The effect of ADAMTS13 on graft-versus-host disease.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) can potentially cure malignant blood disorders and benign conditions such as haemoglobinopathies and immunologic diseases. However, allo-HSCT is associated with significant complications. The most common and debilitating among them is graft-versus-host disease (GVHD). In GVHD, donor-derived T cells mount an alloimmune response against the recipient. The alloimmune response involves several steps, including recognition of recipient antigens, activation and proliferation of T cells in secondary lymphoid organs, and homing into GVHD-targeted organs. Adhesion molecules on T cells and endothelial cells mediate homing of T cells into lymphoid and non-lymphoid tissues. In this study, we showed that Von Willebrand factor (VWF), an adhesion molecule secreted by activated endothelial cells, plays an important role in mouse models of GVHD. We investigated the effect of the VWF-cleaving protease ADAMTS13 on GVHD. We found that ADAMTS13 reduced the severity of GVHD after bone marrow transplantation from C57BL6 donor to BALB/C recipient mice. A recombinant VWF-A2 domain peptide also reduced GVHD in mice. We showed that ADAMTS13 and recombinant VWF-A2 reduced the binding of T cells to endothelial cells and VWF in vitro, and reduced the number of T cells in lymph nodes, Peyer's patches and GVHD-targeted organs in vivo. We identified LFA-1 (αLß2) as the binding site of VWF on T cells. Our results showed that blocking T-cell homing by ADAMTS13 or VWF-A2 peptide reduced the severity of the GVHD after allo-HSCT, a potentially novel method for treating and preventing GVHD.

Proximal Femoral Metastasis From Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma Mimicking Osteosarcoma on Magnetic Resonance Imaging.

The aggressive nature of lung cancer is frequently accompanied by a high incidence of bone metastasis; however, proximal femoral metastasis from lung cancer is comparatively uncommon when compared to other malignancies. In this report, we present the case of a 53-year-old Asian male who presented with pain in the left thigh and back. Magnetic resonance imaging revealed severe bone destruction with involvement of adjacent soft tissue mass at the left thigh, exhibiting imaging findings that mimic osteosarcoma. Subsequent bone biopsy confirmed the diagnosis of epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma with bone metastasis. The patient achieved survival following administration of osimertinib and underwent surgery for femoral metastases without palliative surgery for lung cancer. Therefore, proximal femoral metastasis from EGFR-mutated lung adenocarcinoma should be considered as a differential diagnosis in patients suspected to have osteosarcoma. The imaging findings of proximal femoral metastasis from EGFR-mutated lung adenocarcinoma were presented, and their therapeutic management was discussed.

Study on the expression patterns of inner root sheath-specific genes in Tan sheep hair follicle during different developmental stages.

By analyzing the expression patterns of inner root sheath (IRS) specific genes during different developmental stages of hair follicle (HF) in Tan sheep embryos and at birth, this study aims to reveal the influence of the IRS on crimped wool. Skin tissues from the scapular region of male Tan sheep were collected at 85 days (E85) and 120 days (E120) of fetal development, and at 0 days (D0), 35 days (D35), and 60 days (D60) after birth, with four samples at each stage. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to determine the relative expression levels of IRS type I keratin genes (KRT25, KRT26, KRT27, KRT28), type II keratin genes (KRT71, KRT72, KRT73, KRT74), and the trichohyalin gene (TCHH) in the skin of Tan sheep at different stages. Results showed that the expression levels of all IRS-specific genes peaked at D0, with the expression of all genes significantly higher than at E85 (P < 0.01), except for KRT73 and TCHH. The expression levels of KRT25, KRT26, and KRT72 were also significantly higher than at E120 (P < 0.01). Furthermore, the expression levels of KRT27, KRT28, KRT71, and KRT74 were significantly higher than both at E120 and D35 (P < 0.01). The expression levels of other genes at different stages showed no significant difference (P > 0.05). Conclusion: The IRS-specific genes exhibit the highest expression levels in Tan sheep at the neonatal stage. The expression levels of KRT71, KRT72, and TCHH, which are consistent with the pattern of wool crimp, may influence the morphology of the IRS and thereby affect the crimp of Tan sheep wool.

Hu8F4-CAR T cells with mutated Fc spacer segment improve target specificity and mediate anti-leukemia activity in vivo.

