Multiple Chains Research Articles

General strategies for IgG-like bispecific antibody purification.

Bispecific antibodies (bsAbs) can simultaneously bind two different antigens or epitopes. Their dual-targeting capability enables novel mechanisms of action, gaining therapeutic advantages over conventional monospecific mAbs. In recent years, the number of bsAbs grows rapidly and bsAbs under development are available in diverse formats. In particular, Fc-containing IgG-like bsAbs, which represent the major group, can be constructed in asymmetric or symmetric format. For asymmetric ones, whose assembly requires multiple distinct chains, although numerous strategies have been developed to promote desired chain pairing, product-related variants such as free chains, half molecules and mispaired species are usually present at various levels. For symmetric ones, increased level of aggregates and truncating variants is often associated with their production. In general, bsAbs pose greater challenges to the downstream team than regular mAbs. In the past few years, our team successfully developed the downstream process for over 70 bsAbs in greater than 30 different formats and accumulated substantial experience. This review introduces general strategies that we have used while purifying these challenging molecules.

What hinders the transition towards a bio-based construction sector? A global innovation system perspective on its value chain

The construction sector is heavily polluting and an actual threat to the natural environment, therefore its transition towards becoming bio-based is imperative. This transition is currently unfolding and it is driven in particular by innovation activities taking place along the sector’s value chain. In the upstream segment, bio-based materials are being improved, while novel building techniques in the core segment enable the use of these materials. In this paper, we utilize the global innovation systems (GIS) framework to examine these innovation activities and their valuation dynamics. In particular, we investigate how the GIS of the bio-based construction sector is organized along its value chain, providing insights into the barriers to the sector's sustainability transition. Our empirical analysis, based on a rich set of expert interviews, demonstrates that the GIS configuration changes along the value chain, driven by profound differences in the innovation mode. This situation creates a bottleneck that hinders the sector's transition, where knowledge about bio-based materials developed upstream fails to translate down the value chain. However, we also find that several niche firms cover and integrate multiple value chain segments and overcome this knowledge gap, suggesting that the transition towards a bio-based construction sector could accelerate with further innovation system reconfigurations.

Streamlining RNA Aptamer Selection via Unique Molecular Identifiers and High-Throughput Sequencing.

Aptamers are valuable tools for applications such as cell imaging, drug delivery, and therapeutics. RNA aptamers, in particular, exhibit complex structural diversity and flexibility, affording higher affinity and specificity, broader target recognition, and easier chemical modification compared with DNA aptamers. However, traditional selection methods for RNA aptamers are time-consuming and involve numerous rounds of screening, thus limiting their widespread application. To overcome this challenge, we propose an efficient truncated selection approach termed ID-SELEX. This method incorporates a molecular identification marker whereby each template is labeled with a unique molecular identifier, or UMI. Such incorporation helps mitigate biases introduced by multiple polymerase chain reaction (PCR) amplification during high-throughput sequencing, ensuring accurate identification of aptamer candidates. Utilizing ID-SELEX, we successfully identified a panel of high-quality aptamers targeting the human colon cancer cell line HCT-8 in just 2 rounds of selection. Furthermore, we demonstrated the versatility of this strategy by selecting 6 RNA aptamers targeting mouse myoblast cell line C2C12 with only one round of selection. In summary, RNA aptamer selection based on ID-SELEX utilizes high-throughput sequencing and UMI labeling to enable the rapid screening of RNA aptamers across human and murine cell lines. As such, ID-SELEX has the potential to facilitate RNA aptamer discovery, providing a novel molecular tool for biomedical research, clinical applications, and precision medicine.

