Navß2 Intracellular Fragments Contribute to Aß1-42-Induced Cognitive Impairment and Synaptic Deficit Through Transcriptional Suppression of BDNF.

A pathological hallmark of Alzheimer's disease (AD) is the region-specific accumulation of the amyloid-beta protein (Aß), which triggers aberrant neuronal excitability, synaptic impairment, and progressive cognitive decline. Previous works have demonstrated that Aß pathology induced aberrant elevation in the levels and excessive enzymatic hydrolysis of voltage-gated sodium channel type 2 beta subunit (Navß2) in the brain of AD models, accompanied by alteration in excitability of hippocampal neurons, synaptic deficits, and subsequently, cognitive dysfunction. However, the mechanism is unclear. In this research, by employing cell models treated with toxic Aß1-42 and AD mice, the possible effects and potential mechanisms induced by Navß2. The results reveal that Aß1-42 induces remarkable increases in Navß2 intracellular domain (Navß2-ICD) and decreases in both BDNF exons and protein levels, as well as phosphorylated tropomyosin-related kinase B (pTrkB) expression in cells and mice, coupled with cognitive impairments, synaptic deficits, and aberrant neuronal excitability. Administration with exogenous Navß2-ICD further enhances these effects induced by Aß1-42, while interfering the generation of Navß2-ICD and/or complementing BDNF neutralize the Navß2-ICD-conducted effects. Luciferase reporter assay verifies that Navß2-ICD regulates BDNF transcription and expression by targeting its promoter. Collectively, our findings partially elucidate that abnormal enzymatic hydrolysis of Navß2 induced by Aß1-42-associated AD pathology leads to intracellular Navß2-ICD overload, which may responsible to abnormal neuronal excitability, synaptic deficit, and cognition dysfunction, through its transcriptional suppression on BDNF. Therefore, this work supplies novel evidences that Navß2 plays crucial roles in the occurrence and progression of cognitive impairment of AD by transcriptional regulatory activity of its cleaved ICD.

R2-ISS staging combined with circulating plasma cells improves risk stratification for newly diagnosed multiple myeloma: a single-center real-world study.

We aimed to evaluate if circulating plasma cells (CPC) detected by flow cytometry could add prognostic value of R2-ISS staging. We collected the electronic medical records of 336 newly diagnosed MM patients (NDMM) in our hospital from January 2017 to June 2023. The median overall survival (OS) for patients and R2-ISS stage I-IV were not reached (NR), NR, 58 months and 53 months, respectively. There was no significant difference in OS between patients with stage I and patients with stage II (P = 0.309) or between patients with stage III and patients with stage IV (P = 0.391). All the cases were re-classified according to R2-ISS stage and CPC numbers ≥ 0.05% (CPC high) or<0.05% (CPC low) into four new risk groups: Group 1: R2-ISS stage I + R2-ISS stage II and CPC low, Group 2: R2-ISS stage II and CPC high + R2-ISS stage III and CPC low, Group 3: R2-ISS stage III and CPC high + R2-ISS stage IV and CPC low, Group 4: R2-ISS stage IV and CPC high. The median OS were NR, NR, 57 months and 32 months. OS of Group 1 was significantly longer than that of Group 2 (P = 0.033). OS in Group 2 was significantly longer than that of Group 3 (P = 0.007). OS in Group 3 was significantly longer than that of Group 4 (P = 0.041). R2-ISS staging combined with CPC can improve risk stratification for NDMM patients.

Designing Symmetric Gradient Honeycomb Structures with Carbon-Coated Iron-Based Composites for High-Efficiency Microwave Absorption.

