Low Aggregation Research Articles

Marigold flower like Co3O4 nanoparticles as high performance electrodes for supercapacitors

Transition metal oxides promised as electrode materials for supercapacitors have received much interest, especially cobalt oxide (Co3O4) nanoparticles. However, the low intrinsic electrical conductivity and aggregation of Co3O4 nanoparticles limit their electrochemical performance and impede the commercialization of these electrode materials. The present study describes a simple, and cost-effective solution combustion approach for producing marigold Co3O4 at 300 °C. Further, the effect of vacuum annealing on the microstructural and electrochemical properties is studied to explore the nanostructured samples of Co3O4 as potential electrode material. The electrochemical nature of prepared marigold Co3O4 nanoparticles in 3 M KOH aqueous electrolyte has the highest specific capacitance of 603 Fg−1 at a scan rate of 1 mVs−1 with greater electrochemical stability even after 5000 cycles. The possible reasons for a decrease in specific capacitance on annealing of as prepared Co3O4 at 300 °C are explored in this paper and some significant reasons are highlighted.

A Systematic Review on the Increasing Incidence of Inflammatory Bowel Disease in Southeast Asia: Looking Beyond the Urbanization Phenomenon.

The incidence of inflammatory bowel disease (IBD) has been increasing in Southeast Asia (SEA) in tandem with its economic growth and urbanization over the past 2 decades. Specific characteristics of IBD in SEA are similar to East Asia and the West, such as the declining ratio of ulcerative colitis to Crohn's disease. However, exceptionally low familial aggregation is seen. Smoking is also not a common risk factor in patients with Crohn's disease. The incidence of perianal disease is higher in SEA than in Australia and is comparable to the West. In a multiracial population, such as Singapore and Malaysia, Indians have the highest incidence and prevalence rates, which are likely to be due to important putative mutations. For instance, a higher frequency of the NOD2 predisposing mutation SNP5 and IBD risk allele IGR2198a and IGR2092a were found in Indians. Although differences in the genetic constitution play an important role in the epidemiology and prognosis of IBD in SEA, the emergence of this disease offers a unique opportunity to identify potential exposomes that contribute to its pathogenesis.

Spatial pattern and driving factors of synergistic governance efficiency in pollution reduction and carbon reduction in Chinese cities

This paper is based on the construction of the evaluation system of urban pollution reduction and carbon reduction synergistic governance efficiency indicators. Firstly, we used the NDDF model to measure the efficiency of urban pollution reduction and carbon reduction synergistic governance. We then used the ArcGIS technology and spatial autocorrelation method to explore its spatial distribution pattern, and the spatial econometric model is used to explore its driving factors. The results show that from 2006 to 2020, the synergistic governance efficiency of Chinese cities in terms of pollution reduction and carbon reduction is in a state of continuous improvement, with an increase of 38.07 per cent in 2020 compared with 2006, and overall the synergistic governance efficiency of cities in terms of pollution reduction and carbon reduction shows a pattern of development in which the east is high and the west is low, but there is a tendency for the gap to narrow from one year to the next. There is a positive spatial aggregation of urban pollution reduction and carbon synergistic governance efficiency, which is further shown by the Lisa aggregation diagram that the spatial aggregation of urban pollution reduction and carbon synergistic governance efficiency in China is characterized by urban agglomerations, with the high and high aggregation zones being concentrated in the central and eastern urban agglomerations, such as the urban agglomerations of the middle reaches of the Yangtze River and Guangdong-Fujian-Zhejiang, and the low and low aggregation zones being concentrated in the western urban agglomerations, such as the Lanzhou-Western urban agglomerations and the Guanzhong Plain urban agglomerations. The results of the SDM model indicate that the efficiency of urban pollution reduction and carbon synergistic governance can significantly promote the process of pollution reduction and carbon synergistic governance in neighboring areas. The six drivers, namely, industrial structure, economic development level, innovation level, urbanization rate, population size and foreign direct investment, all have a significant impact on the efficiency of urban pollution reduction and carbon synergistic governance in a local area. The spatial spillover effects of the remaining variables, except for urbanization rate, on the efficiency of urban pollution reduction and carbon synergistic governance are significantly negative. Based on this, corresponding countermeasures are proposed to improve the synergistic governance of urban pollution reduction and carbon reduction.

