Stepping forward: T-cell redirecting bispecific antibodies in cancer therapy.

T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens, thereby engaging with CD3 on the T cell receptor. This linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor cells. These antibodies have emerged as one of the most promising avenues within tumor immunotherapy. However, despite success in treating hematological malignancies, significant advancements in solid tumors have yet to be explored. In this review, we aim to address the critical challenges associated with T cell-redirecting bispecific antibodies and explore novel strategies to overcome these obstacles, with the ultimate goal of expanding the application of this therapy to include solid tumors.

New advances in the diagnosis and treatment of autism spectrum disorders.

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders that affect individuals' social interactions, communication skills, and behavioral patterns, with significant individual differences and complex etiology. This article reviews the definition and characteristics of ASD, epidemiological profile, early research and diagnostic history, etiological studies, advances in diagnostic methods, therapeutic approaches and intervention strategies, social and educational integration, and future research directions. The highly heritable nature of ASD, the role of environmental factors, genetic-environmental interactions, and the need for individualized, integrated, and technology-driven treatment strategies are emphasized. Also discussed is the interaction of social policy with ASD research and the outlook for future research and treatment, including the promise of precision medicine and emerging biotechnology applications. The paper points out that despite the remarkable progress that has been made, there are still many challenges to the comprehensive understanding and effective treatment of ASD, and interdisciplinary and cross-cultural research and global collaboration are needed to further deepen the understanding of ASD and improve the quality of life of patients.

Protect the oceans from Japan's radioisotope dumping.

•Dumping of Fukushima's radioactive wastewater raises marine food web concern.•Tritium seems to be the most problematic compound.•Long-lived radioisotopes Biomagnify up to 50,000 folds in marine fish species.•This threatens fragile deep-sea ecosystems requiring immediate action.•Empowered Routine monitoring is crucial to maintain planetary health.

A Dual-domain Engineered Antibody for Efficient HBV Suppression and Immune Responses Restoration.

Chronic hepatitis B (CHB) remains a major public health concern because of the inefficiency of currently approved therapies in clearing the hepatitis B surface antigen (HBsAg). Antibody-based regimens have demonstrated potency regarding virus neutralization and HBsAg clearance. However, high dosages or frequent dosing are required for virologic control. In this study, a dual-domain-engineered anti-hepatitis B virus (HBV) therapeutic antibody 73-DY is developed that exhibits significantly improved efficacy regarding both serum and intrahepatic viral clearance. In HBV-tolerant mice, administration of a single dose of 73-DY at 2 mg kg-1 is sufficient to reduce serum HBsAg by over 3 log10 IU mL-1 and suppress HBsAg to < 100 IU mL-1 for two weeks, demonstrating a dose-lowering advantage of at least tenfold. Furthermore, 10 mg kg-1 of 73-DY sustainably suppressed serum viral levels to undetectable levels for ≈ 2 weeks. Molecular analyses indicate that the improved efficacy exhibited by 73-DY is attributable to the synergy between fragment antigen binding (Fab) and fragment crystallizable (Fc) engineering, which conferred sustained viral suppression and robust viral eradication, respectively. Long-term immunotherapy with reverse chimeric 73-DY facilitated the restoration of anti-HBV immune responses. This study provides a foundation for the development of next-generation antibody-based CHB therapies.

Ecological risk assessment and transmission of soil heavy metals in pastoral areas of the Tibetan plateau based on network environment analysis.

