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Purpose Talaromyces marneffei (TM) is an opportunistic fungus leading to multi-organ damages and poor prognosis in immunocompromised individuals. TM infections in children are rare and our knowledge to TM infection is insufficient. To investigate the clinical characteristics of TM-infected children and to explore the underlying mechanisms for host against TM, we analysed TM-infected patients diagnosed in our hospital. Methods Eight patients with TM infections have been identified in Shenzhen Children’s Hospital during 2017–2021. Clinical data were collected from medical records. Immunological features were evaluated by flow cytometry. Literatures were also reviewed to summarize the reported inborn errors of immunity (IEIs) with TM infections. Results All 8 children were HIV-negative. The most common symptom of TM infections was fever (8/8), followed by weight loss (7/8), pneumonia (7/8), hepatomegaly (7/8), splenomegaly (6/8), anemia (6/8), lymphadenopathy (5/8), thrombocytopenia (3/8), diarrhea (3/8), rashes or skin lesions (3/8), and osteolytic lesions (1/8). Five children died during the follow-ups. CD3+ T cells were decreased in 6 patients. Eight patients had reduced natural killer cells. All patients went gene sequencing and were finally diagnosed as IEIs, including STAT1 gain-of-function, IL-2 receptor common gamma chain deficiency, adenosine deaminase deficiency, CD40 ligand deficiency, and STAT3 deficiency. Another 4 types of IEIs (CARD9, IFN-γ receptor 1, RelB, and NFKB2 deficiency), have been reported with TM infections based on literature review. Conclusion TM infections resulted in systemic injuries and high mortality. The spectrum of IEIs underlying TM infections indicated that T cell-mediated immunity, IFN-γ, IL-17 signalings and NF-κB pathways were important for host responses against TM infection. In reverse, for HIV-negative children without other secondary immunodeficiencies, IEIs should be considered in TM-infected children.

Cancer treatment is gradually entering an era of precision, with multitude studies in gene testing and immunotherapy. Tumor cells can be recognized and eliminated by the immune system through the expression of tumor-associated antigens, but when the cancer escapes or otherwise suppresses immunity, the balance between cancer cell proliferation and immune-induced cancer cell killing may be interrupted, resulting in tumor proliferation and progression. There has been significant attention to combining conventional cancer therapies (i.e., radiotherapy) with immunotherapy as opposed to treatment alone. The combination of radio-immunotherapy has been demonstrated in both basic research and clinical trials to provide more effective anti-tumor responses. However, the absolute benefits of radio-immunotherapy are dependent on individual characteristics and not all patients can benefit from radio-immunotherapy. At present, there are numerous articles about exploring the optimal models for combination radio-immunotherapy, but the factors affecting the efficacy of the combination, especially with regard to radiosensitivity remain inconclusive. Radiosensitivity is a measure of the response of cells, tissues, or individuals to ionizing radiation, and various studies have shown that the radiosensitivity index (RSI) will be a potential biomarker for predicting the efficacy of combination radio-immunotherapy. The purpose of this review is to focus on the factors that influence and predict the radiosensitivity of tumor cells, and to evaluate the impact and predictive significance of radiosensitivity on the efficacy of radio-immunotherapy combination.

Incidence of premature ovarian failure (POF) is higher with the increase of the pace of life. The etiology of POF is very complex, which is closely related to genes, immune diseases, drugs, surgery, and psychological factors. Ideal animal models and evaluation indexes are essential for drug development and mechanism research. In our review, we firstly summarize the modeling methods of different POF animal models and compare their advantages and disadvantages. Recently, stem cells are widely studied for tumor treatment and tissue repair with low immunogenicity, high homing ability, high ability to divide and self-renew. Hence, we secondly reviewed recently published data on transplantation of stem cells in the POF animal model and analyzed the possible mechanism of their function. With the further insights of immunological and gene therapy, the combination of stem cells with other therapies should be actively explored to promote the treatment of POF in the future. Our article may provide guidance and insight for POF animal model selection and new drug development. Graphical Abstract

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment and have detrimental effects on human health. Embryos are particularly susceptible to environmental insults such as PAHs. We examined the association between prenatal exposure to PAHs and the risk for fetal neural tube defects (NTDs). A case-control study was conducted with 119 NTD cases and 119 controls. A total of 16 PAHs in umbilical cord tissue, determined with gas chromatography–mass spectrometry, were used as in utero exposure markers. Logistic regression and Bayesian kernel machine regression (BKMR) were performed to evaluate the individual and overall effects of PAH exposure on the risk for NTDs, respectively. Median concentrations of 10 PAHs were significantly higher in cases than in controls. In logistic regression, concentrations of four PAHs above the median of all participants were significantly associated with an increased NTD risk, even when potential covariates were adjusted for: phenanthrene, 2.35-fold (95% confidence interval [CI] 1.04–5.34); fluoranthene, 2.37-fold (95% CI 1.02–5.48); pyrene, 2.41-fold (95% CI 1.04–5.62); and benzo(b)fluoranthene, 2.95-fold (95% CI 1.27–6.86). In BKMR, the risk for NTDs increased when PAH concentrations were all above their 65th percentile compared to their median, while no statistical association between a single compound and NTD risk was observed when the remaining nine PAHs were taken into consideration simultaneously. Together these results show that prenatal PAH exposure is a risk factor for NTDs in offspring.

