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Abstract Bispecific antibodies (bsAbs) hold promises for enhanced therapeutic potential surpassing that of their parental monoclonal antibodies. However, bsAbs pose great challenges in their manufacturing, and one of the common reasons is their susceptibility to aggregation. Building on previous studies demonstrating the functionality and potential manufacturability of Fab-scFv format bsAb, this investigation delved into the impact of environmental factors—such as pH, buffer types, ionic strength, protein concentrations, and temperatures—on its stability and the reversal of its self-associated aggregates. Mildly acidic, low-salt conditions were found optimal, ensuring bsAb stability for 30 days even at elevated temperature of 40 °C. Furthermore, these conditions facilitated the reversal of its self-associated aggregates to monomers during the initial 7-day incubation period. Our findings underscore the robustness and resilience of Fab-scFv format bsAb, further confirming its potential manufacturability despite its current absence as commercial products. Graphical Abstract

ObjectiveBy computerized analysis of writing ability assessment data, to accurately assess the quality and proficiency of writing among primary school students, and to provide data support for accurate screening and assessment of those with writing difficulties.MethodsA cross-sectional study was conducted to evaluate the writing ability of 1 085 students from grade 1 to grade 6 in the Experimental Primary School Affiliated to Minjiang Teachers College, Fuzhou, Fujian Province, using the smart handwriting analysis recognition platform (SHARP). The assessment indicators included writing speed, writing control, writing integration, time-on-paper ratio, accuracy of writing outcomes, and overall writing performance.ResultsGirls outperformed boys in writing control, writing integration, time-on-paper ratio, accuracy of writing outcomes, and overall writing performance (PPPPP>0.05). 2) In terms of writing control ability, the overall trend of grades 1 to 6 showed a gradual development, with the performance of writing control ability in grade 3 being better than that in grade 2 (PPP>0.05). 3) In terms of the writing integration ability and time-on-paper ratio, as the grades increased, the higher grades developed better than the lower grades between adjacent grades 1 to 4 (PP>0.05). 4) in terms of the accuracy of writing outcomes, grade 2 was better than grade 1 (PPP>0.05); 5) In terms of overall writing performance, grade 2 performed better than grade 1 (PP>0.05). There was a significant negative correlation between writing control, writing integration and writing outcome accuracy and overall writing performance (r>-0.5), a highly positive correlation between time-on-paper ratio and overall writing performance (r=0.575), and a highly negative correlation between time-on-paper ratio and writing integration (r=-0.999). Writing outcome accuracy explained only 39.1% of the variation in overall writing performance, and writing outcome accuracy, time-on-paper ratio, writing control, and writing integration together explained 71.8% of the variation in overall writing performance.ConclusionAt the primary level, girls generally outperform boys in writing ability, but sex and dominant hand still do not predict overall performance in writing. As the grades increase, students' writing abilities tend to mature. Writing speed reaches a plateau around grades 4-5, writing control develops more rapidly in grades 2-3 and 4-5, and writing integration and time-on-paper ratio enters a relative stable plateau after about grade 4. Accuracy of writing outcomes alone is not suitable as a predictor of overall writing performance; writing control, writing integration, and time-on-paper ratio have strong effects on overall writing performance and can be combined as predictors of overall writing performance.

Patients contracting Age-related Macular Degeneration (AMD) disease cannot properly recognize objects or text through their central vision. After literature reviewed, there is still lack of empirical study how lightweight mobile application, operates without Internet but with object and text recognition capability can help Malaysian AMD patients to see better. This research developed a simple yet useful mobile application using Kotlin Programming and Android Studio with object and text recognition capability to generate audio speech for patients to perceive and understand better. The application yields average precision (mAP) of 42% for object recognition and 83% for text recognition. Despite lower mAP for object recognition, through Unit and Usability Testing conducted on AMD patients, the test results met the requirements and the application successfully supported them to have a better grasp of their surroundings. This research contributed a small step in relieving Malaysian AMD patients to see better and live more independently. Limitations and future improvements were also provided.