The impedance matching of absorbers is a vital factor affecting their microwave absorption (MA) properties. In this work, we controllably synthesized Material of Institute Lavoisier 88C (MIL-88C) with varying aspect ratios (AR) as a precursor by regulating oil bath conditions, followed by one-step thermal decomposition to obtain carbon-coated iron-based composites. Modifying the precursor MIL-88C (Fe) preparation conditions, such as the molar ratio between metal ions and organic ligands (M/O), oil bath temperature, and oil bath time, influenced the phases, graphitization degree, and AR of the derivatives, enabling low filler loading, achieving well-matched impedance, and ensuring outstanding MA properties. The MOF-derivatives 2 (MD2)/polyvinylidene Difluoride (PVDF), MD3/PVDF, and MD4/PVDF absorbers all exhibited excellent MA properties with optimal filler loadings below 20 wt% and as low as 5 wt%. The MD2/PVDF (5 wt%) achieved a maximum effective absorption bandwidth (EAB) of 5.52 GHz (1.90 mm). The MD3/PVDF (10 wt%) possessed a minimum reflection loss (RLmin) value of - 67.4 at 12.56 GHz (2.13 mm). A symmetric gradient honeycomb structure (SGHS) was constructed utilizing the high-frequency structure simulator (HFSS) to further extend the EAB, achieving an EAB of 14.6 GHz and a RLmin of - 59.0 dB. This research offers a viable inspiration to creating structures or materials with high-efficiency MA properties.

Genome-wide identification of Rosa roxburghii CML family genes identifies an RrCML13-RrGGP2 interaction involved in calcium-mediated regulation of ascorbate biosynthesis.

Calmodulin-like proteins (CMLs) are an essential family of calcium sensors involved in multiple Ca2+-mediated cellular processes in plants. Rosa roxburghii Tratt, known for the abundance of L-ascorbic acid (AsA) in its fruits, is widely distributed in calcium-rich soil of the karst region in southwestern China. The aim of this study was to identify key CMLs that respond to exogenous Ca2+ levels and regulate AsA biosynthesis in R. roxburghii. A genome-wide scan revealed the presence of 41 RrCML genes with 1-4 EF-hand motif (s) unevenly distributed across the 7 chromosomes of R. roxburghii. qRT-PCR analysis revealed that RrCML13, RrCML10, and RrCML36 responded significantly to exogenous Ca2+ treatment, and RrCML13 was positively correlated with GDP-L-galactose phosphorylase encoding gene (RrGGP2) expression and AsA content in the developing fruit. Overexpression of RrCML13 in fruits and roots significantly promoted the transcription of RrGGP2 and the accumulation of AsA, while virus-induced silencing of RrCML13 reduced the transcription of RrGGP2 and the content of AsA. Furthermore, Moreover, the yeast two-hybrid and bimolecular fluorescence complementation (BiFC) analysis confirmed the interaction between RrCML13 and RrGGP2 proteins, indicating that RrCML13 plays a regulatory role in calcium-mediated AsA biosynthesis. This study enhances our understanding of R. roxburghii CMLs and sheds light on the calcium-mediated regulation of AsA biosynthesis.

Distinct biological characteristics of mesenchymal stem cells separated from different components of human placenta.

Mesenchymal stem cells (MSCs) have tremendous potential in cell therapy and regenerative medicine. The placenta-derived MSCs (PMSCs) are becoming favorable sources as they are ethically preferable and rich in MSCs. Although several subgroups of PMSCs have been identified from human term placenta, optimal sources for specific clinical applications remain to be elucidated. This study aimed to isolate MSCs from various components of the placenta, and compare their biological characteristics, including morphology, proliferation, immunophenotype, differentiation potential, growth factor and cytokine secretion, and immunomodulatory properties. Finally, four distinct groups of PMSCs were isolated from the placenta: amniotic membrane-derived MSCs (AM-MSCs), chorionic membrane-derived MSCs (CM-MSCs), chorionic plate-derived MSCs (CP-MSCs), and chorionic villi-derived MSCs (CV-MSCs). The results showed that CV-MSCs had good proliferation ability, and were easier to induce osteogenic and chondrogenic differentiation; CP-MSCs exhibited the strongest inhibitory effect on the proliferation of activated T cells, secreted high levels of EGF and IL-6, and could well differentiate into osteoblasts, adipocytes, and chondroblasts; AM-MSCs showed good growth dynamics in the early generations, were able to grow at high density, and tended to induce differentiation into osteogenic and neural lineages. These findings may provide novel evidence for the selection of seed cells in clinical application.