Cellular senescence serves as a powerful tumor suppressing mechanism that inhibits the proliferation of cancer cells bearing oncogenic mutations at the initial stage of cancer development. RNA-binding proteins (RBPs) play important roles in cancer progression and treatment through distinct functions. However, functions and mechanisms of RNA binding proteins in regulating senescence remain elusive. Here we reported that the RNA binding protein RBM4 contributed to cellular senescence. Depletion of RBM4 induced senescence in different types of cells, including multiple cancer cells. Meanwhile, RBM4 ablation inhibited cancer cell progression both in vitro and in vivo. Specifically, knockdown of RBM4 significantly increased the level of SERPINE1, a known promoter of senescence, thereby inducing the senescence of lung cancer cells. Mechanistically, miR-1244 bound to the 3ʹ-UTR of SERPINE1 to suppress its expression, whereas depletion of RBM4 reduced the level of miR-1244 by promoting the degradation of primary miR-1244 transcripts (pri-miR1244), thus increasing the expression of SERPINE1 and inducing subsequent senescence. Moreover, either SERPINE1 inhibitor or miR-1244 mimics attenuated the RBM4 depletion-induced senescence. Altogether, our study revealed a novel mechanism of RBM4 in the regulation of cancer progression through controlling senescence, providing a new avenue for targeting RBM4 in cancer therapeutics.

Background Distant metastasis, which occurs at a rate of 25% in patients with esophageal cancer (EC), has a poor prognosis, with previous studies reporting an overall survival of only 3–10 months. However, few studies have been conducted to predict distant metastasis in EC, owing to a dearth of reliable biomarkers. The purpose of this study was to develop and validate an accurate model for predicting distant metastasis in patients with EC. Methods A total of 299 EC patients were enrolled and randomly assigned to a training cohort (n = 207) and a validation cohort (n = 92). Logistic univariate and multivariate regression analyses were used to identify clinical independent predictors and create a clinical nomogram. Radiomic features were extracted from contrast-enhanced computed tomography (CT) images taken prior to treatment, and least absolute shrinkage and selection operator (Lasso) regression was used to screen the associated features, which were then used to develop a radiomic signature. Based on the screened features, four machine learning algorithms were used to build radiomics models. The joint nomogram with radiomic signature and clinically independent risk factors was developed using the logical regression algorithm. All models were validated and compared by discrimination, calibration, reclassification, and clinical benefit. Results Multivariable analyses revealed that age, N stage, and degree of pathological differentiation were independent predictors of distant metastasis, and a clinical nomogram incorporating these factors was established. A radiomic signature was developed by a set of sixteen features chosen from 851 radiomic features. The joint nomogram incorporating clinical factors and radiomic signature performed better [AUC(95% CI) 0.827(0.742–0.912)] than the clinical nomogram [AUC(95% CI) 0.731(0.626–0.836)] and radiomics predictive models [AUC(95% CI) 0.754(0.652–0.855), LR algorithms]. Calibration and decision curve analyses revealed that the radiomics–clinical nomogram outperformed the other models. In comparison with the clinical nomogram, the joint nomogram's NRI was 0.114 (95% CI 0.075–0.345), and its IDI was 0.071 (95% CI 0.030–0.112), P = 0.001. Conclusions We developed and validated the first radiomics–clinical nomogram for distant metastasis in EC which may aid clinicians in identifying patients at high risk of distant metastasis.

R1234yf is characterized by low global warming potential (GWP) and it is a very promising candidate to substitute traditional refrigerant in the near future. The condensation heat transfer of low GWP refrigerant R1234yf was experimentally studied in detailed in this study. The influence of tube diameter was also discussed. HTCs were measured in horizontal tubes with the inner diameter (ID) of 2 and 4 mm, and the flow patterns taken during experiment were used to analyze the results. Different effects including mass fluxes, vapor quality, thermophysical properties, flow pattern and tube diameter on the HTC were also analyzed. Under the same mass flux and vapor quality, the flow patterns within ID 4 mm and 2 mm are significantly different. The turbulence between the vapor and liquid interface become gentle within ID 2 mm compared that within ID 4 mm by observation. At high mass fluxes, the HTCs within ID 2 mm tube are close to or even higher than that within ID 4 mm tube. When reducing the tube diameter, the influence of thermophysical properties, especially the surface tension on heat transfer is more obvious. Based on the laminar liquid film analytical solution and single phase forced convective heat transfer correlation, also considering the influence of surface tension and gravity, a new heat transfer correlation is developed with the experimental data using R1234yf, R134a and R32 within tube inner diameter 2 mm. The comparison shows that the mean deviation is 13.5%.

