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Distribution networks in China and several other countries are predominantly neutral inefficiently grounding systems (NIGSs), and more than 80% of the faults in distribution networks are single-phase-to-ground (SPG) faults. Because of the weak fault current and imperfect monitoring equipment configurations, methods used to determine the faulty line sections with SPG faults in NIGSs are ineffective. The development and application of distribution-level phasor measurement units (PMUs) provide further comprehensive fault information for fault diagnosis in a distribution network. When an SPG fault occurs, the transient energy of the faulted line section tends to be higher than the sum of the transient energies of other line sections. In this regard, transient energy-based fault location algorithms appear to be a promising resolution. In this study, a field test plan was designed and implemented for a 10 kV distribution network. The test results demonstrate the effectiveness of the transient energy-based SPG location method in practical distribution networks.

The increasing permeation of the distributed generators in the power system brings great challenges for fault diagnosis, especially for the distribution networks with ungrounded neutral or grounded by Peterson coil as the fault current is limited and easily affected by the noises and interferences. A single phase‐to‐ground fault section identification method is proposed based on feature extraction of the synchronous waveforms and the calculation of the eigenvalues for the time‐sequenced features. First, several fault features are defined and extracted from the synchronous current waveforms obtained by the fault recorders. Then, the topology related fault feature matrix is constructed using the time‐series features obtained from different measurement sites, and the eigenvalues of the matrix are calculated based on the random matrix theory. Lastly, using the distribution characteristics of the eigenvalues, improved K‐means clustering algorithm is utilised in classifying the fault cases and identifying the faulty sections. The effectiveness of the proposed scheme is verified by IEEE 34 nodes test system and a multi‐feeder distribution network.

Objective To establish the orthogonal partial least square （OPLS） model for the estimation of early postmortem interval （PMI） of asphyxial death rats in four ambient temperatures based on gas chromatography-mass spectrometry （GC-MS） metabolomics. Methods The 96 rats were divided into four temperature groups （5 ℃, 15 ℃, 25 ℃ and 35 ℃）. Each temperature group was further divided into 3 h, 6 h, 12 h and 24 h after death, and 6 other rats were taken as the control group. The cardiac blood was collected at the set time points for the four temperature groups and 0 h after death for the control group for the metabolomics analysis by GC-MS. By OPLS analysis, the variable importance in projection （VIP）>1 and the result of Kruskal-Wallis test P

Bacterioplankton communities are closely related to river alterations and biogeochemical processes in freshwater reservoirs. Affected by reservoir regulation and hydrological variation, regulated rivers can create distinctive patterns in bacterioplankton communities. In this study, we conducted 16S rRNA V4 amplicon high-throughput sequencing to investigate compositional changes in the bacterioplankton community and its environmental responses to damming effects in the Pengxi River, the largest tributary on the northern bank of the Three Gorges Reservoir (TGR). The bacterial community was dominated by the phyla Proteobacteria and Actinobacteria, accounting for 51.0% and 13.1% of all sequences, respectively. Distinct differences in the bacterioplankton community composition were observed between the backwater and riverine areas, and the dominant taxa showed clear shifts at the class level between the upper stream and backwater area sites along the Pengxi River. Conductivity, transparency and temperature were considered the major environmental factors driving the bacterioplankton composition variation. Additionally, the functional profiles of the bacterioplankton community corresponded with compositional changes in reservoir regulation by TGR. Therefore, these results provide insights into dam effects on the bacterioplankton community in the Pengxi River, and further research should focus on the potential ecological processes of river regulation by dams or reservoirs.