Lysine acetylproteome analysis reveals the lysine acetylation in developing fruit and a key acetylated protein involved in sucrose accumulation in Rosa roxburghii Tratt.

Lysine acetylation is a common post-translational modification of proteins in plants. Rosa roxburghii Tratt. is an economically important fruit tree known for its high nutritional value. However, the characteristics of acetylome-related proteins during fruit development in this crop remain unknown. This study aimed to explore the global acetylproteome of R. roxburghii fruit to identify key lysine-acetylated proteins associated with its quality traits. A total of 4280 acetylated proteins were identified, among them, 981 proteins exhibited differential acetylation (DA) while 19 proteins showed increased acetylation level consistently on individual sites. Functional classification revealed that these DA proteins were primarily associated with central metabolic pathways, carbohydrate metabolism, terpenoids and polyketides metabolism, lipid metabolism, and amino acid metabolism, highlighting the importance of lysine acetylation in fruit quality formation. Notably, the most significant up-regulated acetylation occurred in sucrose synthase (SuS1), a key enzyme in sucrose biosynthesis. Enzyme assays, RNA-seq and proteome analysis indicated that SuS activity, which was independent of its transcriptome and proteome level, may be enhanced by up-acetylation, ultimately increasing sucrose accumulation. Thus, these findings offer a better understanding of the global acetylproteome of R. roxburghii fruit, while also uncover a novel mechanism of acetylated SuS-mediated in sucrose metabolism in plant. SIGNIFICANCE: Rosa roxburghii Tratt. is an important horticultural crop whose commercial value is closely linked to its fruit quality. Acetylation modification is a post-translational mechanism observed in plants, which regulates the physiological functions and metabolic fluxes involved in various biological processes. The regulatory mechanism of lysine acetylation in the fruit quality formation in perennial woody plants has not been fully elucidated, while most of the research has primarily focused on annual crops. Therefore, this study, for the first time, uses Rosaceae fruits as the research material to elucidate the regulatory role of lysine-acetylated proteins in fruit development, identify key metabolic processes influencing fruit quality formation, and provide valuable insights for cultivation strategies.

Investigation of the effects of irradiation and aging on the tribological behavior of ultra-high molecular weight polyethylene/graphene oxide composites under water lubrication.

Ultra-high molecular weight polyethylene/graphene oxide (PE-UHMW/GO) composites have demonstrated potential in artificial joint applications. The tribological behavior of irradiated PE-UHMW/GO composites under water lubrication remained unclear, which limited their application range. In this study, the PE-UHMW/GO composites were gamma irradiated at 100 KGy in a vacuum and subsequently aged at 80 °C for 21 days in air. We assessed their water absorption, and mechanical and tribological properties post-treatment. Notably, gamma irradiation markedly enhanced the mechanical and tribological performance of PE-UHMW/GO composites. Irradiated composites had a 6.11% increase in compressive strength and a 25.72% increase in yield strength compared to unirradiated composites. Additionally, under water lubrication, the irradiated composites showed improved wear resistance and a reduced friction coefficient. The irradiation enhancement can be attributed to the irradiation-induced strengthening of the interface bonding between GO and PE-UHMW. Conversely, accelerated aging led to oxidative degradation, negatively impacting these properties. Aged composites exhibited lower compressive and yield strengths, higher friction coefficients, and diminished anti-wear properties compared to the irradiated composites. The wear mechanism evolved from predominantly fatigue wear in irradiated PE-UHMW/GO to a mix of abrasive and fatigue wear post-aging. While GO and aging influenced water absorption, irradiation had a minimal effect. These insights significantly contribute to the application potential of irradiated PE-UHMW/GO composites in artificial joints.

