and Ccnd1 severely impaired the reconstitution capacity of HSC, which phenocopies Mettl3-deficient HSC. Dysfunction of Ythdf3 and Mettl3 results in a translational defect of Ccnd1. Ythdf3 and Mettl3 regulate HSC by transmitting m6A RNA methylation on the 5’ untranslated region of Ccnd1. Enforced Ccnd1 expression completely rescued the defect of Ythdf3-/- HSC and partially rescued Mettl3-compromised HSC. Taken together, this study identified, for the first time, that Ccnd1 is the target of METTL3 and YTHDF3 to transmit the m6A RNA methylation signal and thereby regulate the reconstitution capacity of HSC.

ObjectivesThis study aimed at assessing the association between maternal methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) gene polymorphisms, maternal dietary habits, and their interactions with the risk of ventricular septal defects (VSD) in offspring.MethodsFrom November 2017 to March 2019, a case-control study comprising 360 mothers of VSD cases and 504 mothers of healthy infants was conducted in Han Chinese populations. The main exposures of interest were maternal dietary habits in early pregnancy and MTHFD1 gene polymorphisms. Logistic regression models were used to estimate the main effects and interaction effects.ResultsIt was observed that maternal excessive intake of pickled vegetables (aOR = 1.85, 95%CI: 1.45–2.37), smoked foods (aOR = 1.93, 95%CI: 1.48–2.51), barbecued foods (aOR = 1.74, 95%CI: 1.28–2.36), and fried foods (aOR = 1.68, 95%CI: 1.30–2.17) were associated with a higher risk of VSD in offspring, whereas maternal excessive intake of fresh meat (aOR = 0.61, 95%CI: 0.47–0.79), fish and shrimp (aOR = 0.29, 95%CI: 0.23–0.38), fresh eggs (aOR = 0.54, 95%CI: 0.42–0.70), fresh fruits or vegetables (aOR = 0.44, 95%CI: 0.33–0.60), soy foods (aOR = 0.65, 95%CI: 0.53–0.80), and milk products (aOR = 0.49, 95%CI: 0.40–0.59) could contribute significantly to a lower risk of VSD in offspring. Furthermore, the genetic polymorphisms of maternal MTHFD1 gene at rs1950902 (GA vs. GG: aOR = 0.67, 95%CI: 0.50–0.90) and rs2236222 (GG vs. AA: aOR = 2.75, 95%CI: 1.57–4.83) were significantly associated with the risk of VSD in offspring. In addition, there was a significant interaction effect between maternal dietary habits and MTHFD1 gene polymorphisms on the risk of VSD.ConclusionsMaternal dietary factors, MTHFD1 genetic polymorphisms, and their interactions were all associated with the risk of VSD in offspring. However, further research in diverse ethnic populations and with a larger sample size is warranted to corroborate our findings.Trial RegistrationRegistered in Chinese Clinical Trial Registry Center; registration number, ChiCTR1800016635; registration date, 06/14/2018 (Retrospectively registered); URL of trial registry record, https://www.chictr.org.cn/showproj.aspx?proj=28300.

Objectives. The purpose of this study was to explore the effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on urine albumin to creatinine ratio (UACR) in type 2 diabetes mellitus (T2DM) patients and to recommend appropriate medication care scheme. Methods. 8371 T2DM patients from four dapagliflozin studies and two canagliflozin studies were collected for analyzing with nonlinear mixed effect model (NONMEM). The change rates of UACR from baseline were intended to be evaluation indicators. Results. In the present study, there was no significant difference in the effects on UACR using dapagliflozin or canagliflozin treatment in T2DM patients. The maximal effect (Emax) and the treatment duration of reaching half of Emax (ET50) from SGLT-2 inhibitors on UACR in T2DM patients were -19.2% and 0.448 weeks, respectively. Further, the treatment duration to reach 25%, 50%, 75%, and 80% Emax was 0.150 weeks, 0.448 weeks, 1.344 weeks, and 1.792 weeks, respectively. Namely, for achieving the plateau period (80% of Emax) of SGLT-2 inhibitors on UACR in T2DM patients, 10 mg/day dapagliflozin (or 100 mg/day canagliflozin) should be taken for at least 1.792 weeks. Conclusions. To our knowledge, the present study explored the effects of SGLT-2 inhibitors on UACR in T2DM patients, meanwhile, recommended appropriate medication care scheme for the first time.

Stem cells possess regenerative powers and multidirectional differentiation potential and play an important role in disease treatment and basic medical research. Urine-derived stem cells (USCs) represent a newly discovered type of stem cell with biological characteristics similar to those of mesenchymal stromal cells (MSCs), including their doubling time and immunophenotype. USCs are noninvasive and can be readily obtained from voided urine and steadily cultured. Based on advances in this field, USCs and their secretions have increasingly emerged as ideal sources. USCs may play regulatory roles in the cellular immune system, oxidative stress, revascularization, apoptosis and autophagy. This review summarizes the applications of USCs in tissue regeneration and various disease treatments. Furthermore, by analysing their limitations, we anticipate the development of more feasible therapeutic strategies to promote USC-based individualized treatment.

