Development of the Fetal Brain Corticocortical Structural Network during the Second-to-Third Trimester Based on Diffusion MRI.

During the second-to-third trimester, the neuronal pathways of the fetal brain experience rapid development, resulting in the complex architecture of the interwired network at birth. While diffusion MRI-based tractography has been employed to study the prenatal development of structural connectivity network (SCN) in preterm neonatal and postmortem fetal brains, the in utero development of SCN in the normal fetal brain remains largely unknown. In this study, we utilized in utero dMRI data from human fetuses of both sexes between 26 and 38 gestational weeks to investigate the developmental trajectories of the fetal brain SCN, focusing on intrahemispheric connections. Our analysis revealed significant increases in global efficiency, mean local efficiency, and clustering coefficient, along with significant decrease in shortest path length, while small-worldness persisted during the studied period, revealing balanced network integration and segregation. Widespread short-ranged connectivity strengthened significantly. The nodal strength developed in a posterior-to-anterior and medial-to-lateral order, reflecting a spatiotemporal gradient in cortical network connectivity development. Moreover, we observed distinct lateralization patterns in the fetal brain SCN. Globally, there was a leftward lateralization in network efficiency, clustering coefficient, and small-worldness. The regional lateralization patterns in most language, motor, and visual-related areas were consistent with prior knowledge, except for Wernicke's area, indicating lateralized brain wiring is an innate property of the human brain starting from the fetal period. Our findings provided a comprehensive view of the development of the fetal brain SCN and its lateralization, as a normative template that may be used to characterize atypical development.

The impact of road environments on rural periodic market travel satisfaction: a heterogeneity analysis of travel modes.

Introduction: Travel satisfaction as experienced by rural residents is closely related to personal physical and mental health, as well as rural economic conditions. An improved rural road environment can be expected to enhance villagers' satisfaction with regards to visits to markets, but to date this has not been established empirically. Methods: In this study, a questionnaire was designed to obtain local residents' evaluations of road environment characteristics for periodic market travel. And we use an Oprobit regression model and Importance-Performance Map Analysis (IPMA) to explore the heterogeneity of the 14 key elements of the "home-to-market" road environment impact on villagers' satisfaction under different modes of travel. Results: The results of the study reveal that villagers expressed dissatisfaction with the current lack of sidewalks and non-motorized paths, and except for road traffic disturbances and road deterioration, which did not significantly affect mode of travel, other factors proved significant. Significantly, bus services are associated with a significant positive effect on walking, non-motorized and bus travel satisfaction, while distance travel also affects walking, non-motorized and motorized travel satisfaction. It is worth noting that greening and service facilities negatively affect motorized travel satisfaction. In summary, road width, sidewalks, bus service, and road deterioration, are among the elements most in need of urgent improvement for all modes of travel. Discussion: The characteristics of the road environment that influence satisfaction with travel to the periodic market vary by travel mode, and this study is hoped to provide data support and optimization recommendations for the improvement of the rural road environment in China and other countries.

One-step electrodeposition synthesis of NiFePS on carbon cloth as self-supported electrodes for electrochemical overall water splitting.

Electrocatalytic water splitting (EWS) for hydrogen production is considered an ideal strategy for utilizing renewable energy, reducing fossil fuel consumption, and addressing environmental pollution issues. Traditional noble metal electrocatalysts have excellent performance, but their cost is high. Developing efficient, stable, and relatively inexpensive dual functional electrocatalysts is crucial for promoting large-scale EWS hydrogen production processes. Herein, a simple one-step electrodeposition method was used to grow nickel-iron phosphorus-sulfides (NiFePS) on the surface of hydrophilic treated carbon cloth (CC). The resultant NiFePS/CC with a phosphorus to sulfur ratio of 1:4 exhibited the best electrocatalytic performance, requiring only -91 mV and 216 mV overpotentials to generate the current densities of 10 mA·cm-2 in hydrogen evolution reaction (HER) and oxygen evolution reaction (OER), respectively. When it was used as a bifunctional electrocatalyst to overall water splitting (OWS), a voltage of 1.536 V can generate a current density of 10 mA·cm-2. The excellent electrocatalytic performance can be ascribed to two factors: 1) the CC with excellent conductivity serves as a growth substrate, reducing the impedance of charge transfer from the electrode to the electrolyte and accelerating the electron transfer rate; 2) The large number of ultra-thin nanosheets formed on the surface of the catalyst increase the electrochemical specific surface area, expose more reaction sites, and thus improve the electrocatalytic reaction performance. This work provides a new approach for designing efficient non-noble metal electrocatalysts for water splitting.

