Mechanisms and treatments of methamphetamine and HIV-1 co-induced neurotoxicity: a systematic review.

Combination antiretroviral therapy (cART) has dramatically reduced mortality in people with human immunodeficiency virus (HIV), but it does not completely eradicate the virus from the brain. Patients with long-term HIV-1 infection often show neurocognitive impairment, which severely affects the quality of life of those infected. Methamphetamine (METH) users are at a significantly higher risk of contracting HIV-1 through behaviors such as engaging in high-risk sex or sharing needles, which can lead to transmission of the virus. In addition, HIV-1-infected individuals who abuse METH exhibit higher viral loads and more severe cognitive dysfunction, suggesting that METH exacerbates the neurotoxicity associated with HIV-1. Therefore, this review focuses on various mechanisms underlying METH and HIV-1 infection co-induced neurotoxicity and existing interventions targeting the sigma 1 receptor, dopamine transporter protein, and other relevant targets are explored. The findings of this review are envisaged to systematically establish a theoretical framework for METH abuse and HIV-1 infection co-induced neurotoxicity, and to suggest novel clinical treatment targets.

Effects of degree of milling on bran layer structure, physicochemical properties and cooking quality of brown rice.

Effects of varying degree of milling (DOM) (0-22%) on the bran layer structure, physicochemical properties, and cooking quality of brown rice were explored. As the DOM increased, bran degree, protein, lipid, dietary fiber, amylose, mineral elements, and color parameters (a* and b* values) of milled rice decreased while starch and L* value increased. Microscopic fluorescence images showed that the pericarp, combined seed coat-nucellus layer, and aleurone layer were removed in rice processed at DOM of 6.6%, 9.2%, and 15.4%, respectively. The pasting properties, thermal properties, and palatability of rice increased as the DOM increased. Principal component and correlation analysis indicated that excessive milling lead to a decline in nutritional value of rice with limited impact on enhancing palatability. Notably, when parts of aleurone cell wall were retained, rice samples exhibited high cooking and sensory properties. It serves as a potential guide to the production of moderately milled rice.

Precise tracking of nanoparticles in plant roots.

One of the foremost challenges in nanobiotechnology is obtaining direct evidence of nanoparticles' absorption and internalization in plants. Although confocal laser scanning microscopy (CLSM) or transmission electron microscopy (TEM) are currently the most commonly used tools to characterize nanoparticles in plants, subjectivity of researchers, incorrect sample handling, inevitable fluorescence leakage and limitations of imaging instruments lead to false positives and non-reproducibility of experimental results. This protocol provides an easy-to-operate dual-step method, combining CLSM for macroscopic tissue examination and TEM for cellular-level analysis, to effectively trace single particles in plant roots with accuracy and precision. In addition, we also provide detailed methods for processing plant materials before imaging, including cleaning, and staining, to maximize the accuracy and reliability of imaging. This protocol involves currently commonly used nanomaterial types, such as metal-based and doped carbon-based materials, and enables accurate localization of nanoparticles with different sizes at the cell level in Arabidopsis thaliana root samples either through contrast or element mapping analysis. It serves as a valuable reference and benchmark for scholars in plant science, chemistry and environmental studies to understand the interaction between plant roots and nanomaterials and to detect the distribution of nanomaterials in plants. Excluding plant culture time, the protocol can be completed in 4-5 d.

ß-Ionone enhances the inhibitory effects of 5-fluorouracil on the proliferation of gastric adenocarcinoma cells by the GSK-3ß signaling pathway.

