Risk factors for the outcome and prognosis of multiple myeloma patients with pathological fractures undergoing percutaneous vertebroplasty.

This study focuses on the clinical features affecting the outcome and prognosis of multiple myeloma (MM) associated with spinal fractures. We retrospectively analyzed the clinical data of 194 MM patients with pathologic thoracic or lumbar spine fractures admitted to Dongying People's Hospital from April 2005 to February 2021. Patients were categorized into effective and ineffective groups based on post-treatment pain scores and mobility to analyze the influencing factors on the efficacy. Univariate analysis showed that age ≥60 years, number of vertebral fractures ≥2, and conservative treatment were associated with the outcomes. The number of vertebral fractures ≥2 (OR=2.198, P=0.034) and conservative treatment (OR=1.685, P=0.012) were identified as independent risk factors. In addition, survival curves were depicted using the Kaplan-Meier method, and independent risk factors affecting 2-year survival included efficacy (HR=17.924, P<0.001), age (HR=3.544, P=0.003) and International Staging System staging (HR=10.770, P=0.001). Finally, we constructed a high-accuracy prognostic model for predicting 2-year survival of MM patients with pathologic fractures (AUC=0.756). In conclusion, this study identified independent risk factors affecting the outcome and survival of MM patients with morbid fractures by systematically analyzing clinical characteristics and constructing a survival prediction model, thus providing effective guideline for clinical treatment.

Correlation analysis between biomechanical characteristics of lower extremities during front roundhouse kick in Taekwondo and effective scores of electronic protectors.

Objective: The purpose of this study is to analyze the inherent relationship between the score values and the biomechanical characteristics of the forward kicking motion, we aim to identify the fundamental variables influencing the score values of the forward kicking motion and establish the key biomechanical factors that effectively trigger scoring in the forward kicking motion. Methods: The DaeDo electronic scoring system was used with the Vicon optical motion capture system and the Kistler 3D force platform to obtain kinematic and kinetic variables of the front roundhouse kick motion. Linear bivariate correlation analysis and principal component analysis were used to analyze the associations between kinematic, kinetic variables, and scoring values, and summarize key biomechanical factors for effectively scoring. Results: The peak ankle plantar flexion angle and knee extension torque of the kicking leg showed a significant negative correlation with scoring values (r < 0, p < 0.05), while other variables showed no statistical significance. The peak knee flexion angle and hip extension angular velocity of the supporting leg showed a significant positive correlation with scoring values (r > 0, p < 0.01), while the peak ankle plantar flexion torque showed a significant negative correlation with scoring values (r < 0, p < 0.05), and other variables showed no statistically significant correlation. The absolute values of eigenvectors of the first and second principal components, which included hip angular velocity, ankle angle, knee torque, and hip torque, were relatively large, indicating their strong influence on effective scoring triggering. Conclusion: Maintaining ankle dorsiflexion and a larger knee flexion angle in the kicking leg is favorable for triggering scoring. Higher knee flexion angle and hip extension angular velocity in the supporting leg are also advantageous for triggering scoring. "Body posture" and "Strength" are key factors that effectively trigger scoring.

Deoxynivalenol triggers mitotic catastrophe and apoptosis in C2C12 myoblasts.

Deoxynivalenol (DON), commonly known as vomitoxin, is a mycotoxin produced by fungi and is frequently found as a contaminant in various cereal-based food worldwide. While the harmful effects of DON have been extensively studied in different tissues, its specific impact on the proliferation of skeletal muscle cells remains unclear. In this study, we utilized murine C2C12 myoblasts as a model to explore the influence of DON on their proliferation. Our observations indicated that DON exhibits dose-dependent toxicity, significantly inhibiting the proliferation of C2C12 cells. Through the application of RNA-seq analysis combined with gene set enrichment analysis, we identified a noteworthy downregulation of genes linked to the extracellular matrix (ECM) and condensed chromosome. Concurrently with the reduced expression of ECM genes, immunostaining analysis revealed notable changes in the distribution of fibronectin, a vital ECM component, condensing into clusters and punctate formations. Remarkably, the exposure to DON induced the formation of multipolar spindles, leading to the disruption of the normal cell cycle. This, in turn, activated the p53-p21 signaling pathway and ultimately resulted in apoptosis. These findings contribute significant insights into the mechanisms through which DON induces toxicity within skeletal muscle cells.

Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Cutaneous T-Cell Lymphoma: A First-in-Human Phase I/II Study.

Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light, aiming to induce apoptosis in T-cells and thereby modulate immune responses. However, conventional 8-MOP-ECP lacks cell selectivity, killing both healthy and diseased cells, and has shown limited treatment efficacy. An alternative approach under investigation involves the use of 5-aminolevulinic acid (ALA) in conjunction with light, referred to as ALA-based photodynamic therapy. Our previous ex vivo studies suggest that ALA-ECP exhibits greater selectivity and efficiency in killing T-cells derived from patients with T-cell-mediated disorders compared to those treated with 8-MOP-ECP. We have conducted a clinical phase I-(II) study evaluating ALA-ECP safety and tolerability in cutaneous T-cell lymphoma (CTCL). Here, 20 ALA-ECP treatments were administered to one CTCL patient, revealing no significant changes in vital signs. Two adverse events were reported; both evaluated by the Internal Safety Review Committee as non-serious. In addition, five conceivable events with mainly mild symptoms took place. During the study period, a 53% reduction in skin involvement and a 50% reduction in pruritus was observed. In conclusion, the results indicate that ALA-ECP treatment is safe and well tolerated.

Intermolecular charge transfer and solid-state solvent effect synergistically induce near-infrared thermally activated delay fluorescence in the guest-host system.

The host matrix is an important means to tune emission color and improve luminescence efficiency of near-infrared (NIR) thermally activated delay fluorescence (TADF) light-emitting diodes. However, the mechanism of NIR TADF of the guest-host systems is still unclear. Namely, there is a controversy on whether the formation of J-aggregation, solid-state solvent effect, molecular polarization or intermolecular charge transfer (CT) is responsible for the NIR TADF. Here, the morphologies, geometrical and electronic structures, and photophysical properties are explored by combining molecular dynamics simulation, density functional theory and thermal vibration correlation function theory for the guest-host (TPAAP: TPBi) films with different concentrations. It is found that the red TADF is generated largely by the solid-state solvent effect in the low 1 wt% doped film while the NIR TADF is attributed to the synergistic effect of solid-state solvent and guest-guest intermolecular CT in the high 20 wt% film. These findings provide a deeper understanding of the mechanism of NIR-TADF of the guest-host systems.

Current and further outlook on the protective potential of Antrodia camphorata against neurological disorders.

Prevalent neurological disorders such as Alzheimer's disease, Parkinson's disease, and stroke are increasingly becoming a global burden as society ages. It is well-known that degeneration and loss of neurons are the fundamental underlying processes, but there are still no effective therapies for these neurological diseases. In recent years, plenty of studies have focused on the pharmacology and feasibility of natural products as new strategies for the development of drugs that target neurological disorders. Antrodia camphorata has become one of the most promising candidates, and the crude extracts and some active metabolites of it have been reported to play various pharmacological activities to alleviate neurological symptoms at cellular and molecular levels. This review highlights the current evidence of Antrodia camphorata against neurological disorders, including safety evaluation, metabolism, blood-brain barrier penetration, neuroprotective activities, and the potential on regulating the gut-microbiome-brain axis. Furthermore, potential strategies to resolve problematic issues identified in previous studies are also discussed. We aim to provide an overview for the ongoing development and utilization of Antrodia camphorata in cerebral neuropathology.

[Clinical experience of Tianxiong Granules in treatment of hypertension based on treatment principle of supressing Yang and promoting blood circulation].