Macrotexture Prediction for Road Mixtures with Low Nominal Maximum Aggregate Size

Macrotexture Prediction for Road Mixtures with Low Nominal Maximum Aggregate Size

Dollar invoicing, global value chains, and the business cycle dynamics of international trade

This paper reexamines the relationship between monetary policy, exchange rates and international trade in a world characterized by the dominant currency paradigm and global value chains. Using a three-country dynamic stochastic general equilibrium (DSGE) model, it documents key differences between the response of gross and value added trade flows to interest rate shocks, and offers a framework to test them in the data. The exercise uncovers a new margin of adjustment where value added trade flows react significantly to shocks, even as gross trade flows that are typically measured in the data remain relatively flat. This provides a reconciliation between the output effects of textbook models that assume producer currency pricing and no value chains, and the low aggregate exchange rate passthrough and muted adjustment of gross trade flows that has been documented in the data.

IgLM: Infilling language modeling for antibody sequence design

Discovery and optimization of monoclonal antibodies for therapeutic applications relies on large sequence libraries but is hindered by developability issues such as low solubility, high aggregation, and high immunogenicity. Generative language models, trained on millions of protein sequences, are a powerful tool for the on-demand generation of realistic, diverse sequences. We present the Immunoglobulin Language Model (IgLM), a deep generative language model for creating synthetic antibody libraries. Compared with prior methods that leverage unidirectional context for sequence generation, IgLM formulates antibody design based on text-infilling in natural language, allowing it to re-design variable-length spans within antibody sequences using bidirectional context. We trained IgLM on 558 million (M) antibody heavy- and light-chain variable sequences, conditioning on each sequence's chain type and species of origin. We demonstrate that IgLM can generate full-length antibody sequences from a variety of species and its infilling formulation allows it to generate infilled complementarity-determining region (CDR) loop libraries with improved in silico developability profiles. A record of this paper's transparent peer review process is included in the supplemental information.

Probabilistic forecast-based portfolio optimization of electricity demand at low aggregation levels

In the effort to achieve carbon neutrality through a decentralized electricity market, accurate short-term load forecasting at low aggregation levels has become increasingly crucial for various market participants' strategies. Accurate probabilistic forecasts at low aggregation levels can improve peer-to-peer energy sharing, demand response, and the operation of reliable distribution networks. However, these applications require not only probabilistic demand forecasts, which involve quantification of the forecast uncertainty, but also determining which consumers to include in the aggregation to meet electricity supply at the forecast lead time. While research papers have been proposed on the supply side, no similar research has been conducted on the demand side. This paper presents a method for creating a portfolio that optimally aggregates demand for a given energy demand, minimizing forecast inaccuracy of overall low-level aggregation. Using probabilistic load forecasts produced by either ARMA-GARCH models or kernel density estimation (KDE), we propose three approaches to creating a portfolio of residential households' demand: Forecast Validated, Seasonal Residual, and Seasonal Similarity. An evaluation of probabilistic load forecasts demonstrates that all three approaches enhance the accuracy of forecasts produced by random portfolios, with the Seasonal Residual approach for Korea and Ireland outperforming the others in terms of accuracy and computational efficiency.

Nucleic acid strand displacement for indirect determination of foodborne bacteria by capillary electrophoresis and its application in antagonism and bacteriostasis studies.

Foodborne bacteria threaten human's health. Capillary electrophoresis (CE) is a powerful separation means for the determination of bacteria. Direct separation of bacteria suffers from the shortages of low resolution, channel adsorption, and bacterial aggregation. In this work, a method of nucleic acid strand displacement was developed to indirect separate the bacteria by CE. DNA complexes, consisting of probes and aptamers, were mixed with the three bacteria Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The aptamers could specifically bond with bacteria and release the probes. Through the separation of the probes, the bacteria could be indirectly determined by CE. This method avoided the shortages of direct separation of bacteria. Under the optimized conditions, the three probes for the bacteria could be separated and detected within 2.5min by high-speed CE with laser-induced fluorescence detection. The limits of detection for the bacteria were in the range 4.20×106 to 1.75×107 CFU/mL. Finally, the developed method was applied on the study of antagonism of the coexistent bacteria to reveal the relationship between them. Furthermore, the efficiency of bacteriostasis of three traditional Chinese medicines, Coptis chinensis, Schisandra chinensis, and honeysuckle, was also studied by this method.