5-Fluorouracil (5-FU) is widely used in the treatment of gastric cancer, and the emergence of drug resistance and toxic effects has limited its application. Therefore, there is an urgent need for safe and effective novel drugs or new therapies. ß-Ionone (BI) is found in vegetables and fruits and possesses an inhibitory proliferation of tumor cells in vitro and in vivo. In this study, we investigated whether BI could enhance the inhibitory effects of 5-FU on the proliferation of gastric adenocarcinoma cells and the growth of gastric cancer cell xenografts in a mouse model. The effects of BI and 5-FU alone or their combination on the cell viability, apoptosis, and mitochondrial membrane potential, the cell cycle, and its related proteins-Cyclin D1, and CDK4 as well as PCNA and GSK-3ß were evaluated in SGC-7901 cells and MKN45 cells by MTT, MB, flow cytometry and Western blot. In addition, the effects of BI and 5-FU alone or their combination on the growth of SGC-7901 cell xenografts in nude mice were investigated. The results showed that BI significantly enhanced the sensitivity of gastric adenocarcinoma cells to 5-FU in vitro and in vivo, i.e. proliferation inhibited, apoptosis induced and GSK-3ß protein activated. Therefore, our results suggest that BI increases the antitumor effect of 5-FU on gastric adenocarcinoma cells, at least partly from an activated GSK-3ß signaling pathway.

Sodium Houttuyniae attenuates ferroptosis by regulating TRAF6-c-Myc signaling pathways in lipopolysaccharide-induced acute lung injury (ALI).

The impact of Sodium Houttuyniae (SH) on lipopolysaccharide (LPS)-induced ALI has been investigated extensively. However, it remains ambiguous whether ferroptosis participates in this process. This study aimed to find out the impacts and probable mechanisms of SH on LPS-induced ferroptosis. A rat ALI model and type II alveolar epithelial (ATII) cell injury model were treated with LPS. Enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin (HE) staining, and Giemsa staining were executed to ascertain the effects of SH on LPS-induced ALI. Moreover, Transmission electron microscopy, Cell Counting Kit-8 (CCK8), ferrous iron colorimetric assay kit, Immunohistochemistry, Immunofluorescence, Reactive oxygen species assay kit, western blotting (Wb), and qRT-PCR examined the impacts of SH on LPS-induced ferroptosis and ferroptosis-related pathways. Theresults found that by using SH treatment, there was a remarkable attenuation of ALI by suppressing LPS-induced ferroptosis. Ferroptosis was demonstrated by a decline in the levels of glutathione peroxidase 4 (GPX4), FTH1, and glutathione (GSH) and a surge in the accumulation of malondialdehyde (MDA), reactive oxygen species (ROS), NOX1, NCOA4, and Fe2+, and disruption of mitochondrial structure, which were reversed by SH treatment. SH suppressed ferroptosis by regulating TRAF6-c-Myc in ALI rats and rat ATII cells. The results suggested that SH treatment attenuated LPS-induced ALI by repressing ferroptosis, and the mode of action can be linked to regulating the TRAF6-c-Myc signaling pathway in vivo and in vitro.

Peering through the hedge: Multiple datasets yield insights into the phylogenetic relationships and incongruences in the tribe Lilieae (Liliaceae).

The increasing use of genome-scale data has significantly facilitated phylogenetic analyses, contributing to the dissection of the underlying evolutionary mechanisms that shape phylogenetic incongruences, such as incomplete lineage sorting (ILS) and hybridization. Lilieae, a prominent member of the Liliaceae family, comprises four genera and approximately 260 species, representing 43% of all species within Liliaceae. They possess high ornamental, medicinal and edible values. Yet, no study has explored the validity of various genome-scale data in phylogenetic analyses within this tribe, nor have potential evolutionary mechanisms underlying its phylogenetic incongruences been investigated. Here, transcriptome, Angiosperms353, plastid and mitochondrial data, were collected from 50 to 93 samples of Lilieae, covering all four recognized genera. Multiple datasets were created and used for phylogenetic analyses based on concatenated and coalescent-based methods. Evolutionary rates of different datasets were calculated, and divergence times were estimated. Various approaches, including coalescence simulation, Quartet Sampling (QS), calculation of concordance factors (gCF and sCF), as well as MSCquartets and reticulate network inference, were carried out to infer the phylogenetic discordances and analyze their underlying mechanisms using a reduced 33-taxon dataset. Despite extensive phylogenetic discordances among gene trees, robust phylogenies were inferred from nuclear and plastid data compared to mitochondrial data, with lower synonymous substitution detected in mitochondrial genes than in nuclear and plastid genes. Significant ILS was detected across the phylogeny of Lilieae, with clear evidence of reticulate evolution identified. Divergence time estimation indicated that most of lineages in Lilieae diverged during a narrow time frame (ranging from 5.0 Ma to 10.0 Ma), consistent with the notion of rapid radiation evolution. Our results suggest that integrating transcriptomic and plastid data can serve as cost-effective and efficient tools for phylogenetic inference and evolutionary analysis within Lilieae, and Angiosperms353 data is also a favorable choice. Mitochondrial data are more suitable for phylogenetic analyses at higher taxonomic levels due to their stronger conservation and lower synonymous substitution rates. Significant phylogenetic incongruences detected in Lilieae were caused by both incomplete lineage sorting (ILS) and reticulate evolution, with hybridization and "ghost introgression" likely prevalent in the evolution of Lilieae species. Our findings provide new insights into the phylogeny of Lilieae, enhancing our understanding of the evolution of species in this tribe.

