Black phosphorus, an advanced versatile nanoparticles of antitumor, antibacterial and bone regeneration for OS therapy.

Osteosarcoma (OS) is the most common primary malignant bone tumor. In the clinic, usual strategies for OS treatment include surgery, chemotherapy, and radiation. However, all of these therapies have complications that cannot be ignored. Therefore, the search for better OS treatments is urgent. Black phosphorus (BP), a rising star of 2D inorganic nanoparticles, has shown excellent results in OS therapy due to its outstanding photothermal, photodynamic, biodegradable and biocompatible properties. This review aims to present current advances in the use of BP nanoparticles in OS therapy, including the synthesis of BP nanoparticles, properties of BP nanoparticles, types of BP nanoparticles, and modification strategies for BP nanoparticles. In addition, we have discussed comprehensively the application of BP in OS therapy, including single, dual, and multimodal synergistic OS therapies, as well as studies about bone regeneration and antibacterial properties. Finally, we have summarized the conclusions, limitations and perspectives of BP nanoparticles for OS therapy.

Effect of Topical Application of an NSAID Lateral to the Incision on Postoperative Pain Following Unicompartmental Knee Arthroplasty: A Double-Blind Randomized Controlled Trial.

OBJECTIVE: How to minimize postoperative pain following knee replacement surgery has been a great challenge. This study was performed to evaluate the effect of applying a topical nonsteroidal anti-inflammatory drug (NSAID) lateral to the incision for postoperative pain following unicompartmental knee arthroplasty (UKA). METHODS: The randomized controlled trial enrolled 100 patients from August 2023 to January 2024. One hundred patients who underwent UKA were randomized into two groups. The intervention group received a topical NSAID lateral to the incision postoperatively, and the control group received a placebo lateral to the incision postoperatively. The primary outcome measures were the amount of opioid consumption and the visual analogue scale (VAS) score (12, 24, 36, 48, and 72 h after operation) for pain. The secondary outcome measures were the American Knee Society Score (AKSS, preoperation and 1-month follow-up after operation), the time of first analgesic demand, side effects of opioids, operation time, postoperative stay, surgery-related complications, and postoperative incision healing grade. Independent sample t test and paired sample t test were used to compare continuous data. Chi-square test and Fisher's precision probability tests were used to analyze the categorical data. RESULTS: Ninety-eight patients (intervention group, 48 patients; control group, 50 patients) were analyzed. Opioid consumption was significantly lower in the intervention group than in the control group during the first 12 h, 12 to 24 h, and 24 to 48 h postoperatively (p < 0.05). The VAS score for pain within 72 h postoperatively was significantly lower in the intervention group than in the control group (p < 0.05). There was no significant difference in the AKSS, operation time, postoperative stay, complications, or postoperative incision healing grade between the two groups. The time of first analgesic demand for patient-controlled analgesia was significantly later in the intervention group than in the control group (p < 0.05). There were fewer side effects of opioids in the intervention group (8.3%) than in the control group (18.0%). CONCLUSION: Postoperative application of topical NSAIDs lateral to the incision is an effective and safe method for pain management after UKA, helping to decrease the pain score and reduce opioid consumption postoperatively with no increase in side effects.

Fully 3D-Printed Miniature Soft Hydraulic Actuators with Shape Memory Effect for Morphing and Manipulation.

Miniature shape-morphing soft actuators driven by external stimuli and fluidic pressure hold great promise in morphing matter and small-scale soft robotics. However, it remains challenging to achieve both rich shape morphing and shape locking in a fast and controlled way due to the limitations of actuation reversibility and fabrication. Here, we report fully 3D-printed, sub-millimeter thin-plate-like miniature soft hydraulic actuators with shape memory effect for programmable fast shape morphing and shape locking. It combines commercial high-resolution multi-material 3D printing of stiff shape memory polymers (SMPs) and soft elastomers and direct printing of microfluidic channels and 2D/3D channel networks embedded in elastomers in a single print run. We demonstrated leveraging spatial patterning of hybrid compositions and expansion heterogeneity of microfluidic channel networks for versatile hydraulically actuated shape morphing, including circular, wavy, helical, saddle, and warping shapes with various curvatures. The morphed shapes can be temporarily locked and recover to their original planar forms repeatedly by activating shape memory effect of the SMPs. Utilizing the fast shape morphing and locking in the miniature actuators, we demonstrated their potential applications in non-invasive manipulation of small-scale objects and fragile living organisms, multimodal entanglement grasping, and energy-saving manipulators. This article is protected by copyright. All rights reserved.

RedCDR: Dual Relation Distillation for Cancer Drug Response Prediction.