MEH‐PPV/SBS composite films: Localization and luminescence properties of conductive polymers with microphase separation

AbstractThis study reports the synthesis of a flexible light‐emitting polymer film by casting the solution formed by blending poly[2‐methoxy‐5‐((2‐ethylhexyl)oxy)‐1,4‐phenylenevinylene] (MEH‐PPV) with poly(styrene‐co‐butadiene‐co‐styrene) (SBS). Scanning force microscopy (SFM) and differential scanning calorimetry (DSC) confirm that MEH‐PPV molecules are selectively positioned in the polystyrene (PS) domain of the fabricated film. As MEH‐PPV molecules are dissolved in the PS phase without aggregation, the photoluminescence (PL) spectrum of the MEH‐PPV/SBS film exhibits a nanometer‐scale bicontinuous luminescent domain with low aggregation quenching. Furthermore, the MEH‐PPV/SBS film exhibits typical elastomeric characteristics (with linear elasticity, a plateau, and densification regions in its stress–strain curves), and its tensile properties are comparable to those of neat SBS films. As MEH‐PPV molecules are almost absent in the polybutadiene (PB) phase (which influences the bulk‐film elastic properties), the concentration of MEH‐PPV shows very little effect on the elastic properties of the composite film.

Spatiotemporal Distribution Characteristics and Their Driving Forces of Ecological Service Value in Transitional Geospace: A Case Study in the Upper Reaches of the Minjiang River, China

Ecosystem service value (ESV) is a key indicator for evaluating ecosystem services. Thus, a unique quantitative assessment instrument that comprehensively and objectively evaluates ESV is of great significance for protecting regional ecosystems and achieving sustainable development. Based on data for meteorology, hydrology, soil use, and land use, this paper comprehensively employs the InVEST model, spatial autocorrelation, and geographic detectors to study the spatiotemporal characteristics and driving forces of spatial variations in ESV in the upper reaches of the Minjiang River. The results indicate the following: (1) The ecosystem service capacity of the study area has continuously improved, with the ecosystem service value (ESV) increasing by USD 4.078 billion over 20 years. Soil conservation has made the most significant contribution to the growth of ESV, accounting for over 85%. (2) The distribution of ESV exhibits a “lower in the northwest, higher in the southeast” trend. The Moran’s I value for each year exceeds 0.7, indicating characteristics of High–High and Low–Low aggregation. (3) Slope plays a dominant role in causing the spatial differentiation of ESV, contributing 30.9%. Slope is followed by HAI at 19.7% and the urbanization rate at 16.8%. Rainfall has the least impact at 4%. (4) The results from the multi-factorial interactions reveal that all factors experience synergistic enhancement effects when interacting. The spatiotemporal differentiation of ESV is the result of multiple factors acting in conjunction, underscoring the importance of coordinated efforts in ecological restoration and comprehensive environmental management in the upper reaches of the Minjiang River. The methodology of this research could be applied to assess the impact of natural changes and human activities on ESV. The findings offer theoretical support for regional resource and environmental management, as well as ecological compensation decision making.

Self‐Assembled Amphiphilic Camptothecin Nanoparticles with Glutathione‐Responsive and Tumor‐Targeting Ability for Enhanced Colorectal Cancer Therapy

AbstractCamptothecin (CPT) is impeded by low solubility, non‐tumor‐targeting ability, and fast blood clearance. Self‐assembly of hydrophobic drugs into nanostructures, especially nanoparticles (NPs), can improve their anti‐cancer effects. In this study, arginine‐glycine‐aspartic acid (RGD), a hydrophilic and tumor‐targeting peptide, is conjugated with CPT through a glutathione‐cleavable disulfide bond. The synthesized amphiphilic molecule CPT‐ss‐RGD self‐assembled into stable NPs in an aqueous solution with diameters of ≈86nm. They exhibited low critical aggregation concentrations, good stability, and glutathione responsiveness. They can be specifically taken up by CRC cells through RGD integrin‐mediated uptake, and exhibit high toxicity to CRC cells and multicellular tumor spheroids. As expected, CPT‐ss‐RGD NPs prolonged the blood circulation time and enhanced the tumor accumulation of CPT, exhibiting excellent anti‐tumor growth ability and few side effects. Thus, CPT‐ss‐RGD NPs have great clinical translational potential for CRC therapy. The successful self‐assembly of the CPT‐ss‐RGD NPs provides a new method for the self‐delivery of hydrophobic therapeutics in vivo.