The Qinghai-Tibet Plateau is distinguished by its diverse ecosystems and biodiversity, which are highly dependent on their soil. In this study, a comprehensive analysis was conducted to assess the ecological risks in Maqin County, located on the Qinghai-Tibet Plateau, along with the local background values of soil elements, level of element enrichment, and source appointment of soil elements. The findings show that the background soil element levels in Maqin County were greater than the average soil content values in China. The soils in the study area exhibited pollution levels ranging from weak to moderate. The positive matrix factorization (PMF) model was employed to successfully categorized soil elements into four sources: F1 (natural sources), F2 (grazing sources), F3 (volcanic and rock fracture sources), and F4 (intrusive and deep rock source). Based on the characteristics of the ecological communities and the network environmental analysis model, ecological risks were directly introduced through vegetation and soil microorganisms, with subsequent transmission to other components of the ecosystem through the food chain. The integrated risks associated with vegetation, herbivores, soil microorganisms, and carnivores were 0.0106, 0.00193, 0.0282, and 0.00132, respectively. Notably, soil microorganisms were found to be the primary contributors to the total ecological risk in the study area. Furthermore, network environmental analysis and human health risk models revealed that F1, F2, F3, and F4 accounted for 16.85 %, 8.90 %, 21.76 %, and 52.49 % of the input risk of vegetation and soil microorganisms, respectively. Particularly, F4 emerged as the largest contributor to human health risks. This study provides valuable information for the preservation of the ecological environment in pastoral areas, contributing to the global promotion of sustainable ecological practices.

Unraveling the complexities of beryllium contamination in agricultural soils: The case of Qingcheng District, Qingyuan City.

Metal contamination in agricultural soils has received widespread attention; however, the status of beryllium (Be) contamination in agricultural soils has been inadequately studied. This research was conducted to determine the enrichment level and major sources of Be contamination in the agricultural soil in Qingcheng District, Qingyuan City, and to quantify the potential ecological risk and human health risk (PER and HHR) of Be by integrating geological mineral and remote-sensing image maps. The results of principal component analysis followed by multiple linear regression (PCA-MLR) suggest that Be, Sn, Zn, Pb, As, and Cd are mainly derived from anthropogenic activities; V, Ti, Sc, Cr, and Co are mainly derived from medium acidic granites; Al and Si are mainly derived from geological sources; and K and Na are mainly derived from calcium-alkaline materials. Anthropogenic activities are priority material sources owing to the highest contribution. Be contamination poses a slight PER, and the PER level of agricultural soil was moderate. The HHR caused by Be is negligible. The results of this study can serve as the basis for promoting agricultural soil protection and developing and implementing agricultural policies to reduce environmental pollution in the study area.

Recent advances and applications of CRISPR-Cas9 in cancer immunotherapy.

The incidence and mortality of cancer are the major health issue worldwide. Apart from the treatments developed to date, the unsatisfactory therapeutic effects of cancers have not been addressed by broadening the toolbox. The advent of immunotherapy has ushered in a new era in the treatments of solid tumors, but remains limited and requires breaking adverse effects. Meanwhile, the development of advanced technologies can be further boosted by gene analysis and manipulation at the molecular level. The advent of cutting-edge genome editing technology, especially clustered regularly interspaced short palindromic repeats (CRISPR-Cas9), has demonstrated its potential to break the limits of immunotherapy in cancers. In this review, the mechanism of CRISPR-Cas9-mediated genome editing and a powerful CRISPR toolbox are introduced. Furthermore, we focus on reviewing the impact of CRISPR-induced double-strand breaks (DSBs) on cancer immunotherapy (knockout or knockin). Finally, we discuss the CRISPR-Cas9-based genome-wide screening for target identification, emphasis the potential of spatial CRISPR genomics, and present the comprehensive application and challenges in basic research, translational medicine and clinics of CRISPR-Cas9.

Spatial distribution characteristics, influencing factors, and source distribution of soil cadmium in Shantou City, Guangdong Province.