BACKGROUND AIMS: Hu8F4 is a T-cell receptor-like antibody with high affinity for the leukemia-associated antigen PR1/HLA-A2 epitope. Adapted into a chimeric antigen receptor (CAR) format, Hu8F4-CAR is composed of the Hu8F4 single-chain variable fragment, the human IgG1 CH2CH3 extracellular spacer domain, a human CD28 costimulatory domain and the human CD3ζ signaling domain. We have demonstrated high efficacy of Hu8F4-CAR-T cells against PR1/HLA-A2-expressing cell lines and leukemic blasts from patients with acute myeloid leukemia in vitro. Previous studies have shown that modification of the Fc domains of IgG4 CH2CH3 spacer regions can eliminate activation-induced cell death and off-target killing mediated by mouse Fc gamma receptor-expressing cells. METHODS: We generated Hu8F4-CAR(PQ) with mutated Fc receptor binding sites on the CH2 domain of Hu8F4-CAR to prevent unwanted interactions with Fc gamma receptor-expressing cells in vivo. RESULTS: The primary human T cells transduced with Hu8F4-CAR(PQ) can specifically lyse HLA-A2+ PR1-expressing leukemia cell lines in vitro. Furthermore, both adult donor-derived and cord blood-derived Hu8F4-CAR(PQ)-T cells are active and can eliminate U937 leukemia cells in NSG mice. CONCLUSIONS: Herein, we demonstrate that modification of the IgG1-based spacer can eliminate Fc receptor binding-induced adverse effects and Hu8F4-CAR(PQ)-T cells can kill leukemia in vivo.

The molecular genetics of PI3K/PTEN/AKT/mTOR pathway in the malformations of cortical development.

Malformations of cortical development (MCD) are a group of developmental disorders characterized by abnormal cortical structures caused by genetic or harmful environmental factors. Many kinds of MCD are caused by genetic variation. MCD is the common cause of intellectual disability and intractable epilepsy. With rapid advances in imaging and sequencing technologies, the diagnostic rate of MCD has been increasing, and many potential genes causing MCD have been successively identified. However, the high genetic heterogeneity of MCD makes it challenging to understand the molecular pathogenesis of MCD and to identify effective targeted drugs. Thus, in this review, we outline important events of cortical development. Then we illustrate the progress of molecular genetic studies about MCD focusing on the PI3K/PTEN/AKT/mTOR pathway. Finally, we briefly discuss the diagnostic methods, disease models, and therapeutic strategies for MCD. The information will facilitate further research on MCD. Understanding the role of the PI3K/PTEN/AKT/mTOR pathway in MCD could lead to a novel strategy for treating MCD-related diseases.

Artesunate inhibits vasculogenic mimicry in choroidal melanoma through HIF-1 α/ VEGF/PDGF pathway.

Choroidal melanoma (CM), a highly metastatic eye tumor, exhibits vasculogenic mimicry (VM) facilitated by hypoxia-induced angiogenesis. This study explored the inhibitory impact of the anti-malarial drug Artesunate (ART) on CM VM through modulation of the HIF-1α/VEGF/PDGF pathway. Immunohistochemistry (IHC) confirmed VM in CM with elevated VEGF and PDGF expression. Hypoxia promoted CM proliferation, upregulating HIF-1α, VEGF and PDGF. VEGF and PDGF enhanced CM migration, invasion and VM, with HIF-1α playing a crucial role. ART mitigated VM formation by suppressing the HIF-1α/VEGF/PDGF pathway, highlighting its potential as an anti-tumor agent in CM.

An integrated network pharmacology approach reveals that Ampelopsis grossedentata improves alcoholic liver disease via TLR4/NF-κB/MLKL pathway.