Municipal solid waste incineration (MSWI) bottom ash is a type of bulk waste. Its potential activity can be better harnessed after it is ground into a fine powder, leading to reduced carbon emissions. This paper investigates the pore structure of MSWI bottom ash micro powder concrete and its impact on mechanical properties. Standard tests were conducted to evaluate the mechanical properties of MSWI bottom ash micro powder concrete with four blending ratios under three water-binder ratios. Subsequently, a mercury intrusion test was performed to determine its internal pore structure characteristic parameters. Remaining specimens from the macroscopic test were sampled, and concrete specimens were observed using a high-power electronic environmental scanning microscope to analyze morphological characteristics at various multiples and curing ages. The results indicate that the pore structure of MSWI bottom ash micro powder concrete is uniformly distributed, displaying good fractal characteristics conducive to subsequent secondary hydration reactions. The inclusion of MSWI bottom ash micro powder increases concrete porosity, leading to a decrease in compressive strength. However, as the curing age increases, the value tends to approach that of ordinary concrete, suggesting that MSWI bottom ash micro powder exhibits potential hydraulicity, albeit with a slow hydration reaction. The observed pattern of MSWI bottom ash micro powder concrete aligns with that of ordinary concrete, wherein higher porosity corresponds to lower compressive strength. The addition of MSWI bottom ash micro powder increases concrete porosity, resulting in reduced compressive strength.

Background: B-cell maturation antigen (BCMA)-targeted T cell-redirecting immunotherapies, including Chimeric Antigen Receptor (CAR) T-cell therapy and T-cell engagers have demonstrated remarkable success in treating relapsed/refractory (RR) multiple myeloma (MM), a malignancy of plasma cells. However, a significant challenge is the severe side effects associated with T-cell overactivation, leading to cytokine release syndrome and neurotoxicity in MM patients undergoing such therapies. Bispecific NK cell engagers (NKCEs) may offer a promising alternative by redirecting NK cell cytotoxic activity towards tumor cells without triggering cytokine release syndrome. Methods: In this study, we designed a series of BCMA × CD16 NKCEs that simultaneously engage BCMA and CD16 on MM and NK cells, respectively. We evaluated the functionality of these NKCEs in vitro with respect to their molecular design. Results: Our results indicate that the format design of NKCEs influences their functionalities, underscoring the importance of format selection in optimizing NKCE-based therapies for MM. This study provides valuable insights for developing next-generation NKCEs and advancing therapeutic strategies for MM and potentially other malignancies.

Abstract Chronic diseases often lead to metabolic disorders, causing anabolic resistance and increased energy consumption, which result in cachexia. Cachexia, in turn, can lead to major clinical consequences such as impaired quality of life, shortened life expectancy, and increased healthcare expenditure. Existing international diagnostic criteria for cachexia employ thresholds derived from Western populations, which may not apply to Asians due to differing body compositions. To address this issue, the Asian Working Group for Cachexia (AWGC) was initiated. The AWGC comprises experts in cachexia research and clinical practice from various Asian countries and aims to develop a consensus on diagnostic criteria and significant clinical outcomes for cachexia in Asia. The AWGC, composed of experts in cachexia research and clinical practice from several Asian countries, undertook three‐round Delphi surveys and five meetings to reach a consensus. Discussions were held on etiological diseases, essential diagnostic items for cachexia, including subjective and objective symptoms and biomarkers, and significant clinical outcomes. The consensus highlighted the importance of multiple diagnostic factors for cachexia, including chronic diseases, either or both weight loss or low body mass index, and at least one of the following: anorexia, decreased grip strength (5 mg/L [0.5 mg/dL]). The AWGC proposed a significant weight change of 2% or more over a 3–6 month period and suggested a tentative cut‐off value of 21 kg/m2 for low body mass index in diagnosing cachexia. Critical clinical outcomes were determined to be mortality, quality of life as assessed by tools such as EQ‐5D or the Functional Assessment of Anorexia/Cachexia Therapy, and functional status as measured by the Clinical Frailty Scale or Barthel Index, with significant emphasis on patient‐reported outcomes. The AWGC consensus offers a comprehensive definition and user‐friendly diagnostic criteria for cachexia, tailored specifically for Asian populations. This consensus is set to stimulate future research and enhance the multidisciplinary approach to managing cachexia. With plans to develop further guidelines for the optimal treatment, prevention, and care of cachexia in Asians, the AWGC criteria are expected to drive research across chronic co‐morbidities and cancer in Asia, leading to future refinement of diagnostic criteria.