Based on observations over an alpine glacier, we investigate the turbulent flux dissimilarity between momentum and sensible heat transfer in a stably stratified katabatic flow. The flux correlation coefficient RF is employed as a measure of variable levels of the flux similarity, which are found to be modulated by the anisotropy of turbulence. In the katabatic wind regime over this glacier, heat is transported more efficiently than momentum. Based on quadrant analysis, the sweep–ejection differences in the flux fraction constitute turbulence characteristics in terms of the velocity aspect ratio, which unravel dissimilar transport of momentum and heat. Moreover, an innovative method is established for connecting quadrant analysis and cospectral analysis, whereby the hyperbolic quadrant hole size is coupled to the frequency underlying the fast Fourier transform. In extending applications of octant analysis, we introduce a hypothetical octant hole, whose size is solicited as a proxy for the amplitude scale of fluctuating fluxes. The contributions to $${R}_{F}$$ can then be quantified for eddy structures that are associated with different amplitude scales. The katabatic flow structures identified from octant analysis differ in their behaviour so helping illuminate the outcome of flux dissimilarity. Exhibited as a statistical behaviour regardless of amplitude scale, along-wind rapid motions of heated air parcels can modify fractional contributions to the heat flux instead of the momentum flux, with reductions in $${R}_{F}$$ related to decreasing heat-flux fractions. Besides, along-wind slow motions of cooled air parcels cannot modify the flux fractions for both momentum and heat. Thus, the flux dissimilarity due to low-speed low-temperature eddies cannot be explicable in terms of the flux fractions alone. These findings are an incipient step towards physical understanding of the turbulent flux dissimilarity for a stably stratified katabatic flow.

Poplar is raw material for various panel, paper and fiber products. The 12 sample trees of clone Nanlin-895 from four spacings were destructively harvested after thirteen growing seasons to assess the influence of spacing on radial growth and wood properties. Spacing significantly affected tree-ring width and wood basic density (p

Sodium-ion batteries (SIBs) have developed rapidly owing to the high natural abundance, wide distribution, and low cost of sodium. Among the various materials used in SIBs, sodium superion conductor (NASICON)-based electrode materials with remarkable structural stability and high ionic conductivity are one of the most promising candidates for sodium storage electrodes. Nevertheless, the relatively low electronic conductivity of these materials makes them display poor electrochemical performance, significantly limiting their practical application. In recent years, the strategies of enhancing the inherent conductivity of NASICON-based cathode materials have been extensively studied through coating the active material with a conductive carbon layer, reducing the size of the cathode material, combining the cathode material with various carbon materials, and doping elements in the bulk phase. In this paper, we review the recent progress in the development of NASICON-based cathode materials for SIBs in terms of their synthesis, characterization, functional mechanisms, and performance validation/optimization. The advantages and disadvantages of such SIB cathode materials are analyzed, and the relationship between electrode structures and electrochemical performance as well as the strategies for enhancing their electrical conductivity and structural stability is highlighted. Some technical challenges of NASICON-based cathode materials with respect to SIB performance are analyzed, and several future research directions are also proposed for overcoming the challenges toward practical applications.

NOS-NO system activity is closely correlated with ischemia-reperfusion injury (IRI) and NOS subtypes were suggested to play different roles in IRI. In this work, the activity of serum NOS, NO levels, and ischemic necrosis after reperfusion in rabbit with AMI at different time was studied. We also explored the NOS-NO system activity changes and its correlation with myocardial ischemia and necrosis. It shows that after reperfusion in rabbits with AMI, NO-NOS system activities present different changes at each time point due to inactivation of NO and iNOS activation, and different experimental animals, ischemia-reperfusion degree, and length of time will also lead to different research results. Therefore, it is necessary to conduct dynamic observation on animals from different species at multi-temporal point under the state of NOS-NO system activities, and simultaneously detect inflammatory factor, MDA, and SOD indexes. Therefore, it is a must to conduct relevant drug research studies to make NOS-NO system activities maintain the level in favor of ideal myocardial ischemia reperfusion.

