Combined risk factors and risk of upper gastrointestinal cancer mortality in the Linxian general population.

We aimed to explore the association of combined risk factors with risk of death from upper gastrointestinal (UGI) cancer, including esophageal squamous cell carcinoma (ESCC), gastric cardia carcinoma (GCC) and gastric noncardia carcinoma (GNCC) in the Linxian Nutrition Intervention Trial (NIT) cohort. The NIT cohort included 29 584 healthy adults. A combined risk score (CRS) was calculated using a point system method based on 10 risk factors collected at baseline, including gender, smoking, alcohol drinking, body mass index, family history of UGI cancer, drinking tap water, tooth loss and consumption of fresh fruit, eggs and meat. Possible score ranged from 0 to 31, and higher score indicated as poorer health status. Subjects were divided into three groups by the CRS (<12 points, 12 to 20 points and >20 points). The group of CRS <12 points was considered as the reference. During the 30-year follow-up, we identified 4553 UGI cancer deaths. Compared to subjects with a CRS <12 points, the adjusted HRs for CRS of 12 to 20 points and >20 points were 1.69 (95% CI: 1.56-1.83) and 3.06 (95% CI: 2.82-3.33) for UGI cancer mortality, respectively (Ptrend < .001). Comparable associations were also observed for ESCC, GCC and GNCC mortality. Results remained similar across different age groups (Pinteraction > .05). All HRs observed in the second half follow-up period were stronger than that observed in the first half follow-up period. Our study indicated that higher CRS was associated with increased risk of UGI cancer mortality. Appropriate measures should be taken to reduce unhealthy lifestyles.

Glistening formation in a new hydrophobic acrylic intraocular lens.

BACKGROUND: The formation of fluid-filled microvacuoles, termed glistenings, is a common complication of intraocular lenses (IOLs) made from hydrophobic acrylate. Using our well-established in-vitro laboratory method, we evaluated a new IOL material's resistance to glistening formation. METHODS: An in-vitro stress test for glistening induction was performed on 20 samples of hydrophobic acrylic IOLs: ten of the new Eyecryl ASHFY600 (Biotech Vision Care, Ahmedabad, India) compared with ten samples of AcrySof IQ SN60WF (Alcon, Fort Worth, USA). The number of microvacuoles per square millimetre (MV/mm2) was evaluated in five sections of each IOL. The results for each model were compared and rated on a modified Miyata Scale for grading glistening severity. RESULTS: In all cases, glistening number was higher in the central section of the IOL optic than in the periphery. Mean number of MV/mm2 was highest in the central part of the AcrySof IQ SN60WF, with 41.84 (±27.67) MVs/mm2. The lowest number of glistenings was found in the five sections of the Eyecryl ASHFY600 with 0.52 (±0.24) MVs/mm2. Mean value of the Eyecryl ASHFY600 IOL, using the Miyata Scale, was Zero. CONCLUSION: In this in-vitro laboratory study, the new hydrophobic acrylic IOL showed a high resistance to microvacuole formation. Results from this in-vitro study suggest that glistening numbers will be low in clinical use in the Eyecryl ASHFY600.

Single-Cell Analysis of the Impact of Host Cell Heterogeneity on Infection with Foot-and-Mouth Disease Virus.

Viral infection and replication are affected by host cell heterogeneity, but the mechanisms underlying the effects remain unclear. Using single-cell analysis, we investigated the effects of host cell heterogeneity, including cell size, inclusion, and cell cycle, on foot-and-mouth disease virus (FMDV) infection (acute and persistent infections) and replication. We detected various viral genome replication levels in FMDV-infected cells. Large cells and cells with a high number of inclusions generated more viral RNA copies and viral protein and a higher proportion of infectious cells than other cells. Additionally, we found that the viral titer was 10- to 100-fold higher in cells in G2/M than those in other cell cycle phases and identified a strong correlation between cell size, inclusion, and cell cycle heterogeneity, which all affected the infection and replication of FMDV. Furthermore, we demonstrated that host cell heterogeneity influenced the adsorption of FMDV due to differences in the levels of FMDV integrin receptors expression. Collectively, these results further our understanding of the evolution of a virus in a single host cell.IMPORTANCE It is important to understand how host cell heterogeneity affects viral infection and replication. Using single-cell analysis, we found that viral genome replication levels exhibited dramatic variability in foot-and-mouth disease virus (FMDV)-infected cells. We also found a strong correlation between heterogeneity in cell size, inclusion number, and cell cycle status and that all of these characteristics affect the infection and replication of FMDV. Moreover, we found that host cell heterogeneity influenced the viral adsorption as differences in the levels of FMDV integrin receptors' expression. This study provided new ideas for the studies of correlation between FMDV infection mechanisms and host cells.