Agricultural productivity and structural transformation: evidence and questions for African development

ABSTRACT This paper summarizes key findings from the recent literature on agricultural productivity and structural transformation and then identifies priority areas for further research. The paper discusses the macro relevance of agricultural productivity for growth and structural transformation. New theory and data have underscored the importance of agricultural productivity as a proximate cause of low aggregate productivity in the world’s poorest countries, including many in sub-Saharan Africa. Evidence has also emerged on the importance of agricultural productivity growth as a driver of development and growth in the past. But micro evidence and changes in the global context suggest that today’s low-income countries may face a different set of challenges in the years ahead.

MWCNTs dispersion adopting GA and its application towards copper tailings-based cementitious materials

Hydrophobic carbon nanotubes are hardly to disperse in water and prone to agglomerate when poured with Copper Tailing-Based Cementitious Material (CTCM). Multi-walled carbon nanotubes (MWCNTs) + Arabic Gum (GA) dispersions were prepared by a novel method of synergistic optimization of concentration, controlling low-frequency ultrasonic time and setting the ambient temperature with non-toxic anionic surfactant GA as surfactant. The results of UV–Vis spectroscopy showed that the high stability MWCNTs + GA dispersion with low aggregation area (< 1.2%) and low aggregation beam size (< 219 nm) have been prepared by using 1.7 mmol/l GA. The effects of highly stable MWCNTs dispersion on the mechanical properties, microstructure and durability of CTCM were studied. The 28 days compressive strength increased by 21.5%, and the flexural strength increased by 20.5%, almost reaching the mechanical level of the control group. The results of SEM, XRD and EDS showed that GA significantly enhanced the dispersion of MWCNT in aqueous solution at a suitable concentration (mass ratio of GA:CNTs = 1:1). The microstructure of the prepared CTCM by high stability MWCNTs dispersion was optimized obviously, and the mechanical properties and durability were improved significantly. This method solves the dual problem of MWCNTs not being fully dispersed in aqueous solution and being easily re-agglomerated in cementitious materials, as well as finding a breakthrough for the low cost and industrialization of tailings cement-based composite cementitious materials.

Spatial Planning Strategies for Wetlands Based on a Multimethod Approach: The Example of Tianjin in China

Wetlands form a crucial component of ecosystems, and wetland restoration serves as an effective strategy for promoting sustainable urban development. Spatial support is essential for wetland restoration, meaning that research on wetland spatial planning is of considerable importance. Existing studies on wetland spatial planning primarily focus on the analysis of wetland spatial distribution characteristics, with limited exploration of wetland spatial relationships. This paper aims to explore the potential of utilizing both spatial distribution characteristics and spatial relationships to identify wetland spatial issues, thereby facilitating the formulation of wetland spatial planning strategies. Using Tianjin City as a case study, this research applies nearest neighbor analysis, the geographic concentration index, the Gini index, and kernel density analysis to identify the spatial distribution characteristics of wetlands in Tianjin. Additionally, spatial autocorrelation analysis and connectivity analysis are employed to identify the interrelationships among wetlands in Tianjin. Based on the results derived from the analysis of spatial distribution characteristics and spatial relationships, wetland spatial planning strategies are proposed. The effectiveness of these strategies is validated using methods that consider both spatial distribution characteristics and spatial relationships. The findings reveal that, although wetlands in Tianjin are widely distributed, large wetland patches are primarily concentrated in areas with abundant water resources, while the six districts within the city have few or no large patches of wetlands. The spatial distribution of wetlands is highly uneven, exhibiting patterns of high–high aggregation and low–low aggregation. The number of connecting paths between wetland patches is relatively low, indicating a generally low overall connectivity. While medium-sized and larger wetland patches maintain the connectivity of existing wetlands in Tianjin, small wetlands that serve as stepping stones are lacking. Following the implementation of planning strategies, there would be an increase in the wetland area in Tianjin, accompanied by significant improvements in the spatial distribution pattern and spatial relationships of the wetlands.

Internal alkali transport in recycling concrete and its impact on alkali-silica reaction

Recycling concrete (RC) produced with recycled aggregates (RA) obtained from demolished concrete structures bears the risk of an alkali-silica reaction (ASR). In this study, the interplay between aggregate reactivity and alkalis contributed by the cement and the RA is investigated. Three sets of concrete mixtures are produced using RA and natural aggregates, both reactive and non-reactive ones. Caesium either present in the RA or in the mixing water of the RC is used to trace the transport of alkalis and their incorporation in ASR products. The result shows that alkali released by RA can intensify ASR. On the other hand, ASR in RA with a low alkali content but reactive aggregate particles can be triggered by the alkali provided by the new cement paste of the RC. The highest risk of ASR in RC is caused by RA from a source concrete already affected by ASR.