Abstract Background Hydroxychloroquine (HCQ) is a well-known immunomodulator that was recently used in immunoglobulin A (IgA) nephropathy (IgAN) due to its antiproteinuric effects. We investigated the effects of HCQ in patients with IgAN whose proteinuria remained above 1 g/d after conventional immunosuppressive (IS) therapy. Methods This study was a retrospective case-control study. Twenty-six patients with IgAN who received HCQ and had insufficient responses to IS therapy (corticosteroid (CS) therapy with/without IS agents) were included. Twenty-six matched historical controls who received conventional IS therapy were selected using propensity score matching. The clinical data from 6 months were compared. Results Proteinuria at baseline was comparable between the “IS therapy plus HCQ” and “conventional IS therapy” groups (2.35 [interquartile range (IQR), 1.47, 2.98] vs. 2.35 [IQR, 1.54, 2.98] g/d, p = 0.920). A significant reduction in proteinuria was noted in IgAN patients with HCQ treatment (2.35 [IQR, 1.47, 2.98] vs. 1.10 [IQR, 0.85, 1.61] g/d, p = 0.002). The percent reduction in proteinuria at 6 months was similar between the two groups (− 39.81% [− 66.26, − 12.37] vs. -31.99% [− 67.08, − 9.14], p = 0.968). The cumulative frequency of patients with a 50% reduction in proteinuria during the study was also comparable between the two groups (53.8% vs. 57.7%, p = 0.780). No serious adverse events (SAEs) were observed during the study. Conclusions Use of HCQ achieved has similar reduction in proteinuria compared to conventional IS therapy in patients with IgAN who had insufficient responses to IS therapy.

High-speed steel contains a large amount of carbides, the shape and distribution of which have an important influence on its quality. To improve the distribution of carbides in M2 high-speed steel, the temperature field and the shape of the metal pool during the mold-rotation process were investigated in detail using a numerical simulation. Moreover, the effect of the mold-rotation speed on the electroslag remelting process was investigated using a rotating bifilar electroslag remelting furnace under laboratory conditions. The morphology and distribution of carbides in an ESR ingot were observed using an SEM, and the composition of carbides was analyzed through an electrolytic extraction experiment. Results show that with increase in mold rotation speed, the high-temperature zone of the slag pool moves from the core to the edge. Moreover, the temperature distribution becomes uniform. The depth of the metal pool becomes shallow, and the thickness of the two-phase region decreases, which results in a short local solidification time and small secondary dendrite spacing. Correspondingly, with the increase in the mold rotation speed, the slag skin of ESR ingot becomes thin and more uniform than earlier. The cooling intensity of the mold on the ESR ingot is high, and the carbide network begins to break and become thin. The morphology of carbides changes from flake to fine rod. XRD analysis determines whether the mold rotates or not，carbides always comprise M2C, MC, and M6C. However, the content of M2C increases and the contents of MC and M6C decrease with the increase in mold-rotation speed. The main reason for the improvement in the carbide structure is that the mold rotation decreases the metal pool depth and two-phase zone thickness, which improves the solidification conditions and reduces the element segregation.

Background: Musculocontractural Ehlers–Danlos syndrome (mcEDS) is a rare heritable connective tissue disease with various symptoms. The diagnosis of mcEDS is difficult because of the large overlap of clinical symptoms between different EDS subtypes.Methods: We performed karyotype analysis, gene copy number variation detection, whole-exome sequencing, and Sanger sequencing to reveal the underlying genetic etiology of a fetus with structural abnormalities in feet and kidneys.Results: A likely pathogenic mutation [NM_130468.3 c.958C>T (p.Arg320*)] and an uncertain significance mutation [NM_130468.3 c.896A>G (p.Tyr299Cys)] were identified in the carbohydrate sulfotransferase 14 (CHST14) gene by whole-exome sequencing and validated by Sanger sequencing.Conclusion: The two identified mutations appear highly likely to be the genetic causes of the fetal structural abnormalities.

IntroductionTo explore the relationship between serum 25(OH)D, cadmium, and CRP with all-cause mortality among people in diabetic and non-diabetic.MethodsThis study used data from the NHANES (2001–2010). Cox regression was used to analyze the relationship between Serum 25(OH)D, cadmium, CRP, and all-cause, cause-specific mortality. We used restricted cubic splines to explore the dose-response relationship between serum 25(OH)D, cadmium, CRP, and all-cause mortality.ResultsDuring a mean follow-up of 9.1 years, the study included 20,221 participants, 2,945 people with diabetes, and 17,276 people without diabetes. Compared with serum 25(OH)D deficiency group in diabetic patients, the sufficient serum 25(OH)D group was associated with lower all-cause mortality (HR = 0.41, 95%CI 0.28-0.60, P < 0.001) and cardiovascular mortality (HR = 0.46, 95%CI 0.22–0.95, P = 0.04). Compared with the low cadmium group, the high cadmium group was associated with higher all-cause mortality (HR = 1.49, 95%CI 1.06–2.09, P = 0.02). Compared with the low CRP group, the high CRP group was associated with higher all-cause mortality (HR = 1.65, 95%CI 1.24–2.19, P = 0.001) and cancer mortality (HR = 3.25, 95%CI 1.82–5.80, P < 0.001). Restricted cubic splines analysis showed a significant nonlinear association between serum 25(OH)D (P-nonlinearity P < 0.001), cadmium (P-nonlinearity = 0.002), CRP (P-nonlinearity = 0.003), and HR for all-cause mortality risk in diabetic patients. The results were similar among non-diabetic patients, but with different levels of risk. Sensitivity analysis and subgroup analysis presented the results of population studies with different follow-up times, different genders and ages.ConclusionsIn diabetic patients, serum 25(OH)D, cadmium, and CRP were related to all-cause mortality; serum 25(OH)D was related to cardiovascular mortality; CRP was related to cancer mortality. The results were similar among non-diabetic patients, but with different levels of risk.