Atomic Force Microscope Guided SERS Spectra Observation for Au@Ag-4MBA@PVP Plasmonic Nanoparticles.

Recently polymer encapsulated surface-enhanced-Raman-scattering (SERS) probes with internal noble metal core-shell structure has found growing applications in biomedical applications. Here we studied the SERS spectra of Au@Ag-4MBA@PVP (4MBA: 4-mercaptobenzoic acid; PVP: polyvinylpyrrolidone) plasmonic nanoparticles produced from a chemical reduction method. By linking the atomic force microscope (AFM) with the homebuilt confocal Raman spectrometer thus to use AFM images as guidance, we realized the measurement of the SERS spectra from separated nanoparticles. We investigated the cases for single nanoparticles and for dimer structures and report several observed results including SERS spectra linearly scaled with laser power, abrupt boosting and abnormal shape changing of SERS spectra for dimer structures. Based on the finite element method simulation, we explained the observed ratio of SERS signals between the dimer structure and the single nanoparticle, and attributed the observed abnormal spectra to the photothermal effect of these plasmonic nanoparticles. Our study provides valuable guidance for choosing appropriate laser power when applying similar SERS probes to image biological cells.

Single-cell analysis reveals the relevance of foot-and-mouth disease virus persistence to emopamil-binding protein gene expression in host cells.

Foot-and-mouth disease virus (FMDV) infects host cells in either an acute or persistent manner. In this study, we examined the relevance of the establishment of FMDV persistence to the expression of the emopamil-binding protein (EBP) gene in 231 individual persistently infected baby hamster kidney (BHK-21) cells after passages 28, 38, and 68 (PI28, PI38, and PI68). At PI28, the stage at which persistent infection of FDMV becomes unstable, the percentage of cells carrying FMDV was 66.7%, while 80.2% of cells were EBP positive. Additionally, in 55.6% of the EBP-positive cells at PI28, EBP expression was upregulated approximately 149.9% compared to uninfected BHK-21 cells. This was the highest expression level among all cell passages measured. Interestingly, in a parallel experiment, the average EBP expression level in the whole cell population at PI28 was only slightly higher (108.2%) than that in uninfected BHK-21 cells. At PI38, 98.7% of the cells were positive for FMDV 3D (an RNA-dependent RNA polymerase enzyme gene), and its maximum expression level observed at this passage. The expression level of EBP in 78.2% of the total cells, however, was reduced significantly. At PI68, 95.8% of the cells were 3D positive, and the expression of both the EBP and 3D genes were at the lowest levels of all the passages. Our studies using single cells yielded data that are otherwise inaccessible a using whole cell population. These results suggest that the establishment of persistent infection by FMDV is a dynamic process that results from the continuous adaptation and coevolution of viruses and cells to reach an equilibrium.

[Particle Size and Number Density Online Analysis for Particle Suspension with Polarization-Differentiation Elastic Light Scattering Spectroscopy].

The basic principle of polarization-differentiation elastic light scattering spectroscopy based techniques is that under the linear polarized light incidence, the singlely scattered light from the superficial biological tissue and diffusively scattered light from the deep tissue can be separated according to the difference of polarization characteristics. The novel point of the paper is to apply this method to the detection of particle suspension and, to realize the simultaneous measurement of its particle size and number density in its natural status. We design and build a coaxial cage optical system, and measure the backscatter signal at a specified angle from a polystyrene microsphere suspension. By controlling the polarization direction of incident light with a linear polarizer and adjusting the polarization direction of collected light with another linear polarizer, we obtain the parallel polarized elastic light scattering spectrum and cross polarized elastic light scattering spectrum. The difference between the two is the differential polarized elastic light scattering spectrum which include only the single scattering information of the particles. We thus compare this spectrum to the Mie scattering calculation and extract the particle size. We then also analyze the cross polarized elastic light scattering spectrum by applying the particle size already extracted. The analysis is based on the approximate expressions taking account of light diffusing, from which we are able to obtain the number density of the particle suspension. We compare our experimental outcomes with the manufacturer-provided values and further analyze the influence of the particle diameter standard deviation on the number density extraction, by which we finally verify the experimental method. The potential applications of the method include the on-line particle quality monitoring for particle manufacture as well as the fat and protein density detection of milk products.