Long term regular intake of black tea (BT) can lower blood pressure, which is probably due to its antioxidant activity and angiotensin converting enzymes (ACE) inhibitory activity. This study achieves a comprehensive understanding of the relationship between bioactive compounds of BT and its ACE inhibitory activity and antioxidant activity. Phenolic compounds are closely related to antioxidant activity and ACE inhibitory activity. Catechin (C) exhibits stronger inhibitory activity on ACE enzyme than that of other compounds. Molecular docking demonstrates that C could directly bind to ACE active site pockets and Zn(II). Other bioactive compounds are involved in antioxidant and ACE inhibitory activity in varying degrees but no obvious trend is established. Our study proposes a conjecture that some bioactive compounds of BT regulate antioxidant defenses through mechanisms that involve ACE. The mixed mode of in vitro inhibition of ACE and oxidant of BT bioactive compounds needs to be further investigated.

The secondary structures of nucleic acids have an important influence on their cellular functions but can be difficult to identify and classify quickly. Here, we show that an arrayed suite of synthetic hosts and dyes is capable of fluorescence detection of oligonucleotide secondary structures. Multivariate analysis of different fluorescence enhancements-generated using cationic dyes that show affinity for both DNA G-quadruplexes and the synthetic hosts-enables discrimination between G-quadruplex structures of identical length and highly similar topological types. Different G-quadruplexes that display the same folding topology can also be easily differentiated by the number of G-quartets and sequence differences at the 3' or 5' ends. The array is capable of both differentiation and classification of the G-quadruplex structures at the same time. This simple non-invasive sensing method does not require the discovery and synthesis of specific G-quadruplex binding ligands, but employs a simple multicomponent approach to ensure wide applicability.

Background The safety and effectiveness of lung segmentectomy in patients with early non-small cell lung cancer (NSCLC) remains controversial. We have therefore reviewed the clinicopathologic characteristics and survival outcomes of patients treated with lobectomy or segmentectomy for early T (> 2 and ≤ 3 cm) N0M0 NSCLC. Methods We obtained data from the Surveillance, Epidemiology, and End Results database for patients who underwent lobectomy or segmentectomy between 2004 and 2015. To reduce bias and imbalances between the treatment groups, propensity score matching analysis was performed. We used Kaplan–Meier curves to estimate overall survival (OS) and lung cancer-specific survival (LCSS). We conducted univariate and multivariate Cox proportional hazards regression analyses to identify independent prognostic factors for OS and cancer-specific survival, and applied the Cox proportional hazards model to create forest plots. Results Before matching, both univariate and multivariate Cox regression analyses revealed that patients who underwent lobectomy exhibited better OS (P P = 0.001) than patients who underwent segmentectomy. However, after matching, survival differences between the groups were not significant; OS (P = 0.434) and LCSS (P = 0.593). Regression analyses revealed that age and tumor grade were independent predictors of OS and LCSS (P Conclusions Patients with stage T (> 2 and ≤ 3 cm) N0M0 NSCLC undergoing segmentectomy can obtain OS and LCSS similar to those obtained with lobectomy. Further studies are required considering the solid component effects and pathologic tumor types regarding segmentectomies. Additional long-term survival and outcome analyses should be conducted with larger cohorts.

Kawasaki disease is a kind of self-limited systemic vasculitis involving middle and small arteries, which usually occurs in children under 5 years old. Excessive inflammatory response caused by activation of monocytes is one of the important mechanisms of Kawasaki disease. Activated monocytes secrete large amounts of inflammatory mediators such as TNF-α and IL-1β. Activin A, a member of transforming growth factor-β superfamily, is a multifunctional growth and transforming factor. Several experimental evidences pinpoint that Activin A can regulate multiple biological function of the immune system. However, whether Activin A is involved in regulation of activation of monocytes in Kawasaki disease was not well characterized. Here, this study showed that the expression of Activin A in serum decreased in acute-phase Kawasaki disease. Furthermore, Activin A inhibits activin type IIA receptor, activin type IB receptor, CD86 and CD80 expression in over-activated monocytes. In addition, Activin A inhibited Smad3 expression and NF-κB signaling pathways. Specific function and mechanism of Activin A in acute-phase Kawasaki disease need further study.

Background The rhizosphere is the narrow zone of soil immediately surrounding the root, and it is a critical hotspot of microbial activity, strongly influencing the physiology and development of plants. For analyzing the relationship between the microbiome and metabolome in the rhizosphere of tea (Camellia sinensis) plants, the bacterial composition and its correlation to soil metabolites were investigated under three different fertilization treatments (unfertilized, urea, cow manure) in different growing seasons (spring, early and late summer). Results The bacterial phyla Proteobacteria, Bacteroidetes, Acidobacteria and Actinobacteria dominated the rhizosphere of tea plants regardless of the sampling time. These indicated that the compositional shift was associated with different fertilizer/manure treatments as well as the sampling time. However, the relative abundance of these enriched bacteria varied under the three different fertilizer regimes. Most of the enriched metabolic pathways stimulated by different fertilizer application were all related to sugars, amino acids fatty acids and alkaloids metabolism. Organic acids and fatty acids were potential metabolites mediating the plant-bacteria interaction in the rhizosphere. Bacteria in the genera Proteiniphilum, Fermentimonas and Pseudomonas in spring, Saccharimonadales and Gaiellales in early summer, Acidobacteriales and Gaiellales in late summer regulated relative contents of organic and fatty acids. Conclusion This study documents the profound changes to the rhizosphere microbiome and bacterially derived metabolites under different fertilizer regimes and provides a conceptual framework towards improving the performance of tea plantations.