IgA nephropathy (IgAN) and membranous nephropathy (MN) are common glomerulonephritis, the presence of which in the same patient– concurrent of IgAN and MN (cIgAN/MN) has been described occasionally. This study aims to show clinical-pathological features of cIgAN/MN and attempts to suggest underlying pathogenesis using disease-specific biomarkers and a genomics approach. This retrospective cohort study described the clinical and pathological data from 137 patients with cIgAN/MN diagnosed in Peking University First Hospital from 2005 to 2019. One hundred primary IgAN and 100 MN cases were randomly selected as disease controls between the same time interval. Moreover, disease-specific biomarkers and polygenic risk score models were conducted to reveal the underlying pathogenesis. The median age of the cIgAN/MN cases was 45-year-old, and 46% were women. Compared to IgAN, patients with cIgAN/MN had a higher level of 24-hour proteinuria excretion but lower microscopic hematuria. They had a lower median level of galactose-deficient IgA1 (Gd-IgA1, 4.00 versus 5.45 μg/ml, P=0.002) as well as the standardized genetic risk scores of developing IgAN (GRSs: 0.05 versus 0.68, P

Difenoconazole is a type of triazole fungicide that is widely used in the treatment of plant diseases. Triazole fungicides have been shown in several studies to impair the development of the nervous system in zebrafish embryos. There is still little known about difenoconazole-induced neurotoxicity in fish. In this study, zebrafish embryos were exposed to 0.25, 0.5, and 1 mg/L of difenoconazole solution until 120 h post-fertilization (hpf). The difenoconazole-exposed groups showed concentration-dependent inhibitory tendencies in heart rate and body length. Malformation rate and spontaneous movement of zebrafish embryos increased, and the locomotor activity decreased in the highest exposure group. The content of dopamine and acetylcholine was reduced significantly in difenoconazole treatment groups. The activity of acetylcholinesterase (AChE) was also increased after treatment with difenoconazole. Furthermore, the expression of genes involved in neurodevelopment was remarkably altered, which corresponded with the alterations of neurotransmitter content and AChE activity. These results indicated that difenoconazole might affect the development of the nervous system through influencing neurotransmitter levels, enzyme activity, and the expression of neural-related genes, ultimately leading to abnormal locomotor activity in the early stages of zebrafish.

Dynein axonemal heavy chain 5 (DNAH5) is the most mutated gene in primary ciliary dyskinesia (PCD), leading to abnormal cilia ultrastructure and function. Few studies have revealed the genetic characteristics and pathogenetic mechanisms of PCD caused by DNAH5 mutation. Here, we established a child PCD airway organoid directly from the bronchoscopic biopsy of a patient with the DNAH5 mutation. The motile cilia in the organoid were observed and could be stably maintained for an extended time. We further found abnormal ciliary function and a decreased immune response caused by the DNAH5 mutation through single-cell RNA sequencing (scRNA-Seq) and proteomic analyses. Additionally, the directed induction of the ciliated cells, regulated by TGF-β/BMP and the Notch pathway, also increased the expression of inflammatory cytokines. Taken together, these results demonstrated that the combination of multiomics analysis and organoid modelling could reveal the close connection between the immune response and the DNAH5 gene.