Expression of porcine Mx1 with FMDV IRES enhances the antiviral activity against foot-and-mouth disease virus in PK-15 cells.

Foot-and-mouth disease virus (FMDV) is the most contagious pathogen in cloven-hoofed (two-toed) animals. Due to the rapid replication and spread of FMDV, novel therapeutic strategies are greatly needed to reduce or block FMDV shedding in cases of disease outbreak. Here, we generated an IRES-Mx1 construct in which the internal ribosome entry site (IRES) of FMDV was inserted between the promoter and open reading frame (ORF) of porcine myxovirus resistance protein 1 (poMx1). This construct provides more powerful protection against FMDV infection than the IRES-IFN construct that was previously generated by our group. The results indicate that this IRES-Mx1 construct was able to express poMx1 12 h after transfection and induce a robust immune response. In contrast to the control, the proliferation of virus in transfected cells was significantly inhibited, as evaluated by morphology monitoring, real-time RT-PCR, virus titration and Western blot. In addition, we also found that the antiviral activity in cells transfected with pc-IRES-Mx1 was abolished when the JAK/STAT pathway was repressed, which indicates that the antiviral mechanism of poMx1 is JAK/STAT pathway dependent. Taken together, our data suggest that the antiviral activity of poMx1 is possibly produced by affecting the host cells themselves, instead of interacting with the virus directly. The new construct reported here could be used as a novel effective therapy against FMDV infection.

In-vitro assessment of a novel intraocular lens made of crosslinked polyisobutylene.

PURPOSE: To describe and analyse the particularities of the material and the optical quality of the first intraocular lens (IOL) (Eyedeal® lens) made of crosslinked polyisobutylene (xPIB). METHODS: We assessed the material quality using an accelerated ageing process (to provoke glistenings) and compared values with a control, AcrySof® lens. Using the sessile drop method, the contact angle of the new IOL was measured. Images of the lens surface were recorded by scanning electron microscopy (SEM). Optical quality was assessed by measuring the labeled power and modulation transfer function (MTF) using standard metrology equipment (OptiSpheric IOL PRO2). RESULTS: The Eyedeal® lens had an average glistening density result of 7.46 ± 3.78 MV/mm2 compared to the control AcrySof® whose glistenings number was 142.42 ± 72.47 MV/mm2. The contact angle was 97.2° whereas the angle of AcrySof material is between 73.3 ± 2.4° and 84.4 ± 0.1°. Using SEM, Eyedeal® lenses were examined and all appeared to be comparable to modern IOLs made of acrylic materials. The power and MTF values were normal and conformed to ISO standards. CONCLUSIONS: In the laboratory, the new Eyedeal® lens showed equivalence to current hydrophobic- or hydrophilic-acrylic lens models. It showed superiority in its glistening density result compared to the control lens.

Array-wide uniform PEDOT:PSS electroplating from potentiostatic deposition.

Electroplating of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) is important in many neuroelectronic applications but is challenging to achieve uniformity on large-scale microelectrode arrays (MEA) using conventional galvanostatic methods. In this study, we address this challenge through a potentiostatic method and demonstrate highly uniform electroplating of PEDOT:PSS on MEA with more than one hundred electrodes, all at cellular sizes. The validation of this approach involves comparisons with galvanostatic deposition methods, showcasing unparalleled deposition yield and uniformity. Systematic electrochemical characterizations reveal similarities in structure and stability from potentiostatic deposited coatings. The advances developed here establish the potentiostatic method and detailed process to achieve a uniform coating of PEDOT:PSS on large-scale MEA, with broad utility in neuroelectronics.

Nanoscale InGaSb heterostructure membranes on Si substrates for high hole mobility transistors.

As of yet, III-V p-type field-effect transistors (p-FETs) on Si have not been reported, due partly to materials and processing challenges, presenting an important bottleneck in the development of complementary III-V electronics. Here, we report the first high-mobility III-V p-FET on Si, enabled by the epitaxial layer transfer of InGaSb heterostructures with nanoscale thicknesses. Importantly, the use of ultrathin (thickness, ~2.5 nm) InAs cladding layers results in drastic performance enhancements arising from (i) surface passivation of the InGaSb channel, (ii) mobility enhancement due to the confinement of holes in InGaSb, and (iii) low-resistance, dopant-free contacts due to the type III band alignment of the heterojunction. The fabricated p-FETs display a peak effective mobility of ~820 cm(2)/(V s) for holes with a subthreshold swing of ~130 mV/decade. The results present an important advance in the field of III-V electronics.