Hypertension is the most common chronic disease in clinics and has become the most common risk factor for cardiovascular diseases. Because of its high incidence rate, disability rate, and mortality, it has attracted worldwide attention. Despite continuous progress in modern medicine in the treatment of hypertension with new antihypertensive drugs such as Zilebesiran, a nucleic acid drug that acts on microRNA, direct renin inhibitors, and renal sympathetic blockade, the control rate is still not ideal. How to effectively prevent and control hypertension has become one of the urgent clinical challenges to be solved. Traditional Chinese medicine(TCM) has a long record of treating hypertension and has accumulated rich experience, including theoretical understanding, effective single medicine, compound medicine, traditional Chinese patent medicines, and classic famous prescriptions. In TCM, hypertension belongs to the categories of diseases such as dizziness and headache. Previous literature and clinical studies have found that hypertension has key pathogenesis such as fire syndrome, fluid syndrome, deficiency syndrome, and blood stasis syndrome. Among them, the hyperactivity of liver Yang is closely related to blood pressure fluctuations, blood pressure variability, inflammation, and sympathetic activity stimulation. Internal obstruction by blood stasis is closely related to the damage of target organs such as the heart, brain, and kidneys in hypertension. Therefore, the two key pathogenesis of liver yang hyperactivity and internal obstruction by blood stasis run through the entire process of hypertension. Previous studies have found that the effective empirical formula Tianxiong Granules, based on the principles of suppressing Yang and promoting blood circulation, originated from the classic formula Xiongqiong Tianma Pills in Yu Yao Yuan Fang. It is composed of Gastrodiae Rhizoma, Chuanxiong Rhizoma, Puerariae Lobatae Radix, Achyranthis Bidentatae Radix, and Cyathulae Radix and has significant therapeutic effects in the treatment of hypertension. The clinical indications include headache, dizziness, bloating, strong neck, and weak waist and legs. At the same time, it may be accompanied by poor speech, thirst, normal or loose stools, soreness in the waist and legs, lower limb pain, muscle and pulse spasm, menstrual and abdominal pain, dark red tongue, strong pulse strings, or straight and long pulse strings that pass through the mouth of an inch. In the combination rule, it can be used according to the different pathogenesis stages of hypertension patients. In the fire syndrome stage, it is often combined with Tianma Gouteng Decoction and Chaihu Jia Longgu Muli Decoction. In the fluid syndrome stage, it is often combined with Banxia Baizhu Tianma Decoction. In the deficiency syndrome stage, it is often combined with Liuwei Dihuang Pills and Shenqi Pills. In terms of dosage, it is important to focus on the main symptoms and adjust the dosage of key drugs based on blood pressure values. Some drugs can be used in sufficient quantities. By analyzing the compatibility of Tianxiong Granules, clinical application indications, combined formula experience, and dosage application experience, we provide effective treatment methods and more options for TCM to treat hypertension with Yang hyperactivity and blood stasis syndrome.

Development and validation of a GC-MS/MS method for the determination of iodoacetic acid in biological samples.

Iodoacetic acid (IAA) is a halogenated disinfection by-product of growing concern due to its high cytotoxicity, genotoxicity, endocrine disruptor effects, and potential carcinogenicity. However, the data on distribution and excretion of IAA after ingestion by mammals are still scarce. Here, we developed a reliable and validated method for detecting IAA in biological specimens (plasma, urine, feces, liver, kidney, and tissues) based on modified QuEChERS sample preparation combined with gas chromatography-tandem triple quadrupole mass spectrometry (GC-MS/MS). The detection method for IAA exhibited satisfactory recovery rates (62.6-108.0%) with low relative standard deviations (RSD < 12.3%) and a low detection limit for all biological matrices ranging from 0.007 to 0.032 ng/g. The study showed that the proposed method was reliable and reproducible for analyzing IAA in biological specimens. It was successfully used to detect IAA levels in biological samples from rats given gavage administration. The results indicated that IAA was found in various tissues and organs, including plasma, thyroid, the liver, the kidney, the spleen, gastrointestinal tract, and others, 6 h after exposure. This study provides the first data on the in vivo distribution in and excretion of IAA by mammals following oral exposure.

DMC-siERCC2 hybrid nanoparticle enhances TRAIL sensitivity by inducing cell cycle arrest for glioblastoma treatment.