The impact of aggregation between clay and phytoplanktonic cyanobacteria on trace elemental cycling in coastal environments

Clay minerals and cyanobacteria occur ubiquitously in nature, and both independently influence trace metal cycling due to their high specific surface areas and reactivity. Although the surface reactivity of each is well-studied, the reactivity of clay-cyanobacterial aggregates has received less attention. Here, we performed potentiometric acid-base titrations and Cd adsorption experiments on various concentrations of clay-cyanobacterial aggregates using three clay minerals (kaolinite, illite, and montmorillonite) and two model planktonic cyanobacteria, the freshwater species Synechocystis sp. PCC 6803 and marine species Synechococcus sp. PCC 7002. A component additivity surface complexation modeling (CA-SCM) approach was applied to study the impacts of the aggregation processes on the total surface reactivity. Results demonstrate that the CA-SCM approach effectively predicted the acid-base titration and Cd adsorption behaviors of aggregates at low aggregate concentrations (up to 2.5 g of clay/L for acid-base titration and 0.1 g of clay/L for Cd adsorption), indicating the additivity of the reactivity for the two components. However, at higher aggregate concentrations (25 g of clay/L for acid-base titration and 10 g of clay/L for Cd adsorption), the CA-SCM approach overestimates the acid-base titration and Cd adsorption behaviors for the aggregates, indicating significant surface site blockage during aggregation. Our SEM images show that both cyanobacterial species were covered by layered clay minerals at the surfaces and formed relatively larger aggregates at high aggregate concentrations than at low aggregate concentrations. Based on the combined results, we propose that the interaction between clays and cyanobacteria is relatively weak at low aggregate concentrations (e.g., <10 g of aggregate/L), but that significant obstruction of surface adsorption sites occurs at high aggregate concentrations (e.g., >10 g of aggregate/L), possibly due to the encrustation of bacteria by clay minerals. The implication of this work is that where turbid rivers discharge into estuaries or deltas with high primary phytoplankton productivity, aggregation (or flocculation) processes will cause the depression of surface reactivity of the aggregates and lead to a decrease in metal-binding capacity. Therefore, depending on whether the trace elements are nutrients (e.g., phosphorous) or potentially toxic (e.g., cadmium), this process has the potential to impact the marine biosphere. To ground truth this hypothesis, we further analyzed the correlation between total organic carbon (TOC) content and trace metal compositions in a compiled shale database and the results show clear negative correlation between Cd concentration and the concentration of TOC, Al and Si. Although this offers only an indirect assessment of the role of clay-plankton aggregation, as a first-order test it does indeed show that the aggregation between clay minerals and phytoplanktonic bacteria in estuaries is an essential factor that influences trace-elemental cycling.

Magnesium ions regulated ovalbumin-lysozyme heteroprotein complex: Aggregation kinetics, thermodynamics and morphologic structure

This study aims to investigate the mechanism of magnesium ions regulated ovalbumin-lysozyme (OVA-LYS) heteroprotein aggregation behavior via aggregation kinetics model, exploring the relationship between differential aggregation behavior and protein molecular structure, intermolecular interactions and thermal stability. Results showed that the aggregation rate (kapp) and maximum absorbance (Amax) of the OVA-LYS heteroprotein complex were located between OVA and LYS. Meanwhile, the thermal denaturation temperature (Td) and denaturation enthalpy (ΔH) were between the values of OVA and LYS as well. Compared with OVA, the thermal stability of the OVA-LYS heteroprotein complex increased owing to the electrostatic interactions between OVA and LYS, resulting in slower aggregation rate and lower aggregation degree. Molecular dynamics simulations revealed the molecular conformational changes during OVA-LYS binary protein binding and the stability of the complex conformation. Moreover, MgCl2 weakened the OVA-LYS interactions through Debye shielding while increasing thermal stability, allowing the two proteins to aggregate into amorphous precipitates rather than spherical coacervates. Overall, this study provides information to further understand the regulation mechanism of proteins differential aggregation behavior by ions.