The therapeutic role of γδT cells in TNBC.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that presents significant therapeutic challenges due to the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. As a result, conventional hormonal and targeted therapies are largely ineffective, underscoring the urgent need for novel treatment strategies. γδT cells, known for their robust anti-tumor properties, show considerable potential in TNBC treatment as they can identify and eliminate tumor cells without reliance on MHC restrictions. These cells demonstrate extensive proliferation both in vitro and in vivo, and can directly target tumors through cytotoxic effects or indirectly by promoting other immune responses. Studies suggest that expansion and adoptive transfer strategies targeting Vδ2 and Vδ1 γδT cell subtypes have shown promise in preclinical TNBC models. This review compiles and discusses the existing literature on the primary subgroups of γδT cells, their roles in cancer therapy, their contributions to tumor cell cytotoxicity and immune modulation, and proposes potential strategies for future γδT cell-based immunotherapies in TNBC.

Network pharmacology and experimental verification to explore the effect of Hedyotis diffusa on Alzheimer's disease.

This study aimed to explore the active components and the effect of Hedyotis diffusa (HD) against Alzheimer's disease (AD) via network pharmacology, molecular docking, and experimental evaluations. We conducted a comprehensive screening process using the TCMSP, Swiss Target Prediction, and PharmMapper databases to identify the active components and their related targets in HD. In addition, we collected potential therapeutic targets of AD from the Gene Cards, Drugbank, and OMIM databases. Afterward, we utilized Cytoscape to establish both protein-protein interaction (PPI) networks and compound-target (C-T) networks. To gain further insights into the functional aspect, we performed GO and KEGG pathway analyses using the David database. Next, we employed Autodock vina to estimate the binding force between the components and the hub genes. To validate our network pharmacology findings, we conducted relevant experiments on Caenorhabditis elegans, further confirming the reliability of our results. Then a total of six active compounds and 149 therapeutic targets were detected. Through the analysis of the association between active compounds, therapeutic targets, and signaling pathways, it was observed that the therapeutic effect of HD primarily encompassed the inhibition of Aß, suppression of AChE activity, and mitigating oxidative stress. Additionally, our investigation revealed that the key active compounds in HD primarily consisted of iridoids, which exhibited resistance against AD by acting on the Alzheimer's disease pathway and the AGE-RAGE signaling pathway in diabetic complications.

Meta-analysis of Cognitive Function Following Non-severe SARS-CoV-2 Infection.

To effectively diagnose and treat subjective cognitive symptoms in post-acute sequalae of COVID-19 (PASC), it is important to understand objective cognitive impairment across the range of acute COVID-19 severity. Despite the importance of this area of research, to our knowledge, there are no current meta-analyses of objective cognitive functioning following non-severe initial SARS-CoV-2 infection. The aim of this meta-analysis is to describe objective cognitive impairment in individuals with non-severe (mild or moderate) SARS-CoV-2 cases in the post-acute stage of infection. This meta-analysis was pre-registered with Prospero (CRD42021293124) and utilized the PRISMA checklist for reporting guidelines, with screening conducted by at least two independent reviewers for all aspects of the screening and data extraction process. Fifty-nine articles (total participants = 22,060) with three types of study designs met our full criteria. Individuals with non-severe (mild/moderate) initial SARS-CoV-2 infection demonstrated worse objective cognitive performance compared to healthy comparison participants. However, those with mild (nonhospitalized) initial SARS-CoV-2 infections had better objective cognitive performance than those with moderate (hospitalized but not requiring ICU care) or severe (hospitalized with ICU care) initial SARS-CoV-2 infections. For studies that used normative data comparisons instead of healthy comparison participants, there was a small and nearly significant effect when compared to normative data. There were high levels of heterogeneity (88.6 to 97.3%), likely reflecting small sample sizes and variations in primary study methodology. Individuals who have recovered from non-severe cases of SARS-CoV-2 infections may be at risk for cognitive decline or impairment and may benefit from cognitive health interventions.