Waterborne polyurethane nanoparticles incorporating linoleic acid as a potential strategy for controlling antibiotic resistance spread in the mammalian intestine.

Plasmid-mediated conjugative transfer of antibiotic resistance genes (ARGs) within the human and animal intestine represents a substantial global health concern. linoleic acid (LA) has shown promise in inhibiting conjugation in vitro, but its in vivo effectiveness in the mammalian intestinal tract is constrained by challenges in efficiently reaching the target site. Recent advancements have led to the development of waterborne polyurethane nanoparticles for improved drug delivery. In this study, we synthesized four waterborne polyurethane nanoparticles incorporating LA (WPU@LA) using primary raw materials, including N-methyldiethanolamine, 2,2'-(piperazine-1,4-diyl) diethanol, isophorone diisocyanate, castor oil, and acetic acid. These nanoparticles, identified as WPU0.89@LA, WPU0.99@LA, WPU1.09@LA, and WPU1.19@LA, underwent assessment for their pH-responsive release property and biocompatibility. Among these, WPU0.99@LA displayed superior pH-responsive release properties and biocompatibility towards Caco-2 and IPEC-J2 cells. In a mouse model, a dosage of 10 mg/kg/day WPU0.99@LA effectively reduced the conjugation of IncX4 plasmids carrying the mobile colistin resistance gene (mcr-1) by more than 45.1-fold. In vivo toxicity assessment demonstrated that 10 mg/kg/day WPU0.99@LA maintains desirable biosafety and effectively preserves gut microbiota homeostasis. In conclusion, our study provides crucial proof-of-concept support, demonstrating that WPU0.99@LA holds significant potential in controlling the spread of antibiotic resistance within the mammalian intestine.

Association Between Cannabis Use and Brain Structures: A Mendelian Randomization Study.

Background  Observational studies suggested that cannabis use was associated with alternation of brain structures; however, as subjected to confounding factors, they were difficult to make causal inferences and direction determinations. In this study, a two-sample Mendelian randomization (MR) analysis was employed to examine the potential causal association between cannabis use and brain structures. Methods The genome-wide association studies (GWAS) data for lifetime cannabis use (LCU), cannabis use disorder (CUD), and brain cortical and subcortical structures were utilized in this study. Cortical structures were divided into 34 distinct gyral-defined regions with surface area (SA) and thickness (TH) measured. Subcortical structures encompassed volumes from seven specified regions. The primary estimator used in our analysis was inverse-variance weighted (IVW), complemented by MR-Egger and weighted median methods to enhance the robustness of the results. The Cochran's Q test, funnel plots, and MR-Egger intercept tests were used to detect heterogeneity and pleiotropy. Results  No causal relationship was detected between LCU and global cortical SA or TH. However, at the regional cortex level, LCU was associated with decreased TH in the fusiform (ß = -0.0168 mm, SE = 0.00581, P = 0.0039) and lateral occipital (ß = -0.0141 mm, SE = 0.00531, P = 0.0079) regions, while increasing TH in the postcentral region (ß = 0.0093 mm, SE = 0.00445, P = 0.0374). At the subcortical level, LCU was found to increase the brainstem volume (ß = 0.224 mm3, SE = 0.09, P = 0.0128). CUD did not show any causal association with brain structure at either cortical or subcortical levels. Nonetheless, after applying multiple comparison corrections, the P values for the MR analysis of causal relationships between cannabis use and these brain structures did not meet the significance threshold. Conclusion  The evidence for cannabis use causally influencing brain structures is insufficient.