Recently, immunotherapy targeting tumor-infiltrating lymphocytes (TILs) has emerged as a critical and promising treatment in several types of cancer. However, not all cancer types have been tested in immunotherapeutic trials, and different patients and cancer types may have unpredictable clinical outcomes. This situation has created a particular exigency for analyzing the prognostic significance of tumor-infiltrating T cells (TIL-T) and B cells (TIL-B) across different cancer types. To address the critical role of TILs, the abundances of TIL-T and TIL-B cells, as determined by the protein levels of LCK and CD20, were analyzed across heterogeneous human malignancies. TIL-T and TIL-B cells showed varying prognostic significances across heterogeneous cancer types. Additionally, distinct distributions of TIL-T and TIL-B cells were observed in different cancer and tumor microenvironment (TME) subtypes. Next, we analyzed the cellular context for the TME communication network involving the well-acknowledgeable chemokine receptors of TIL-T and TIL-B cells, implying the functional interactions with TME. Additionally, these chemokine receptors, expressed by TIL-T and TIL-B cells, were remarkably correlated with the levels of TIL-T or TIL-B cell infiltrations across nearly all the cancer types, indicating these chemokine receptors as universal targets for up- and down-regulating the TIL-T and TIL-B cells. Lastly, we provide the prognostic landscape of TIL-T and TIL-B cells across 30 cancer types and the subgroups defined by gender, histopathology, histological grade, therapeutic approach, drug, and TME subtype, which are intended to be a resource to fuel the investigations of TILs, with important implications for cancer immunotherapy.

BackgroundPatients suffering from chronic heart failure (CHF) show an increased prevalence of sarcopenia. Levosimendan is an effective drug for the treatment of heart failure, but its effect on sarcopenia is still unclear. We aimed to explore whether levosimendan could enhance skeletal muscle contractibility, improve skeletal muscle atrophy, and thus improve exercise tolerance of individuals with heart failure.MethodsC57BL6/J mice were used to establish the heart failure with sarcopenia model and injected of levosimendan. Mice were separated into control group, sham operation group, HF group, HF + solvent group, HF + levosimendan group, HF + sarcopenia group, HF + sarcopenia + solvent group, HF + sarcopenia + levosimendan group (n = 5–12). After the treatment, exercise capacity and cardiac function were evaluated. Muscle morphology, inflammation level and apoptosis levels were detected, in which mitochondrial function and oxidative stress level were also assessed.ResultLevosimendan could increase forelimb grip strength/body weight, hanging impulse, maximum running distance and time in mice with HF and sarcopenia (P < 0.0001 for all), and these improvements were independent of EF (P = 0.0019 for hanging impulse, P < 0.001 for forelimb grip strength/body weight and maximum running distance). Levosimendan directly increased the CSA of gastrocnemius in mice with HF and sarcopenia (P < 0.0001). After levosimendan injection, the proportion of slow muscle fibers increased (P < 0.0001), but this improvement of muscle fiber typing might be attributed to improved cardiac function (P > 0.05). Levosimendan also maintained mitochondrial membrane potential, decreased cleaved caspase-3 (P = 0.034), cleaved caspase-9 (P < 0.0001), Bax expression (P < 0.0001), and increased Bcl2 expression (P = 0.0036). This effect is independent of improved cardiac function (P = 0.028 for bax, P < 0.001 for cleaved caspase-9 and Bcl2). IL-6, TNF-α expression (P < 0.0001 for both) decreased, and SOD activity (P = 0.0038), GSH/GSSG ratio (P = 0.002) significantly increased in skeletal muscle after injection of levosimendan. The improvement in oxidative stress level was attributed to improved cardiac function (P > 0.05).ConclusionLevosimendan reduce the loss of skeletal muscle mitochondrial membrane potential, decrease the apoptosis, alleviate the inflammation and oxidative stress, and ultimately improve the exercise capacity of mice with heart failure and sarcopenia. Therefore, levosimendan may be a potential drug for the treatment of heart failure with sarcopenia.

Aims. The present study is aimed at exploring the effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on weight in type 2 diabetes mellitus (T2DM) and therapeutic regimen recommendations. Methods. 20,019 patients with T2DM were enrolled. The maximal effect (Emax) models, whose evaluation index was change rate of body weight from baseline value, were used to analyze data using nonlinear mixed effect modeling (NONMEM). Results. For SGLT-2 inhibitors, canagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin and tofogliflozin, the Emax, and treatment duration to reach half of the maximal effects (ET50) were -3.72% and 3.35 weeks, -5.59% and 16.8 weeks, -2.84% and 3.42 weeks, -3.43% and 3.09 weeks, -3.04% and 4.38 weeks, and -2.45% and 3.16 weeks, respectively. In addition, for T2DM patients, 100 mg/day canagliflozin needs to be taken 13.4 weeks for the plateau of effect on weight; 10 mg/day empagliflozin needs to be taken 67.2 weeks for the plateau of effect on weight; 5 mg/day ertugliflozin needs to be taken 13.68 weeks for the plateau of effect on weight; 50 mg/day ipragliflozin needs to be taken 12.36 weeks for the plateau of effect on weight; 2.5 mg/day luseogliflozin needs to be taken 17.52 weeks for the plateau of effect on weight; 20 mg/day tofogliflozin needs to be taken 12.64 weeks for the plateau of effect on weight. Conclusions. This was the first study to explore effects of SGLT-2 inhibitors on weight in T2DM; meanwhile, the optimum dosages and treatment durations on weight from canagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, and tofogliflozin were recommended, respectively.

Left ventricular hypertrophy (LVH) has been classified separately as an independent risk factor for hypertension. However, comparisons between different body size indices and left ventricular hypertrophy (LVH) in hypertensive populations have not been reported yet. In this study, we enrolled 4,639 hypertensive patients from rural China. Anthropometric indices and cardiovascular disease risk factor variables were measured and analyzed using Spearman’s correlation, logistic regression, and receiver operating characteristic (ROC) curve analyses. Patients in the highest quartile of body size indices were more likely to have left ventricular hypertrophy than those in the lowest quartile; these indices were BMI (adjusted OR: 3.55, 95% CI: 2.90; 4.35), WC (adjusted OR: 2.23, 95% CI: 1.84; 2.70), WHR (adjusted OR: 1.44, 95% CI: 1.18; 1.75), and WHtR (adjusted OR: 3.23, 95% CI: 2.62; 3.99). The areas under the ROC curves of BMI (AUC: 0.628, 95% CI: 0.612; 0.644), WHtR (AUC: 0.628, 95% CI: 0.560; 0.593), WHR (AUC: 0.530, 95% CI: 0.513; 0.547), and WC (AUC: 0.576, 95% CI: 0.513; 0.547) were all above 0.5, which indicated that the four anthropometric indicators may be associated with LVH. The four anthropometric indicators of obesity were identified as risk factors for LVH. Weight control might help reduce the risk of left ventricular hypertrophy.