Quantum confinement effects in nanoscale-thickness InAs membranes.

Nanoscale size effects drastically alter the fundamental properties of semiconductors. Here, we investigate the dominant role of quantum confinement in the field-effect device properties of free-standing InAs nanomembranes with varied thicknesses of 5-50 nm. First, optical absorption studies are performed by transferring InAs "quantum membranes" (QMs) onto transparent substrates, from which the quantized sub-bands are directly visualized. These sub-bands determine the contact resistance of the system with the experimental values consistent with the expected number of quantum transport modes available for a given thickness. Finally, the effective electron mobility of InAs QMs is shown to exhibit anomalous field and thickness dependences that are in distinct contrast to the conventional MOSFET models, arising from the strong quantum confinement of carriers. The results provide an important advance toward establishing the fundamental device physics of two-dimensional semiconductors.

The progress of research into pseudophosphatases.

Pseudophosphatases are a class of phosphatases that mutate at the catalytically active site. They play important parts in many life processes and disorders, e.g., cell apoptosis, stress reaction, tumorigenesis, axon differentiation, Charcot-Marie-Tooth, and metabolic dysfunction. The present review considers the structures and action types of pseudophosphatases in four families, protein tyrosine phosphatases (PTPs), myotube protein phosphatases (MTMs), phosphatases and tensin homologues (PTENs) and dual specificity phosphatases (DUSPs), as well as their mechanisms in signaling and disease. We aimed to provide reference material for the research and treatment of related diseases.

High-Efficient Vacuum Ultraviolet-Ozone Assist-Deposited Polydopamine for Poly(lactic-co-glycolic acid)-Coated Pure Zn toward Biodegradable Cardiovascular Stent Applications.

Zinc is a prospective metal for biodegradable cardiovascular stent applications, but the excessively released Zn2+ during degradation remains a huge challenge in biocompatibility. Considerable efforts have been made to develop a high-efficient surface modification method, while maintaining adhesion strength, mechanical support, and vascular compatibility. Biomimetic polydopamine (PDA) can adhere to Zn tightly, subsequently achieving robust chemical bonds with poly(lactic-co-glycolic acid) (PLGA) coating. However, the deposition of PDA on Zn depends on the controlled conditions such as a sensitive pH and a long period of time. Herein, we introduce vacuum ultraviolet-ozone (VUV/O3) assist-deposition technology to accelerate the polymerization of PDA on pure Zn, which shortens the process to 40 min at a moderate pH of 8.5 and improves the deposition rate by 1-2 orders of magnitude under sufficient active oxygen species (ROS). Additionally, PLGA/PDA coating enhances the corrosion resistance, and their effective protection maintains the mechanical properties after long-term corrosion. Moreover, the controlled Zn2+ release contributes to the superior in vitro biocompatibility, which inhibits the hemolysis rate and smooth muscle cell (SMC) proliferation. The enhanced endothelial cell (EC) proliferation is promising to promote the re-endothelialization, avoiding in-stent restenosis and neointimal hyperplasia. Such modified Zn might be a viable candidate for the treatment of cardiovascular diseases.

[Effects of addition of organic carbon with different chemical structure on the fate and accumulation of exogenous carbon in red and sandy soils]. / çº¢å£¤å’Œé£Žæ²™åœŸæ·»åŠ ä¸åŒåŒ–å­¦ç»“æž„æœ‰æœºç¢³å¯¹å¤–æºç¢³åŽ»å‘åŠç´¯ç§¯è´¡çŒ®çš„å½±å“.

Plant litter input has important influences on soil CO2 emission and soil organic carbon (SOC) formation in terrestrial ecosystem. However, it is not well known for the fate of carbon when exogenous organic matters with different chemical structures are added to soil with different textures. In this study, we added the uniformly 13C-labelled substrates of glucose, starch, and cellulose to red soil and sandy soil, and compared the net 13C accumulation and recovery and its proportions in soil releasing CO2, SOC, dissolved organic carbon (DOC) and microbial biomass carbon (MBC) pools. The results showed that δ13C values increased after exogenous substrate additions in CO2, SOC, DOC, and MBC, and that the peaks of δ13C in CO2 pool appeared delay with increasing chemical structure complexity. The fate of exogenous C and its contributions of different C pools were significantly influenced by exogenous C types, soil types, and incubation times. In sandy soil, the added exogenous C was more mineralized as CO2, with the net accumulation and recovery of 13C in CO2 pool decreasing in the order of glucose>starch>cellulose. In red soil, more exogenous C was transferred to SOC pool, with the net accumulation and recovery of 13C in SOC pool decreasing in the order of glucose>starch>cellulose. Our results implied that the chemical structure of exogenous substrates and soil texture together controlled the fate and accumulation of exogenous organic carbon.