Age-dependent functional development pattern in neonatal brain: An fMRI-based brain entropy study.

The relationship between brain entropy (BEN) and early brain development has been established through animal studies. However, it remains unclear whether the BEN can be used to identify age-dependent functional changes in human neonatal brains and the genetic underpinning of the new neuroimaging marker remains to be elucidated. In this study, we analyzed resting-state fMRI data from the Developing Human Connectome Project, including 280 infants who were scanned at 37.5-43.5 weeks postmenstrual age. The BEN maps were calculated for each subject, and a voxel-wise analysis was conducted using a general linear model to examine the effects of age, sex, and preterm birth on BEN. Additionally, we evaluated the correlation between regional BEN and gene expression levels. Our results demonstrated that the BEN in the sensorimotor-auditory and association cortices, along the 'S-A' axis, was significantly positively correlated with postnatal age (PNA), and negatively correlated with gestational age (GA), respectively. Meanwhile, the BEN in the right rolandic operculum correlated significantly with both GA and PNA. Preterm-born infants exhibited increased BEN values in widespread cortical areas, particularly in the visual-motor cortex, when compared to term-born infants. Moreover, we identified five BEN-related genes (DNAJC12, FIG4, STX12, CETN2, and IRF2BP2), which were involved in protein folding, synaptic vesicle transportation and cell division. These findings suggest that the fMRI-based BEN can serve as an indicator of age-dependent brain functional development in human neonates, which may be influenced by specific genes.

Atomically Resolved Defect-Engineering Scattering Potential in 2D Semiconductors.

Engineering atomic-scale defects has become an important strategy for the future application of transition metal dichalcogenide (TMD) materials in next-generation electronic technologies. Thus, providing an atomic understanding of the electron-defect interactions and supporting defect engineering development to improve carrier transport is crucial to future TMDs technologies. In this work, we utilize low-temperature scanning tunneling microscopy/spectroscopy (LT-STM/S) to elicit how distinct types of defects bring forth scattering potential engineering based on intervalley quantum quasiparticle interference (QPI) in TMDs. Furthermore, quantifying the energy-dependent phase variation of the QPI standing wave reveals the detailed electron-defect interaction between the substitution-induced scattering potential and the carrier transport mechanism. By exploring the intrinsic electronic behavior of atomic-level defects to further understand how defects affect carrier transport in low-dimensional semiconductors, we offer potential technological applications that may contribute to the future expansion of TMDs.

Local thermal adaption mediates the sensitivity of Daphnia magna to nanoplastics under global warming scenarios.

The toxicity of nanoplastics at environmentally relevant concentrations has received widespread attention in the context of global warming. Despite numerous studies on the impact of mean temperature (MT), the effects of daily temperature fluctuations (DTFs) on the ecotoxicity of nanoplastics remains largely unexplored. Moreover, the role of evolutionary adaptation in assessing long-term ecological risks is unclear. Here, we investigated the effects of polystyrene nanoplastics (5 µg L-1) on Daphnia magna under varying MT (20 °C and 24 °C) and DTFs (0 °C, 5 °C, and 10 °C). Capitalizing on a space-for-time substitution approach, we further assessed how local thermal adaptation affect the sensitivity of Daphnia to nanoplastics under global warming. Our results indicated that nanoplastics exposure in general reduced heartbeat rate, thoracic limb activity and feeding rate, and increased CytP450, ETS activity and Hgb concentrations. Higher MT and DTFs enhanced these effects. Notably, clones originating from their respective sites performed better under their native temperature conditions, indicating local thermal adaptation. Warm-adapted low-latitude D. magna showed stronger nanoplastics-induced increases in CytP450, ETS activity and Hgb concentrations under local MT 24 °C, while cold-adapted high-latitude D. magna showed stronger nanoplastics-induced decreases in heartbeat rate, thoracic limb activity and feeding rate under high MT than under low MT.

A hybridization-induced charge-transfer state energy arrangement reduces nonradiative energy loss in organic solar cells.

Here, we explain why the Energy Gap Law and the energy inversion related to the charge-transfer state have opposite effects on the trend of nonradiative energy loss of organic solar cells. The root is the existing condition of energy inversion. There is indeed a certain probability of energy inversion, but it will eventually be implicit or explicit as determined by the hybridization, which depends on the electron-withdrawing unit of the donor, giving rise to different stacking sites. The triplet-state hybridization leads to an explicit characteristic, while singlet-state hybridization leads to an implicit characteristic.