Based on multi-omics data and drug information, predicting the response of cancer cell lines to drugs is a crucial area of research in modern oncology, as it can promote the development of personalized treatments. Despite the promising performance achieved by existing models, most of them overlook the variations among different omics and lack effective integration of multi-omics data. Moreover, the explicit modeling of cell line/drug attribute and cell line-drug association has not been thoroughly investigated in existing approaches. To address these issues, we propose RedCDR, a dual relation distillation model for cancer drug response (CDR) prediction. Specifically, a parallel dual-branch architecture is designed to enable both the independent learning and interactive fusion feasible for cell line/drug attribute and cell line-drug association information. To facilitate the adaptive interacting integration of multi-omics data, the proposed multi-omics encoder introduces the multiple similarity relations between cell lines and takes the importance of different omics data into account. To accomplish knowledge transfer from the two independent attribute and association branches to their fusion, a dual relation distillation mechanism consisting of representation distillation and prediction distillation is presented. Experiments conducted on the GDSC and CCLE datasets show that RedCDR outperforms previous state-of-the-art approaches in CDR prediction. The source code is available at https://github.com/mhxu1998/RedCDR.

Cardioprotective potentials of myricetin on doxorubicin-induced cardiotoxicity based on biochemical and transcriptomic analysis.

Doxorubicin (DOX) is a commonly used anthracycline in cancer chemotherapy. The clinical application of DOX is constrained by its cardiotoxicity. Myricetin (MYR) is a natural flavonoid widely present in many plants with antioxidant and anti-inflammatory properties. However, MYR's beneficial effects and mechanisms in alleviating DOX-induced cardiotoxicity (DIC) remain unknown. C57BL/6 mice were injected with 15 mg/kg of DOX to establish the DIC, and MYR solutions were administrated by gavage to investigate its cardioprotective potentials. Histopathological analysis, physiological indicators assessment, transcriptomics analysis, and RT-qPCR were used to elucidate the potential mechanism of MYR in DIC treatment. MYR reduced cardiac injury produced by DOX, decreased levels of cTnI, AST, LDH, and BNP, and improved myocardial injury and fibrosis. MYR effectively prevented DOX-induced oxidative stress, such as lowered MDA levels and elevated SOD, CAT, and GSH activities. MYR effectively suppressed NLRP3 and ASC gene expression levels to inhibit pyroptosis while regulating Caspase1 and Bax levels to reduce cardiac cell apoptosis. According to the transcriptomic analysis, glucose and fatty acid metabolism were associated with differential gene expression. KEGG pathway analysis revealed differential gene enrichment in PPAR and AMPK pathways, among others. Following validation, MYR was found to alleviate DIC by regulating glycolipid metabolism and AMPK pathway-related genes. Our findings demonstrated that MYR could mitigate DIC by regulating the processes of oxidative stress, apoptosis, and pyroptosis. MYR is critical in improving DOX-induced myocardial energy metabolism abnormalities mediated by the AMPK signaling pathway. In conclusion, MYR holds promise as a therapeutic strategy for DIC.

Exploring Alashan Ground Squirrel (Spermophilus alashanicus) Diversity: Metagenomic and Transcriptomic Datasets from the Helan Mountains.

This study investigates the adaptive strategies of the Alashan Ground Squirrel (Spermophilus alashanicus) in response to habitat changes, as rodents are sensitive indicators of ecosystem changes. Despite its ecological importance, the genome and microbiome of this species have not been thoroughly studied. This research fills this gap by presenting the first comprehensive metagenomic and transcriptomic datasets of the species. Transcriptomic data was collected from five tissue types, including heart, liver, cecum, muscle, and blood, resulting in the assembly of 72,156 unigenes. Metagenomic sequencing identified predominant bacterial groups such as Firmicutes, Bacteroidetes, Verrucomicrobia, Urovircota, and Proteobacteria. Our workflow involved RNA and DNA extraction, library preparation, assembly, and annotation, yielding valuable insights into gene discovery, microbial composition, and further genome and microbial function studies. In conclusion, our findings have significant implications for understanding the adaptive mechanisms of this species in response to environmental changes.

LncRNA-LncDACH1 mediated phenotypic switching of smooth muscle cells during neointimal hyperplasia in male arteriovenous fistulas.

Arteriovenous fistulas (AVFs) are the most common vascular access points for hemodialysis (HD), but they have a high incidence of postoperative dysfunction, mainly due to excessive neointimal hyperplasia (NIH). Our previous studies have revealed a highly conserved LncRNA-LncDACH1 as an important regulator of cardiomyocyte and fibroblast proliferation. Herein, we find that LncDACH1 regulates NIH in AVF in male mice with conditional knockout of smooth muscle cell-specific LncDACH1 and in male mice model of AVF with LncDACH1 overexpression by adeno-associated virus. Mechanistically, silence of LncDACH1 activates p-AKT through promoting the expression of heat shock protein 90 (HSP90) and serine/arginine-rich splicing factor protein kinase 1 (SRPK1). Moreover, LncDACH1 is transcriptionally activated by transcription factor KLF9 that binds directly to the promoter region of the LncDACH1 gene. In this work, during AVF NIH, LncDACH1 is downregulated by KLF9 and promotes NIH through the HSP90/ SRPK1/ AKT signaling axis.