Development of a prognostic nomogram for esophageal squamous cell carcinoma patients received radiotherapy based on clinical risk factors.

Purpose: The goal of the study was to create a nomogram based on clinical risk factors to forecast the rate of locoregional recurrence-free survival (LRFS) in patients with esophageal squamous cell carcinoma (ESCC) who underwent radiotherapy (RT). Methods: In this study, 574 ESCC patients were selected as participants. Following radiotherapy, subjects were divided into training and validation groups at a 7:3 ratio. The nomogram was established in the training group using Cox regression. Performance validation was conducted in the validation group, assessing predictability through the C-index and AUC curve, calibration via the Hosmer-Lemeshow (H-L) test, and evaluating clinical applicability using decision curve analysis (DCA). Results: T stage, N stage, gross tumor volume (GTV) dose, location, maximal wall thickness (MWT) after RT, node size (NS) after RT, Δ computer tomography (CT) value, and chemotherapy were found to be independent risk factors that impacted LRFS by multivariate cox analysis, and the findings could be utilized to create a nomogram and forecast LRFS. the area under the receiver operating characteristic (AUC) curve and C-index show that for training and validation groups, the prediction result of LRFS using nomogram was more accurate than that of TNM. The LRFS in both groups was consistent with the nomogram according to the H-L test. The DCA curve demonstrated that the nomogram had a good prediction effect both in the groups for training and validation. The nomogram was used to assign ESCC patients to three risk levels: low, medium, or high. There were substantial variations in LRFS between risk categories in both the training and validation groups (p<0.001, p=0.003). Conclusions: For ESCC patients who received radiotherapy, the nomogram based on clinical risk factors could reliably predict the LRFS.

Evaluation of decellularized caprine small intestine submucosa encapsulated with nano-formulations of cerium oxide and curcumin in the management of burn wound.

The management of burn injuries presents a significant challenge in clinical settings, yet an optimal solution remains elusive. Therefore, this study aimed to develop a topical therapeutic formulation to address the complex issues hindering burn wound healing. Emphasizing the sustained presence of bioactive principles, we synthesized a bioactive gel derived from decellularized caprine small intestine submucosa (D-CIS) and encapsulated it with nano-formulations of cerium oxide and curcumin to create a burn wound dressing material with enhanced properties. The choice of encapsulated components was guided by their antimicrobial, antioxidant, and immune-modulating characteristics, along with their inherent ability to gradually release bioactive substances. The encapsulated (cerium oxide and curcumin) D-CIS bioactive gel demonstrated a range of properties, including antimicrobial, antioxidant, and anti-inflammatory effects, along with sustained release kinetics of bioactive molecules. These combined effects facilitated accelerated burn wound healing by mitigating oxidative stress, reducing inflammation, and promoting cell recruitment for epithelial and vascular regeneration. This study contributes to the development of a novel bioactive gel incorporating cerium oxide and curcumin, offering a promising approach to enhance burn wound healing.

Mitochondrial Dysfunction Induced by Ambient Fine Particulate Matter and Potential Mechanisms.