Abstract Background The balance between T helper 17 (Th17) cells and regulatory T cells (Tregs) is involved in immunological tolerance. Destruction of immunological tolerance by dendritic cell (DC)-mediated T cells is involved in the pathogenesis of ulcerative colitis (UC). Qingchang Huashi granule (QCHS) has been confirmed in the treatment of UC involved by inhibiting the activation of DCs. The aim of this study was to investigate the mechanism through which QCHS restores the Th17/Treg balance by modulating DCs in the treatment of UC. Methods The effects of QCHS on Th17 cells, Tregs and DCs were detected in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis model. Furthermore, we injected QCHS-treated DCs into colitis model to test whether QCHS modulates the Th17/Treg balance via DCs. Tregs and Th17 cells were analyzed by FACS. IL-10, IL-17, and Foxp3 were measured by ELISA, Western blot and qRT-PCR. Results Both QCHS and QCHS-treated DCs improved colonic histopathology, diminished Th17 cell differentiation and inhibited IL-17 production while promoting CD4+CD25+Foxp3+ Treg differentiation and augmenting IL-10 and Foxp3 expression in colitis mice. Additionally, QCHS reduced CD86 and MHC-II expression on DCs, decreased IL-12 production ex vivo and restored the Th17/Treg ratio in the colitis model. Conclusion The findings of this study indicate that QCHS ameliorates TNBS-induced colitis by restoring the DC-mediated Th17/Treg balance.

Abstract Background Rhododendron molle (Ericaceae) is a traditional Chinese medicinal plant, its flower and root have been widely used to treat rheumatism and relieve pain for thousands of years in China. Chemical studies have revealed that R. molle contains abundant secondary metabolites such as terpenoinds, flavonoids and lignans, some of which have exhibited various bioactivities including antioxidant, hypotension and analgesic activity. In spite of immense pharmaceutical importance, the mechanism underlying the biosynthesis of secondary metabolites remains unknown and the genomic information is unavailable. Results To gain molecular insight into this plant, especially on the information of pharmaceutically important secondary metabolites including grayanane diterpenoids, we conducted deep transcriptome sequencing for R. molle flower and root using the Illumina Hiseq platform. In total, 100,603 unigenes were generated through de novo assembly with mean length of 778 bp, 57.1% of these unigenes were annotated in public databases and 17,906 of those unigenes showed significant match in the KEGG database. Unigenes involved in the biosynthesis of secondary metabolites were annotated, including the TPSs and CYPs that were potentially responsible for the biosynthesis of grayanoids. Moreover, 3376 transcription factors and 10,828 simple sequence repeats (SSRs) were also identified. Additionally, we further performed differential gene expression (DEG) analysis of the flower and root transcriptome libraries and identified numerous genes that were specifically expressed or up-regulated in flower. Conclusions To the best of our knowledge, this is the first time to generate and thoroughly analyze the transcriptome data of both R. molle flower and root. This study provided an important genetic resource which will shed light on elucidating various secondary metabolite biosynthetic pathways in R. molle, especially for those with medicinal value and allow for drug development in this plant.

Meplazumab is an anti-CD147 humanized IgG2 antibody. The purpose of this study was to characterize the nonclinical safety, tolerance and efficacy evaluation of meplazumab treating chloroquine resistant Plasmodium falciparum. Meplazumab was well tolerated in repeat-dose toxicology studies in cynomolgus monkeys. No observed adverse effect level was 12 mg/kg. No difference between genders in the primary toxicokinetic parameters after repeat intravenous injection of meplazumab. No increased levels of drug exposure and drug accumulation were observed in different gender and dose groups. Meplazumab had a low cross-reactivity rate in various tissues and did not cause hemolysis or aggregation of red blood cells. The biodistribution and excretion results indicated that meplazumab was mainly distributed in the plasma, whole blood, and hemocytes, and excreted in the urine. Moreover, meplazumab effectively inhibited the parasites from invading erythrocytes in humanized mice in a time-dependent manner and the efficacy is superior to that of chloroquine. All these studies suggested that meplazumab is safe and well tolerated in cynomolgus monkeys, and effectively inhibits P. falciparum from invading into human red blood cells. These nonclinical data facilitated the initiation of an ongoing clinical trial of meplazumab for antimalarial therapy.

Abstract Background Controversies existed surrounding the use of hematocrit to guide early fluid therapy in acute pancreatitis (AP). The association between hematocrit, early fluid therapy, and clinical outcomes in ward AP patients needs to be investigated. Methods Data from prospectively maintained AP database and retrospectively collected details of fluid therapy were analyzed. Patients were stratified into three groups: Group 1, hematocrit 44% at 24 h; Group 3: hematocrit >44% on admission and decreased thereafter during first 24 h. “Early” means first 24 h after admission. Baseline characteristics, early fluid rates, and clinical outcomes of the three groups were compared. Results Among the 628 patients, Group 3 had a higher hematocrit level, greater baseline predicted severity, faster fluid rate, and more fluid volume in the first 24 h compared with Group 1 or 2. Group 3 had an increased risk for persistent organ failure (POF; odds ratio 2, 95% confidence interval [1.1–3.8], P = 0.03) compared with Group 1 after adjusting for difference in baseline clinical severity scores, there was no difference between Group 2 and Group 3 or Group 1. Multivariate regression analyses revealed that hemoconcentration and early faster fluid rate were risk factors for POF and mortality (both P