System-wide identification of novel de-ubiquitination targets for USP10 in gastric cancer metastasis through multi-omics screening.

OBJECTIVE: Ubiquitin-specific peptidase 10 (USP10), a typical de-ubiquitinase, has been found to play a double-edged role in human cancers. Previously, we reported that the expression of USP10 was negatively correlated with the depth of gastric wall invasion, lymph node metastasis, and prognosis in gastric cancer (GC) patients. However, it remains unclear whether USP10 can regulate the metastasis of GC cells through its de-ubiquitination function. METHODS: In this study, proteome, ubiquitinome, and transcriptome analyses were conducted to comprehensively identify novel de-ubiquitination targets for USP10 in GC cells. Subsequently, a series of validation experiments, including in vitro cell culture studies, in vivo metastatic tumor models, and clinical sample analyses, were performed to elucidate the regulatory mechanism of USP10 and its de-ubiquitination targets in GC metastasis. RESULTS: After overexpression of USP10 in GC cells, 146 proteins, 489 ubiquitin sites, and 61 mRNAs exhibited differential expression. By integrating the results of multi-omics, we ultimately screened 9 potential substrates of USP10, including TNFRSF10B, SLC2A3, CD44, CSTF2, RPS27, TPD52, GPS1, RNF185, and MED16. Among them, TNFRSF10B was further verified as a direct de-ubiquitination target for USP10 by Co-IP and protein stabilization assays. The dysregulation of USP10 or TNFRSF10B affected the migration and invasion of GC cells in vitro and in vivo models. Molecular mechanism studies showed that USP10 inhibited the epithelial-mesenchymal transition (EMT) process by increasing the stability of TNFRSF10B protein, thereby regulating the migration and invasion of GC cells. Finally, the retrospective clinical sample studies demonstrated that the downregulation of TNFRSF10B expression was associated with poor survival among 4 of 7 GC cohorts, and the expression of TNFRSF10B protein was significantly negatively correlated with the incidence of distant metastasis, diffuse type, and poorly cohesive carcinoma. CONCLUSIONS: Our study established a high-throughput strategy for screening de-ubiquitination targets for USP10 and further confirmed that inhibiting the ubiquitination of TNFRSF10B might be a promising therapeutic strategy for GC metastasis.

Restoration of vegetation in the Yellow River Basin of Inner Mongolia is limited by geographic factors.

Studying the relationships between vegetation cover and geography in the Mongolian region of the Yellow River Basin will help to optimize local vegetation recovery strategies and achieve harmonious human relations. Based on MOD13Q1 data, the spatial and temporal variations in fractional vegetation cover (FVC) in the Mongolian Yellow River Basin during 2000-2020 were investigated via trend and correlative analysis. The results are as follows: (1) From 2000 to 2020, the vegetation cover in the Mongolian section of the Yellow River Basin recovered well, the mean increase in the FVC was 0.001/a, the distribution of vegetation showed high coverage in the southeast and low coverage in the northwest, and 31.19% of the total area showed an extremely significant and significant increase in vegetation cover. (2) The explanatory power of each geographic factor significantly differed. Precipitation, soil type, air temperature, land use type and slope were the main driving factors influencing the spatial distribution of the vegetation cover, and for each factor, the explanatory power of its interaction with other factors was greater than that of the single factor. (3) The correlation coefficients between FVC and temperature and precipitation are mainly positive. The mean value of the FVC and its variation trend are characterized by differences in terrain and soil characteristics, population density and land use. Land use conversion can reflect the characteristics of human activities, and positive effects, such as returning farmland to forest and grassland and afforestation of unused land, promote the significant improvement of regional vegetation, while negative effects, such as urban expansion, inhibit the growth of vegetation.

Regulating the mobility of lattice oxygen on hollow cobalt-manganese sub-nanospheres for enhanced catalytic oxidation of toluene and o-xylene.