Study on the ability of indoor plants to absorb and purify benzene pollution.

The ability of indoor plants to purify benzene pollution is the basic basis for the selection of plants for ecological remediation of indoor benzene pollution. In this study, the purification rate and the purification amount per unit leaf area of 13 test plants at three benzene concentrations were determined by indoor fumigation experiments, and the benzene absorption and purification abilityability of indoor plants were comprehensively evaluated. The results showed that (1) there was a significant correlation between benzene concentration and purification rate and purification amount per unit leaf area. (2) At the three concentrations, Spathiphyllum floribundum showed the highest purification rate and Sansevieria trifasciata var. laurentii showed the highest purification per unit leaf area. (3) The combined results showed that Sansevieria trifasciata var. laurentii, Spathiphyllum floribundum and Aloe arborescens were the strongest absorbers and purifiers, while Podocarpus nagi and Anthurium andraeanum 'Pink champin' had the weakest absorption and purification capacity. The results of this study provide a theoretical basis and reference for the selection of plants with strong capacities to adsorb and purify benzene pollution in indoor air.

Exploring Integrin α5ß1 as a Potential Therapeutic Target for Pulmonary Arterial Hypertension: Insights from Comprehensive Multicenter Preclinical Studies.

Pulmonary arterial hypertension (PAH) is characterized by obliterative vascular remodeling of the small pulmonary arteries (PA) and progressive increase in pulmonary vascular resistance (PVR) leading to right ventricular (RV) failure. Although several drugs are approved for the treatment of PAH, mortality remains high. Accumulating evidence supports a pathological function of integrins in vessel remodeling, which are gaining renewed interest as drug targets. However, their role in PAH remains largely unexplored. We found that the arginine-glycine-aspartate (RGD)-binding integrin α5ß1 is upregulated in PA endothelial cells (PAEC) and PA smooth muscle cells (PASMC) from PAH patients and remodeled PAs from animal models. Blockade of the integrin α5ß1 or depletion of the α5 subunit resulted in mitotic defects and inhibition of the pro-proliferative and apoptosis-resistant phenotype of PAH cells. Using a novel small molecule integrin inhibitor and neutralizing antibodies, we demonstrated that α5ß1 integrin blockade attenuates pulmonary vascular remodeling and improves hemodynamics and RV function in multiple preclinical models. Our results provide converging evidence to consider α5ß1 integrin inhibition as a promising therapy for pulmonary hypertension. One sentence summary: The α5ß1 integrin plays a crucial role in pulmonary vascular remodeling.

Comparative transcriptomic and proteomic kinetic analysis of adeno-associated virus production systems.

Recombinant adeno-associated virus (rAAV) is a major gene delivery vehicle. We have constructed a stable rAAV producer cell line by integrating essential rAAV genome, viral and helper genes into the genome of HEK293 cell under the control of inducible promoters. Upon induction, the cell line produces transducing rAAV. To gain insight into enhancing rAAV productivity and vector quality, we performed a comparative transcriptomic and proteomic analysis of our synthetic cell line GX2 and two wild-type AAV (wtAAV) production systems, one by virus co-infection and the other by multi-plasmid transfection. The three systems had different kinetics in viral component synthesis but generated comparable copies of AAV genomes; however, the capsid titer of GX2 was an order of magnitude lower compared to those two wtAAV systems, indicating that its capsid production may be insufficient. The genome packaging efficiency was also lower in GX2 despite it produced higher levels of Rep52 proteins than either wtAAV systems, suggesting that Rep52 protein expression may not limit genome packaging. In the two wtAAV systems, VP were the most abundant AAV proteins and their levels continued to increase, while GX2 had high level of wasteful cargo gene expression. Furthermore, upregulated inflammation, innate immune responses, and MAPK signaling, as well as downregulated mitochondrial functions, were commonly observed in either rAAV or wtAAV systems. Overall, this comparative multi-omics study provided rich insights into host cell and viral factors that are potential targets for genetic and process intervention to enhance the productivity of synthetic rAAV producer cell lines. KEY POINTS: • wtAAV infection was more efficient in producing full viral particles than the synthetic cell GX2. • Capsid protein synthesis, genome replication, and packaging may limit rAAV production in GX2. • wtAAV infection and rAAV production in GX2 elicited similar host cell responses.