Abstract Background The COVID-19 pandemic has become a great threat to public health, which has greatly impacted the study and life of undergraduate students in China. This study aims to perform a survey of their knowledge, attitude and practice (KAP) associated with COVID-19. Methods A cross-sectional survey was designed to gather information regarding the COVID-19 related KAP among undergraduates during the home isolation in the outbreak. Subjects were recruited from 10 universities in Shaanxi Province, China. Enrollees voluntarily submitted their answers to a pre-designed questionnaire online. Results A total of 872 subjects (female, 534; male, 338) were enrolled with ages from 17 to 25 years old. This cohort included 430 medical and 442 non-medical students, 580 freshmen and 292 higher school year students. There were 453 from public schools and 442 from private school, residing in 28 regions and provinces at the time of study. Results showed that appropriate knowledge was acquired by 82.34% subjects; the levels were significantly higher in undergraduates from public universities and medical majors than those from private schools and non-medical majors (p

Abstract Background The efficacy and safety of ambrisentan has been previously evaluated in Chinese patients with pulmonary arterial hypertension (PAH). This post-hoc analysis assessed the efficacy and safety of ambrisentan in a subgroup of connective tissue disease (CTD) patients with PAH. Methods In this open-label, single-arm study, patients received ambrisentan 5 mg once daily for 12 weeks, followed by 12-week dose titration period (dose up to 10 mg). Efficacy endpoints included change from baseline in exercise capacity (measured by 6-min walk test [6MWT]), N-terminal pro B type natriuretic peptide (NT-proBNP) plasma levels, WHO Functional Class (FC) and Borg Dyspnoea Index (BDI) scores from baseline to weeks 12 and 24. Safety endpoints included time to clinical worsening and incidence of adverse events (AEs). Results In total, 71 Chinese patients with CTD-PAH were included in this analysis. Ambrisentan treatment significantly improved exercise capacity (6MWT) from baseline (mean: 366.4 m) to week 12 (63.8 m, p

Abstract Background The outbreak of coronavirus disease 2019 (COVID-19) has caused a public catastrophe and global concern. The main symptoms of COVID-19 are fever, cough, myalgia, fatigue and lower respiratory tract infection signs. Almost all populations are susceptible to the virus, and the basic reproduction number (R 0) is 2.8–3.9. The fight against COVID-19 should have two aspects: one is the treatment of infected patients, and the other is the mobilization of the society to avoid the spread of the virus. The treatment of patients includes supportive treatment, antiviral treatment, and oxygen therapy. For patients with severe acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation (ECMO) and circulatory support are recommended. Plasma therapy and traditional Chinese medicine have also achieved good outcomes. This review is intended to summarize the research on this new coronavirus, to analyze the similarities and differences between COVID-19 and previous outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and to provide guidance regarding new methods of prevention, diagnosis and clinical treatment based on autodock simulations. Methods This review compares the multifaceted characteristics of the three coronaviruses including COVID-19, SARS and MERS. Our researchers take the COVID-19, SARS, and MERS as key words and search literatures in the Pubmed database. We compare them horizontally and vertically which respectively means concluding the individual characteristics of each coronavirus and comparing the similarities and differences between the three coronaviruses. Results We searched for studies on each outbreak and their solutions and found that the main biological differences among SARS-CoV-2, SARS-CoV and MERS-CoV are in ORF1a and the sequence of gene spike coding protein-S. We also found that the types and severity of clinical symptoms vary, which means that the diagnosis and nursing measures also require differentiation. In addition to the common route of transmission including airborne transmission, these three viruses have their own unique routes of transmission such as fecal-oral route of transmission COVID-19. Conclusions In evolutionary history, these three coronaviruses have some similar biological features as well as some different mutational characteristics. Their receptors and routes of transmission are not all the same, which makes them different in clinical features and treatments. We discovered through the autodock simulations that Met124 plays a key role in the efficiency of drugs targeting ACE2, such as remdesivir, chloroquine, ciclesonide and niclosamide, and may be a potential target in COVID-19.

Plant metacaspases mediate immune response following activation by Ca2+. Here, via crystallography and functional analyses, the authors show that a linker domain in Arabidopsis Metacaspase 4 blocks substrate access to the active site but is cleaved multiple times in the presence of Ca2+ to allow enzyme activation.

Dysregulation of mRNA alternative splicing is prevalent in cancers. Here, the authors characterized the landscape of aberrant alternative splicing during the development of prostate cancer, progression and therapeutic resistance and show that splicing modulator, E7107, reduces growth in castration-resistant prostate cancer.

Abstract Background CD8+CD28− T suppressor (Ts) cells play critical role in transplant tolerance. Our previous study has generated CD8+CD28− Ts cells in vitro which exert robust allospecific suppressive capacity in vitro. Results CD8+CD28− Ts cells were expanded by stimulating human CD8+ T cells with allogeneic antigen presenting cells in the presence of the common gamma chain cytokines IL-2, IL-7 and IL-15 in vitro, and were further verified in vitro through day 7 to 11 for their persistency of the allospecific suppressive capacity. When CD8+CD28− Ts cells were adoptively transferred into NOG mice, their capacity to inhibit CD4+ T cell proliferation in allospecific manner remained potent on 11 days after their injection. The mechanisms for expansion of CD8+CD28− Ts cells by the common gamma chain cytokines were investigated. These included promoting CD8+CD28− T cells proliferation, converting CD8+CD28+ T cells to CD8+CD28− T cells and decreasing CD8+CD28− T cell death. Furthermore, the expanded CD8+CD28− Ts cells showed upregulation of the co-inhibitory molecule Tim-3 and down-regulation of the cytotoxic molecule granzyme B. Conclusions In summary, these results demonstrated that the in vitro-expanded human CD8+CD28− T cells retained potent allospecific suppressive capacity in vivo and depicted multiple mechanisms for the expansion of Ts cells, which might promote further bench to clinic research.