ABSTRACTT-cell-engaging bispecific antibodies (T-bsAbs) are promising immunotherapies for cancer treatment due to their capability of redirecting T-cells toward destroying tumor cells. Numerous T-bsAb formats have been developed, each with advantages and disadvantages in terms of developability, immunogenicity, effector functions, and pharmacokinetics. Here, we systematically compared T-bsAbs produced using eight different formats, evaluating the effect of molecular design of T-bsAbs on their manufacturability and functionality. These eight T-bsAb formats were constructed using antigen-binding fragments (Fabs) and single-chain variable fragments (scFvs) of antibodies linked to the crystallizable fragment (Fc) domain of immunoglobulin G. To ensure a fair comparison of growth and production data, we used recombinase-mediated cassette exchange technology to generate the T-bsAb-producing CHO cell lines. The produced T-bsAbs were assessed for their purification profile and recovery, binding capability, and biological activities. Our findings indicated that the manufacturability of bsAbs was adversely affected with increased number of scFv building blocks, while the functionality was affected by the combination of multiple factors, including the binding affinity and avidity of targeting moieties and the flexibility and geometry of formats. These results provide valuable insights into the impact of the format design on the optimal production and function of T-bsAbs.

KIAA1199, a major glycosaminoglycan component of the extracellular matrix, was reported to induce a fibrosis-like process. However, the relationship between KIAA1199 and liver fibrosis remains unclear. The liver fibrosis mouse model was established with carbon tetrachloride (CCl4). Here, we found that KIAA1199 was upregulated in CCl4-induced liver fibrosis. The expression of KIAA1199 was also increased in TGF-β-stimulated LX-2 cells. To clarify the impact of KIAA1199 in hepatic stellate cells (HSCs), we downregulated the expression of KIAA1199 in LX-2 cells by RNA interference. Cell proliferation, apoptosis, and migration were determined by CCK-8, flow cytometry, and transwell assay. We found that KIAA1199 knockdown reduced the expression of fibrosis markers α-SMA and COL1A1. Depletion of KIAA1199 inhibited cell proliferation by downregulating cyclin B1 and cyclin D1 and promoted cell apoptosis by upregulating Bax and downregulating Bcl-2. Moreover, KIAA1199 knockdown decreased matrix metalloproteinase-2 (MMP-2) and MMP-9 expression to inhibit the migration ability of LX-2 cells. Silencing KIAA1199 also suppressed the epithelial–mesenchymal transition phenomenon. Collectively, our study revealed that KIAA1199 knockdown alleviated the activation, proliferation, and migration of HSCs, while promoting apoptosis of HSCs, which suggests that KIAA1199 may be a potential regulator of liver fibrosis.