ERCC2 plays a pivotal role in DNA damage repair, however, its specific function in cancer remains elusive. In this study, we made a significant breakthrough by discovering a substantial upregulation of ERCC2 expression in glioblastoma (GBM) tumor tissue. Moreover, elevated levels of ERCC2 expression were closely associated with poor prognosis. Further investigation into the effects of ERCC2 on GBM revealed that suppressing its expression significantly inhibited malignant growth and migration of GBM cells, while overexpression of ERCC2 promoted tumor cell growth. Through mechanistic studies, we elucidated that inhibiting ERCC2 led to cell cycle arrest in the G0/G1 phase by blocking the CDK2/CDK4/CDK6/Cyclin D1/Cyclin D3 pathway. Notably, we also discovered a direct link between ERCC2 and CDK4, a critical protein in cell cycle regulation. Additionally, we explored the potential of TRAIL, a low-toxicity death ligand cytokine with anticancer properties. Despite the typical resistance of GBM cells to TRAIL, tumor cells undergoing cell cycle arrest exhibited significantly enhanced sensitivity to TRAIL. Therefore, we devised a combination strategy, employing TRAIL with the nanoparticle DMC-siERCC2, which effectively suppressed the GBM cell proliferation and induced apoptosis. In summary, our study suggests that targeting ERCC2 holds promise as a therapeutic approach to GBM treatment.

Chondroitin sulphate modified MoS2 nanoenzyme with multifunctional activities for treatment of Alzheimer's disease.

Nano-MoS2 exhibit oxidoreductase-like activities, and has been shown to effectively eliminate excessive intracellular ROS and inhibit Aß aggregation, thus demonstrating promising potential for anti-Alzheimer's disease (anti-AD) intervention. However, the low water dispersibility and high toxicity of nano-MoS2 limits its further application. In this study, we developed a chondroitin sulphate (CS)-modified MoS2 nanoenzyme (CS@MoS2) by harnessing the excellent biocompatibility of CS and the exceptional activities of nano-MoS2 to explore its potential in anti-AD research. Promisingly, CS@MoS2 significantly inhibited Aß1-40 aggregation and prevented toxic injury in SH-SY5Y cells caused by Aß1-40. In addition, CS@MoS2 protected these cells from oxidative stress damage by regulating ROS production, as well as promoting the activities of SOD and GSH-Px. CS@MoS2 also modulated the intracellular Ca2+ imbalance and downregulated Tau hyperphosphorylation by activating GSK-3ß. CS@MoS2 suppressed p-NF-κB (p65) translocation to the nucleus by inhibiting MAPK phosphorylation, and modulated the expression of downstream anti- and proinflammatory cytokines. Owing to its multifunctional activities, CS@MoS2 effectively improved spatial learning, memory, and anxiety in D-gal/AlCl3-induced AD mice. Taken together, these results indicate that CS@MoS2 has significant potential for improving the therapeutic efficacy of the prevention and treatment of AD, while also presenting a novel framework for the application of nanoenzymes.

SRSF1 Is Required for Mitochondrial Homeostasis and Thermogenic Function in Brown Adipocytes Through its Control of Ndufs3 Splicing.

RNA splicing dysregulation and the involvement of specific splicing factors are emerging as common factors in both obesity and metabolic disorders. The study provides compelling evidence that the absence of the splicing factor SRSF1 in mature adipocytes results in whitening of brown adipocyte tissue (BAT) and impaired thermogenesis, along with the inhibition of white adipose tissue browning in mice. Combining single-nucleus RNA sequencing with transmission electron microscopy, it is observed that the transformation of BAT cell types is associated with dysfunctional mitochondria, and SRSF1 deficiency leads to degenerated and fragmented mitochondria within BAT. The results demonstrate that SRSF1 effectively binds to constitutive exon 6 of Ndufs3 pre-mRNA and promotes its inclusion. Conversely, the deficiency of SRSF1 results in impaired splicing of Ndufs3, leading to reduced levels of functional proteins that are essential for mitochondrial complex I assembly and activity. Consequently, this deficiency disrupts mitochondrial integrity, ultimately compromising the thermogenic capacity of BAT. These findings illuminate a novel role for SRSF1 in influencing mitochondrial function and BAT thermogenesis through its regulation of Ndufs3 splicing within BAT.

Imaging and Liquid Biopsy for Distinguishing True Progression From Pseudoprogression in Gliomas, Current Advances and Challenges.