Toxicity study of mineral medicine haematitum.

ETHNOPHARMACOLOGICAL RELEVANCE: Haematitum, a time-honored mineral-based Chinese medicine, has been used medicinally in China for over 2000 years. It is now included in the Chinese Pharmacopoeia and used clinically for treating digestive and respiratory diseases. The Chinese Materia Medica records that it is toxic and should not be taken for a long period, but there are few research reports on the toxicity of Haematitum and its potential toxicity mechanisms. AIM OF THE STUDY: This study aimed to evaluate the toxicity of Haematitum and calcined Haematitum, including organ toxicity, neurotoxicity, and reproductive toxicity. Further, it is also necessary to explore the mechanism of Haematitum toxicity and to provide a reference for the safe clinical use of the drug. MATERIALS AND METHODS: The samples of Haematitum and calcined Haematitum decoctions were prepared. KM mice were treated with samples by gavage for 10 days, and lung damage and apoptosis were assessed by HE staining and TUNEL staining of lung tissues respectively. Metabolomics analysis was performed by HPLC-MS. Metallomics analysis was performed by ICP-MS. In addition, C. elegans was used as a model for 48 h exposure to examine the neurotoxicity and reproductive toxicity-related indices of Haematitum, including locomotor behaviors, growth and development, reproductive behaviors, AChE activities, sensory behaviors, apoptosis, and ROS levels. RESULTS: The use of large doses of Haematitum decoction caused lung damage in mice. Neither calcined Haematitum decoction nor Haematitum decoction at clinically used doses showed organ damage. Metabolomics results showed that disorders in lipid metabolic pathways such as sphingolipid metabolism and glycerophospholipid metabolism may be important factors in Haematitum-induced pulmonary toxicity. High doses of Haematitum decoction caused neurological damage to C. elegans, while low doses of Haematitum decoction and calcined Haematitum decoction showed no significant neurotoxicity. Decoction of Haematitum and calcined Haematitum did not show reproductive toxicity to C. elegans. Toxicity was also not observed in the control group of iron (Ⅱ) and iron (Ⅲ) ions in equal amounts with high doses of Haematitum. CONCLUSIONS: Haematitum is relatively safe for routine doses and short-term use. Calcination can significantly reduce Haematitum toxicity, and this study provides a reference for safe clinical use.

Mitigating cadmium exposure risk in rice with foliar nano-selenium: Investigations through Caco-2 human cell line in-vivo bioavailability assay.