Objective To investigate the distribution of human papillomavirus (HPV) subtypes in women with different age and analyze the relationship between HPV and cervical lesions. Methods A cross-sectional study was conducted on 4 084 patients who underwent colposcopy for pathological examination and HPV genotyping assay in our hospital from January 2015 to June 2020. The patients are classified into 5 groups in respect to the age and 6 groups (the cervicitis, CIN Ⅰ, CIN Ⅱ, CIN Ⅲ, cervical carcinoma in situ and cervical cancer groups) in respect to pathological results respectively. Chi-square test was used to analyze the difference among groups mentioned and to analyze the overall situation of HPV infection, the positive rate of detection of HPV, subtype distribution, infection with single and multiple HPV genotypes among different age groups. Spearman's correlation analysis was used to analyze distribution characteristics of HPV subtypes infection and cervical lesion among different age groups. Results The positive rate of HPV was 93.24% (3808/4 084) different in 5 age groups(Chi-square=11.400 P=0.022). The single subtype infection accounted for 64.67%, and the difference of single subtype infection and multiple subtypes infection was statistically significant among different age groups(Chi-square=70.736, P < 0.001). HPV16(31.88%)、HPV52(25.20%)、HPV58 (14.57%)、HPV18 (11.12%)and HPV51(7.81%)were the top 5 among 23 subtypes of HPV detected. The distribution difference of positive rate of HPV was statistically significant among different lesion groups (P < 0.05). In the cervical cancer group, most patients were infected with HPV16, HPV 18, HPV 52, HPV 58, and HPV 33. Spearman's correlation analysis showed there was a significant correlation between age and cervical lesions (r=0.051, P=0.001). Positive rate of cervical cancer were 0.29% in age 18~29, 1.08% in 30~39, 3.52% in age 40~49, 4.09% in age 50~59 and 10.37% in age 60~82. Conclusion HPV16, HPV 52, HPV 58 and HPV 18 are the most prevalent subtypes among 4 084 patients. HPV16 and HPV18 are relevant with cervical cancer. The risk of cervical cancer is significantly higher for women older than 40. The positive rate of cervical cancer increases with the age.

Summary: Plasmodium parasites contribute to one of the highest global infectious disease burdens. To achieve this success, the parasite has evolved a range of specialized subcellular compartments to extensively remodel the host cell for its survival. The information to fully understand these compartments is likely hidden in the so far poorly characterized Plasmodium species spatial proteome. To address this question, we determined the steady-state subcellular location of more than 12,000 parasite proteins across five different species by extensive subcellular fractionation of erythrocytes infected by Plasmodium falciparum, Plasmodium knowlesi, Plasmodium yoelii, Plasmodium berghei, and Plasmodium chabaudi. This comparison of the pan-species spatial proteomes and their expression patterns indicates increasing species-specific proteins associated with the more external compartments, supporting host adaptations and post-transcriptional regulation. The spatial proteome offers comprehensive insight into the different human, simian, and rodent Plasmodium species, establishing a powerful resource for understanding species-specific host adaptation processes in the parasite.

In recent years， the price of domestic thermal coal has been high. For cost consideration， thermal power plants generally burn lignite now. In addition， the frequency of deep peak shaving of thermal power units has increased significantly to consume new energy power. During the unit start-up and low-load operation， because of the low furnace flame temperature, the combustion of pulverized coal is not sufficient， causing a great risk of spontaneous combustion after being transported to the ash silo through the ash handling system. The paper analyzes the spontaneous combustion of ash silo during the commissioning of start-up for an ultra-supercritical unit that adopts pure lignite. Measures such as hot water warming furnace start-up， stratified ash storage and reasonable control of ash storage level are taken， which can reduce low-load running time by 54%， prevent concentrated accumulation of unburned pulverized coal. In addition， by increasing the evenness of fluidization air and reducing heat storage of ash silo， operation stability and safety of the unit is guaranteed， which provides a reference for the prevention and control of self-combustion in ash silo of lignite-fired units.