BACKGROUND: Alcohol-related liver damage is the most prevalent chronic liver disease, which creates a heavy public health burden worldwide. The leaves of Ampelopsis grossedentata have been considered a popular tea and traditional herbal medicine in China for more than one thousand years, and possess anti-inflammatory, antioxidative, hepatoprotective, and antiviral activities. PURPOSE: We explored the protective effects of Ampelopsis grossedentata extract (AGE) against chronic alcohol-induced hepatic injury (alcoholic liver disease, ALD), aiming to elucidate its underlying mechanisms. METHODS: Firstly, UPLC-Q/TOF-MS analysis and network pharmacology were used to identify the constituents and elucidate the potential mechanisms of AGE against ALD. Secondly, C57BL/6 mice were pair-fed the Lieber-DeCarli diet containing either isocaloric maltodextrin or ethanol, AGE (150 and 300 mg/kg/d) and silymarin (200 mg/kg) were administered to chronic ethanol-fed mice for 7 weeks to evaluate the hepatoprotective effects. Serum biochemical parameters were determined, hepatic and ileum sections were used for histologic examination, and levels of inflammatory cytokines and oxidative stress in the liver were examined. The potential molecular mechanisms of AGE in improving ALD were demonstrated by RNA-seq, Western blotting analysis, and immunofluorescence staining. RESULTS: Ten main constituents of AGE were identified using UPLC-Q/TOF-MS and 274 potential ALD-related targets were identified. The enriched KEGG pathways included Toll-like receptor signaling pathway, NF-κB signaling pathway, and necroptosis. Moreover, in vivo experimental studies demonstrated that AGE significantly reduced serum aminotransferase levels and improved pathological abnormalities after chronic ethanol intake. Meanwhile, AGE improved ALD in mice by down-regulating oxidative stress and inflammatory cytokines. Furthermore, AGE notably repaired damaged intestinal epithelial barrier and suppressed the production of gut-derived lipopolysaccharide by elevating intestinal tight junction protein expression. Subsequent RNA-seq and experimental validation indicated that AGE inhibited NF-κB nuclear translocation, suppressed IκB-α, RIPK3 and MLKL phosphorylation and alleviated hepatic necroptosis in mice. CONCLUSION: In this study, we have demonstrated for the first time that AGE protects against alcoholic liver disease by regulating the gut-liver axis and inhibiting the TLR4/NF-κB/MLKL-mediated necroptosis pathway. Therefore, our present work provides important experimental evidence for AGE as a promising candidate for protection against ALD.

Comparison of Infection Risks Between Various Inhaled and Intranasal Corticosteroids: A Pharmacovigilance Analysis Based on the FAERS Database.

Purpose: This study conducted a pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) database to compare the infection risk of inhaled or nasal Beclomethasone, Fluticasone, Budesonide, Ciclesonide, Mometasone, and Triamcinolone Acetonide. Methods: We used proportional imbalance analysis to evaluate the correlation between ICS /INCs and infection events. The data was extracted from the FAERS database from April 2015 to September 2023. Further analysis was conducted on the clinical characteristics, site of infection, and pathogenic bacteria of ICS and INCs infection adverse events (AEs). We used bubble charts to display their top 5 infection adverse events. Results: We analyzed 21,837 reports of infection AEs related to ICS and INCs, with an average age of 62.12 years. Among them, 61.14% of infection reports were related to females. One-third of infections reported to occur in the lower respiratory tract with Fluticasone, Budesonide, Ciclesonidec, and Mometasone; over 40% of infections reported by Triamcinolone Acetonide were eye infections; the rate of oral infections caused by Beclomethasone were 7.39%. The reported rates of fungal and viral infections caused by beclomethasone were 21.15% and 19.2%, respectively. The mycobacterial infections caused by Budesonide and Ciclesonidec account for 3.29% and 2.03%, respectively. Bubble plots showed that the ICS group had more fungal infections, oral infections, pneumonia, tracheitis, etc. The INCs group had more eye symptoms, rhinitis, sinusitis, nasopharyngitis, etc. Conclusion: Women who use ICS and INCs are more prone to infection events. Compared to Budesonide, Fluticasone seemed to have a higher risk of pneumonia and oral candidiasis. Mometasone might lead to more upper respiratory tract infections. The risk of oral infection was higher with Beclomethasone. Beclomethasone causes more fungal and viral infections, while Ciclesonide and Budesonide are more susceptible to mycobacterial infections.

Design, Synthesis, and Antitumor Activity of Isoliquiritigenin Amino Acid Ester Derivatives.

Isoliquiritigenin (ISL) is a chalcone that has shown great potential in the treatment of cancer. However, its relatively weak activity and low water solubility limit its clinical application. In this study, we designed and synthesized 21 amino acid ester derivatives of ISL and characterized the compounds using 1H NMR and 13C NMR. Among them, compound 9 (IC50 = 14.36 µM) had a better inhibitory effect on human cervical cancer (Hela) than ISL (IC50 = 126.5 µM), and it was superior to the positive drug 5-FU (IC50 = 33.59 µM). The mechanism of the action experiment showed that compound 9 could induce Hela cell apoptosis and autophagy through the PI3K/Akt/mTOR pathway.