De novo peptides as potential antimicrobial agents

The phenomenon of antimicrobial resistance threatens our ability to treat common infections. The clinical pipeline for new antimicrobials is pretty much dry and hence, there is a need for the development of new antimicrobial agents with low toxicities to help fight resistant microorganisms. This work aimed to design antimicrobial peptides with low toxicities using a database filtering technology and evaluate their bioactivities. The physicochemical properties of the designed peptides were explored with molecular dynamics (MD) simulations. Microbroth dilution and hemolytic assays were used to assess the peptides' antimicrobial activity and toxicity. The activity of combinations of the peptides and some standard antibiotics was tested by the checkerboard method. In general, the designed peptides had a charge of +2, chain length of 13, and hydrophobicity of 61%. The predicted secondary structures of the peptides were either extended conformations or alpha-helices, and these structures were found to fluctuate during the MD simulations, where coils, bends, and helices dominated. , of the peptides, BRG003, BRG004 and BRG002 had the greatest aggregation propensities, whereas BRG001, BRG005, and BRG006 exhibited lower aggregation propensities. The minimum inhibitory concentration (MIC) of the peptides ranged from 0.015 to >1.879 μM, with BRGP-001 exhibiting high activity against MRSA with an MIC of 15 nM. BRGP-005 and BRGP-006 exhibited synergistic effects against Escherichia coliR when used in combination with erythromycin. At the minimum hemolytic concentration, the percentage of lysed erythrocytes was lower for all the peptides in comparison to the reference peptide, indicating low hemolytic activity. The study revealed the importance of peptide self-association in the antimicrobial activity of the peptides. These peptides provide a basis for the design of potent antimicrobial peptides that can further be developed for use in antimicrobial therapy.

High Miscibility‐Induced Reduction of Trap Density in All‐Polymer Solar Cells Using Hybrid Cyclohexyl‐Hexyl Side Chains

AbstractReducing the trap density within organic solar cells is of vital importance to realize high power conversion efficiency (PCE); however, research focusing on this aspect is limited in all‐polymer solar cells (All‐PSCs). In this work, it is found that the trap density can be dramatically reduced by simultaneously obtaining high miscibility of donor and acceptor and ordered packing in blend films through substituting ethylhexyl with hybrid cyclohexyl‐hexyl side chains in the design of the polymer donor. D18‐ChCl with hybrid cyclohexyl‐hexyl chains has a slightly lower aggregation behavior relative to the D18‐Cl counterpart, but reveals synchronously higher miscibility and crystallinity in a blend with the acceptor PYF‐T‐o. Such a morphology evolution positively affects the electronic properties of the device—prolongs the carrier lifetime, facilitates exciton dissociation, and lowers the energy disorder. As a result, the All‐PSC devices based on D18‐ChCl exhibited a remarkable PCE of 17.1%, with a low trap density of 2.65 × 1015 cm−3, a low energy disorder of 47 meV as well as outstanding stability and mechanical durability. This result demonstrates that hybrid cyclohexyl‐hexyl alkyl engineering delicately improves miscibility, drives low trap density, and refines device performance, which brings vibrancy to the All‐PSC research field.

Decreasing hydrophobicity or shielding hydrophobic areas of CH2 attenuates low pH-induced IgG4 aggregation.

Protein aggregation is a major challenge in the development of therapeutic monoclonal antibodies (mAbs). Several stressors can cause protein aggregation, including temperature shifts, mechanical forces, freezing-thawing cycles, oxidants, reductants, and extreme pH. When antibodies are exposed to low pH conditions, aggregation increases dramatically. However, low pH treatment is widely used in protein A affinity chromatography and low pH viral inactivation procedures. In the development of an IgG4 subclass antibody, mAb1-IgG4 showed a strong tendency to aggregate when temporarily exposed to low pH conditions. Our findings showed that the aggregation of mAb1-IgG4 under low pH conditions is determined by the stability of the Fc. The CH2 domain is the least stable domain in mAb1-IgG4. The L309E, Q311D, and Q311E mutations in the CH2 domain significantly reduced the aggregation propensity, which could be attributed to a reduction in the hydrophobicity of the CH2 domain. Protein stabilizers, such as sucrose and mannose, could also attenuate low pH-induced mAb1-IgG4 aggregation by shielding hydrophobic areas and increasing protein stability. Our findings provide valuable strategies for managing the aggregation of protein therapeutics with a human IgG4 backbone.