Abstract Background Induced pluripotency in cancer cells by ectopic expression of pluripotency-regulating factors may be used for disease modeling of cancers. MicroRNAs (miRNAs) are negative regulators of gene expression that play important role in reprogramming somatic cells. However, studies on the miRNA expression profile and the expression patterns of the mesenchymal-epithelial transition (MET)/epithelial-mesenchymal transition (EMT) genes in induced pluripotent cancer (iPC) cells are lacking. Methods iPC clones were generated from two colorectal cancer (CRC) cell lines by retroviral transduction of the Yamanaka factors. The iPC clones obtained were characterized by morphology, expression of pluripotency markers and the ability to undergo in vitro tri-lineage differentiation. Genome-wide miRNA profiles of the iPC cells were obtained by microarray analysis and bioinformatics interrogation. Gene expression was done by real-time RT-PCR and immuno-staining; MET/EMT protein levels were determined by western blot analysis. Results The CRC-iPC cells showed embryonic stem cell-like features and tri-lineage differentiation abilities. The spontaneously-differentiated post-iPC cells obtained were highly similar to the parental CRC cells. However, down-regulated pluripotency gene expression and failure to form teratoma indicated that the CRC-iPC cells had only attained partial pluripotency. The CRC-iPC cells shared similarities in the genome-wide miRNA expression profiles of both cancer and pluripotent embryonic stem cells. One hundred and two differentially-expressed miRNAs were identified in the CRC-iPC cells, which were predicted by bioinformatics analysis be closely involved in regulating cellular pluripotency and the expression of the MET/EMT genes, possibly via the phosphatidylinositol-3 kinases-protein kinase B (PI3K-Akt) and transforming growth factor beta (TGF-β) signaling pathways. Irregular and inconsistent expression patterns of the EMT vimentin and Snai1 and MET E-cadherin and occludin proteins were observed in the four CRC-iPC clones analyzed, which suggested an epithelial/mesenchymal hybrid phenotype in the partially reprogrammed CRC cells. MET/EMT gene expression was also generally reversed on re-differentiation, also suggesting epigenetic regulation. Conclusions Our data support the elite model for cancer cell-reprogramming in which only a selected subset of cancer may be fully reprogrammed; partial cancer cell reprogramming may also elicit an epithelial-mesenchymal mixed phenotype, and highlight opportunities and challenges in cancer cell-reprogramming.

We have proposed an improved Sparsity Preserving Projection (SPP) method to implement target feature extraction. It combines the SPP feature extraction using the idea of the Locality Preserving Projection (LPP) scheme to build a new objective function, which can not only maintain the relationship of sparse reconstruction between the samples but also minimize the distance between similar sample types in the projection space. Experimental results with Moving and Stationary Target Acquisition and Recognition (MSTAR) Synthetic Aperture Radar (SAR) data sets show that the average recognition rate using the proposed method is up to 97.81% without knowing the target to be azimuth, which can improve the target recognition result even further for obvious reasons. The proposed method is an effective one for SAR target recognition.

Shannon’s source entropy formula is not appropriate to measure the uncertainty of non-stationary processes. In this paper, we propose a new entropy measure for non-stationary processes, which is greater than or equal to Shannon’s source entropy. The maximum entropy of the non-stationary process has been considered, and it can be used as a design guideline in cryptography.

Metagenomics provides quantitative measurements for microbial species over time. To obtain a global overview of an experiment and to explore the full potential of a given dataset, intuitive and interactive visualization tools are needed. Therefore, we established BioSankey to visualize microbial species in microbiome studies over time as a Sankey diagram. These diagrams are embedded into a project-specific webpage which depends only on JavaScript and Google API to allow searches of interesting species without requiring a web server or connection to a database. BioSankey is a valuable tool to visualize different data elements from single or dual RNA-seq datasets and additionally enables a straightforward exchange of results among collaboration partners.

First, the shortcoming of existing location algorithm based on RSSI（received signal strength indication） in WSN（wireless sensor network） was analyzed.Then, supported by plenty of experimental data in different time and space, the distance evaluation model combining with packet lost rate and RSSI which aim at real environment and location algorithm based on this model was provided.It was regarded as a new kind of exploration for research of wireless location.Location experiments were used to evaluate the capability of this algorithm, which proves that WSN nodes running this algorithm can normally work and precision and stability are upper.