Abstract Background Hydroxychloroquine (HCQ), a well-known immunomodulator, has recently been found to be a promising and safe anti-proteinuric agent for treating IgA nephropathy (IgAN). We aimed to compare the efficacy and safety of HCQ and corticosteroid treatment in patients with IgAN. Methods This is a case-control study. Ninety-two patients with IgAN who received HCQ in addition to routine renin-angiotensin-aldosterone system inhibitors (RAASi) therapy were included. Ninety-two matched historical controls who received corticosteroids were selected by propensity score matching. The clinical data over 6 months were compared. Results Baseline proteinuria levels were comparable between the HCQ and corticosteroid groups (1.7 [1.2, 2.3] vs. 1.8 [1.3, 2.5] g/d, p = 0.96). The percentage reduction in proteinuria at 6 months was smaller in the HCQ group than in the corticosteroid group (− 48.5% [− 62.6, − 31.4] vs. -62.9% [− 81.1, − 34.9], p = 0.006). The time averaged proteinuria within the 6 months of observation was comparable for the HCQ and corticosteroid groups (1.1 [0.8, 1.5] vs. 1.1 [0.5, 1.8] g/d, p = 0.48). The cumulative frequency of patients with a 50% reduction in proteinuria during the study was also comparable between the two groups (52.2% vs. 62.0%, p = 0.25). However, six of the 92 (6.5%) patients suffered from severe adverse events (SAEs) in the corticosteroid group, while no SAEs were observed in the HCQ group (6.5% vs. 0%, p = 0.03). Conclusions The antiproteinuric effect of HCQ might be slightly inferior to that of corticosteroids over 6 months in patients with IgAN who were deemed to be candidates for HCQ and not corticosteroids treatment. However, HCQ treatment was safer than corticosteroid treatment.

We present PandaX-II constraints on candidate WIMP-nucleon effective interactions involving the nucleon or WIMP spin, including, in addition to standard axial spin-dependent (SD) scattering, various couplings among vector and axial currents, magnetic and electric dipole moments, and tensor interactions. The data set corresponding to a total exposure of 54-ton-days is reanalyzed to determine constraints as a function of the WIMP mass and isospin coupling. We obtain WIMP-nucleon cross section bounds of 1.6×10−41 cm2 and 9.0×10−42 cm2 (90% c.l.) for neutron-only SD and tensor coupling, respectively, for a mass MWIMP∼40GeV/c2. The SD limits are the best currently available for MWIMP>40GeV/c2. We show that PandaX-II has reached a sensitivity sufficient to probe a variety of other candidate spin-dependent interactions at the weak scale. Keywords: PandaX-II experiment, WIMP dark matter, Spin-dependent effective interactions

Abstract Background Stereotactic ablative radiotherapy (SABR) shows a remarkable local control of non-small cell lung cancer (NSCLC) metastases, partially as a result of host immune status. However, the predictors of immune cells for tumor response after SABR are unknown. To that effect, we investigated the ability of pre-SABR immune cells in peripheral blood to predict early tumor response to SABR in patients with lung metastases from NSCLC. Methods This study included 70 patients with lung metastases from NSCLC who were undergoing SABR. We evaluated the early tumor response 1 month and 6 months after SABR in these patients following RECIST 1.1 guidelines. Pre-SABR peripheral CD8+ T cell count, CD8+CD28+ T-cell count, CD8+CD28− T-cell count, CD4+ T-cell count, and Treg-cell count were measured using flow cytometry. Results Increased CD8+CD28+ T-cell counts (14.43 ± 0.65 vs. 10.21 ± 0.66; P = 0.001) and CD4/Treg ratio (16.96 ± 1.76 vs. 11.91 ± 0.74; P = 0.011) were noted in 1-month responsive patients, compared with non-responsive patients. In univariate logistic analyses, high CD8+CD28+ T-cell counts (OR 0.12, 95% CI 0.03–0.48; P = 0.003), CD4/Treg ratio (OR 0.24, 95% CI 0.06–0.90; P = 0.035), and BED10 (OR 0.91, 95% CI 0.84–0.99; P = 0.032) predicted a 1-month tumor response to SABR. According to multivariate logistic analyses, the CD8+CD28+ T-cell count predicted a 1-month tumor response to SABR (OR 0.19, 95% CI 0.04–0.90; P = 0.037) independently. Furthermore, we confirmed the independent predictive value of the CD8+CD28+ T-cell count in predicting tumor response to SABR in 41 patients 6 months after treatment (OR 0.08, 95% CI 0.01–0.85; P = 0.039). Conclusions A pre-SABR CD8+CD28+ T-cell count could predict early tumor response to SABR in patients with lung metastases from NSCLC. Larger, independently prospective analyses are warranted to verify our findings.