Evolutionary trends in human mandibles and dentition from Neolithic to current Chinese.

OBJECTIVES: This study aimed to systematically compare Neolithic mandibles and dentition with modern Chinese, and thereby discern human evolutionary trends. MATERIALS AND METHODS: Neolithic remains of 45 adults unearthed at the Zhangqiu Jiaojia site, were compared with clinical records of 48 patients at Shandong University. All samples were scanned by cone beam computed tomography (CBCT) using identical parameters. Digital imaging and communications in medicine images were collected, three-dimensional models reconstructed, and morphology measurements obtained using Mimics software. RESULTS: Neolithic mandibles were significantly larger in their vertical and sagittal dimensions (P < .05), but similar in horizontal width to modern humans. Their condyles had fewer bird beak and crooked finger shaped morphologies than modern mandibles (P < .05). Neolithic third molars were more often erupted than in modern mandibles, and their Position A, class I and II, and vertical impactions were more common (P < .05). Neolithic teeth were generally smaller in crown lengths and in cross-sectional areas, than their modern counterparts (P < .05). CONCLUSIONS: Neolithic mandibles were larger than modern humans, who have refined diets and mandibular atrophy. They had fewer abnormally shaped condylar morphologies, and much fewer third molar impactions than in modern humans. However, modern dentition particularly their crowns are larger, likely through genetic influx from migrations.

Establishment of persistent infection with foot-and-mouth disease virus in BHK-21 cells.

BACKGROUND: Foot-and-mouth disease virus (FMDV) is able to cause persistent infection in ruminants besides acute infection and disease. Since the mechanisms of viral persistence and the determining factors are still unknown, in vitro systems help explore and reveal mechanisms of persistence in vivo by providing useful models for the study of RNA genome mutations and evolution. Ammonium chloride, a lysosomotropic agent that raises intralysosomal pH, reduces the yield of FMDV during infection of BHK-21 cells. RESULTS: The persistent infection with FMDV serotype O in BHK-21 cells was selected and established readily after treatment of ammonium chloride that acts primarily on the cells. Intact virions were observed located inside the endosomes. Viral genome RNAs and specific proteins were detected in the persistent cells to validate the establishment of viral persistence. Infection of the persistent viruses could not form plaques in host cells but virulence was enhanced. Basing on analysis and comparison of cDNA sequences of resident viruses and wild type viruses, 15 amine acid mutations were found, all of which were located in nonstructural proteins rather than in structural proteins. CONCLUSIONS: Therefore, persistent infection of cell cultures with FMDV is successfully established with some distinctive features. It would be worthwhile to further investigate the mechanisms of viral persistence.

Fabrication and characterization of silk fibroin coating on APTES pretreated Mg-Zn-Ca alloy.

To delay the degradation of magnesium alloys, silk fibroin as a natural organic polymer coating was fabricated on a 3-amino-propyltriethoxysilane (APTES) pretreated Mg-Zn-Ca alloy. APTES pretreatment coated the surface of magnesium alloys with amino groups, which can bond with functional groups in silk fibroin to form a compact coating/substrate interface. The influences of the APTES concentration and drying temperature on the coating adhesion and interface were investigated to explore the optimal parameters in the fabrication process. The nanoporous silk fibroin films completely covered the APTES pretreated Mg-Zn-Ca surface, which reached a thickness of ~7 µm. The chemical states for the coated Mg-Zn-Ca alloy were compared to those of the bare Mg-Zn-Ca alloy and the APTES pretreated Mg-Zn-Ca alloy to illustrate the coating mechanism. During in vitro degradation and electrochemical measurements in simulated body fluid (SBF), the samples with the silk fibroin coating showed remarkably improved corrosion resistance and a slower degradation rate compared to those of the bare samples, suggesting that the silk fibroin coating was an effective protection coating for the substrates and can delay the degradation of magnesium alloys. Moreover, a model for the in vitro degradation was proposed. In vitro cell experiments confirmed the excellent biocompatibility of silk fibroin coated Mg-Zn-Ca structure.