An Empirical Study on the Assessment of the Impact of Service Quality on Customer Repurchase Intention in Retail Chain Stores of Khulna District of Bangladesh

Purpose: The study aims to identify how various aspects of service quality impact customer repurchase intention in retail chain stores in Bangladesh. Methodology: The study has been conducted following the quantitative research method. Data were gathered from 100 shoppers via direct surveys done at multiple retail chain stores in Khulna city of Bangladesh. A questionnaire with a five-point Likert scale was used in the study to collect consumer feedback on several elements related to service quality and repurchase intention. SPSS 25 (Statistical Package for the Social Sciences) was used to analyze the data for Reliability tests, correlations analysis, and regression analysis. Findings: The data show that responsiveness, assurance, and empathy have a substantial effect on customers' likelihood of repurchasing from retail chain stores. Surprisingly, tangible elements such as store appearance and reliability had little influence on customers' propensity to return. Practical Implications: According to the findings, retailers should focus on developing a customer-centric strategy that emphasizes prompt service, trust-building efforts, and encouraging sympathetic relationships. Originality/Value: The study has transformative potential for the retail chain sector, guiding strategic adjustments for enhanced customer experiences, competitive advantages, and long-term growth. Limitations: While the study provides useful insights, its limitations include a limited geographic scope, small sample size and inherent biases caused by the convenience sampling method. To clarify subtle customer behaviors across multiple retail landscapes, future research should include broad retail segments and locales.

A Deficiency in Glutamine-Fructose-6-Phosphate Transaminase 1 (Gfpt1) in Skeletal Muscle Results in Reduced Glycosylation of the Delta Subunit of the Nicotinic Acetylcholine Receptor (AChRδ).

The neuromuscular junction (NMJ) is the site where the motor neuron innervates skeletal muscle, enabling muscular contraction. Congenital myasthenic syndromes (CMS) arise when mutations in any of the approximately 35 known causative genes cause impaired neuromuscular transmission at the NMJ, resulting in fatigable muscle weakness. A subset of five of these CMS-causative genes are associated with protein glycosylation. Glutamine-fructose-6-phosphate transaminase 1 (Gfpt1) is the rate-limiting enzyme within the hexosamine biosynthetic pathway (HBP), a metabolic pathway that produces the precursors for glycosylation. We hypothesized that deficiency in Gfpt1 expression results in aberrant or reduced glycosylation, impairing the proper assembly and stability of key NMJ-associated proteins. Using both in vitro and in vivo Gfpt1-deficient models, we determined that the acetylcholine receptor delta subunit (AChRδ) has reduced expression and is hypo-glycosylated. Using laser capture microdissection, NMJs were harvested from Gfpt1 knockout mouse muscle. A lower-molecular-weight species of AChRδ was identified at the NMJ that was not detected in controls. Furthermore, Gfpt1-deficient muscle lysates showed impairment in protein O-GlcNAcylation and sialylation, suggesting that multiple glycan chains are impacted. Other key NMJ-associated proteins, in addition to AChRδ, may also be differentially glycosylated in Gfpt1-deficient muscle.

Effect of mesh aluminum alloy on hydrogen and propane explosion characteristics

In order to explore the effect of mesh aluminum alloy (MAA) on the explosion characteristics of different types of gases, experiments were conducted by filling MAA in hydrogen and propane explosion pipes. The explosion characteristic parameters of hydrogen and propane with different volume fractions under the action of MAA were obtained. The chain reaction process and thermodynamic reaction mechanism of hydrogen and propane explosions were studied using the numerical simulation software CHEMKIN-PRO and Materials Studio. The experimental results show that MAA significantly promotes hydrogen explosions but inhibits propane explosions. Simulation results show that ·H, ·O, and ·OH are key radicals in the hydrogen explosion process. As the hydrogen volume fraction increases, the number of radicals in the reaction system also increases. When MAA is filled in the hydrogen explosion test pipe, the turbulence of the flame structure inside the pipe increases the collision probability between key radicals such as ·H, ·O, and ·OH, sharply increasing the temperature of the explosion reaction system, resulting in a promoting effect of MAA on hydrogen explosions. When MAA is introduced into the propane explosion test pipe, it creates a barrier and wall effect. This reduces the number of key radicals in the reaction system and lowers the likelihood of radical collisions, which slows down the rates of multiple chain reactions and inhibits the propane explosion. Thermodynamically, it can be seen that propane requires more energy than hydrogen for key elementary reactions to explode, making it more difficult to react.

DockQ v2: improved automatic quality measure for protein multimers, nucleic acids, and small molecules.