Background The study was conducted to examine changes in diagnostic and staging imaging methods for lung cancer in China over a 10‐year period and to determine the relationships between such changes and socioeconomic development. Methods This was a hospital‐based, nationwide, multicenter retrospective study of primary lung cancer cases. The data were extracted from the 10‐year primary lung cancer databases at eight tertiary hospitals from various geographic areas in China. The chi‐squared test was used to assess the differences and the Cochran–Armitage trend test was used to estimate the trends of changes. Results A total of 7184 lung cancer cases were analyzed. Over the 10‐year period, the utilization ratio of diagnostic imaging methods, such as chest computed tomography (CT) and chest magnetic resonance imaging (MRI), increased from 65.79% to 81.42% and from 0.73% to 1.96%, respectively, while the utilization ratio of chest X‐ray declined from 50.15% to 30.93%. Staging imaging methods, such as positron emission tomography‐CT, neck ultrasound, brain MRI, bone scintigraphy, and bone MRI increased from 0.73% to 9.29%, 22.95% to 47.92%, 8.77% to 40.71%, 42.40% to 62.22%, and 0.88% to 4.65%, respectively; abdominal ultrasound declined from 83.33% to 59.9%. These trends were more notable in less developed areas than in areas with substantial economic development. Conclusion Overall, chest CT was the most common radiological diagnostic method for lung cancer in China. Imaging methods for lung cancer tend to be used in a diverse, rational, and regionally balanced manner.

In this work, magnetic tetraethylenepentamine (TEPA)-modified carboxyl–carbon nanotubes were synthesized, characterized, and used as adsorbents to conduct magnetic solid-phase extraction (MSPE) for the preconcentration of seven local anesthetic drugs (procaine, lidocaine, mepivacaine, oxybuprocaine, bupivacaine, tetracaine, and cinchocaine) from human plasma. The separation and determination of analytes were performed on high-performance liquid chromatography with UV detection. Several factors affected the extraction efficiency, such as the amount of adsorbents used, extraction time, sample pH, and optimization of elution conditions. Under optimal conditions, satisfactory linear relationships were obtained in the range of 0.02–5.00 mg/L, with the limits of detection (LOD) ranging from 0.003 mg/L to 0.008 mg/L. The recoveries of analytes for spiked human plasma were in the range of 82.0–108%. Moreover, the precision with intra-day and inter-day RSD values were obtained in the range of 1.5–7.7% and 1.5–8.3%. The results indicated that this method could determine the concentration of seven local anesthetic drugs in human plasma with high precision and repeatability and provide support for the clinical monitoring of the concentration of local anesthetic drugs in human plasma.

Small and fragmented arable land is a key challenge for small-scale agricultural countries, resulting in low labor productivity, ecological damage, and inefficient land use. To cope with this challenge, the farmland transfer (FLT) policy is implemented to establish modern agriculture based on specialization and scale enlargement. Despite the rising body of literature, an overview of the effect of this policy is lacked. This paper aimed to examine the multi-dimensional effects of FLT in China. A systematic search of the Web of Science and Scopus databases revealed 26 full-text peer-reviewed articles. We found that FLT had both positive and negative effects, and its effects were mainly mediated by intermediary factors. Non-contingent FLT and post-FLT actions were responsible for the adverse effects of FLT. In the literature, the influence of FLT on the environment is the most concerning issue. The results also show that the existing evidence on the effect of FLT is insufficient; therefore, this paper proposes to further exploration of the multi-dimensional effects of FLT, institutional feedback, and trade-offs. While FLT offers the potential to address socio-economic and environmental challenges, this study suggests that an institutional framework that takes into account spatial and temporal aspects, land-use, market systems, and household conditions is needed to promote favorable development, and mitigate potential land market problems and ensure sustainable development. Despite significant limitations remain, the literature on the socio-economic and environmental effects of FLT is increasing.