Air pollution is one of the major environmental threats contributing to the global burden of disease. Among diverse air pollutants, fine particulate matter (PM2.5) poses a significant adverse health impact and causes multi-system damage. As a highly dynamic organelle, mitochondria are essential for cellular energy metabolism and vital for cellular homeostasis and body fitness. Moreover, mitochondria are vulnerable to external insults and common targets for PM2.5-induced cellular damage. The resultant impairment of mitochondrial structure and function initiates the pathogenesis of diverse human diseases. This review mainly summarizes the in vivo and in vitro findings of PM2.5-induced mitochondrial dysfunction and its implication in PM2.5-induced health effects. Furthermore, recent advances toward the underlying mechanisms of PM2.5 and its components-induced mitochondrial dysfunction are also discussed, with an attempt to provide insights into the toxicity of PM2.5 and basic information for devising appropriate intervention strategies.

Exploring the relationship between lipid metabolism and cognition in individuals living with stable-phase Schizophrenia: a small cross-sectional study using Olink proteomics analysis.

BACKGROUND: Cognitive impairment is a core symptom of schizophrenia. Metabolic abnormalities impact cognition, and although the influence of blood lipids on cognition has been documented, it remains unclear. We conducted a small cross-sectional study to investigate the relationship between blood lipids and cognition in patients with stable-phase schizophrenia. Using Olink proteomics, we explored the potential mechanisms through which blood lipids might affect cognition from an inflammatory perspective. METHODS: A total of 107 patients with stable-phase schizophrenia and cognitive impairment were strictly included. Comprehensive data collection included basic patient information, blood glucose, blood lipids, and body mass index. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and the MATRICS Consensus Cognitive Battery (MCCB). After controlling for confounding factors, we identified differential metabolic indicators between patients with mild and severe cognitive impairment and conducted correlation and regression analyses. Furthermore, we matched two small sample groups of patients with lipid metabolism abnormalities and used Olink proteomics to analyze inflammation-related differential proteins, aiming to further explore the association between lipid metabolism abnormalities and cognition. RESULTS: The proportion of patients with severe cognitive impairment (SCI) was 34.58%. Compared to patients with mild cognitive impairment (MCI), those with SCI performed worse in the Attention/Alertness (t = 2.668, p = 0.009) and Working Memory (t = 2.496, p = 0.014) cognitive dimensions. Blood lipid metabolism indicators were correlated with cognitive function, specifically showing that higher levels of TG (r = -0.447, p < 0.001), TC (r = -0.307, p = 0.002), and LDL-C (r = -0.607, p < 0.001) were associated with poorer overall cognitive function. Further regression analysis indicated that TG (OR = 5.578, P = 0.003) and LDL-C (OR = 5.425, P = 0.001) may be risk factors for exacerbating cognitive impairment in individuals with stable-phase schizophrenia. Proteomics analysis revealed that, compared to individuals with stable-phase schizophrenia and normal lipid metabolism, those with hyperlipidemia had elevated levels of 10 inflammatory proteins and decreased levels of 2 inflammatory proteins in plasma, with these changes correlating with cognitive function. The differential proteins were primarily involved in pathways such as cytokine-cytokine receptor interaction, chemokine signaling pathway, and IL-17 signaling pathway. CONCLUSION: Blood lipids are associated with cognitive function in individuals with stable-phase schizophrenia, with higher levels of TG, TC, and LDL-C correlating with poorer overall cognitive performance. TG and LDL-C may be risk factors for exacerbating cognitive impairment in these patients. From an inflammatory perspective, lipid metabolism abnormalities might influence cognition by activating or downregulating related proteins, or through pathways such as cytokine-cytokine receptor interaction, chemokine signaling pathway, and IL-17 signaling pathway.

[Response of branch attributes of Larix kaempferi to climate variables]. / 日本落叶松枝条属性特征对气候变量的响应.