RATIONALE AND OBJECTIVES: Gliomas are aggressive brain tumors with a poor prognosis. Assessing treatment response is challenging because magnetic resonance imaging (MRI) may not distinguish true progression (TP) from pseudoprogression (PsP). This review aims to discuss imaging techniques and liquid biopsies used to distinguish TP from PsP. MATERIALS AND METHODS: This review synthesizes existing literature to examine advances in imaging techniques, such as magnetic resonance diffusion imaging (MRDI), perfusion-weighted imaging (PWI) MRI, and liquid biopsies, for identifying TP or PsP through tumor markers and tissue characteristics. RESULTS: Advanced imaging techniques, including MRDI and PWI MRI, have proven effective in delineating tumor tissue properties, offering valuable insights into glioma behavior. Similarly, liquid biopsy has emerged as a potent tool for identifying tumor-derived markers in biofluids, offering a non-invasive glimpse into tumor evolution. Despite their promise, these methodologies grapple with significant challenges. Their sensitivity remains inconsistent, complicating the accurate differentiation between TP and PSP. Furthermore, the absence of standardized protocols across platforms impedes the reliability of comparisons, while inherent biological variability adds complexity to data interpretation. CONCLUSION: Their potential applications have been highlighted, but gaps remain before routine clinical use. Further research is needed to develop and validate these promising methods for distinguishing TP from PsP in gliomas.

Postbiotics in colorectal cancer: intervention mechanisms and perspectives.

Colorectal cancer (CRC) is a common malignancy affecting the gastrointestinal tract worldwide. The etiology and progression of CRC are related to factors such as environmental influences, dietary structure, and genetic susceptibility. Intestinal microbiota can influence the integrity of the intestinal mucosal barrier and modulate intestinal immunity by secreting various metabolites. Dysbiosis of the intestinal microbiota can affect the metabolites of the microbial, leading to the accumulation of toxic metabolites, which can trigger chronic inflammation or DNA damage and ultimately lead to cellular carcinogenesis and the development of CRC. Postbiotics are preparations of inanimate microorganisms or their components that are beneficial to the health of the host, with the main components including bacterial components (e.g., exopolysaccharides, teichoic acids, surface layer protein) and metabolites (e.g., short-chain fatty acids, tryptophan metabolite, bile acids, vitamins and enzymes). Compared with traditional probiotics, it has a more stable chemical structure and higher safety. In recent years, it has been demonstrated that postbiotics are involved in regulating intestinal microecology and improving the progression of CRC, which provides new ideas for the prevention and diagnosis of CRC. In this article, we review the changes in intestinal microbiota in different states of the gut and the mechanisms of anti-tumor activity of postbiotic-related components, and discuss the potential significance of postbiotics in the diagnosis and treatment of CRC. This reviews the changes and pathogenesis of intestinal microbiota in the development of CRC, and summarizes the relevant mechanisms of postbiotics in resisting the development of CRC in recent years, as well as the advantages and limitations of postbiotics in the treatment process of CRC.

Development of a tool for assessing the clinical competency of Chinese master's nursing students based on the mini-CEX: a Delphi method study.

OBJECTIVE: To construct a scientific and systematic competency evaluation tool for master of nursing specialists (MNS) and to provide a reference for the training, assessment and competency evaluation of MNS. METHODS: A first draft of the indicators for assessing MNS core competencies was developed on the basis of published research and group discussions. Between June and December 2020, the indicators were revised using two rounds of the Delphi expert consultation method, with questionnaires completed by 16 experts from five provinces in China. RESULTS: The valid retrieval rate of the two questionnaires was 100.00%, and the coefficient of expert authority was 0.931. The Kendall's concordance coefficients of the two rounds of questionnaires were 0.136 (p<0.05) and 0.147 (p<0.05), respectively. Consensus was reached on the seven dimensions and 52 items of the MNS competency assessment instrument. The instrument dimensions included nurse‒patient communication (9 items), health assessment (7 items), clinical decision-making (8 items), operational skills (7 items), health promotion (6 items), humanistic care (9 items) and organisational effectiveness (6 items). CONCLUSIONS: The MNS competency assessment tool constructed in this study is focused and highly credible. The findings can be used as a guide for the training, assessment and competence evaluation of MNS in the future.

[Influencing factors of traumatic arthritis after ankle fracture surgery and construction of risk prediction model].