With a 10% reversible compressive strain in more than 10 deformation cycles, the shape memory polymer composites (SMPCs) could be used for deployable structure and releasing mechanism. In this paper, without traditional electro-explosive devices or motors/controllers, the deployable SMPC flexible solar array system (SMPC-FSAS) is studied, developed, ground-based tested, and finally on-orbit validated. The epoxy-based SMPC is used for the rolling-out variable-stiffness beams as a structural frame as well as an actuator for the flexible blanket solar array. The releasing mechanism is primarily made of the cyanate-based SMPC, which has a high locking stiffness to withstand 50 g gravitational acceleration and a large unlocking displacement of 10 mm. The systematical mechanical and thermal qualification tests of the SMPC-FSAS flight hardware were performed, including sinusoidal sweeping vibration, shocking, acceleration, thermal equilibrium, thermal vacuum cycling, and thermal cycling test. The locking function of the SMPC releasing mechanisms was in normal when launching aboard the SJ20 Geostationary Satellite on 27 Dec., 2019. The SMPC-FSAS flight hardware successfully unlocked and deployed on 5 Jan., 2020 on geostationary orbit. The triggering signal of limit switches returned to ground at the 139 s upon heating, which indicated the successful unlocking function of SMPC releasing mechanisms. A pair of epoxy-based SMPC rolled variable-stiffness tubes, which clapped the flexible blanket solar array, slowly deployed and finally approached an approximate 100% shape recovery ratio within 60 s upon heating. The study and on-orbit successful validation of the SMPC-FSAS flight hardware could accelerate the related study and associated productions to be used for the next-generation releasing mechanisms as well as space deployable structures, such as new releasing mechanisms with low-shocking, testability and reusability, and ultra-large space deployable solar arrays.

In this paper, Ni2P nanoparticles is incorporated onto the graphene & carbon nanotubes composite (Ni2P NPs/rGO & CNTs) to form flexible free-standing intertwining network film anodes for improving the cycle-life of sodium-ion batteries (SIBs). Benefited from the volume accommodation by this Ni2P NPs/rGO & CNTs structure and its excellent electronic conductive network along with high mechanical strength, such an anode-based SIB shows a superior capacity retention with a stable and long cycle-life at high current densities. For Ni2P NPs/rGO & CNTs electrode, it remains a capacity of 224 mAh g−1 after 100 cycles, at a high current density of 0.5 A g−1, the Ni2P NPs/rGO & CNTs can still maintain a stable reversible capacity of ~ 150 mAh g−1 after 500 cycles, after cycling at a rate as high as 1 A g−1, the reversible capacity of the Ni2P NPs/rGO/CNT can still sustain stable capacities at 91 mAh g−1 after 2000 cycles, respectively. Even at 5 A g−1, it still exhibits a high rate capacity of 65 mAh g−1, thus exhibiting an excellent sodium storage kinetics.

Land subsidence along significant linear engineering is mainly affected by long-term over-extraction of groundwater, mining of mineral resources, and karst collapse. In this paper, combined with the engineering geological and hydrogeological conditions, a three-dimensional fluid-solid model of land subsidence is established based on groundwater seepage and Biot’s consolidation theories, in order to analyze and forecast the evolution law of the groundwater and land subsidence. The numerical results are verified using field monitoring data (InSAR and high-precision level measurement results). On the basis of monitoring and numerical results, the induced factors and distribution characteristics of land subsidence along the high-speed railway line are determined. According to different groundwater exploitation schemes, the development and evolution laws of ground subsidence in the future are predicted to analyze the influence of ground subsidence on high-speed railway line. The results suggest that (1) the main influencing factors of land subsidence in DK306~DK313 and DK411~DK414 sections are groundwater over-extraction, while DK276~DK279 section is coal mining, DK368~DK372 section requires a special research; (2) the decrease of land subsidence rate and differential subsidence are shown to be nonlinear with the reduction of groundwater withdrawal; (3) under the same mining conditions of groundwater, the land subsidence rate and differential subsidence are declining with time; (4) the surface differential subsidence is obviously sensitive to groundwater exploitation.