The complete chloroplast genomes of Polygonatum hunanense, P. verticillatum, and P. caulialatum and their phylogenetic positions.

Polygonatum hunanense H.H. Liu & B.Z. Wang (2021) and P. verticillatum (L.) All. (1875) have been widely used as foods and as folk medicines in China and India, and P. caulialatum S. R. Yi (2021) has recently been described as a new medical plant in China. There is at present a lack of genome information regarding the species. Hence, this study reports the complete chloroplast genomes of the three species. The genomes of P. hunanense, P. verticillatum, and P. caulialatum were 155,583 bp, 155,650 bp, and 155,352 bp in length, respectively. They contained large single-copy (LSC) regions of 84,412 bp, 84,404 bp, and 84,285 bp, small single-copy (SSC) regions of 18,427 bp, 18,416 bp, and 18,463 bp, and a pair of inverted repeats of 26,372 bp, 26,415 bp, and 26,302 bp, respectively. The chloroplast genomes of P. hunanense, P. verticillatum, and P. caulialatum had 133 (103 unique) genes, consisting of 87 protein-coding genes, 38 ribosomal ribonucleic acid (RNA) genes, and eight transfer RNA genes, respectively. A maximum-likelihood phylogenetic tree showed that P. kingianum Coll. et Hemsl. var. grandifolium D.M. Liu & W.Z. Zeng (1991) was closer to P. cyrtonema Hua (1892) rather than to P. kingianum Coll. et Hemsl. (1890), further supporting its status as a unique species of the genus. Moreover, P. verticillatum was separated from the easily confused herb P. cirrhifolium (Wall.) Royle (1839), while P. caulialatum was closest to P. humile Fisch. ex Maxim. (1859). This research provides a foundation for further study of these herbs.

Effect of nutritional status on adverse clinical events in elderly patients with nonvalvular atrial fibrillation: A retrospective cohort study.

OBJECTIVE: To explore the influence of nutritional status on adverse clinical events in elderly patients with nonvalvular atrial fibrillation. METHODS: This retrospective observational cohort study included 196 patients, 75-102-years-old, with nonvalvular atrial fibrillation, hospitalized in our hospital. The nutritional status was assessed using Mini-Nutritional Assessment-Short Form (MNA-SF). Patients with MNA-SF scores of 0-11 and 12-14 were included in the malnutrition and nonmalnutrition groups, respectively. RESULTS: The average age of the malnutrition group was higher than that of the nonmalnutrition group, and the levels of body mass index (BMI), hemoglobin (HGB), and albumin (ALB) were significantly lower than those of the nonmalnutrition group, with statistical significance (p < .05). The incidence of all-cause death in the malnutrition group was higher than that in the nonmalnutrition group (p = .007). Kaplan-Meier curve indicated that malnutrition patients have a higher risk of all-cause death (log-rank test, p = .001) and major bleeding events (p = .017). Multivariate Cox proportional hazard regression analysis corrected for confounders showed that malnutrition was an independent risk factor of all-cause death (HR = 1.780, 95%CI:1.039-3.050, p = .036). The malnutrition group had a significantly high incidence of major bleeding than the nonmalnutrition group (p = .026), and there was no significant difference in the proportion of anticoagulation therapy (p = .082) and the incidence of ischemic stroke/systemic embolism (p = .310) between the two groups. CONCLUSIONS: Malnutrition is an independent risk factor of all-cause death in elderly patients with atrial fibrillation. The incidence of major bleeding in malnourished elderly patients with atrial fibrillation is high, and the benefit of anticoagulation therapy is not obvious.

Population structure and diversification of Gymnospermium kiangnanense, a plant species with extremely small populations endemic to eastern China.