OBJECTIVE: To explore risk factors of post-operative traumatic arthritis in patients with ankle fracture,and to establish risk prediction model. METHODS: Totally 550 patients with ankle fracture treated from May 2020 to May 2022 were selected as research objects and divided into modeling group (385 patients) and verification group (165 patients) according to 7:3. In modeling group,patients were classified as occurrence group (112 patients) and non-occurrence group (273 patients) according to whether traumatic arthritis occurred after opertaion. Age,body mass index(BMI),gender,smoking history,diabetes history,injury type,fracture type,operation time,manual labor,open injury,osteoporosis,poor reduction,postoperative weight-bearing time,vascular injury,and surgical method were recorded; risk factors of traumatic arthritis in ankle fracture patients were analyzed by single factor and multi factor logistic regression analyses; R software was used to build the prediction model of line graph;receiver operating characteristic (ROC) curve and calibration graph were applied to verify the discrimination and consistency of the model. RESULTS: One hundred and twelve of 385 patients with ankle fracture were developed to post-operative traumatic arthritis,and 275 did not. Univariate analysis showed that there were significant differences in age,BMI,fracture type,operation time,physical labor aboveⅡ,open injury,osteoporosis and poor reduction between two groups (P<0.05). Multivariate Logistic regression analysis showed that age (OR=2.887),BMI (OR=4.042),fracture type (OR=4.244),operation time (OR=2.665),physical labor above gradeⅡ(OR=5.099),osteoporosis (OR=10.219),and poor reduction (OR=3.112) were independent risk factors for traumatic arthritis after ankle fracture (P<0.05). Based on the above risk factors,an nomogram model was established to predict the risk of postoperative traumatic arthritis in ankle fracture patients,and internal and external verification was conducted. The results showed calibration curve of modeling group and verification group showed a good fit between correction curve and ideal curve,indicating that the predicted risk of postoperative traumatic arthritis by the model was basically consistent with actual risk. Area runder ROC curve analysis results showed 0.867[(95%CI(0.826,0.908)] and 0.882 [95%CI(0.827,0.938)],respectively,indicating that the prediction model had good prediction ability. CONCLUSION: Age,BMI,fracture type,operation time,physical labor above gradeⅡ,osteoporosis and poor reduction are all risk factors for post-operative traumatic arthritis in patients with ankle fracture. The prediction model based on the above risk factors could effectively evaluate risk of post-operative traumatic arthritis in patients with ankle fracture.

Resveratrol ameliorates glioblastoma inflammatory response by reducing NLRP3 inflammasome activation through inhibition of the JAK2/STAT3 pathway.

OBJECTIVES: The aim of this study was to investigate the anti-tumor effect of resveratrol (RSV) on glioblastoma (GBM) and its specific mechanism in improving the inflammatory response of the tumor microenvironment. The tumor microenvironment of GBM is highly neuroinflammatory, inducing tumor immunosuppression. Therefore, ameliorating the inflammatory response is an important focus for anti-tumor research. METHODS: The anti-tumor effect of RSV on GBM was demonstrated through in vitro cellular assays, including CCK-8, EdU, PI staining, Transwell, wound healing assay, and flow cytometry. Potential mechanisms of RSV's anti-GBM effects were identified through network pharmacological analysis. In addition, the relationship of RSV with the JAK2/STAT3 signaling pathway and the inflammasome NLRP3 was verified using Western blot. RESULTS: RSV significantly inhibited cell viability in GBM cell lines LN-229 and U87-MG. Furthermore, it inhibited the proliferation and invasive migration ability of GBM cells, while promoting apoptosis. Network pharmacological analysis revealed a close association between the anti-GBM effects of RSV and the JAK/STAT signaling pathway, as well as inflammatory responses. Western blot analysis confirmed that RSV inhibited the over-activation of the inflammasome NLRP3 through the JAK2/STAT3 signaling pathway. Partial reversal of RSV's inhibition of inflammasome NLRP3 was observed with the addition of the JAK/STAT agonist RO8191. CONCLUSIONS: In vitro, RSV can exert anti-tumor effects on GBM and improve the inflammatory response in the GBM microenvironment by inhibiting the activation of the JAK2/STAT3 signaling pathway. These findings provide new insights into potential therapeutic targets for GBM.