The Loess Plateau is the largest apple cultivation region in the world. However, the role of rain-fed apple orchards as carbon sinks or sources, including the dynamic variation and influencing factors, are still unclear. In this study, the net ecosystem CO2 exchange (NEE) was monitored by an eddy covariance (EC) system in Loess Plateau apple orchards during 2016–2017. The results demonstrated that the annual NEE was higher in 2016 (− 698.0 g C m−2 year−1) than in 2017 (− 554.0 g C m−2 year−1). Particularly, the amount of orchard CO2 uptake was significantly greater in 2016 (− 772.0 g C m−2) than in 2017 (− 642.1 g C m−2) during the carbon sink period. This difference may be attributed to the higher NEE in 2016 compared to 2017 during the fast and slow growth periods. In addition, a higher daily NEE occurred to the higher air temperature (Ta), which promoted early sprouting in 2016 (− 3.91 g C m−2 day−1) compared to 2017 (− 2.86 g C m−2 day−1) during the fast growth period. The daily NEE in 2016 (− 2.59 g C m−2 day−1) was remarkably higher than that in 2017 (− 1.41 g C m−2 day−1) during the slow growth period, owing to the greater number of cloudy and rainy days and lower temperatures in 2017. Overall, the present study demonstrated the key role played by the amount of precipitation and temperature in regulating the NEE during the growth season and provided accurate quantitative information on the carbon budget in apple orchards.

A biosimilar needs to demonstrate its similarity to the originator reference product (RP) in terms of structural and functional properties as well as nonclinical and clinical outcomes. The aim was to assess the analytical similarity between the trastuzumab biosimilar HLX02 and Europe-sourced Herceptin® (EU-Herceptin®) and China-sourced Herceptin® (CN-Herceptin®) following a quality-by-design (QbD) quality study and tier-based quality attribute evaluation. A panel of highly sensitive and orthogonal methods, including a novel Fc gamma receptor IIIa (FcγRIIIa) affinity chromatography technique that enables quantitative comparison of glycan effects on effector function, was developed for the assessment. To ensure the full product variability was captured, ten batches of HLX02 were compared with 39 RP batches with expiry dates from August 2017 to March 2021. The extensive three-way similarity assessment demonstrated that HLX02 is highly similar to the RPs. Furthermore, the %afucose, %galactose, and FcγRIIIa affinity of the RPs were observed to first decrease and then return to the original level in relation to their expiry dates, and the RP batches can be subgrouped by their FcγRIIIa affinity chromatograms. HLX02 is demonstrated to be more similar to the RPs of the high FcγRIIIa affinity group. Besides having an overall high analytical similarity to both EU-Herceptin® and CN-Herceptin®, HLX02 is more similar to Herceptin® with high FcγRIIIa affinity, a result that demonstrates the power of the novel FcγRIIIa affinity chromatography technology in biosimilarity evaluation.

D2D (Device-to-Device) communication has become a crucial part of 4G and 5G networks. It can not only decrease the transmit power of user equipments (UEs) and increase area spectral efficiency of cellular networks, but also offload traffic from cellular networks and alleviate scarcity of spectrum resources by using in-band communication. In this paper, we consider a real tele-communication scenario in which the mobile UEs are primarily located in hotspots and cell edges. By integrating Poisson Hole Process with Thomas Cluster Process, a kind of D2D-Aided Underlaying Cellular Networks (D2D-UCNs) is built. In the D2D-UCNs, we first investigate the aggregation interference of the typical UE and D2D user by using stochastic geometry. Subsequently we analyze their coverage probability and area spectral efficiency. The simulation results show that the coverage probability of D2D users and UEs can be effectively guaranteed by establishing exclusion zone, whilst the area spectral efficiency of the D2D-UCNs can be maximized by optimizing the number of simultaneously active D2D links.

Signal transducer and activator of transcription 1 (STAT1) is a transcription factor that mediates cellular responses to interferons (IFNs) and other cytokines and growth factors in diverse cell types. STAT1 gain-of-function (GOF) mutations result in an unexpectedly wide range of clinical features. It remains unclear why STAT1 GOF mutations result in such a broad spectrum of phenotypes. We analyzed the clinical, molecular, and phenotypic characteristics of nine Chinese patients with STAT1 GOF mutations. This study enrolled nine patients with STAT1 GOF mutations including five novel mutations. We discuss the molecular and phenotypic characterization such as unique Penicillium marneffei lymphadenitis. Patients with STAT1 GOF mutations had defects in both innate and adaptive immunity, including impaired T cell receptor (TCR) diversity; reduced numbers of naive and effector memory CD4+ T cells, memory B cells, and NK cells; and defects in the production of IL-17A and IFN-γ. In addition, experiments with primary immune cells revealed that enhanced STAT1 phosphorylation resulted from not only lower rates of STAT1 dephosphorylation but also increased total STAT1 expression. Our report provides the first comprehensive overview of the molecular genetics, clinical heterogeneity, and underlying immunological abnormalities of patients with STAT1 GOF mutations in China. In further study, to find the relationship between different STAT1 GOF mutations and clinical phenotype as well as the mechanism of increased total STAT1 expression will be needed.