Identification and analysis of MAPK cascade gene families of Camellia oleifera and their roles in response to cold stress.

BACKGROUND: Low-temperature severely limits the growth and development of Camellia oleifera (C. oleifera). The mitogen-activated protein kinase (MAPK) cascade plays a key role in the response to cold stress. METHODS AND RESULTS: Our study aims to identify MAPK cascade genes in C. oleifera and reveal their roles in response to cold stress. In our study, we systematically identified and analyzed the MAPK cascade gene families of C. oleifera, including their physical and chemical properties, conserved motifs, and multiple sequence alignments. In addition, we characterized the interacting networks of MAPKK kinase (MAPKKK)-MAPK kinase (MAPKK)-MAPK in C. oleifera. The molecular mechanism of cold stress resistance of MAPK cascade genes in wild C. oleifera was analyzed by differential gene expression and real-time quantitative reverse transcription-PCR (qRT-PCR). CONCLUSION: In this study, 21 MAPKs, 4 MAPKKs and 55 MAPKKKs genes were identified in the leaf transcriptome of C. oleifera. According to the phylogenetic results, MAPKs were divided into 4 groups (A, B, C and D), MAPKKs were divided into 3 groups (A, B and D), and MAPKKKs were divided into 2 groups (MEKK and Raf). Motif analysis showed that the motifs in each subfamily were conserved, and most of the motifs in the same subfamily were basically the same. The protein interaction network based on Arabidopsis thaliana (A. thaliana) homologs revealed that MAPK, MAPKK, and MAPKKK genes were widely involved in C. oleifera growth and development and in responses to biotic and abiotic stresses. Gene expression analysis revealed that the CoMAPKKK5/CoMAPKKK43/CoMAPKKK49-CoMAPKK4-CoMAPK8 module may play a key role in the cold stress resistance of wild C. oleifera at a high-elevation site in Lu Mountain (LSG). This study can facilitate the mining and utilization of genetic resources of C. oleifera with low-temperature tolerance.

Graph Representation Learning Based on Specific Subgraphs for Biomedical Interaction Prediction.

Discovering the novel associations of biomedical entities is of great significance and can facilitate not only the identification of network biomarkers of disease but also the search for putative drug targets. Graph representation learning (GRL) has incredible potential to efficiently predict the interactions from biomedical networks by modeling the robust representation for each node. However, the current GRL-based methods learn the representation of nodes by aggregating the features of their neighbors with equal weights. Furthermore, they also fail to identify which features of higher-order neighbors are integrated into the representation of the central node. In this work, we propose a novel graph representation learning framework: a multi-order graph neural network based on reconstructed specific subgraphs (MGRS) for biomedical interaction prediction. In the MGRS, we apply the multi-order graph aggregation module (MOGA) to learn the wide-view representation by integrating the multi-hop neighbor features. Besides, we propose a subgraph selection module (SGSM) to reconstruct the specific subgraph with adaptive edge weights for each node. SGSM can clearly explore the dependency of the node representation on the neighbor features and learn the subgraph-based representation based on the reconstructed weighted subgraphs. Extensive experimental results on four public biomedical networks demonstrate that the MGRS performs better and is more robust than the latest baselines.

A Platinum-Aluminum Bimetallic Salen Complex for Pro-senescence Cancer Therapy.

Cell senescence is defined as irreversible cell cycle arrest, which can be triggered by telomere shortening or by various types of genotoxic stress. Induction of senescence is emerging as a new strategy for the treatment of cancer, especially when sequentially combined with a second senolytic drug capable of killing the resulting senescent cells, however severely suffering from the undesired off-target side effects from the senolytic drugs. Here, we prepare a bimetalic platinum-aluminum salen complex (Alumiplatin) for cancer therapy-a combination of pro-senesence chemotherapy with in situ senotherapy to avoid the side effects. The aluminum salen moiety, as a G-quadruplex stabilizer, enhances the salen's ability to induce cancer cell senescence and this phenotype is in turn sensitive to the cytotoxic activity of the monofunctional platinum moiety. It exhibits an excellent capability for inducing senescence, a potent cytotoxic activity against cancer cells both in vitro and in vivo, and an improved safety profile compared to cisplatin. Therefore, Alumiplatin may be a good candidate to be further developed into safe and effective anticancer agents. This novel combination of cell senescence inducers with genotoxic drugs revolutionizes the therapy options of designing multi-targeting anticancer agents to improve the efficacy of anticancer therapies.

Nanoscale doping of polymeric semiconductors with confined electrochemical ion implantation.