A total of 511 topsoils and 139 deep soil samples were collected to analyze the distribution characteristics, regional differentiation factors, and contamination sources of Cd in Shantou City, and to assess its environmental, ecological, and human health risks. We used a combination of multivariate statistics and geostatistics to quantify the distribution and level of Cd contamination in the study area, and an absolute principal component scores-multiple linear regression model to resolve the sources of contamination and their contribution values, combined with the health risk model to assess the human health risk from each source. The result exhibited that the average value of soil Cd content was 0.100 mg/kg, which was lower than the threshold value of soil environmental quality standard, but higher than the 0.070 mg/kg background value of soil. The high-value areas of surface Cd content in the study area were distributed in the western, northern, and northeastern parts of Shantou, and the source of Cd in the soil was a mix of anthropogenic and natural contamination. The non-carcinogenic and carcinogenic risks of heavy metal Cd exposure pathways are: oral ingestion > dermal contact > inhalation. The human health risk posed by Cd is below the reference threshold, indicating that the Cd contents in the soil have no unacceptable health risk to the residents. Among industrial sources, natural sources, and unknown sources with potential carcinogenic and non-carcinogenic risks, natural sources were the main source of contamination for adults and children. Among the different soil types, paddy, and red soils had relatively high Cd content, and among the different soil-forming parent materials, the Cd content in soils developed on Quaternary sediments was significantly higher than that other parent materials. Among the different land use types, the Cd content of soil for construction land was the highest. This study provides a scientific foundation and reference for the prevention of soil Cd contamination in Shantou City and the analysis of soil contamination sources in areas with similar contamination patterns.

Iron-Modified Biochar Strengthens Simazine Adsorption and Decreases Simazine Decomposition in the Soil.

Currently, modified biochar has been successfully used in the remediation of soil polluted with heavy metals. However, the effects of the modified biochar on pesticides (such as simazine) are still unclear. Herein, the environmental fate of simazine, such as decomposition, leaching, and adsorption in unamended soil, in the soil amended with unmodified and modified biochar (biochar + FeCl3, biochar + FeOS, biochar + Fe) were evaluated. In addition, an incubation experiment was also performed to observe the influence of modified biochar on the microbial community and diversity in the soil. The results showed that modified biochar significantly decreased the decomposition of simazine in the soil compared to its counterpart. Modified biochar also reduced the concentration of simazine in the leachate. Compared with the control, soil microbial biomass in the soil amended with unmodified biochar, biochar + FeCl3, biochar + Fe, and biochar + FeOS was decreased by 5.3%, 18.8%, 8.7%, and 18.1%, respectively. Furthermore, modified biochar changed the structure of the microbial community. This shows that modified biochar could increase the soil adsorption capacity for simazine and change the amount and microbial community that regulates the fate of simazine in the soil. This study concludes that iron-modified biochar has positive and negative effects on the soil. Therefore, its advantages and side effects should be considered before applying it to the soil.

Recent progress in antibody-based therapeutics for triple-negative breast cancer.

INTRODUCTION: Triple-negative breast cancer (TNBC) is a subtype of severely aggressive breast cancer that lacks the expression of oestrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor 2 (HER2) and is highly metastatic and related to a poor prognosis. Current standard treatments are still limited to systemic chemotherapy, radiotherapy, and surgical resection. More effective treatments are urgently needed. AREAS COVERED: The immunogenicity of TNBC has provided opportunities for the development of targeted immunotherapy. In this review, we focus on the recent development in antibody-based drug modalities, including angiogenesis inhibitors, immune checkpoint inhibitors, antibody-drug conjugates, immunoconjugates, T cell-redirecting bispecific antibodies and CAR-T cells, and their mechanisms of action in TNBC. EXPERT OPINION: At present, the treatment of TNBC is still a major challenge that needs to be addressed. Novel immunotherapies are promising opportunities for improving the management of this aggressive disease.

Evaluating a Sampling Regime for Estimating the Levels of Contamination and the Sources of Elements in Soils Collected from a Rapidly Industrialized Town in Guangdong Province, China.