Background: Gymnospermium kiangnanense is the only species distributed in the subtropical region within the spring ephemeral genus Gymnospermium. Extensive human exploitation and habitat destruction have resulted in a rapid shrink of G. kiangnanense populations. This study utilizes microsatellite markers to analyze the genetic diversity and structure and to deduce historical population events of extant populations of G. kiangnanense. Methods: A total of 143 individuals from eight extant populations of G. kiangnanense, including two populations from Anhui Province and six populations from Zhejiang Province, were analyzed with using 21 pairs of microsatellite markers. Genetic diversity indices were calculated using Cervus, GENEPOP, GenALEX. Population structure was assessed using genetic distance (UPGMA), principal coordinate analysis (PCoA), Bayesian clustering method (STRUCTURE), and molecular variation analysis of variance (AMOVA). Population history events were inferred using DIYABC. Results: The studied populations of G. kiangnanense exhibited a low level of genetic diversity (He = 0.179, I = 0.286), but a high degree of genetic differentiation (FST = 0.521). The mean value of gene flow (Nm ) among populations was 1.082, indicating prevalent gene exchange via pollen dispersal. Phylogeographic analyses suggested that the populations of G. kiangnanense were divided into two lineages, Zhejiang (ZJ) and Anhui (AH). These two lineages were separated by the Huangshan-Tianmu Mountain Range. AMOVA analysis revealed that 36.59% of total genetic variation occurred between the two groups. The ZJ lineage was further divided into the Hangzhou (ZJH) and Zhuji (ZJZ) lineages, separated by the Longmen Mountain and Fuchun River. DIYABC analyses suggested that the ZJ and AH lineages were separated at 5.592 ka, likely due to the impact of Holocene climate change and human activities. Subsequently, the ZJZ lineage diverged from the ZJH lineage around 2.112 ka. Given the limited distribution of G. kiangnanense and the significant genetic differentiation among its lineages, both in-situ and ex-situ conservation strategies should be implemented to protect the germplasm resources of G. kiangnanense.

Therapeutic Inhibition of LincRNA-p21 Protects Against Cardiac Hypertrophy.

BACKGROUND: Cardiac hypertrophy is an adaptive response to pressure overload aimed at maintaining cardiac function. However, prolonged hypertrophy significantly increases the risk of maladaptive cardiac remodeling and heart failure. Recent studies have implicated long noncoding RNAs in cardiac hypertrophy and cardiomyopathy, but their significance and mechanism(s) of action are not well understood. METHODS: We measured lincRNA-p21 RNA and H3K27ac levels in the hearts of dilated cardiomyopathy patients. We assessed the functional role of lincRNA-p21 in basal and surgical pressure-overload conditions using loss-of-function mice. Genome-wide transcriptome analysis revealed dysregulated genes and pathways. We labeled proteins in proximity to full-length lincRNA-p21 using a novel BioID2-based system. We immunoprecipitated lincRNA-p21-interacting proteins and performed cell fractionation, ChIP-seq (chromatin immunoprecipitation followed by sequencing), and co-immunoprecipitation to investigate molecular interactions and underlying mechanisms. We used GapmeR antisense oligonucleotides to evaluate the therapeutic potential of lincRNA-p21 inhibition in cardiac hypertrophy and associated heart failure. RESULTS: lincRNA-p21 was induced in mice and humans with cardiomyopathy. Global and cardiac-specific lincRNA-p21 knockout significantly suppressed pressure overload-induced ventricular wall thickening, stress marker elevation, and deterioration of cardiac function. Genome-wide transcriptome analysis and transcriptional network analysis revealed that lincRNA-p21 acts in trans to stimulate the NFAT/MEF2 (nuclear factor of activated T cells/myocyte enhancer factor-2) pathway. Mechanistically, lincRNA-p21 is bound to the scaffold protein KAP1 (KRAB-associated protein-1). lincRNA-p21 cardiac-specific knockout suppressed stress-induced nuclear accumulation of KAP1, and KAP1 knockdown attenuated cardiac hypertrophy and NFAT activation. KAP1 positively regulates pathological hypertrophy by physically interacting with NFATC4 to promote the overactive status of NFAT/MEF2 signaling. GapmeR antisense oligonucleotide depletion of lincRNA-p21 similarly inhibited cardiac hypertrophy and adverse remodeling, highlighting the therapeutic potential of inhibiting lincRNA-p21. CONCLUSIONS: These findings advance our understanding of the functional significance of stress-induced long noncoding RNA in cardiac hypertrophy and demonstrate the potential of lincRNA-p21 as a novel therapeutic target for cardiac hypertrophy and subsequent heart failure.

Construction and Modification of Nitrogen-Rich Polycyclic Frameworks: A Promising Fused Tricyclic Host-Guest Energetic Material with Heat Resistance, High Energy, and Low Sensitivity.