We established a mixed-effects model incorporating climatic factors for the base diameter and length of the primary branches of Larix kaempferi using stepwise regression, based on climatic data from a total of 40 standard plots located in Xiaolongshan, Gansu Province, Changlinggang Forest Farm in Jianshi County, Hubei Province, and Dagujia Forest Farm in Qingyuan County, Liaoning Province, as well as the data from 120 L. kaempferi sample trees. Additionally, we created prediction charts for the fixed effects portion of the optimal mixed model to determine the relationship between climatic factors and base diameter and branch length, to explore the differential response of L. kaempferi branches to climatic variables. The results showed that the base diameter mixing model with annual mean temperature and water vapor deficit and the branch length mixing model with annual mean temperature had the best fitting effect, with R2 of 0.6152 and 0.6823, respectively. Based on the fixed effects prediction chart of the mixed model, the overall basal diameter showed an increasing trend with the increases of relative branch depth. The average basal diameter size was in an order of young-aged plantation

[Characteristics of soybean climate potential productivity in frigid region and its response to climate change]. / å¯’åœ°å¤§è±†æ°”å€™ç”Ÿäº§æ½œåŠ›ç‰¹å¾åŠå ¶å¯¹æ°”å€™å˜åŒ–çš„å“åº”.

A comprehensive understanding of the evolution of soybean climate potential productivity and its response to climate change in Heilongjiang Province can offer reference and basis for further tapping soybean production potential and realizing stable and high yield of soybean in the frigid region. Based on meteorological data from 80 meteorological stations in Heilongjiang Province from 1961 to 2020, we estimated photosynthesis, light temperature, and climate potential productivity of soybean by the stepwise correction method, examined the spatiotemporal variations by spatial interpolation and statistical analysis methods, and analyzed the impact of changes in climate factors such as radiation, temperature, and precipitation on climate potential productivity. The results showed that during the study period, the average values of photosynthesis potential productivity (YQ), light-temperature potential productivity (YT), and climate potential productivity (YW) of soybean in Heilongjiang Province were 7533, 6444, and 3515 kg·hm-2, respectively. The temporal changes of those variables showed significant increasing trends, with increases of 125.9, 182.9, and 116.1 kg·hm-2·(10 a)-1, respectively. For the spatial distribution, YQ, YT, YW were characterized by high values in plains and lower in the mountains, and gradually decreased from southwest to northeast. Compared with that during 1961-1990, the high value zone of YW in period 1991-2020 expanded by 7.1%, and the low value zone decreased by 5.1%. YW showed a significant response to climate change. The potential temperature growth period was extended due to climate warming. The continuous increase in thermal resources, combined with relatively sufficient precipitation, effectively alleviated the negative impact of the decline in light resources on soybean production in Heilongjiang Province. The projected "warm and humid" climate would comprehensively boost climate potential productivity of soybean in Heilongjiang Province.

Bridging agro-science and human nutrition: zinc nanoparticles and biochar as catalysts for enhanced crop productivity and biofortification.

The integration of zinc nanoparticles (Zn NPs) with biochar offers a transformative approach to sustainable agriculture by enhancing plant productivity and human nutrition. This combination improves soil health, optimizes nutrient uptake, and increases resilience to environmental stressors, leading to superior crop performance. Our literature review shows that combining Zn NPs with biochar significantly boosts the crop nutrient composition, including proteins, vitamins, sugars, and secondary metabolites. This enhancement improves the plant tolerance to environmental challenges, crop quality, and shelf life. This technique addresses the global issue of Zn deficiency by biofortifying food crops with increased Zn levels, such as mung beans, lettuce, tomatoes, wheat, maize, rice, citrus, apples, and microgreens. Additionally, Zn NPs and biochar improve soil properties by enhancing water retention, cation exchange capacity (CEC), and microbial activity, making soils more fertile and productive. The porous structure of biochar facilitates the slow and sustained release of Zn, ensuring its bioavailability over extended periods and reducing the need for frequent fertilizer applications. This synergy promotes sustainable agricultural practices and reduces the environmental footprint of the traditional farming methods. However, potential ecological risks such as biomagnification, nanoparticle accumulation, and toxicity require careful consideration. Comprehensive risk assessments and management strategies are essential to ensure that agricultural benefits do not compromise the environmental or human health. Future research should focus on sustainable practices for deploying Zn NPs in agriculture, balancing food security and ecological integrity and positioning this approach as a viable solution for nutrient-efficient and sustainable agriculture.