Promoting lattice oxygen mobility of Co-based catalysts is crucial to making progress in catalytic oxidation technology. The addition of manganese, a transition metal with similar ionic radius to cobalt and variable valence, was supposed to enhance the mobility of lattice oxygen species of Co-based oxide. A range of hollow CoMnaOx sub-nanosphere catalysts with different Mn/Co ratios was synthesized via a template-sacrificed method, and the effects of different Mn/Co ratios on the structural properties of the catalysts and their catalytic performance for benzene series volatile organic compounds (VOCs) oxidation were investigated. Hollow CoMn2Ox sub-nanosphere exhibited good catalytic activity for oxidation of toluene (T90 = 265 °C) and o-xylene (T90 = 297 °C), as well as excellent recycling ability and water resistance. By adjusting the Mn/Co ratio, metal ions enter into the different tetrahedral or octahedral active sites. Compared with Co3O4, the desorption temperature of surface lattice oxygen on CoMn2Ox decreased by 110 °C. These results demonstrate that the addition of manganese can encourage the electron transfer on CoMnaOx, indicating that the introduction of the appropriate amount of manganese accelerates the activation of gas O2 and mobility of surface lattice oxygen species, thereby expediting the oxidation of benzene series VOCs.

Polyacrylamide/sodium alginate/sodium chloride photochromic hydrogel with high conductivity, anti-freezing property and fast response for information storage and electronic skin.

Photochromic hydrogels have promising prospects in areas such as wearable device, information encryption technology, optoelectronic display technology, and electronic skin. However, there are strict requirements for the properties of photochromic hydrogels in practical engineering applications, especially in some extreme application environments. The preparation of photochromic hydrogels with high transparency, high toughness, fast response, colour reversibility, excellent electrical conductivity, and anti-freezing property remains a challenge. In this study, a novel photochromic hydrogel (PAAm/SA/NaCl-Mo7) was prepared by loading ammonium molybdate (Mo7) and sodium chloride (NaCl) into a dual-network hydrogel of polyacrylamide (PAAm) and sodium alginate (SA) using a simple one-pot method. PAAm/SA/NaCl-Mo7 hydrogel has excellent conductivity (175.9 S/cm), water retention capacity and anti-freezing properties, which can work normally at a low temperature of -28.4 °C. In addition, the prepared PAAm/SA/NaCl-Mo7 hydrogel exhibits fast response (<15 s), high transparency (>70 %), good toughness (maximum elongation up to 1500 %), good cyclic compression properties at high compressive strains (60 %), good biocompatibility (78.5 %), stable reversible discolouration and excellent sensing properties, which can be used for photoelectric display, information storage and motion monitoring. This work provides a new inspiration for the development of flexible electronic skin devices.

Cartilage-Inspired, High-Strength, and Heat-Tolerant Lubricating Hydrogels by Macrophase Separation.

Hydrogels are considered as a potential cartilage replacement material based on their structure being similar to natural cartilage, which are of great significance in repairing cartilage defects. However, it is difficult for the existing hydrogels to combine the high load bearing and low friction properties (37 °C) of cartilage through sample methods. Herein, we report a facile and new fabrication strategy to construct the PNIPAm/EYL hydrogel by using the macrophase separation of supersaturated N-isopropylacrylamide (NIPAm) monomer solution to promote the formation of liposomes from egg yolk lecithin (EYL) and asymmetric template method. The PNIPAm/EYL hydrogels possess a relatively high compressive strength (more than 12 MPa), fracture energy (9820 J/m2), good fatigue resistance, lubricating properties, and excellent biocompatibility. Compared with the PNIPAm hydrogel, the friction coefficient (COF 0.046) of PNIPAm/EYL hydrogel is reduced by 50%. More importantly, the COF (0.056) of PNIPAm/EYL hydrogel above lower critical solution temperature (LCST) does not increase significantly, exhibiting heat-tolerant lubricity. The finite element analysis further proves that PNIPAm/EYL hydrogel can effectively disperse the applied stress and dissipate energy under load conditions. This work not only provides new insights for the design of high-strength lubricating hydrogels but also lays a foundation for the treatment of cartilage injury as a substitute material.

A patient with BRAF N581S mutation-positive lung adenocarcinoma demonstrates durable response to combined anlotinib and tislelizumab: A case report and literature review.

BACKGROUND: Targeted therapy with combined dabrafenib and trametinib has been proven to provide clinical benefits in patients with BRAF V600E mutation-positive NSCLC. Nevertheless, the treatment strategy for NSCLC patients with BRAF non-V600E mutations remains limited. CASE PRESENTATION: Here, we present a NSCLC patient with a BRAF N581S mutation, which is a class III BRAF mutation, and this patient had a durable response to targeted therapy with combined anlotinib and tislelizumab. CONCLUSION: We hope to bring more attention to rare non-V600 BRAF mutations by presenting this case of NSCLC.

Engineering Spatially Adjacent Redox Sites with Synergistic Spin Polarization Effect to Boost Photocatalytic CO2 Methanation.