The construction and modification of novel energetic frameworks to achieve an ideal balance between high energy density and good stability are a continuous pursuit for researchers. In this work, a fused [5,6,5]-tricyclic framework was utilized as the energetic host to encapsulate the oxidant molecules for the first time. A series of new pyridazine-based [5,6] and [5,6,5] fused polycyclic nitrogen-rich skeletons and their derivatives were designed and synthesized. Two strategies, amino oxidation and host-guest inclusion, were used to modify the skeleton in only one step. All compounds exhibit good comprehensive properties (Td (onset) > 200 °C, ρ > 1.85 g cm-3, Dv > 8400 m s-1, IS > 20 J, FS > 360 N). Benefiting from the pyridazine-based fused tricyclic structure with more hydrogen bonding units and larger conjugated systems, the first example of [5,6,5]-tricyclic host-guest energetic material triamino-9H-pyrazolo[3,4-d][1,2,4]triazolo[4,3-b]pyridazine-diperchloric acid (10), shows high decomposition temperature (Td (onset) = 336 °C), high density and heats of formation (ρ = 1.94 g cm-3, ΔHf = 733.4 kJ mol-1), high detonation performance (Dv = 8820 m s-1, P = 36.2 GPa), high specific impulse (Isp = 269 s), and low sensitivity (IS = 30 J, FS > 360 N). The comprehensive performance of 10 is superior to that of high-energy explosive RDX and heat-resistant explosives such as HNS and LLM-105. 10 has the potential to become a comprehensive advanced energetic material that simultaneously satisfies the requirements of high-energy and low-sensitivity explosives, heat-resistant explosives, and solid propellants. This work may give new insights into the construction and modification of a nitrogen-rich polycyclic framework and broaden the applications of fused polycyclic framework for the development of host-guest energetic materials.

Hierarchical NiCo2Se4 Arrays Composed of Atomically Thin Nanosheets: Simultaneous Improvements in Thermodynamics and Kinetics for Electrocatalytic Water Splitting in Neutral Media.

The inefficiency of electrocatalysts for water splitting in neutral media stems from a comprehensive impact of poor intrinsic activity, a limited number of active sites, and inadequate mass transport. Herein, hierarchical ultrathin NiCo2Se4 nanosheets are synthesized by the selenization of NiCo2O4 porous nanoneedles. Theoretical and experimental investigations reveal that the intrinsic hydrogen evolution reaction (HER) activity primarily originate from the NiCo2Se4, whereas the high oxygen evolution reaction (OER) performance is related to the NiCoOOH due to the structural reconstruction. The abundant Se and O vacancies introduced by atomically thin nanostructure modulate the electronic structure of NiCo2Se4 and NiCoOOH, thereby improving the intrinsic HER and OER activities, respectively. COMSOL simulation demonstrate the edges of extended nanosheets from the main body significantly promote the charge aggregation, boosting the reduction and oxidation current during HER/OER process. This charge aggregation effect notably exceeds the tip effect for the nanoneedle, highlighting the unique advantage of the hierarchical nanosheet structure. Benefiting from abundant vacancies and unique nanostructure, the hierarchical ultrathin nanosheet simultaneously improve the thermodynamics and kinetics of the electrocatalyst. The optimized samples display an overpotential of 92 mV for HER and 214 mV for OER at 100 mA cm-2, significantly surpassing the performance of currently reported HER/OER catalysts in neutral media.

[A nomogram for predicting residual back pain after percutaneous vertebroplasty for osteoporotic vertebral compression fractures].