Abstract Background Universal gene targets are in persistent demand by real‐time quantitative polymerase chain reaction (RT‐qPCR)‐based methods in acute leukemia (AL) diagnosis and monitoring. Human Krüppel‐like factor 3 (hKLF3), a newly cloned human transcription factor, has proved to be a regulator of hematopoiesis. Methods Sanger sequencing was performed in bone marrow (BM) samples from 17 AL patients for mutations in hKLF3 coding exons. hKLF3 expression in peripheral blood (PB) and BM samples from 45 AL patients was dynamically detected by RT‐qPCR. PB samples from 31 healthy donors were tested as normal controls. Results No mutation was sequenced in hKLF3 coding exons. hKLF3 expression in PB of AL was significantly lower than that in healthy donors [0.30 (0.02‐1.07) vs 1.18 (0.62‐3.37), P

Soil productivity (SP) without external fertilization influence is an important indicator for the capacity of a soil to support crop yield. However, there have been difficulties in estimating values of SPs for soils after various long-term field treatments because the treatment without external fertilization is used but is depleted in soil nutrients, leading to erroneous estimation. The objectives of this study were to estimate the change of SP across different cropping seasons using pot experiments, and to evaluate the steady SP value (which is defined by the basal contribution of soil itself to crop yield) after various long-term fertilization treatments in soils at different geographical locations. The pot experiments were conducted in Jinxian of Jiangxi Province with paddy soil, Zhengzhou of Henan Province with fluvo-aquic soil, and Gongzhuling of Jilin Province with black soils, China. Soils were collected after long-term field fertilization treatments of no fertilizer (control; CK-F), chemical fertilizer (NPK-F), and combined chemical fertilizer with manure (NPKM-F). The soils received either no fertilizer (F0) or chemical fertilizer (F1) for 3–6 cropping seasons in pots, which include CK-P (control; no fertilizer from long-term field experiments for pot experiments), NPK-P (chemical fertilizer from long-term field experiments for pot experiments), and NPKM-P (combined chemical and organic fertilizers from long-term field experiments for pot experiments). The yield data were used to calculate SP values. The initial SP values were high, but decreased rapidly until a relatively steady SP was achieved at or after about three cropping seasons for paddy and fluvo-aquic soils. The steady SP values in the third cropping season from CK-P, NPK-P, and NPKM-P treatments were 37.7, 44.1, and 50.0% in the paddy soil, 34.2, 38.1, and 50.0% in the fluvo-aquic soil, with the highest value observed in the NPKM-P treatment for all soils. However, further research is required in the black soils to incorporate more than three cropping seasons. The partial least squares path mode (PLS-PM) showed that total N (nitrogen) and C/N ratio (the ratio of soil organic carbon and total N) had positive effects on the steady SP for all three soils. These findings confirm the significance of the incorporation of manure for attaining high soil productivity. Regulation of the soil C/N ratio was the other main factor for steady SP through fertilization management.

Gastric cancer (GC) is the most common cancer with a poor prognosis and the third leading cause of cancer death in the world, for which no effective therapeutic target exists. We tested the hypothesis that FAM46C might be involved in regulation of proliferation and apoptosis in GC. FAM46C was down-regulated and its expression negatively correlated with the expression of β-catenin that drives proliferation and apoptosis. Overexpression of FAM46C inhibited cell proliferation, induced G1 phase arrest and promoted apoptosis. Activation of Wnt/β-catenin signaling pathway in GC cell lines quenched the effect of FAM46C overexpression. On the other hand, FAM46C silencing attenuated DKK1-mediated inhibition of G1 phase, cessation of proliferation and induction apoptosis. Together, these data show that FAM46C shows tumor suppressor properties and such effects are mediated, at least in part, by Wnt/β-catenin in GC.

The progression of a disease associates with changes in genomic activity, but it remains a challenge to screen genetic biomarkers for clinical applications. The disease progression, in dynamic network methods (DNM), can be analogous to an animated film composed of discrete frames, where each frame represents a temporary state of the time-varying gene-gene interaction network. The major shortage therein is that the transition between two neighboring temporary states was beyond investigation. Here, we develop an updated computational methodology named after VD-analysis. Because single-gene biomarkers were not approved capable of representing a complex biological process, we firstly introduce V-structure — a gene module composed of three genes and two interactions among them — and define it as unit module. We then identify the perturbed pathways that mark the disease progression, followed with the V-structures identified which drive the pathway perturbations. Such driver V-structures can be taken as eligible biomarkers for clinical applications. To test the feasibility of this method, we apply it to a time course dataset of gene expression related to mouse type-II diabetes (T2D). Result indicates that the whole process of T2D is exactly divided into 3 stages and that the driver V-structures inferred for each stage are qualified biomarkers. In summary, our method contributes to the description of dynamic disease progression and the V-structure biomarkers facilitate the treatments of disease.

Cyclosporin A (CsA) is a common immunosuppressant, but its use is limited as it can cause chronic kidney injury. Oxidative stress and apoptosis play a key role in CsA‐induced nephrotoxicity. This study investigated the protective effect of 5‐aminolevulinic acid and iron (5‐ALA/SFC) on CsA‐induced injury in murine proximal tubular epithelial cells (mProx24). 5‐ALA/SFC significantly inhibited apoptosis in CsA‐treated mProx24 cells with increases in heme oxygenase (HO)‐1, nuclear factor E2‐related factor 2 (Nrf2), and p38, and Erk‐1/2 phosphorylation. Moreover, 5‐ALA/SFC suppressed production of reactive oxygen species in CsA‐exposed cells and inhibition of HO‐1 suppressed the protective effects of 5‐ALA/SFC. In summary, 5‐ALA/SFC may have potential for development into a treatment for the anti‐nephrotoxic/apoptotic effects of CsA.