Identification of glycosyltransferase genes for diagnosis of T-cell mediated rejection and prediction of graft loss in kidney transplantation.

BACKGROUND: Glycosylation is a complex and fundamental metabolic biosynthetic process orchestrated by multiple glycosyltransferases (GT) and glycosidases enzymes. Functions of GT have been extensively examined in multiple human diseases. Our study investigated the potential role of GT genes in T-cell mediated rejection (TCMR) and possible prediction of graft loss of kidney transplantation. METHODS: We downloaded the microarray datasets and GT genes from the GEO and the HUGO Gene Nomenclature Committee (HGNC) databases, respectively. Differentially expressed GT genes (DE-GTGs) were obtained by differential expression and Venn analysis. A TCMR diagnostic model was developed based on the hub DE-GTGs using LASSO regression and XGboost machine learning algorithms. In addition, a predictive model for graft survival was constructed by univariate Cox and LASSO Cox regression analysis. RESULTS: We have obtained 15 DE-GTGs . Both GO and KEGG analyses showed that the DE-GTGs were mainly involved in the glycoprotein biosynthetic process. The TCMR diagnostic model exhibited high diagnostic potential with generally highly correlated accuracies [aera under the curve (AUC) of 0.83]. The immune characteristics analysis revealed that higher levels of immune cell infiltration and immune responses were observed in the high-risk group than in the low-risk group. In particular, the Kaplan-Meier survival analysis revealed that renal grafts in the high-risk group have poor prognostic outcomes than the low-risk group. The predictive AUC values of 1-, 2- and 3-year graft survival were 0.76, 0.81, and 0.70, respectively. CONCLUSION: Our results indicated that GT genes could be used for diagnosis of TCMR and prediction of graft loss in kidney transplantation. These results provide new perspectives and tools for diagnosing, treating and predicting kidney transplant-related diseases.

Protein-Induced DNA Dumbbell Amplification (PINDA) and its applications to food hazards detection.

Quantification of trace amounts of proteins is technically challenging because proteins cannot be directly amplified like nucleic acids. To improve the analytical sensitivity and to complement conventional protein analysis methods, we developed a highly sensitive and homogeneous detection strategy called Protein-Induced DNA Dumbbell Amplification (PINDA). PINDA combines protein recognition with exponential nucleic acid amplification by using protein binding probes made of DNA strands conjugated to protein affinity ligands. When a pair of probes bind to the same target protein, complementary nucleic acid sequences that are conjugated to each probe are brought into close proximity. The increased local concentration of the probes results in the formation of a stable dumbbell structure of the nucleic acids. The DNA dumbbell is readily amplifiable exponentially using techniques such as loop-mediated isothermal amplification. The PINDA assay eliminates the need for washing or separation steps, and is suitable for on-site applications. Detection of the model protein, thrombin, has a linear range of 10 fM-100 pM and detection limit of 10 fM. The PINDA technique is successfully applied to the analysis of dairy samples for the detection of ß-lactoglobulin, a common food allergen, and Salmonella enteritidis, a foodborne pathogenic bacterium. The PINDA assay can be easily modified to detect other targets by changing the affinity ligands used to bind to the specific targets.

Crystallographic plane-induced selective mineralization of nanohydroxyapatite on fibrous-grained titanium promotes osteointegration and biocorrosion resistance.