OBJECTIVE: To construct percutaneous vertebroplasty for predicting osteoporotic vertebral compression fractures (OVCFs) nomogram of residual back pain (RBP) after percutaneous vertebroplasty(PVP). METHODS: Clinical data of 245 OVCFs patients who were performed PVP from January 2020 to December 2022 were retrospectively analyzed, including 47 males and 198 females, aged from 65 to 77 years old with an average of (71.47±9.03) years old, and were divided into RBP group and non-RBP group according to whether RBP occurred. Gender, age, comorbidities, fracture stage, body mass index (BMI), bone mineral density (BMD), visual analogue scale (VAS), Oswestry disability index (ODI) and other general information were collected; anterior vertebral height (AVH), anterior vertebral height ratio (AVH), anterior vertebral height ratio(AVHR), Cobb angle, intravertebral vacuum cleft (IVC), thoracolumbar fascia (TLF) injury, paravertebral muscle steatosis, injection volume and leakage of bone cement, bone cement dispersion pattern, anterior vertebral height recovery ratio (AVHRR), Cobb angle changes, etc. imaging parameters before operation and 24 h after operation were collected. Univariate analysis was performed to analysis above factors, and multivariate Logistic regression model was used to investigate independent risk factors for postoperative RBP, and Nomogram model was constructed and verified;receiver operating characteristic(ROC) curve and calibration curve were used to determine predictive performance and accuracy of the model, and Hosmer-Lemeshow (H-L) test was used for evaluation. The area under curve (AUC) of ROC was calculated, and Harrell consistency index (C index) was used to evaluate the predictive efficiency of model;decision curve analysis (DCA) was used to evaluate clinical practicability of model. RESULTS: There were 34 patients in RBP group and 211 patients in non-RBP group. There were no significant differences in gender, age, comorbidities, fracture stage, BMI, BMD, VAS, ODI, AVH, AVHR and Cobb angle between two groups (P>0.05). Univariate analysis showed 6 patients occurred IVC in RBP group and 13 patients in non-RBP, the number of IVC in RBP group was higher than that in non-RBP group (χ2=5.400, P=0.020);6 patients occuured TLF injury in RBP group and 11 patients in non-RBP group, the number of TLF injury in RBP group was higher than that in non-RBP group (χ2=7.011, P=0.008);In RBP group, 18 patients with grade 3 to 4 paraptebral steatosis and 41 patients in non-RBP group, RBP group was higher than non-RBP group (χ2=21.618, P<0.001), and the proportion of bone cement mass in RBP group was higher than non-RBP group (χ2=6.836, P=0.009). Multivariate Logistic regression analysis showed IVC (χ2=4.974, P=0.025), TLF injury (χ2=5.231, P=0.023), Goutallier grade of paravertebral steatosis >2 (χ2=15.124, P<0.001) and proportion of bone cement (χ2=4.168, P=0.038) were independent risk factors for RBP after PVP. ROC curve of model showed AUC of original model was 0.816[OR=2.862, 95%CI (0.776, 0.894), P<0.001]. The internal verification of model through 200 bootstrap samples showed the value of C index was 0.936, and calibration curve showed predicted probability curve was close to actual probability curve. H-L goodness of fit test results were χ2=5.796, P=0.670. DCA analysis results showed the decision curve was above None line and All line when the threshold value ranged from 6% to 71%. CONCLUSION: IVC, TLF combined injury, paravertebral muscle steatosis with Goutallier grade> 2, and bone cement diffusion with mass type are independent risk factors for RBP after PVP. The risk prediction model for RBP after PVP established has good predictive performance and good clinical practicability.

Identification of Dendrobium Using Laser-Induced Breakdown Spectroscopy in Combination with a Multivariate Algorithm Model.

Dendrobium, a highly effective traditional Chinese medicinal herb, exhibits significant variations in efficacy and price among different varieties. Therefore, achieving an efficient classification of Dendrobium is crucial. However, most of the existing identification methods for Dendrobium make it difficult to simultaneously achieve both non-destructiveness and high efficiency, making it challenging to truly meet the needs of industrial production. In this study, we combined Laser-Induced Breakdown Spectroscopy (LIBS) with multivariate models to classify 10 varieties of Dendrobium. LIBS spectral data for each Dendrobium variety were collected from three circular medicinal blocks. During the data analysis phase, multivariate models to classify different Dendrobium varieties first preprocess the LIBS spectral data using Gaussian filtering and stacked correlation coefficient feature selection. Subsequently, the constructed fusion model is utilized for classification. The results demonstrate that the classification accuracy of 10 Dendrobium varieties reached 100%. Compared to Support Vector Machine (SVM), Random Forest (RF), and K-Nearest Neighbors (KNN), our method improved classification accuracy by 14%, 20%, and 20%, respectively. Additionally, it outperforms three models (SVM, RF, and KNN) with added Principal Component Analysis (PCA) by 10%, 10%, and 17%. This fully validates the excellent performance of our classification method. Finally, visualization analysis of the entire research process based on t-distributed Stochastic Neighbor Embedding (t-SNE) technology further enhances the interpretability of the model. This study, by combining LIBS and machine learning technologies, achieves efficient classification of Dendrobium, providing a feasible solution for the identification of Dendrobium and even traditional Chinese medicinal herbs.

The emerging role and mechanism of HMGA2 in breast cancer.