Optimizing Typha biochar with phosphoric acid modification and ferric chloride impregnation for hexavalent chromium remediation in water and soil.

Considering the persistent and covert nature of heavy metal soil contamination, the sustainable development of ecological environments and food safety is at significant risk. Our study focuses on remediating soils contaminated with chromium (Cr); we introduce an advanced remediation material, iron oxide phosphoric acid-loaded activated biochar (HFBC), synthesized through pyrolysis. This HFBC displays greater microporosity, fewer impurities, and enhanced efficiency for the remediation process. Our research utilized a comprehensive set of analytical techniques, including Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Photoelectron Spectroscopy (XPS), alongside adsorption studies to elucidate the Cr removal mechanism. The effectiveness of HFBC in remediation was influenced by several factors: the pH level, dosage of HFBC, the initial concentration of Cr, and the ambient temperature. Our results indicated an optimal chromium (VI) adsorption capacity of 55.5 mg/g by HFBC at a pH of 6.0 and a temperature of 25 °C, with the process adhering to the pseudo-second-order kinetic model and the Langmuir adsorption isotherm, thus suggesting spontaneity in the uptake method. Moreover, this mechanism encompasses both adsorption and reduction reactions. Using HFBC in pot experiments with cabbage indicated not only an increase in soil pH and cation exchange capacity (CEC), but also a surge in bacterial community abundance. Significant reductions in bioavailable chromium were also recorded. Interestingly, HFBC addition bolstered the growth of cabbage, while concurrently diminishing chromium accumulation within the plant, particularly notable as the HFBC application rate increased. In summation, the HFBC produced in our study has demonstrated convincing efficacy in removing chromium from aqueous solutions and soil. Moreover, the positive agronomic implications of its use, such as enhanced plant growth and reduced heavy metal uptake by plants, indicate its high potential for operational value in the domain of environmental remediation of heavy metals.

Reprint of: Recessive APC2 missense variants associated with epilepsies without neurodevelopmental disorders.

OBJECTIVES: The APC2 gene, encoding adenomatous polyposis coli protein-2, is involved in cytoskeletal regulation in neurons responding to endogenous extracellular signals and plays an important role in brain development. Previously, the APC2 variants have been reported to be associated with cortical dysplasia and intellectual disability. This study aims to explore the association between APC2 variants and epilepsy. METHODS: Whole-exome sequencing (WES) was performed in cases (trios) with epilepsies of unknown causes. The damaging effects of variants were predicted by protein modeling and in silico tools. Previously reported APC2 variants were reviewed to analyze the genotype-phenotype correlations. RESULTS: Four pairs of compound heterozygous missense variants were identified in four unrelated patients with epilepsy without brain malformation/intellectual disability. All variants presented no or low allele frequencies in the controls. The missense variants were predicted to be damaging by silico tools, and affect hydrogen bonding with surrounding amino acids or decreased protein stability. Patients with variants that resulted in significant changes in protein stability exhibited more severe and intractable epilepsy, whereas patients with variants that had minor effect on protein stability exhibited relatively mild phenotypes. The previously reported APC2 variants in patients with complex cortical dysplasia with other brain malformations-10 (CDCBM10; MIM: 618677) were all truncating variants; in contrast, the variants identified in epilepsy in this study were all missense variants, suggesting a potential genotype-phenotype correlation. SIGNIFICANCE: This study suggests that APC2 is potentially associated with epilepsy without brain malformation/intellectual disability. The genotype-phenotype correlation helps to understand the underlying mechanisms of phenotypic heterogeneity.

Multi-modal molecular determinants of clinically relevant osteoporosis subtypes.

Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

Interleukin-12: Structure, Function, and Its Impact in Colorectal Cancer.

Interleukin 12 (IL-12) is a heterodimer consisting of 2 subunits, p35 and p40, with unique associations and interacting functions with its family members. IL-12 is one of the most important cytokines regulating the immune system response and is integral to adaptive immunity. IL-12 has shown marked therapeutic potential in a variety of tumor types. This review therefore summarizes the characteristics of IL-12 and its application in tumor treatment, focusing on its antitumor effects in colorectal cancer (CRC) and potential radiosensitization mechanisms. We aim to provide a current reference for IL-12 and other potential CRC treatment strategies.