The contamination of paddy fields by cadmium and lead is a major issue in China. The consumption of rice grown in heavy metals contaminated areas poses severe health risks to humans, where bioavailability and bioaccessibility remains the critical factor for risk determination. Selenium nanoparticles (Se-NPs) can mitigate the toxicity of heavy metals in plants. However, there exists limited information regarding the role of Se-NPs in dictating cadmium (Cd) toxicity in rice for human consumption. Moreover, the impact of Se-NPs under simultaneous field and laboratory controlled conditions is rarely documented. To address this knowledge gap, a field experiment was conducted followed by laboratory scale bioavailability assays. Foliar application of Se-NPs and selenite (at 5, 10 mg L-1) was performed to assess their efficiency in lowering Cd accumulation, promoting Se biofortification in rice grains, and evaluating Cd exposure risk from contaminated rice. Obtained results indicate that foliar treatments significantly reduced the heavy metal accumulation in rice grains. Specifically, Se-NP 10 mg L-1 demonstrated higher efficiency, reducing Cd and Pb by 56 and 32 % respectively. However, inconsistent trends for bioavailable Cd (0.03 mg kg-1) and bioaccessible (0.04 mg kg-1) were observed while simulated human rice intake. Furthermore, the foliage application of Se-NPs and selenite improved rice quality by elevating Se, Zn, Fe, and protein levels, while lowering phytic acid content in rice grains. In summary, this study suggests the promising potential of foliage spraying of Se-NPs in lowering the health risks associated with consuming Cd-contaminated rice.

Weight status changes from childhood to adulthood were associated with cardiometabolic outcomes in adulthood.

AIM: Few studies have assessed the association between weight changes from childhood to adulthood and cardiometabolic factors in adulthood. The aim of this study was to explore the relationships between weight changes from childhood to adulthood and cardiometabolic factors in adulthood using national Chinese data. METHODS: We included 649 participants from the China Health and Nutrition Survey from 1989 to 2009 and divided them into four groups by their body mass index from 6 to 37 years of age. They were selected using multistage random cluster sampling from 15 areas with large variations in economic and social development. Poisson regression models assessed associations between weight status changes and cardiometabolic outcomes in adulthood. RESULTS: The risk of multiple abnormal cardiometabolic outcomes in adulthood was increased in the 126 subjects with normal weight in childhood but overweight or obesity in adulthood and the 28 with obesity at both ages, compared to the 462 with normal weight at both ages. There was insufficient evidence to demonstrate that the 33 who had weight issues as children, but not as adults, had an increased risk. CONCLUSION: Being overweight or obese in both childhood and adulthood or during adulthood only increased the risk of abnormal cardiometabolic outcomes in adulthood. Larger studies need to investigate whether weight problems in childhood, but not adulthood, increase the risk.

NOT gated T cells that selectively target EGFR and other widely expressed tumor antigens.

Here, we show that a NOT gated cell therapy (Tmod) can exploit antigens such as epidermal growth factor receptor (EGFR) and human leukocyte antigen-E (HLA-E) which are widely expressed on cancer cells. Noncancerous cells-despite high expression of these antigens-are protected from cytotoxicity by the action of an inhibitory receptor ("blocker") via a mechanism that involves blocker modulation of CAR surface expression. The blocker is triggered by the product of a polymorphic HLA allele (e.g., HLA-A∗02) deleted in a significant subset of solid tumors via loss of heterozygosity. Moreover, Tmod constructs that target mouse homologs of EGFR or HLA-E for activation, and a mouse-equivalent of HLA-A∗02 for inhibition, protect mice from toxicity caused by the CAR alone. The blocker also controls graft vs. host response in allogeneic T cells in vitro, consistent with the use of Tmod cells for off-the-shelf therapy without additional gene-editing.

Revealing core functional microorganisms in the fermentation process of Qicaipaojiao (Capsicum annuum L.) based on microbial metabolic network.