Mice selectively expressing a PPAR[gamma] dominant-negative mutation in vascular smooth muscle exhibit RhoBTB1 deficiency and hypertension. Our rationale was to use genetic complementation to uncover the mechanism of action of RhoBTB1 in vascular smooth muscle. Inducible smooth muscle-specific restoration of RhoBTB1 fully corrected hypertension and arterial stiffness by improving vasodilator function. Notably, the cardiovascular protection occurred despite the preservation of increased agonist-mediated contraction and RhoA and Rho kinase activity, suggesting that RhoBTB1 selectively controls vasodilation. RhoBTB1 augmented the cyclic 3',5'-monophosphate (cGMP) response to NO by restraining the activity of phosphodiesterase 5 (PDE5) through its action as a substrate adaptor delivering PDE5 to the Cullin-3 E3 ring ubiquitin ligase complex for ubiquitination, thereby inhibiting PDE5. Angiotensin II infusion also caused RhoBTB1 deficiency and hypertension, which were prevented by smooth muscle-specific RhoBTB1 restoration. We conclude that RhoBTB1 protected against hypertension, vascular smooth muscle dysfunction, and arterial stiffness in at least 2 models of hypertension., Introduction PPAR[gamma] is a ligand-activated transcription factor known to regulate fatty acid metabolism. The clinical significance of PPAR[gamma] is best illustrated by the improvement in glycemic control in patients with [...]

A natural reserve’s forest is an important base for promoting natural education, scientific research, biodiversity conservation and carbon accounting. Dynamic monitoring of the forest type and forest aboveground biomass (AGB) in a nature reserve is an important foundation for assessing the forest succession stage and trend. Based on the Landsat images covering the National Nature Reserve of Yaoluoping in Anhui province spanning from 1987 to 2020, a total of 42 Landsat scenes, the forest cover product set was first developed by using the well-established vegetation change tracker (VCT) model. On this basis, a new vegetation index, NDVI_DR, which considers the phenological characteristics of different forest types, was proposed to distinguish coniferous forest from broad-leaved forest. Next, multiple modeling factors, including remote sensing spectral signatures, vegetation indices, textural measures derived from gray level co-occurrence matrix and wavelet analysis and topographic attributes, were compiled to model the AGB in 2011 by forest type separately by using the stochastic gradient boosting (SGB) algorithm. Then, using the 2011 Landsat image as the base, all the Landsat images in the other years involved in the modelling were relatively normalized by using the weighted invariant pixels (WIP) method, followed by an extrapolation of the 2011 AGB model to other years to create a time-series of AGB. The results showed that the overall accuracy of the VCT-based forest classification products was over 90%. The annual forest type classifications derived from NDVI_DR thresholding gained an overall accuracy above 92%, with a kappa coefficient above 0.8. The 2011 forest-type-dependent SGB-based AGB estimation model achieved an independent validation R2 at 0.63 and an RMSE at 11.18 t/ha for broad-leaved forest, and 0.61 and 14.26 t/ha for coniferous forest. The mapped time-series of AGB showed a gradual increasing trend over the past three decades. The driving factors responsible for the observed forest cover and AGB changes were analyzed to provide references for reasonable protection and development. The proposed methodology is a reliable tool for evaluating the management status, which can be extended to other similar regions.

It is one of the important safety problems in the process of mining shallow coal seams in western China that the rock mass affected by mining stress breaks and forms a penetrating fracture, leading to a sand burst in the working face. The self-developed test system is used to carry out the experimental study on the flow characteristics of Aeolian sand in fractures. The research work is focused on the influence of several parameters, such as the thickness of the Aeolian sand layer, the fracture opening, and the fracture dip angle on the velocity of sand particles in fractures. The results show the following: (1) The influence of fracture opening and fracture angle on sand burst rate is much greater than that of sand thickness. No matter what the fracture angle and fracture opening value are, the influence weight of sand thickness on sand burst rate is almost zero. (2) When other conditions are unchanged, with the increase of fracture dip angle, the sand burst rate increases significantly, and the relationship between the sand burst rate and the fracture dip angle is exponential. (3) The influence weight of fracture opening is the largest. With the increase of fracture opening, the sand burst rate increases logarithmically. Finally, according to the test results, the relation equation which can simultaneously describe the influence of fracture opening and fracture inclination on the rate of the sand burst is fitted. This study can provide a theoretical basis and scientific guidance for the prevention and control of coal mine sand inrush disasters caused by roof cracking in western coal mines.