Myosin heavy chain 7 (MYH7) is a major causative gene for hypertrophic cardiomyopathy, but the affected signaling pathways and therapeutics remain elusive. In this research, we identified ventricle myosin heavy chain like (vmhcl) as a zebrafish homolog of human MYH7, and we generated vmhcl frameshift mutants. We noted vmhcl-based embryonic cardiac dysfunction (VEC) in the vmhcl homozygous mutants and vmhcl-based adult cardiomyopathy (VAC) phenotypes in the vmhcl heterozygous mutants. Using the VEC model, we assessed 7 known cardiomyopathy signaling pathways pharmacologically and 11 candidate genes genetically via CRISPR/Cas9 genome editing technology based on microhomology-mediated end joining (MMEJ). Both studies converged on therapeutic benefits of mTOR or mitogen-activated protein kinase (MAPK) inhibition of VEC. While mTOR inhibition rescued the enlarged nuclear size of cardiomyocytes, MAPK inhibition restored the prolonged cell shape in the VEC model. The therapeutic effects of mTOR and MAPK inhibition were later validated in the VAC model. Together, vmhcl/myh7 loss of function is sufficient to induce cardiomyopathy in zebrafish. The VEC and VAC models in zebrafish are amenable to both efficient genetic and chemical genetic tools, offering a rapid in vivo platform for discovering candidate signaling pathways of MYH7 cardiomyopathy.

Cadmium (Cd) speciation ratio in arable land determines the Cd exposure risk and Cd uptake in crops. However, the driving mechanisms of Cd speciation change on the vertical scale of paddy fields remain poorly understood. In this study, the effects of plow layer and plow pan on Cd speciation distribution were investigated in a long-term Cd-contaminated rice ecosystem. The Cd accumulative effect within rice grain was enhanced with high levels of activated Cd speciation ratios in soils. Activated Cd speciation ratios were higher in plow layer soils, while stabilized Cd speciation ratios were elevated in plow pan soils. Soil physicochemical properties and soil microbes synergistically affected the Cd speciation changes in different ways between the two soil layers. Soil pH and organic elements in plow layer environment directly hindered the transformation of stabilized Cd speciation, while in plow pan environment, soil pH and organic elements indirectly decreased activated Cd speciation ratios and resulted in the accumulation of stabilized Cd speciation via regulating the predominant bacterial taxa. This study will improve our understanding of how soil environments regulate Cd speciation distributions in rice ecosystems and help to seek effective remediation methods of Cd-contaminated paddy fields to reduce the Cd accumulation in rice.

As a subunit of the nucleosome remodeling and histone deacetylation (NuRD) complex, GATA zinc finger domain containing 2B (GATAD2B) plays a vital role in chromatin modification and transcriptional regulation. To further investigate the role of GATAD2B in cell fate determination of human ESCs, we generated two GATAD2B homozygous knockout human ESC lines by CRISPR/Cas9 technology. The cell line exhibits normal karyotype and typical stem cell morphology, following the high expression of pluripotent genes and differentiation potential in vitro. These cell lines will provide cell resources to investigate epigenetic regulation in extensive biological processes as menthioned above.

Cardiovascular diseases (CVD) are a significant cause of human health harm. In the past, stem cell therapy was reported to have functional defects, such as immune rejection, tumorigenicity, and infusion toxicity. Exosomes are extracellular vesicles with lipid bilayer membrane structure, containing proteins, lipids, mRNA, miRNA, DNA, and other molecules, which can mediate various biological functions such as immune response, inflammatory response, cell migration, and differentiation intercellular communication. Exosomal miRNAs have outstanding advantages in disease diagnosis and curative effect prediction. Likewise, paracrine factors could also mediate the main therapeutic effect of mesenchymal stem cells. Research has shown that mesenchymal stem cell-derived micro-exosomes, which may come from stem cells, accumulate in the ischemic tissue and regulate cell proliferation, apoptosis, inflammation, and angiogenesis sites of myocardial injury after being transplanted. This review reviewed the molecular mechanisms of exosomes and internal microRNAs derived from mesenchymal stem cells in cardiac ischemic injury repair.

Background: Adalimumab, golimumab, infliximab, certolizumab, and etanercept are five anti-tumor necrosis factor (anti-TNF) medicines that have been approved for use in rheumatology. Apart from their well-established therapeutic usefulness, -it is unclear to what extent -they are linked to an increased risk of various side effects. The present meta-analysis was carried out to assess the risk of infection and other side effects after anti-TNF- α for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.Methods: We searched PubMed, Cinahl (via Ebsco), Scopus, and Web of Sciences databases for trials comparing anti-TNF medications to placebo or no therapy in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis from August 2006 to August 2020. A total of 23 articles were used for meta-analysis. The Cochrane Collaboration’s risk of bias tool was used to assess the methodological quality of the included studies. In addition, a random-effects model was used to calculate the pooled odds ratio, and Forest plots were constructed to determine the risk of infections and cancer following the use of anti-TNF treatment.Results: Treatment with anti-TNFα agents resulted in an increase in the risk of serious infections (OR: 1.72, 95% CI: 1.56–1.90, p < 0.00001) and an increase in cancer risk (OR: 1.36, 95% CI: 1.20–1.53, p < 0.00001) whereas the risk of developing tuberculosis was not significantly different with anti-TNFα agents versus those without treatment with anti-TNFα agents (OR: 2.55, 95% CI: 0.40–16.23, p = 0.32) although the number of studies is limited to make a definitive conclusion. The risk of bias of the included studies was unclear to high across most domains, and there was evidence of publication bias for most outcomes.Conclusion: The present meta-analysis suggests an increased risk of infectious adverse events, including overall adverse events and cancer following anti-TNFα treatment, whereas the risk of tuberculosis was not significantly different. Although anti-TNF agents have shown promise to treat inflammatory conditions, their use should be balanced by the risk-benefit ratio as suggested by the meta-analysis.