It is important to assess the quality of modeled biomolecules to benchmark and assess the performance of different prediction methods. DockQ has emerged as the standard tool for assessing the quality of protein interfaces in model structures against given references. However, as predictions of large multimers with multiple chains become more common, DockQ needs to be updated with more functionality for robustness and speed. Moreover, as the field progresses and more methods are released to predict interactions between proteins and other types of molecules, such as nucleic acids and small molecules, it becomes necessary to have a tool that can assess all types of interactions. Here, we present a complete reimplementation of DockQ in pure Python. The updated version of DockQ is more portable, faster and introduces novel functionalities, such as automatic DockQ calculations for multiple interfaces and automatic chain mapping with multi-threading. These enhancements are designed to facilitate comparative analyses of protein complexes, particularly large multi-chain complexes. Furthermore, DockQ is now also able to score interfaces between proteins, nucleic acids, and small molecules. DockQ v2 is available online at: https://wallnerlab.org/DockQ.

Innovation and Practice of Diversified Business Model of New Energy Power Generation Enterprises

With the growing global demand for clean energy, new energy power generation enterprises are facing new opportunities and challenges. This paper explores the diversified business model of new energy power generation enterprises. Firstly, the theoretical basis of the business model of new energy power generation enterprises is analyzed, including the characteristics and income sources of single and multiple industrial chain models. The advantages and applications of different business models are analyzed through the study of cases at home and abroad, such as the European aggregated generation side resource model, the United States focused on controllable load demand response model, and the domestic cases of Shanghai and Shenzhen virtual power plant projects and distributed photovoltaic power generation. Then it puts forward the diversified business model innovation strategy of new energy power generation enterprises, covering the innovation of comprehensive energy services, the development of power side energy storage business, and the expansion of key businesses and profit models. Finally, the research conclusions are summarized and the future research directions are prospected. In short, the exploration of diversified business models of new energy power generation enterprises is of great significance to promote the development of clean energy and improve the competitiveness of enterprises.

The impact of social participation on the quality of life among older adults in China: a chain mediation analysis of loneliness, depression, and anxiety.

This cross-sectional study investigates the impact of social participation on the quality of life (QOL) among older adults in China. Using convenience sampling, data were collected from 508 individuals aged 60 and above (M_age = 70.53 ± 7.90 years; 56.5% women). Statistical analyses were conducted using SPSSAU software, including Pearson correlation analysis to assess relationships between social participation, psychological health indicators (loneliness, depression, and anxiety), and QOL. Multiple regression analysis and chain mediation analysis were subsequently performed to explore the mediating effects of loneliness, depression, and anxiety on the relationship between social participation and QOL. The results indicated significant correlations between social participation and loneliness (r = -0.313, p < 0.001), depression (r = -0.487, p < 0.001), anxiety (r = -0.305, p < 0.001), and QOL (r = 0.476, p < 0.001). The mediation analysis revealed significant chain mediation effects of loneliness, depression, and anxiety on the relationship between social participation and QOL (β = 0.006, p < 0.001, 95% CI [0.001, 0.007]). Higher levels of social participation were associated with lower levels of loneliness, which in turn reduced depression and anxiety, thereby enhancing QOL. These findings highlight the importance of promoting social participation to improve psychological wellbeing and QOL among older adults in China. The study advocates for active social engagement and the provision of relevant services, as well as psychological support and emotional counseling for those facing mental health challenges due to insufficient social participation.

The relationship between loneliness and sleep quality: multiple chain mediating roles

The relationship between loneliness and sleep quality: multiple chain mediating roles

Al-Doped CuS Colloidal Nanocrystals as a Highly Efficient Electrochemiluminescence Emitter for the Ultrasensitive Detection of Circulating Tumor DNA.