To compare the glycaemic response of whole grain oat kernels and pearled oats cooked under normal pressure or higher pressure and examine whether replacing half of the rice in a given meal with either of the two oat grains could make a difference in acute glycaemic responses. In a randomised crossover trial, ten healthy subjects consumed two groups of test meals: (1) oat grain-only, including whole grain oats cooked under normal pressure (WONP) and higher pressure (WOHP) as well as their pearled oat counterparts, PONP and POHP; and (2) mixed meals of aforementioned oat grains and cooked rice (OG + R), including WONP + R, WOHP + R, PONP + R and POHP + R. A postprandial blood glucose test, texture profile analysis and in vitro carbohydrate digestion assay were carried out for each test meal. Compared with the rice reference, oat grain-only meals induced lower glucose levels at all time points, lower peak values and smaller glucose excursions at 120 min (P

The quality factor is a key parameter of micro-electro-mechanical system resonators, and the internal friction of structural materials in the micro resonator caused by thermoelastic damping has been limiting the improvement of the quality factor. In this paper, thermoelastic damping models of trilayered composite microplates with three kinds of boundary conditions are studied. Then the convergence of thermoelastic damping with different material combinations is analyzed, and that with three kinds of boundary conditions is also analyzed. Next, the finite element model is compared with the analytical model, and the accuracy of the analytical model is verified. Finally, the effects of the coating material and the coating thickness on thermoelastic damping of micro resonators are analyzed. The results show that the Zener modulus of the coating material has a great influence on the convergence of the analytical model; the boundary condition has little effect on the convergence of the analytical model; the maximum thermoelastic damping of composite plates is related to Zener modulus of coating; the maximum thermoelastic damping of composite plates is related to the thickness of coating.

BackgroundTumor microenvironment (TME) is a dynamic cellular milieu to promote tumor angiogenesis, growth, proliferation, and metastasis, while derailing the host anti-tumor response. TME impedes bispecific antibody (BsAb) or chimeric antigen receptor (CAR)-driven T cells infiltration, survival, and cytotoxic efficacy. Modulating tumor infiltrating myeloid cells (TIMs) could potentially improve the efficacy of BsAb.MethodsWe evaluated the effects of TIM modulation on BsAb-driven T cell infiltration into tumors, their persistence, and in vivo anti-tumor response. Anti-GD2 BsAb and anti-HER2 BsAb built on IgG-[L]-scFv platform were tested against human cancer xenografts in BALB-Rag2−/−IL-2R-γc-KO (BRG) mice. Depleting antibodies specific for polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC), monocytic MDSC (M-MDSC), and tumor associated macrophage (TAM) were used to study the role of each TIM component. Dexamethasone, an established anti-inflammatory agent, was tested for its effect on TIMs.ResultsBsAb-driven T cells recruited myeloid cells into human tumor xenografts. Each TIM targeting therapy depleted cells of interest in blood and in tumors. Depletion of PMN-MDSCs, M-MDSCs, and particularly TAMs was associated with enhanced T cell infiltration into tumors, significantly improving tumor control and survival in multiple cancer xenograft models. Dexamethasone premedication depleted monocytes in circulation and TAMs in tumors, enhanced BsAb-driven T cell infiltration, and anti-tumor response with survival benefit.ConclusionReducing TIMs markedly enhanced anti-tumor effects of BsAb-based T cell immunotherapy by improving intratumoral T cell infiltration and persistence. TAM depletion was more effective than PMN- or M-MDSCs depletion at boosting the anti-tumor response of T cell engaging BsAb.

The extraction of macromolecules from nano-self-assembled material can be used as a laboratory model for enhancing oil recovery in reservoirs. By combining Darcy’s law and Poiseuille equation, an improved nuclear magnetic resonance (NMR) permeability model, suitable for macromolecular flow in mesopores is obtained. The calibration coefficients in the Coates equation are expressed in terms of the physical parameters of pore throat ratio rb/rt, tortuosity, and thickness of bond film in the improved model. The results show that the proportion of irreducible fluid to total fluid obtained through NMR characterization can reflect the variation tendency of irreducible macromolecule and water. By simplifying the pores of the extracted samples, the thickness model of irreducible macromolecule and water is established with the total thicknesses calculated as 1.482 nm, 1.585 nm, 1.674 nm, and 1.834 nm. The corresponding permeability results obtained from the NMR characterization (KNMR) are 7.39 mD, 6.02 mD, 5.27 mD, and 6.25 mD. The permeability results obtained from mercury intrusion experiment (KHG) are 5.10 mD, 4.73 mD, 5.82 mD, and 5.56 mD, and those from the Darcy flow experiment (KD) are 4.1 mD and 5.19 mD. The absolute deviation between KNMR and KHG varies from 0.69 to 2.29 mD, while that between KNMR and KD is 1.58 mD. This method can be applied to the enhanced recovery of shale oil.