Background and Purpose: The availability of oncology biosimilars is deemed as a fundamental strategy to achieve sustainable health care. However, there is scarce systematic evidence on economic effectiveness of cancer biosimilars. We aimed to synthesize evidence from pharmacoeconomic evaluation of oncology biosimilars globally, provide essential data and methodological reference for involved stakeholders.Materials and Methods: This systematic review was conducted in PubMed, embase, the Cochrane library, CRD, ISPOR and NICE utill December 31, 2019. Information on basic characteristics, evaluation methodology and results were extracted. Quality of included studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards Checklist.Results: For 17 studies identified (13 from Europe and four from United States), the overall quality was generally acceptable. A total of seven biological molecules involved with filgrastim, EPOETIN α, and trastuzumab leading the three. The mostly common evaluation perspective was payer, but the time horizon varied greatly. There were ten studies which adopted cost minimization analysis to evaluate efficiency while seven studies adopted budget impact analysis to address affordability, with cost ratio and cost saving being its corresponding primary endpoint. Although the comparability of included studies was limited and specific results were largely affected by uptake and price discount rates of the oncology biosimilar, the comprehensive results consistently favored its promotion.Conclusion: Globally, the economic evaluation of cancer biosimilars is in its initial phase. However, limited evidence from developed countries consistently supported both cost-effectiveness of efficiency and affordability of oncology biosimilars, while they were largely affected by uptake and price discount rate.

Objective: Herpes simplex viruses (HSVs) are widely spread throughout the world, causing infections from oral, and genital mucous membrane ulcerations to severe viral encephalitis. Glycoprotein B (gB) was the first HSV envelope glycoprotein identified to induce cell fusion. This glycoprotein initiates viral entry and thereby determines the infectivity of HSV, as well as oncolytic HSV (oHSV). Clarifying its molecular characterization and enlarging its motif reservoir will help to engineer oHSV and in cancer treatment applications. Only in recent years has the importance of gB been acknowledged in HSV infection and oHSV engineering. Although gB-modified oHSVs have been developed, the detailed molecular biology of gB needs to be illustrated more clearly in order to construct more effective oHSVs.Method: Here, we performed a systematic comparative sequence analysis of gBs from the 9 HSV-1 and 2 HSV-2 strains, including HSV-1-LXMW, which was isolated by our lab. Online software was implemented to predict gB secondary structure and motifs. Based on extensive literature reviews, a functional analysis of the predicted motifs was performed.Results: Here, we reported the DNA and predicted amino acid sequences of our recently isolated HSV-1-LXMW and found that the strain was evolutionarily close to HSV-1 strains F, H129, and SC16 based on gB analysis. The 22 novel motifs of HSV gB were identified for the first time. An amino acid sequence alignment of the 11 HSV strains showed that the gB motifs are conserved among HSV strains, suggesting that they are functional in vivo. Additionally, we found that certain amino acids within the 13 motifs out of the 22 were reported to be functional in vivo. Furthermore, the gB mutants and gB-engineered oHSVs were also summarized.Conclusion: Our identification of the 22 novel motifs shed light on HSV gB biology and provide new options for gB engineering to improve the efficiency and safety of oHSVs.

Based on the development status of low permeability reservoirs, an intelligent nano-flooding agent is needed to improve the displacement efficiency of reservoirs. Janus particles have the characteristics of small size and strong interfacial activity, and the solid surfactant of Janus particles has attracted more and more attention of petroleum researchers. Janus smart nanosheets were developed by Pickering emulsion preparation. Controllable assemblies of Janus smart nanosheets were formed by adjusting the preparation ratio. The structure and properties of smart nanosheets were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy and interfacial tensiometer. The nanosheets have hydrophilic and hydrophilic properties. The particle size of silica nanoparticle is 10 nm. After surface modification and high shear stress treatment, nanosheet was formed. The thickness of nanosheet dispersed in aqueous solution was 30.2 nm. Experimental results show that at a given temperature, the Janus nanosheet system with low concentration can achieve ultra-low interfacial tension of 10−4 mN /m, and the nanosheets have good emulsifying ability. The results provide basic insights into the bio-assembly behavior and emulsifying properties of Janus smart nanosheets, and further prove their potential for enhancing oil recovery.