The integration of oxidation and reduction half-reactions to amplify their synergy presents a considerable challenge in CO2 photoconversion. Addressing this challenge requires the construction of spatially adjacent redox sites while suppressing charge recombination at these sites. This study introduces an innovative approach that utilizes spatial synergy to enable synergistic redox reactions within atomic proximity and employs spin polarization to inhibit charge recombination. We incorporate Mn into Co3O4 as a catalyst, in which Mn sites tend to enrich holes as water activation sites, while adjacent Co sites preferentially capture electrons to activate CO2, forming a spatial synergy. The direct H transfer from H2O at Mn sites facilitates the formation of *COOH on adjacent Co sites with remarkably favorable thermodynamic energy. Notably, the incorporation of Mn induces spin polarization in the system, significantly suppressing the recombination of photogenerated charges at redox sites. This effect is further enhanced by applying an external magnetic field. By synergizing spatial synergy and spin polarization, Mn/Co3O4 exhibits a CH4 production rate of 23.4 µmol g-1 h-1 from CO2 photoreduction, showcasing a 28.8 times enhancement over Co3O4. This study first introduces spin polarization to address charge recombination issues at spatially adjacent redox sites, offering novel insights for synergistic redox photocatalytic systems.

Bulevirtide monotherapy in patients with chronic HDV: Efficacy and safety results through week 96 from a phase III randomized trial.

BACKGROUND & AIMS: Bulevirtide (BLV), a first-in-class entry inhibitor, is approved in Europe for the treatment of chronic hepatitis delta (CHD). BLV monotherapy was superior to delayed treatment at week (W) 48, the primary efficacy endpoint, in the MYR301 study (NCT03852719). Here, we assessed if continued BLV therapy until W96 would improve virologic and biochemical response rates, particularly among patients who did not achieve virologic response at W24. METHODS: In this ongoing, open-label, randomized phase III study, patients with CHD (N = 150) were randomized (1:1:1) to treatment with BLV 2 mg/day (n = 49) or 10 mg/day (n = 50), each for 144 weeks, or to delayed treatment for 48 weeks followed by BLV 10 mg/day for 96 weeks (n = 51). Combined response was defined as undetectable hepatitis delta virus (HDV) RNA or a decrease in HDV RNA by ≥2 log10 IU/ml from baseline and alanine aminotransferase (ALT) normalization. Other endpoints included virologic response, ALT normalization, and change in HDV RNA. RESULTS: Of 150 patients, 143 (95%) completed 96 weeks of the study. Efficacy responses were maintained and/or improved between W48 and W96, with similar combined, virologic, and biochemical response rates between BLV 2 and 10 mg. Of the patients with a suboptimal early virologic response at W24, 43% of non-responders and 82% of partial responders achieved virologic response at W96. Biochemical improvement often occurred independently of virologic response. Adverse events were mostly mild, with no serious adverse events related to BLV. CONCLUSIONS: Virologic and biochemical responses were maintained and/or increased with longer term BLV therapy, including in those with suboptimal early virologic response. BLV monotherapy for CHD was safe and well tolerated through W96. IMPACT AND IMPLICATIONS: In July 2023, bulevirtide was fully approved for the treatment of chronic hepatitis delta (CHD) in Europe based on clinical study results from up to 48 weeks of treatment. Understanding the efficacy and safety of bulevirtide over the longer term is important for healthcare providers. In this analysis, we demonstrate that bulevirtide monotherapy for 96 weeks in patients with CHD was associated with continued improvements in combined, virologic, and biochemical responses as well as liver stiffness from week 48 at both the 2 mg and 10 mg doses. Patients with suboptimal virologic responses to bulevirtide at week 24 also benefited from continued therapy, with the majority achieving virologic response or biochemical improvement by week 96. GOV IDENTIFIER: NCT03852719.

Gut microbial genomes with paired isolates from China illustrate probiotic and cardiometabolic effects.

The gut microbiome displays genetic differences among populations, and characterization of the genomic landscape of the gut microbiome in China remains limited. Here, we present the Chinese Gut Microbial Reference (CGMR) set, comprising 101,060 high-quality metagenomic assembled genomes (MAGs) of 3,707 nonredundant species from 3,234 fecal samples across primarily rural Chinese locations, 1,376 live isolates mainly from lactic acid bacteria, and 987 novel species relative to worldwide databases. We observed region-specific coexisting MAGs and MAGs with probiotic and cardiometabolic functionalities. Preliminary mouse experiments suggest a probiotic effect of two Faecalibacillus intestinalis isolates in alleviating constipation, cardiometabolic influences of three Bacteroides fragilis_A isolates in obesity, and isolates from the genera Parabacteroides and Lactobacillus in host lipid metabolism. Our study expands the current microbial genomes with paired isolates and demonstrates potential host effects, contributing to the mechanistic understanding of host-microbe interactions.