Herein, CuS colloidal nanocrystals (NCs) with adjustable band gap and good film forming ability have been synthesized as new ECL materials. Furthermore, the band gap and oxygen vacancy (OV) content of CuS NCs are regulated by Al3+ doping, which significantly improves the ECL response of CuS NCs. First, the band gap of CuS-Al NCs decreases after doping with Al3+, which makes it easier for electrons to transition across the band gap. At the same time, the oxygen vacancy of CuS-Al NCs increases, which is conducive to improving the conductivity and promoting charge transfer, thus improving the ECL performance of CuS-Al NCs. Circulating tumor DNA (ctDNA) is an important tumor marker, and its sensitive monitoring is of great significance for tumor diagnosis, treatment, and prognosis detection. Therefore, an ECL biosensor for ultrasensitive detection of circulating tumor DNA (ctDNA) was prepared by using CuS-Al NCs as luminescent material and combining multiple antidromic hybrid chain reaction (anti-HCR) strategy mediated by the target. Compared with the process of target-induced HCR generation, this strategy first forms multiple HCR products and then destroys the already formed HCR products by target-induced destruction, which enhances the sensitivity of target response and improves the reaction efficiency. The constructed biosensor has good detection performance, and the detection limit is as low as 2.74 aM. This work puts forward the luminescence phenomenon of colloidal nanocrystals as new ECL materials, which broadens the application of ECL technology in ultrasensitive biochemical detection.

An automated convergence diagnostic for phylogenetic MCMC analyses.

Assessing convergence of Markov chain Monte Carlo (MCMC) based analyses is crucial but challenging, especially so in high dimensional and complex spaces such as the space of phylogenetic trees (treespace). In practice, it is assumed that the target distribution is the unique stationary distribution of the MCMC and convergence is achieved when samples appear to be stationary. Here we leverage recent advances in computational geometry of the treespace and introduce a method that combines classical statistical techniques and algorithms with geometric properties of the treespace to automatically evaluate and assess practical convergence of phylogenetic MCMC analyses. Our method monitors convergence across multiple MCMC chains and achieves high accuracy in detecting both practical convergence and convergence issues within treespace. Furthermore, our approach is developed to allow for real-time evaluation during the MCMC algorithm run, eliminating any of the chain post-processing steps that are currently required. Our tool therefore improves reliability and efficiency of MCMC based phylogenetic inference methods and makes analyses easier to reproduce and compare. We demonstrate the efficacy of our diagnostic via a well-calibrated simulation study and provide examples of its performance on real data sets. Although our method performs well in practice, a significant part of the underlying treespace probability theory is still missing, which creates an excellent opportunity for future mathematical research in this area. The open source package for the phylogenetic inference framework BEAST2, called ASM, that implements these methods, making them accessible through a user-friendly GUI, is available from https://github.com/rbouckaert/asm/. The open source Python package, called tetres, that provides an interface for these methods enabling their applications beyond BEAST2 can be accessed at https://github.com/bioDS/tetres/.

Net-zero life cycle supply chain assessment of heat pump technologies

In this study, a comparative life cycle assessment of different heat pump technologies based on multiple supply chain scenarios according to the UK market has been conducted. In addition to conventional heat pumps – air-source heat pump (ASHP), ground-source heat pump (GSHP), and water-source heat pump (WSHP) - a novel hydrogen-source heat pump (HSHP) has been studied from an environmental aspect. Different supply chain scenarios have been developed for all technologies based on the leading supplier of heat pump components in the UK. Results showed that the manufacturing and operation of heat pumps are the main causes of the environmental impacts. Among the four technologies studied, ASHP had the highest negative environmental impacts across most categories. HSHP stands out with notably lower carbon emissions compared to other cases. However, in certain impact categories, HSHP exhibited more significant consequences, especially concerning land use and land-related pollution. Regarding CO2 emissions, ASHP is projected to achieve the most substantial reduction, with expected reductions of 23 %, 60 %, and 97 % by 2030, 2040, and 2050, respectively. GSHP, WSHP, and HSHP are also predicted to experience significant CO2 emission reductions of 94 %, 95 %, and 59 % by 2050, aligning with the UK's net-zero goal.