Paojiao, a typical Chinese traditional fermented pepper, is favored by consumers for its unique flavor profile. Microorganisms, organic acids, amino acids, and volatile compounds are the primary constituents influencing the development of paojiao's flavor. To elucidate the key flavor compounds and core microorganisms of Qicaipaojiao (QCJ), this study conducted a comprehensive analysis of the changes in taste substances (organic acids and amino acids) and volatile flavor compounds during QCJ fermentation. Key flavor substances in QCJ were identified using threshold aroma value and odor activity value and the core microorganisms of QCJ were determined based on the correlation between dominant microorganisms and the key flavor substances. During QCJ fermentation, 16 key taste substances (12 free amino acids and 4 organic acids) and 12 key aroma substances were identified. The fermentation process involved 10 bacteria and 7 fungal genera, including Lactiplantibacillus, Leuconostoc, Klebsiella, Pichia, Wickerhamomyces, and Candida. Correlation analysis revealed that the core functional microorganisms encompassed representatives from 8 genera, including 5 bacterial genera (Lactiplantibacillus, Weissella, Leuconostoc, Klebsiella, and Kluyvera) and 3 fungal genera (Rhodotorula, Phallus, and Pichia). These core functional microorganisms exhibited significant correlations with approximately 70 % of the key flavor substances (P < 0.05). This study contributes to an enhanced understanding of flavor formation mechanisms and offers valuable insight into flavor quality control in food fermentation processes.

Age-effects of sport education model on basic psychological needs and intrinsic motivation of adolescent students: A systematic review and meta-analysis.

OBJECTIVE: This study explores the age effects of the sport education model(SEM) on the impact of basic psychological needs (autonomy, competence, relatedness) and intrinsic motivation (interest, enjoyment, satisfaction) among adolescent students. METHOD: Retrieval of relevant literature from PubMed, Web of Science, Scopus, and China National Knowledge Infrastructure (CNKI). The search period ranged from the starting year to January 7, 2024. Subsequently, literature screening, data extraction, and quality assessment will be conducted, and data analysis will be performed using "Review Manager 5.4" software. RESULT: Overall, SEM has a positive and statistically significant impact on the basic psychological needs (MD = 0.36,95% CI [0.22, 0.50]) and intrinsic motivation (MD = 0.75, 95% CI [0.58, 0.93]) of adolescent students (P<0.01). Subgroup analysis revealed age effects on the impact of SEM on the basic psychological needs of adolescent students: pre-peak height velocity (PRE-PHV) (MD = 0.39, 95% CI [0.23, 0.56], I2 = 45%, P<0.01), mid-peak height velocity (MID-PHV) (MD = 0.22, 95% CI [0.01, 0.42], I2 = 82%, P<0.05), post-peak height velocity (POST-PHV) (MD = 1.27, 95% CI [0.79, 1.74], I2 = 0%, P<0.01). Similarly, age effects were found for intrinsic motivation: MID-PHV (MD = 0.86, 95% CI [0.62, 1.11], I2 = 68%, P<0.01), POST-PHV (MD = 0.56, 95% CI [0.40, 0.72], I2 = 0%, P<0.01). CONCLUSION: The SEM is an effective approach to enhancing the basic psychological needs and intrinsic motivation of adolescent students. However, it exhibits age effects among students at different developmental stages. Specifically, in terms of enhancing basic psychological needs, the model has the greatest impact on POST-PHV students, followed by PRE-PHV students, while the improvement effect is relatively lower for MID-PHV students. The enhancement effect on intrinsic motivation diminishes with increasing age.

Photochemical Strategies toward Precision Targeting against Multidrug-Resistant Bacterial Infections.

Infectious diseases pose a serious threat and a substantial economic burden on global human and public health security, especially with the frequent emergence of multidrug-resistant (MDR) bacteria in clinical settings. In response to this urgent need, various photobased anti-infectious therapies have been reported lately. This Review explores and discusses several photochemical targeted antibacterial therapeutic strategies for addressing bacterial infections regardless of their antibiotic susceptibility. In contrast to conventional photobased therapies, these approaches facilitate precise targeting of pathogenic bacteria and/or infectious microenvironments, effectively minimizing toxicity to mammalian cells and surrounding healthy tissues. The highlighted therapies include photodynamic therapy, photocatalytic therapy, photothermal therapy, endogenous pigments-based photobleaching therapy, and polyphenols-based photo-oxidation therapy. This comprehensive exploration aims to offer updated information to facilitate the development of effective, convenient, safe, and alternative strategies to counter the growing threat of MDR bacteria in the future.