Glycosylation end products mediate damage and apoptosis of periodontal ligament stem cells induced by the JNK-mitochondrial pathway.

BACKGROUND: Recent studies have confirmed the bidirectional relationship between the two and the exacerbation of periodontitis by type II diabetes mellitus (T2DM), the pathogenic mechanism has not yet been clarified, AGEs has been linked to the pathogenesis of both periodontitis and T2DM, JNK signaling pathway might play a important role to explain the inner mechanism. OBJECTIVES: To study advanced glycation end products (AGEs) activate the innate immune system of the host by activating oxidative stress and affecting cellular signal transduction in periodontal ligament stem cells (PDLSCs);Results: TNF-α and/or AGEs can induce the formation of endogenous ROS in PDLSCs, thereby activating the downstream JNK signalling pathway, leading to the initiation of the mitochondria-mediated apoptotic pathway and the induction of PDLSC apoptosis. CONCLUSION: we hypothesized that the JNK pathway is a key link in the apoptosis of PDLSCs mediated by TNF-α and/or AGEs. MATERIALS AND METHODS: PDLSCs from healthy volunteers were extracted, cultured and stimulated with TNF-a and/or AGEs, Flow cytometry, CCK-8, multidifferential assay, RT-PCR, apoptosis assay, Transmission electron microscopy and Western blotting were recruit to detect the internal relations between AGEs and PDLSCs.

Mandibular molar C-shaped root canals in 5th millennium BC China.

OBJECTIVE: The aim of this study was to analyze the occurrence and variations in C-shaped canals in ancient Chinese teeth and compare the differences of these features between ancient and age-matched modern populations. DESIGN: Approximately 5000-year-old craniofacial bone remains were collected from the fossils of 38 individuals (total: 68 mandibular second molars) excavated from the Jiaojia site. The control group comprised of an equal number of randomly selected modern samples. We used cone-beam computed tomography to scan the mandible along the apex-crown axis and analyzed the canal morphology, based on Fan's categorization criterion, at 2 mm, 5 mm, and 8 mm to the apical level. Grooves on the lingual and buccal sides were also recorded. RESULTS: The proportion of C-shaped roots among ancient samples on the left and right sides were 48.57 % (17/35 teeth) and 54.55 % (18/33 teeth), respectively, and 51.47 % (35/68 teeth) in the total sample. Conversely, in the control group, 44.12 % (15/34) and 38.24 % (13/34) occurred on the left and right sides, respectively, and 41.18 % (28/68) in the total sample. Among the C-shaped canals from the Jiaojia site samples, the classification type changed between two adjacent levels in 84.31 % of samples. Approximately 35 (51.5 %) teeth had a fused root, 20 (29.41 %) had one shallow buccal and one deep lingual groove. The occurrence of C-shape variation was not significantly correlated with time (p＞0.05). CONCLUSIONS: This study identified a high rate of C-shaped root canals among individuals of Jiaojia who lived approximately 5000 years ago.

The ELISA Detectability and Potency of Pegfilgrastim Decrease in Physiological Conditions: Key Roles for Aggregation and Individual Variability.

PEGylated recombinant human granulocyte colony stimulating factor (pegfilgrastim) is used clinically to accelerate immune reconstitution following chemotherapy and is being pursued for biosimilar development. One challenge to overcome in pegfilgrastim biosimilar development is establishing pharmacokinetic (PK) similarity, which is partly due to the degree of PK variability. We herein report that commercially available G-CSF and PEG ELISA detection kits have different capacities to detect pegfilgrastim aggregates that rapidly form in vitro in physiological conditions. These aggregates can be observed using SDS-PAGE, size-exclusion chromatography, dynamic light scattering, and real-time NMR analysis and are associated with decreased bioactivity as reflected by reduced drug-induced cellular proliferation and STAT3 phosphorylation. Furthermore, individual variability in the stability and detectability of pegfilgrastim in human sera is also observed. Pegfilgrastim levels display marked subject variability in sera from healthy donors incubated at 37 °C. The stability patterns of pegfilgrastim closely match the stability patterns of filgrastim, consistent with a key role for pegfilgrastim's G-CSF moiety in driving formation of inactive aggregates. Taken together, our results indicate that individual variability and ELISA specificity for inactive aggregates are key factors to consider when designing and interpreting studies involving the measurement of serum pegfilgrastim concentrations.