Gaogang Town, a typical urban center within the Pearl River Delta region of China, suffers contamination of soils with metals/metalloids due to rapid development of industrial activities and agriculture. Few studies have been conducted to systematically describe the main sources, influencing factors, and ecological risks of metals/metalloids in soils in China. In this study, 312 surface soil samples were collected, and 15 elements were detected by plasma emission spectroscopy, atomic fluorescence spectroscopy, and atomic emission spectrometry. Element content features were analyzed by index of geo-accumulation (Igeo), pollution load index (PLI), potential ecological risk index (RI), positive matrix factorization model (PMF), and geostatistical analysis. The PLI value is between 0 and 1, indicating that the whole study area is lightly polluted. Combining PMF model and geostatistical analysis, soil elements in surface soils of Gaogang town were quantitatively apportioned into four sources: parent material and basic substances (23.5%), natural sources (32.2%), agricultural activities and industrial pollution (22.9%), and transportation (21.4%). The comprehensive analysis results show that polluted areas are mainly distributed on roads, rivers, and industrial and human activity areas. The main sources of ecological risks are factory pollution and human activity. Finally, we found that a quarter of the sampling density was the best sample size for this study.

Effect of light combination on the characteristics of dissolved organic matter and chemical forms of Cd in the rhizosphere of Arabidopsis thaliana involved in phytoremediation.

Light, one of the most important natural resources for plant species, significantly influences the biomass yield and nutrient uptake capacity in plants. Light sources with different spectra combinations can impact the bioavailability, toxicity, and solubility of heavy metals in soils by altering the concentrations and fractionations of soil dissolved organic matter (DOM). A series of light irradiation treatments were performed to evaluate the influence of red, yellow, and blue lights on the characteristics of DOM in the rhizosphere soils of Arabidopsis thaliana. The results showed that monochromatic red light significantly raised the levels of DOM and proportions of hydrophilic fractionations in the rhizosphere of A. thaliana relative to the control, while monochromatic blue light had the opposite effect. Moreover, the proportions of hydrophobic acid, which can mobilize Cd effectively, also raised with increasing doses of red light, which stimulated Cd mobilization. The application of yellow light not only increased the levels of hydrophobic acid in monochromatic red light treatment but also decreased the proportion of hydrophobic fractions in monochromatic blue light treatment, partially weakening the negative impacts of pure blue light on soil Cd activation. Moreover, DOM from the combined red, yellow, and blue lights resulted in a significantly stronger Cd extraction efficiency than the other light irradiation treatments, consequently enhancing the Cd phytoextraction efficiency of A. thaliana. The findings of this study demonstrated that a suitable light combination could enhance the phytoremediation effect of A. thaliana by activating soil Cd, and this method can be extrapolated to the real field, where light irradiation can be easily applied and modulated.

Influences of elevated O3 and CO2 on Cd distribution in different Festuca arundinacea tissues.

It is necessary to reveal the responses of the biomass production and metal accumulation capacity of different plants to the variations of atmospheric conditions and soil metals, with the acceleration of urbanization and industrialization. In the present study, a series of experiments were designed to study the individual and interactive influences of O3 and CO2 fumigation on the biomass yield, variation in different leaf types, distribution of cadmium (Cd) in various tissues, and phytoremediation efficiency of Festuca arundinacea using open top chambers. The results found that an elevated O3 content of 80 ppb, a potential O3 content predicted for 2050, decreased the total dry mass of F. arundinacea and increased the proportion of falling leaf tissues of the species significantly. Under the same ambient CO2 levels, O3 fumigation increased the Cd concentrations in the roots and the fresh, mature, senescent, and dead leaf tissues by 27.8%, 133.3%, 94.4%, 125.3%, and 48.6%, respectively. An elevated CO2 content (550 ppm) promoted the biomass yield of F. arundinacea, particularly in the falling leaf tissues. The results of the combined O3 and CO2 treatment showed that CO2 fumigation alleviated the negative effects of O3 on plant growth and increased the accumulation capacity in different plant tissues. Significantly more Cd was accumulated in senescent and dead leaves under the synergistic action of CO2 and O3, suggesting that the phytoremediation effect on F. arundinacea using the falling leaves harvesting method could be improved under the future atmospheric environment of high CO2 and O3 levels.