Reactive molecular dynamics simulations of poly(vinyl alcohol) gasification in supercritical carbon dioxide

Supercritical fluid gasification technology, as an environmentally friendly technology, can convert organic components of plastic waste into fuels and chemical materials. Moreover, the utilization of CO2 as the gasification environment holds significant importance for reducing carbon emissions. To better comprehend the microscopic mechanism of plastic gasification in supercritical environment, this sthdy used the Reactive Force Field (ReaxFF) molecular dynamics method to study the gasification process of long-chain poly(vinyl alcohol) molecule in supercritical H2O/CO2 under different reaction conditions. The result illustrated that during the gasification process, poly(vinyl alcohol) initially depolymerized into multiple long carbon chain (C5+) molecular fragments. Subsequently, these fragments underwent cleavage into short carbon chains and various gaseous small molecules. In this reaction, O radicals generated by CO2 decomposition play a crucial role in promoting the cleavage of plastic C–C bonds. In addition, through the analysis of the products and chemical bonds, we found that increasing temperature and prolonging reaction time significantly enhance the gasification efficiency and hydrogen production of plastics. Conversely, exceedingly high pressure inhibits the gasification reaction.

Understanding lived experiences and perceptions of perinatal depression in Nigeria: a qualitative evidence synthesis

Background Perinatal depression is a common mental health disorder which spans during and after pregnancy. Unfortunately, there is poor healthcare-seeking behaviour for this treatable condition. Additionally, maternal healthcare workers sometimes overlook the signs and symptoms, failing to diagnose it adequately. This review aims to provide a framework for understanding the in-depth perceptions and implementation gaps surrounding perinatal depression in Nigeria. Methods This study employed a rigorous qualitative evidence synthesis methodology to gather and analyse both published and unpublished qualitative research on the lived experiences and perceptions of perinatal depression in Nigeria. The research was conducted by searching multiple electronic databases, citation chaining, and checking reference lists. The studies were then screened by title, abstract, and full text, and the quality of the included studies was evaluated using the Critical Appraisal Skills Programme (CASP) checklist for appraising a qualitative study. The data extracted from these studies were then synthesized using the ‘best-fit’ framework method, which combines deductive and inductive approaches to analysis. Results 10 eligible papers were identified. Data were organised into themes eight themes mapped to an already existing framework: Recognitions of perinatal mental distress, labelling of mental distress, symptom patterns, social norms, roles and expectations, supernatural factors, physical/bodily issues, coping strategies, help-seeking from professionals/medical institutions. No study was excluded as a result of methodological limitations. Conclusions The review highlights the significance of integrating mental health services into routine perinatal care and the need for comprehensive interventions that consider sociocultural factors. The findings emphasize the importance of increasing awareness and education among women and healthcare providers to improve early detection and intervention. Healthcare professionals play a crucial role in identifying and managing perinatal depression; therefore, it is essential to provide them with comprehensive and regular training.

Impact of Public Health Emergencies on the Willingness of Rural Migrant Workers to Return Home: Evidence from China

In 2022, under the combined influence of the COVID-19 pandemic and the economic downturn. The employment landscape is grim, particularly for rural migrant workers, who are under immense pressure to secure employment. This study used structural equation modeling and bootstrapping methods to identify the influencing factors of migrant workers’ willingness to return home during public health emergencies and the potential multiple causal relationships, based on 2879 questionnaires on the employment status of migrant workers who are from Chongqing in 2022. The result of this study will be used as a reference by policymakers to formulate employment policies. The results show that: (1) Public health emergencies have no discernible direct impact on people’s willingness to return home. However, they have a significant positive effect on hometown belongings and a significant negative effect on income level and employment stability. These effects are ranked in order of influence: sense of belonging to hometown &gt; income level &gt; employment stability. (2) The willingness to return home is significantly impacted negatively by employment stability and income level, but it is significantly positively impacted by hometown belonging, with employment stability having the biggest impact. (3) There is a substantial inverse relation between income level and sense of belonging to hometown; the higher the income level, the stronger the capacity to withstand outside threats, and the greater the propensity to remain employed. (4) Three pathways exist by which public health emergencies affect migrant workers’ willingness to return home: “PHE→ES→HI”, “PHE→IL→HI”, and “PHE→ES→IL→HI”. (5) Income level and employment stability have multiple chain’mediating effects between public health emergencies and the willingness to return home, while only income level plays a partial mediating role between employment stability and the willingness to return hometown.