High mobility group AT-hook 2 (HMGA2) is a member of the non-histone chromosomal high mobility group (HMG) protein family, which participate in embryonic development and other biological processes. HMGA2 overexpression is associated with breast cancer (BC) cell growth, proliferation, metastasis, and drug resistance. Furthermore, HMGA2 expression is positively associated with poor prognosis of patients with BC, and inhibiting HMGA2 signaling can stimulate BC cell progression and metastasis. In this review, we focus on HMGA2 expression changes in BC tissues and multiple BC cell lines. Wnt/ß-catenin, STAT3, CNN6, and TRAIL-R2 proteins are upstream mediators of HMGA2 that can induce BC invasion and metastasis. Moreover, microRNAs (miRNAs) can suppress BC cell growth, invasion, and metastasis by inhibiting HMGA2 expression. Furthermore, long noncoding RNAs (LncRNAs) and circular RNAs (CircRNAs) mainly regulate HMGA2 mRNA and protein expression levels by sponging miRNAs, thereby promoting BC development. Additionally, certain small molecule inhibitors can suppress BC drug resistance by reducing HMGA2 expression. Finally, we summarize findings demonstrating that HMGA2 siRNA and HMGA2 siRNA-loaded nanoliposomes can suppress BC progression and metastasis.

The long noncoding RNA CARDINAL attenuates cardiac hypertrophy by modulating protein translation.

One of the features of pathological cardiac hypertrophy is enhanced translation and protein synthesis. Translational inhibition has been shown to be an effective means of treating cardiac hypertrophy, although system-wide side effects are common. Regulators of translation, such as cardiac-specific long noncoding RNAs (lncRNAs), could provide new, more targeted therapeutic approaches to inhibit cardiac hypertrophy. Therefore, we generated mice lacking a previously identified lncRNA named CARDINAL to examine its cardiac function. We demonstrate that CARDINAL is a cardiac-specific, ribosome-associated lncRNA and show that its expression was induced in the heart upon pathological cardiac hypertrophy and that its deletion in mice exacerbated stress-induced cardiac hypertrophy and augmented protein translation. In contrast, overexpression of CARDINAL attenuated cardiac hypertrophy in vivo and in vitro and suppressed hypertrophy-induced protein translation. Mechanistically, CARDINAL interacted with developmentally regulated GTP-binding protein 1 (DRG1) and blocked its interaction with DRG family regulatory protein 1 (DFRP1); as a result, DRG1 was downregulated, thereby modulating the rate of protein translation in the heart in response to stress. This study provides evidence for the therapeutic potential of targeting cardiac-specific lncRNAs to suppress disease-induced translational changes and to treat cardiac hypertrophy and heart failure.

Organic amendments temporarily change arsenic speciation and bioaccessibility in a lead and arsenic co-contaminated urban soil.

Organic amendments often reduce the bioaccessibility of soil lead (Pb) but not that of soil arsenic (As). The effect of Pb on As bioaccessibility is rarely studied in co-contaminated soils. In a field study, we assessed the effect of mushroom compost, leaf compost, noncomposted biosolids, and composted biosolids amendments on As speciation in a co-contaminated (As and Pb) soil at 7, 349, and 642 days after amending soils and the change of As speciation during an in vitro bioaccessibility extraction (gastric solution, pH 2.5) using bulk X-ray absorption near-edge structure spectroscopy. Soil was contaminated by coal combustion and other diffuse sources and had low As bioaccessibility (7%-12%). Unamended soil had As(III) sorbed onto pyrite (As(III)-pyrite; ∼60%) and As(V) adsorbed onto Fe oxy(hydr)oxides (As(V)-Fh; ∼40%). In amended soils, except in composted biosolids-amended soils, at 7 days, As(V)-Fh decreased to 15%-26% and redistributed into As(III)-Fh and/or As(III)-pyrite. This transformation was most pronounced in mushroom compost amended soil resulting in a significant (46%) increase of As bioaccessibility compared to the unamended soil. Composted biosolids-amended soils had relatively stable As(V)-Fh. Lead arsenate formed during the in vitro extraction in amended soils, except in composted biosolids-amended soils. Arsenic speciation and bioaccessibility were similar in 349- and 642-day in all the amended and unamended soils. Reduction of As(V)-Fh to As(III) forms in the short term in three of the amended soils showed the potential to increase As bioaccessibility. The formation of stable lead arsenate during the in vitro extraction would counteract the short-term increase of As bioaccessibility in those amended soils.