Reconstructing Kaolinite Compounds for Remarkably Enhanced Adsorption of Congo Red.

Organic dyes are widely used in many important areas, but they also bring many issues for water pollution. To address the above issues, a reconstructed kaolinite hybrid compound (γ-AlOOH@A-Kaol) was obtained from raw kaolinite (Kaol) in this work. The product was then characterized by X-ray diffraction (XRD), Fourier-transform infrared (ATR-FTIR), Brunauer-Emmett-Teller (BET), and scanning electron microscopy (SEM), and the absorption properties of γ-AlOOH@A-Kaol for congo red were further studied. The results demonstrated that flower-like γ-AlOOH with nanolamellae were uniformly loaded on the surface of acid-treated Kaol with a porous structure (A-Kaol). In addition, the surface area (36.5 m2/g), pore volume (0.146 cm3/g), and pore size (13.0 nm) of γ-AlOOH@A-Kaol were different from those of A-Kaol (127.4 m2/g, 0.127 cm3/g, and 4.28 nm, respectively) and γ-AlOOH (34.1 m2/g, 0.315 cm3/g, and 21.5 nm, respectively). The unique structure could significantly enhance the sorption capacity for congo red, which could exceed 1000 mg/g. The reasons may be ascribed to the abundant groups of -OH, large specific surface area, and porous structure of γ-AlOOH@A-Kaol. This work provides an efficient route for comprehensive utilization and production of Kaol-based compound materials that could be used in the field of environmental conservation.

Efficacy of a novel affitoxin targeting MOMP against Chlamydia trachomatis in vitro and in vivo.

Targeted therapy is an attractive approach for treating infectious diseases. Affibody molecules have similar capability to antibodies that facilitate molecular recognition in both diagnostic and therapeutic applications. Targeting major outer membrane protein (MOMP) for treating infection of Chlamydia trachomatis, one of the most common sexually transmitted pathogens, is a promising therapeutic approach. Previously, we have reported a MOMP-specific affibody (ZMOMP:461) from phage display library. Here, we first fused it with modified Pseudomonas Exotoxin (PE38KDEL) and a cell-penetrating peptide (CPP) to develop an affitoxin, Z461X-CPP. We then verified the addition of both toxin and CPPs that did not affect the affinitive capability of ZMOMP:461 to MOMP. Upon uptake by C.trachomatis-infected cells, Z461X-CPP induced cell apoptosis in vitro. In animal model, Z461X significantly shortened the duration of C. trachomatis infection and prevented pathological damage in mouse reproductive system. These findings provide compelling evidence that the MOMP-specific affitoxin has great potential for targeting therapy of C. trachomatis infection.

Interference of hemoglobin variants with HbA1c measurements: comparison of 6 commonly used HbA1c methods with the IFCC reference method.

BACKGROUND: Glycated hemoglobin, or hemoglobin A1c (HbA1c), serves as a crucial marker for diagnosing diabetes and monitoring its progression. We aimed to assess the interference posed by common Hb variants on popular HbA1c measurement systems. METHODS: A total of 63 variant and nonvariant samples with target values assigned by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) reference method were included. We assessed 6 methods for measuring HbA1c in the presence of HbS, HbC, HbD, HbE, and fetal hemoglobin (HbF): 2 cation-exchange high-performance liquid chromatography (HPLC) methods (Bio-Rad D-100 and HLC-723 G8), a capillary electrophoresis (CE) method (Sebia Capillarys 3 TERA), an immunoassay (Roche c501), an enzyme assay system (Mindray BS-600M), and a boronate affinity method (Primus Premier Hb9210). RESULTS: The HbA1c results for nonvariant samples from the 6 methods were in good agreement with the IFCC reference method results. The Bio-Rad D-100, Capillarys 3, Mindray BS-600M, Premier Hb9210, and Roche c501 showed no interference from HbS, HbC, HbD, and HbE. Clinically significant interference was observed for the HLC-723 G8 standard mode. Elevated HbF levels caused significant negative biases for all 6 methods, which increased with increasing HbF concentration. CONCLUSION: Elevated levels of HbF can severely affect HbA1c measurements by borate affinity, immunoassays, and enzyme assays.