Lycopene-Loaded Microemulsion Regulates Neurogenesis in Rats with Aß-Induced Alzheimer's Disease Rats Based on the Wnt/ß-catenin Pathway.

Objective: To investigate the effects of lycopene-loaded microemulsion (LME) on the cognitive function and neurogenesis in the dentate gyrus (DG) of the hippocampus and subventricular (SVZ) region of rats with amyloid ß- (Aß-) induced Alzheimer's disease (AD) and its mechanism based on the Wnt/ß-catenin pathway. Methods: Healthy Wistar rats were divided into four groups: the blank control (CON), AD control, traditional lycopene (LOO), and LME groups. The CON and AD groups were fed with normal saline, while the LOO group was fed with traditional lycopene, and the LME group was fed with lycopene-loaded microemulsion. Behavioral tests were performed after three weeks of gastric administration. Immunofluorescence-labeled cells were used to observe the differentiation and maturation of new nerve cells in the DG of the hippocampus and SVZ region. qRT-PCR and Western blotting detected the expression of neurogenesis genes and Wnt/ß-catenin pathway-related proteins, respectively. Results: On the Morris water maze test, LME rats had significantly shortened movement trajectory on the searching platform, reduced escape latency time, and increased residence time on the original platform quadrant. In addition, more LME rats crossed the platform when it was removed. Thus, LME can improve the spatial learning and memory of Aß-induced AD rats. On qRT-PCR, LME significantly increased Reelin, Nestin, and Pax6 gene expressions, which regulate neurogenesis. Immunofluorescence showed that LME could significantly increase BrdU+, Dcx+, BrdU+/Neun+, BrdU+/Dcx+ cells in the DG and SVZ regions, thus promoting neurogenesis. LME also reduced the number of Iba1+ and Iba1+/BrdU+ cells, thus reducing the neuroinflammatory response. On Western blot, LME upregulated the Wnt/ß-catenin pathway by upregulating Wnt3a, ß-catenin, Disheveled (Dvl), and p-GSK3ß and downregulating p-ß-catenin and GSK3ß. Conclusion: LME attenuates cognitive impairment in Aß-induced AD rats by promoting neurogenesis in the hippocampus and SVZ region through upregulating the Wnt/ß-catenin pathway.

Decreased Levels of Serum IL-34 Associated with Cognitive Impairment in Vascular Dementia.

OBJECTIVE: Interleukin- (IL-) 34 is a new type of cytokine with neuroprotective effects discovered in recent years. However, the relationship between IL-34 and vascular dementia (VaD) has not yet been elucidated. The purpose of this study is to determine whether IL-34 is involved in cognitive impairment of VaD. METHODS: From January 2017 to December 2020, 84 VaD patients and 60 healthy controls who attended Qingpu Branch of Zhongshan Hospital were prospectively included in the study. Once included in the study, demographic features of all research subjects are collected. They include age, gender, education, white blood cells (WBC), neutrophil, lymphocyte, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), triglycerides (TG), and total cholesterol (TC). Meanwhile, the Montreal Cognitive Assessment (MoCA) scale was used to assess the cognitive function of participants. The serum IL-34 level was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: There was no significant difference between the demographic features of VaD patients and healthy controls (p > 0.05). However, the serum IL-34 levels of VaD patients and healthy controls are 27.6 ± 3.9 pg/ml and 41.8 ± 6.0 pg/ml, respectively, and there is a significant statistical difference between them (p < 0.001). The results of bivariate correlation analysis showed that serum IL-34 levels were significantly positively correlated with MoCA scores (r = 0.371, p = 0.023). Further regression analysis showed that IL-34 was still correlated with MoCA after adjusting for demographic features (ß = 0.276, p = 0038). CONCLUSIONS: Serum IL-34 levels in VaD patients were significantly reduced, which may be an independent predictor of cognitive impairment in VaD patients.