The (002) crystallographic plane-oriented hydroxyapatite (HA) and anatase TiO2 enable favorable hydrophilicity, osteogenesis, and biocorrosion resistance. Thus, the crystallographic plane control in HA coating and crystalline phase control in TiO2 is vital to affect the surface and interface bioactivity and biocorrosion resistance of titanium (Ti) implants. However, a corresponding facile and efficient fabrication method is absent to realize the HA(002) mineralization and anatase TiO2 formation on Ti. Herein, we utilized the predominant Ti(0002) plane of the fibrous-grained titanium (FG Ti) to naturally form anatase TiO2 and further achieve a (002) basal plane oriented nanoHA (nHA) film through an in situ mild hydrothermal growth strategy. The formed FG Ti-nHA(002) remarkably improved hydrophilicity, mineralization, and biocorrosion resistance. Moreover, the nHA(002) film reserved the microgroove-like topological structure on FG Ti. It could enhance osteogenic differentiation through promoted contact guidance, showing one order of magnitude higher expression of osteogenic-related genes. On the other hand, the nHA(002) film restrained the osteoclast activity by blocking actin ring formation. Based on these capacities, FG Ti-nHA(002) improved new bone growth and binding strength in rabbit femur implantation, achieving satisfactory osseointegration within 2 weeks.

The Effect of Placebo on Pruritus in Patients with Chronic Urticaria: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

BACKGROUND: The anti-pruritic effect of placebo in patients with chronic urticaria has gained increasing attention in clinical research. However, the extent of placebo effect and its influencing factors in the treatment of chronic urticaria are not well understood. OBJECTIVE: The objective of this systematic review and meta-analysis was to investigate the effect of placebo on pruritus in patients with chronic urticaria and to explore relevant influencing factors. METHODS: PubMed, Embase, Web of Science, Cochrane Library, and PsycINFO were searched from inception to 10 July, 2024. Primary outcome included pruritus scores. The secondary outcomes focused on global symptoms and quality of life. Subgroup analyses and meta-regression analyses were conducted based on drug types, sample size, participants' age, and other variables. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system and a trial sequential analysis were employed to establish the reliability of evidence. RESULTS: A total of 65 eligible publications (including 67 randomized controlled trials) involving 10,704 patients with chronic urticaria were included. The pruritus scores decreased following placebo treatment (moderate evidence). In addition, favorable results were observed in global symptoms (moderate evidence) and quality of life (low evidence) after placebo treatment. Subgroup analyses indicated that the type of active medication in intervention groups was an influencing factor of placebo effect of pruritus. Meta-regression analyses demonstrated that the anti-pruritic effect of placebo was inversely correlated with sample size and positively correlated with participants' age. A trial sequential analysis provided further support for the anti-pruritic effect of placebo. CONCLUSIONS: A substantial improvement of pruritus after placebo treatment was observed in patients with chronic urticaria. The anti-pruritic effect of placebo varied with sample size, participants' age, and type of active medication used. Future research should further investigate the effect size of placebo and clarify the potential mechanism. PROSPERO REGISTRATION: The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42023482608.

Heat Shock Protein 90 Interactome-Mediated Proteolysis Targeting Chimera (HIM-PROTAC) Degrading Glutathione Peroxidase 4 to Trigger Ferroptosis.

Targeted protein degradation (TPD) is an emerging therapeutic paradigm aimed at eliminating the disease-causing protein with aberrant expression. Herein, we report a new approach to inducing intracellular glutathione peroxidase 4 (GPX4) protein degradation to trigger ferroptosis by bridging the target protein to heat shock protein 90 (HSP90), termed HSP90 interactome-mediated proteolysis targeting chimera (HIM-PROTAC). Different series of HIM-PROTACs were synthesized and evaluated, and two of them, GDCNF-2/GDCNF-11 potently induced ferroptosis via HSP90-mediated ubiquitin-proteasomal degradation of GPX4 in HT-1080 cells with DC50 values of 0.18 and 0.08 µM, respectively. In particular, GDCNF-11 showed 15-fold more ferroptosis selectivity over GPX4 inhibitor ML162. Moreover, these two degraders effectively suppress tumor growth in the mice model with relatively low toxicity as compared to the combination therapy of GPX4 and HSP90 inhibitors. In general, this study demonstrated the feasibility of degrading GPX4 via HSP90 interactome, and thus provided a significant complement to existing TPD strategies.