Safety and efficacy of B cell maturation antigen-directed CAR T-cell therapy in patients with relapsed/refractory multiple myeloma and concurrent light chain amyloidosis.

Clinical trials evaluating chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory multiple myeloma (RRMM) have typically excluded patients with AL amyloidosis. As a result, there are limited data on the safety and efficacy of CAR T-cell therapy in this patient population. We retrospectively reviewed eight consecutive patients with RRMM and AL amyloidosis who were treated with standard of care CAR T-cell therapy. Cytokine release syndrome was seen in 75% of patients (grade ≥3: 0%) and immune effector cell-associated neurotoxicity syndrome (grade 1) in only one patient. Low-grade cytopenias were common (any grade/grade ≥3: neutropenia 62.5%/37.5%, anemia 37.5%/0%, thrombocytopenia 25%/0%). CAR T-cell therapy led to rapid and deep responses with a median time to best response of 43 days and a hematologic very good partial response or better rate of 62.5%. Overall, we found that commercial CAR T-cell therapy was feasible, and effective in patients with RRMM and concurrent AL amyloidosis.

Automated multiplexed affinity-based enrichment of peptides for LC-MS/MS plasma proteomics.

Plasma proteomics offers high potential for biomarker discovery, as plasma is collected through a minimally invasive procedure and constitutes the most complex human-derived proteome. However, the wide dynamic range poses a significant challenge. Here, we propose a semi-automated method based on the use of multiple single chain variable fragment antibodies, each enriching for peptides found in up to a few hundred proteins. This approach allows for the analysis of a complementary fraction compared to full proteome analysis. Proteins from pooled plasma were extracted and digested before testing the performance of 29 different antibodies with the aim of reproducibly maximizing peptide enrichment. Our results demonstrate the enrichment of 3662 peptides not detected in neat plasma or negative controls. Moreover, most antibodies were able to enrich for at least 155 peptides across different levels of abundance in plasma. To further reduce analysis time, a combination of antibodies was used in a multiplexed setting. Repeated sample analyses showed low coefficients of variation, and the method is flexible in terms of affinity binders. It does not impose drastic increases in instrument time, thus showing excellent potential for usage in large scale discovery projects.

Near-Infrared II Agent with Excellent Overall Performance for Imaging-Guided Photothermal Thrombolysis.

Near-infrared II (NIR-II) imaging and photothermal therapy hold tremendous potential in precision diagnosis and treatment within biological organisms. However, a significant challenge is the shortage of NIR-II fluorescent probes with both high photothermal conversion coefficient (PCE) and fluorescence quantum yield (ΦF). Herein, we address this issue by integrating a large conjugated electron-withdrawing core, multiple rotors, and multiple alkyl chains into a molecule to successfully generate a NIR-II agent 4THTPB with excellent PCE (87.6%) and high ΦF (3.2%). 4THTPB shows a maximum emission peak at 1058 nm, and the emission tail could extend to as long as 1700 nm. These characteristics make its nanoparticles (NPs) perform well in NIR-II high-resolution angiography, thereby allowing for precise diagnosis of thrombus through NIR-II imaging and enabling efficient photothermal thrombolysis. This work not only furnishes a NIR-II agent with excellent overall performance but also provides valuable guidance for the design of high-performance NIR-II agents.

An Analysis of Lexical Cohesion in the Text “After Twenty Years”

Lexical cohesion plays an important role in forming a discourse, which effectively connects different part of the text and contributes to the main idea. In terms of short stories, lexical cohesion aims to linguistically enhance plot description, image building and theme expression. This study investigates the lexical devices in the short story After Twenty Years written by O. Henry. By means of discourse analysis, it turns out that O. Henry takes advantage of both reiteration and collocation. For one thing, four kinds of lexical cohesion, including repetition, synonym or near-synonym, superordinate, and general word, are all used in the text to form lexical cohesion. For another, multiple collocation chains manage to integrate the scene, the characters, and the plot from different dimensions. The overall result shows that the short story is highly cohesive, which largely makes it a great work around the world.