Effects of decapitation and root cutting on phytoremediation efficiency of Celosia argentea.

Decapitation and root cutting can influence plant physiological features, such as height, dry weight, and transpiration rate, which partly determine the success of phytoremediation. In this study, the effects of three root cutting intensities (10%, 25%, and 33%), decapitation, and their combination on the phytoremediation efficiency of Celosia argentea were evaluated. Decapitation increased the biomass yield of C. argentea roots and leaves and significantly improved the species' Cd decontamination ability. Root cutting, especially 33% cutting treatment, decreased the root dry weight. The 10% and 25% root cutting treatments increased the leaf biomass yield by 58.6% and 41.4%, respectively, compared with the untreated control, even compensating for the loss of roots, but 33% root cutting decreased the leaf dry weight. Low and moderate root cutting intensity (10% and 25%) increased the leaf Cd content by 33.4% and 24.9%, respectively, and was associated with improved transpiration rate. The highest root and leaf dry weights were observed for the combination of decapitation and 10% root cutting, which increased the biomass yield of underground and aerial parts by 109.9% and 286.2%, respectively. In addition, decapitation offset the negative effects of 33% root cutting on plant growth, indicated by the higher dry weight relative to the control. Decapitated C. argentea accumulated 11.0, 7.5, and 0.7 times more Cd with the 10%, 25%, and 33% root cutting treatments, respectively, compared with the control. The combination of root cutting and decapitation was a practicable and economical method of enhancing the Cd decontamination capacity of C. argentea.

Characterization of ADCs by Capillary Electrophoresis.

Capillary electrophoresis (CE) is a highly efficient separation technique that resolves ions based on their electrophoretic mobility in the presence of an applied voltage. It has been broadly applied for characterizing biotherapeutics including ADCs. In this chapter, step-by-step procedures for characterizing ADCs using CE will be described with focus placed on reduced and non-reduced capillary electrophoresis sodium dodecyl sulfate (CE-SDS) for purity determination and imaged capillary isoelectric focusing (iCIEF) for charge heterogeneity analysis.

Rapid magnetic solid-phase extraction based on alendronate sodium grafted mesoporous magnetic nanoparticle for the determination of trans-resveratrol in peanut oils.

In the present study, a rapid and effective method based on alendronate sodium grafted mesoporous magnetic nanoparticle (Fe3O4@ANDS) extraction for the determination of trans-resveratrol (TRA) in peanut oils was developed by coupling with HPLC-UV detection. The Fe3O4@ANDS was prepared via Lewis acid/base interaction which was simply carried out in mild aqueous condition without the using of organic solvent. The resultant Fe3O4@ANDS encompassed amino group on its surface, and it was employed as magnetic solid-phase extraction adsorbent for purification and enrichment of TRA from peanut oils through hydrogen bond interaction. Under the optimized conditions, the whole pretreatment process could be accomplished within 10 min without time-consuming concentrated and reconstituted process. The linearity range of the proposed method was 1-10,000 ng/g with satisfactory correlation coefficient (R2) of 0.9992. The recoveries in spiked oil samples were in the range of 78.6-118.9% with the RSDs less than 3.3% (intra-day) and 15.2% (inter-day). The limit of detection for TRA in peanut oils was 0.3 ng/g which was comparative to the reported methods by using LC-MS/MS detection. Finally, the established method was successfully applied to the analysis of TRA in several peanut oils with different brands from local market as well as other kinds of vegetable oils.

A binary matrix for the rapid detection and characterization of small-molecule cardiovascular drugs by MALDI-MS and MS/MS.

A mixture of α-cyano-4-hydroxycinnamic acid and 1,5-diaminonaphthalene was discovered as a novel binary matrix for the qualitative analysis of 14 small-molecule (~250-550 Da) cardiovascular drugs by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and MS/MS in either positive or negative ion mode.