Background Uniportal video-assisted thoracoscopic surgery (VATS) lobectomy has emerged as a promising and exciting approach for minimally invasive thoracic surgeries. However, nearly all reported uniportal VATS lobectomies are performed via an intercostal route, and chest wall trauma remains an issue. Here, we report the use of a novel uniportal VATS technique involving a subxiphoid route for pulmonary lobectomies. Methods We retrospectively analyzed perioperative data for patients who underwent subxiphoid uniportal and traditional three-port VATS lobectomies from January 2016 to January 2017 at our hospital. Results During the study period, 37 patients successively underwent subxiphoid uniportal VATS lobectomies, including three synchronous bilateral pulmonectomies; 68 patients underwent traditional three-port VATS. There were no surgical or 30-day postoperative mortalities, and no significant between-group differences were found in the number of retrieved lymph nodes, number of explored nodal stations, blood loss, drainage time, postoperative complications, or length of hospital stay. Operative time was longer in the subxiphoid uniportal VATS group than in the traditional three-port VATS group (P P Conclusions Subxiphoid uniportal VATS lobectomy is a safe and feasible surgical procedure associated with reduced surgical trauma and postoperative pain as well as improved cosmetic results compared with traditional VATS. Moreover, this procedure is better suited for patients receiving synchronous bilateral pulmonectomy. Further long-term follow-up analyses involving more patients are ongoing. Trial registry number ClinicalTrials.gov NCT03051438.

Thermoelastic damping (TED) is considered to be the main internal energy dissipation mechanism in microresonators, the study of which has become increasingly significant in the design of microresonators with high quality factor. In this paper, the bilayered cantilever, fixed-fixed and fully clamped rectangular microplate resonators are taken as the research object, and then three theoretical models of thermoelastic damping with three-dimensional heat conduction are built. The analysis on convergence items of the present three-dimensional models with different combinations of materials are carried out, and the influence of material plating on TED in Si microplate resonators is also analyzed. The analysis on the effects of the geometry size and boundary conditions on thermoelastic damping of microresonators at the first-order natural frequency are both carried out. Moreover, in order to verify the validation and accuracy of the present three-dimensional (3-D) models, the previous one-dimensional (1-D) models and the FEM models built in this paper are used to compare with the present models. Finally, the validation and accuracy of the present three-dimensional models are confirmed.

A self-healing hydrogel was synthesized via the multi-component reaction of azobenzene-methacrylamide, β-CD and 3-methacrylamido phenylboronic acid. The orthogonal method was applied to analyze the influence of host–guest inclusion complexation, cross-linker and phenylboronic acid monomers content on mechanical properties and healing efficiency of the hydrogel. The results indicated that hydrogel showed autonomic self-healing behavior. The hydrogel demonstrated light-switchable self-healing ability and pH-sensitive swelling ratio. It was found that hydrogel showed high elongation, excellent resilience and low elastic hysteresis. The design of the combined host–guest interactions and boronate esters on the hydrogel showed advantage for improving the mechanical, self-healing and recovery properties simultaneously.

Peroxynitrite (ONOO−), known as a kind of reactive nitrogen species, is a significant factor involved in a broad spectrum of physiological and pathological processes. However, their biological functions remain to be controversial or poorly characterized yet, mainly because of the lack of reliable methods for sensitive and specific detection of ONOO− in vitro and in vivo. Thus, approaches that enable noninvasive visualized imaging of ONOO− will be of enormous benefit in understanding the processes of related diseases and developing novel drugs. During the last decades, fluorescent probes, with high sensitivity and real-time spatial imaging capacity, receive more and more attention. Herein, we strive to summarize the current fluorescent probes for ONOO−, including small-molecular fluorescent probes, nanoparticles-based fluorescent probes, and genetically encoded fluorescent probes. Furthermore, the challenges and attempt to give an outlook on the possible further developments are discussed.

Identifying proteins that regulate fin injury is critical to our understanding of regeneration as it relates to both acute wound injury and tissue formation. We have cloned the full-length cDNA of the actinodin4 (and4) gene of Misgurnus anguillicaudatus (MaAnd4) by the RACE method (GenBank Accession No. MG385835). Quantitative RT-PCR analysis during fin regeneration indicated a sudden increase in MaAnd4 expression, with a peak at 3 days post amputation (dpa). In situ analysis showed that MaAnd4 is located in the distal blastema and cells lining the regions of actinotrichia formation at 3 dpa. The highest levels of MaAnd4 expression were observed in the adult testis as well as in the gastrulae during embryonic development. Southern blotting confirmed the existence of and4 in teleosts but not in tetrapods examined. The results show the expression of this gene in actinotrichia formation and its association with fin/limb regeneration ability in teleosts.