Summary: Activation of nucleic acid sensing Toll-like receptors (TLRs) in B cells is involved in antiviral responses by promoting B cell activation and germinal center responses. In order to take advantage of this natural pathway for vaccine development, synthetic pathogen-like antigens (PLAs) constructed of multivalent antigens with encapsulated TLR ligands can be used to activate B cell antigen receptors and TLRs in a synergistic manner. Here we report a PLA-based coronavirus disease 2019 (COVID-19) vaccine candidate designed by combining a phage-derived virus-like particle carrying bacterial RNA as TLR ligands with the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein as the target antigen. This PLA-based vaccine candidate induces robust neutralizing antibodies in both mice and non-human primates (NHPs). Using a NHP infection model, we demonstrate that the viral clearance is accelerated in vaccinated animals. In addition, the PLA-based vaccine induces a T helper 1 (Th1)-oriented response and a durable memory, supporting its potential for further clinical development.

Purpose: To investigate the effect of subclinical hypothyroidism on pregnancy outcomes of women early in their pregnancy with different thyroid-stimulating hormone levels and thyroid peroxidase antibody–negative status and to explore reasonable thyroid-stimulating hormone levels for subclinical hypothyroidism in early pregnancy. Methods: A total of 2378 women early in their pregnancy were studied retrospectively. The baseline characteristics were collected from medical records. Pregnancy outcomes were compared between the euthyroidism and subclinical hypothyroidism groups that were diagnosed by 2011 or 2017 American Thyroid Association guidelines. In addition, the effect of different maternal thyroid-stimulating hormone levels on adverse pregnancy outcomes was analyzed using binary logistic regression. Results: According to the 2011 American Thyroid Association diagnostic criteria of subclinical hypothyroidism, the prevalence of pregnancy outcomes was not significantly higher in the subclinical hypothyroidism group than in the euthyroidism group. However, pregnant women with subclinical hypothyroidism identified by the 2017 American Thyroid Association criteria had a higher risk of premature delivery (odds ratio = 3.93; 95% confidence interval = 1.22–12.64), gestational diabetes mellitus (odds ratio = 2.69; 95% confidence interval = 1.36–5.32), and gestational anemia (odds ratio = 3.28; 95% confidence interval = 1.60–6.75). Moreover, no differences in the prevalence of adverse pregnancy outcomes were observed between the mildly elevated thyroid-stimulating hormone group (2.5

The purpose of this study is to investigate whether mutations in key genes affect the prognosis of breast cancer patients, and base mutations is discussed by combining the physical properties of the electron–ion interaction pseudopotential. We study 994 breast cancer mutation samples, including 15,015 mutation genes, and use social network algorithm to screen key genes. In order to analyze the relationship between electron–ion interaction pseudopotential and mutation of key genes, this paper proposes the E difference formula. It not only analyses gene mutation at the physical level, but also explains the mutation rule of single base. Simultaneously, we use the Kaplan–Meier to analyze the overall survival rate of breast cancer samples and use Tarone-Ware to test. The results showed that mutations in GATA3, PIK3CA, and TP53 are significant difference in overall survival rate of breast cancer ( CI = 95 % , P < 0.05 ). Proteins often interact to form protein complexes, and driving protein function. Therefore, by constructing protein–protein interaction network and finding modular proteins of key genes, we can find genes closely related to key genes. Finally, the results of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology function enrichment analysis show that key genes played an important role in metabolic pathways and biological functions. In clinical medicine, screening for key gene mutations may help predict survival in breast cancer patients.

Inactivity is a significant risk factor for cardiovascular disease. Exercise may greatly enhance the metabolism and function of the cardiovascular system, lower several risk factors, and prevent the development and treatment of cardiovascular disease while delivering easy, physical, and emotional enjoyment. Exercise regulates the cardiovascular system by reducing oxidative stress and chronic inflammation, regulating cardiovascular insulin sensitivity and the body’s metabolism, promoting stem cell mobilization, strengthening autophagy and myocardial mitochondrial function, and enhancing cardiovascular damage resistance, among other effects. Appropriate exercise intervention has become an essential adjuvant therapy in clinical practice for treating and rehabilitating various cardiovascular diseases. However, the prescription of exercise for preventing and treating cardiovascular diseases, particularly the precise selection of individual exercise techniques and their volume, remains controversial. Using multiomics to explain further the molecular process underlying the positive effects of exercise on cardiovascular health will not only improve our understanding of the effects of exercise on health but also establish a scientific basis and supply new ideas for preventing and treating cardiovascular diseases by activating the endogenous protective mechanisms of the body and suggesting more specific exercise prescriptions for cardiovascular rehabilitation.

We present a new scheme of picosecond optical parametric chirped pulse amplification (OPCPA) in which a Fourier-transform-limit 5.0 ps pulse is optically sheared from a single-longitudinal-mode 1064 nm CW laser. The pulse is amplified and frequency-doubled as the pump in order to maintain the pump narrow bandwidth and picosecond duration simultaneously, which is very important to ensure the high temporal contrast for an OPCPA amplifier. Combined with the cross-polarized wave generation (XPW), a compound frontend for the high-power femtosecond laser system that delivers a 1 Hz chirped pulse train is established. The experiments provide an output pulse energy of 17.1 mJ, a spectrum bandwidth 71 nm (FWHM), and a pulse duration 16.4 fs. The pulse contrast reaches 1:10−12 several picoseconds before the peak of the main pulse, which is the best value of the available measuring instruments.

Olsen phosphorus (Olsen P) is an important indicator of soil labile phosphorus. Determining the effect of fertilization on Olsen P and P fractions (labile phosphorus, medium labile phosphorus and stable phosphorus) can guide the application of phosphate fertilizer. Therefore, it is of great significance to clarify the changes of Olsen P and P fractions and the influencing factors under long-term fertilization. This study investigated changes in Olsen P and P fractions in haplic phaeozems soils (0–20 cm) in two 30-year fertilization sites (Harbin, Gongzhuling) of northern China. Four treatments were examined: treatment with no fertilizer or manure (CK), nitrogen and potassium (NK), nitrogen, phosphorus and potassium (NPK), and manure, nitrogen, phosphorus and potassium (MNPK). The results showed that after NK application, Olsen P decreased by an average of 1.5 mg kg−1 for every 100 kg ha−2 of soil phosphorus lost due to continuous phosphorus uptake by the crop; with NPK, Olsen P increased by an average of 17.6 mg kg−1 for every 100 kg ha−2 of P surplus; with MNPK, the increase curve of Olsen P was similar to an S-curve with periods of rapid growth and periods of equilibrium. In the equilibrium period of Olsen P, the equilibrium values were 52.0 and 156.2 mg kg−1 in Harbin and Gongzhuling. After 20 years of long-term different fertilization, labile P (LP), medium labile P (MLP) and stable P (SP) decreased by 21.1, 16.6 and 15.1 mg kg−1 on average for the treatment without P application (NK), and the percentage decreases were 2.8, 5.7 and 2.1%, respectively. With the treatment of NPK, LP and MLP increased by 25.5 and 79.2 mg kg−1, and the percentage increases were 1.8 and 16.1%. With the treatment of MNPK, the increase in LP and MLP was significantly higher than that with NPK. Soil organic carbon (SOC), total nitrogen (TN) and carbon/nitrogen (C/N) had the greatest effects on Olsen P and P fractions and the total contribution rate was >40%. In summary, fertilization system caused significant changes in Olsen P and P fractions. After about 20 years of long-term combined application of MNPK, the growth of Olsen P can be kept constant. SOC and TN had important effects on Olsen P and P fractions in black soil. Therefore, the application of phosphorus fertilizer should be adjusted according to the type and time of fertilization in black soil in order to avoid waste of phosphorus fertilizer.

α- and β-carotenes belong to the most essential carotenoids in the human body and display remarkable pharmacological value for health due to their beneficial antioxidant activities. Distinct high α-/β-carotene stoichiometries have gained increasing attention for their effective preventions of Alzheimer’s disease, cardiovascular disease, and cancer. However, it is extremely difficult to obtain α-carotene in nature, impeding the accumulations of high α-/β-carotene stoichiometries and excavation of their antioxidant activities. Herein, we developed a dynamically operable strategy based on lycopene cyclases (LCYB and LCYE) for concurrently enriching α- and β-carotenes along with high stoichiometries in E. coli. Membrane-targeted and promoter-centered approaches were firstly implemented to spatially enhance catalytic efficiency and temporally boost expression of TeLCYE to address its low competitivity at the starting stage. Dynamically temperature-dependent regulation of TeLCYE and TeLCYB was then performed to finally achieve α-/β-carotene stoichiometries of 4.71 at 37 °C, 1.65 at 30 °C, and 1.06 at 25 °C, respectively. In the meantime, these α-/β-carotene ratios were confirmed to result in diverse antioxidative activities. According to our knowledge, this is the first time that both the widest range and antioxidant activities of high α/β-carotene stoichiometries were reported in any organism. Our work provides attractive potentials for obtaining natural products with competitivity and a new insight on the protective potentials of α-/β-carotenes with high ratios for health supply.

Since commercial non-woven air filtering materials have unstable filtering efficiency and poor moisture permeability for the abundant condensed aerosol particles in the highly humid atmospheric environment, the PLLA/PAN composite fiber material with a hydrophobic and hydrophilic gradient structure is designed and prepared by using electrode sputtering electro spinning technology. By characterizing and testing the filtrating effect of SEM, XRD, FTIR, wettability, mechanical property, N2 adsorption isotherm, and BET surface area, NaCl aerosol of PLLA fiber, PAN fiber, and PLLA/PAN composite fiber membranes, the study found that the electrode sputtering electrospinning is fine, the fiber mesh is dense, and fiber distribution is uniform when the diameter of the PAN fiber is 140–300 nm, and the PLLA fiber is 700–850 nm. In this case, PLLA/PAN composite fiber materials gather the hydrophobicity of PLLA fiber and the hydrophilicity of PAN fiber; its electrostatic effect is stable, its physical capturing performance is excellent, it can realize the step filtration of gas-solid liquid multiphase flow to avoid the rapid increase of air resistance in a high-humidity environment, and the filtrating efficiency η of NaCl aerosol particles with 0.3 μm reaches 99.98%, and the quality factor QF 0.0968 Pa−1. The manufacturing of PLLA/PAN composite fiber material provides a new method for designing and developing high-performance air filtration materials and a new technical means for the large-scale production of high-performance, high-stability, and low-cost polylactic acid nanofiber composites.

The biomimetic olfactory and gustatory biosensing devices have broad applications in many fields, such as industry, security, and biomedicine. The development of these biosensors was inspired by the organization of biological olfactory and gustatory systems. In this review, we summarized the most recent advances in the development of detection strategies for chemical sensing based on olfactory and gustatory biomimetic biosensors. First, sensing mechanisms and principles of olfaction and gustation are briefly introduced. Then, different biomimetic sensing detection strategies are outlined based on different sensing devices functionalized with various molecular and cellular components originating from natural olfactory and gustatory systems. Thereafter, various biomimetic olfactory and gustatory biosensors are introduced in detail by classifying and summarizing the detection strategies based on different sensing devices. Finally, the future directions and challenges of biomimetic biosensing development are proposed and discussed.