Nanoresolved doping of polymeric semiconductors can overcome scaling limitations to create highly integrated flexible electronics, but remains a fundamental challenge due to isotropic diffusion of the dopants. Here we report a general methodology for achieving nanoscale ion-implantation-like electrochemical doping of polymeric semiconductors. This approach involves confining counterion electromigration within a glassy electrolyte composed of room-temperature ionic liquids and high-glass-transition-temperature insulating polymers. By precisely adjusting the electrolyte glass transition temperature (Tg) and the operating temperature (T), we create a highly localized electric field distribution and achieve anisotropic ion migration that is nearly vertical to the nanotip electrodes. The confined doping produces an excellent resolution of 56 nm with a lateral-extended doping length down to as little as 9.3 nm. We reveal a universal exponential dependence of the doping resolution on the temperature difference (Tg - T) that can be used to depict the doping resolution for almost infinite polymeric semiconductors. Moreover, we demonstrate its implications in a range of polymer electronic devices, including a 200% performance-enhanced organic transistor and a lateral p-n diode with seamless junction widths of <100 nm. Combined with a further demonstration in the scalability of the nanoscale doping, this concept may open up new opportunities for polymer-based nanoelectronics.

Carboxymethylated Rhizoma alismatis polysaccharides reduces the risk of calcium oxalate stone formation by reducing cellular inflammation and oxidative stress.

This study aims to elucidate the mechanism and potential of Rhizoma alismatis polysaccharides (RAPs) in preventing oxidative damage to human renal proximal tubule epithelial cells. The experimental approach involved incubating HK-2 cells with 100 nm calcium oxalate monohydrate for 24 h to establish a cellular injury model. Protection was provided by RAPs with varying carboxyl group contents: 3.57%, 7.79%, 10.84%, and 15.33%. The safeguarding effect of RAPs was evaluated by analyzing relevant cellular biochemical indicators. Findings demonstrate that RAPs exhibit notable antioxidative properties. They effectively diminish the release of reactive oxygen species, lactate dehydrogenase, and malondialdehyde, a lipid oxidation byproduct. Moreover, RAPs enhance superoxide dismutase activity and mitochondrial membrane potential while attenuating the permeability of the mitochondrial permeability transition pore. Additionally, RAPs significantly reduce levels of inflammatory factors, including NLRP3, TNF-α, IL-6, and NO. This reduction corresponds to the inhibition of overproduced pro-inflammatory mediator nitric oxide and the caspase 3 enzyme, leading to a reduction in cellular apoptosis. RAPs also display the ability to suppress the expression of the HK-2 cell surface adhesion molecule CD44. The observed results collectively underscore the substantial anti-inflammatory and anti-apoptotic potential of all four RAPs. Moreover, their capacity to modulate the expression of cell surface adhesion molecules highlights their potential in inhibiting the formation of kidney stones. Notably, RAP3, boasting the highest carboxyl group content, emerges as the most potent agent in this regard.

Multi-Stimulus Least-Squares Transformation With Online Adaptation Scheme to Reduce Calibration Effort for SSVEP-Based BCIs.

Steady-state visual evoked potential (SSVEP), one of the most popular electroencephalography (EEG)-based brain-computer interface (BCI) paradigms, can achieve high performance using calibration-based recognition algorithms. As calibration-based recognition algorithms are time-consuming to collect calibration data, the least-squares transformation (LST) has been used to reduce the calibration effort for SSVEP-based BCI. However, the transformation matrices constructed by current LST methods are not precise enough, resulting in large differences between the transformed data and the real data of the target subject. This ultimately leads to the constructed spatial filters and reference templates not being effective enough. To address these issues, this paper proposes multi-stimulus LST with online adaptation scheme (ms-LST-OA). METHODS: The proposed ms-LST-OA consists of two parts. Firstly, to improve the precision of the transformation matrices, we propose the multi-stimulus LST (ms-LST) using cross-stimulus learning scheme as the cross-subject data transformation method. The ms-LST uses the data from neighboring stimuli to construct a higher precision transformation matrix for each stimulus to reduce the differences between transformed data and real data. Secondly, to further optimize the constructed spatial filters and reference templates, we use an online adaptation scheme to learn more features of the EEG signals of the target subject through an iterative process trial-by-trial. RESULTS: ms-LST-OA performance was measured for three datasets (Benchmark Dataset, BETA Dataset, and UCSD Dataset). Using few calibration data, the ITR of ms-LST-OA achieved 210.01±10.10 bits/min, 172.31±7.26 bits/min, and 139.04±14.90 bits/min for all three datasets, respectively. CONCLUSION: Using ms-LST-OA can reduce calibration effort for SSVEP-based BCIs.

SIRPB1 regulates inflammatory factor expression in the glioma microenvironment via SYK: functional and bioinformatics insights.

BACKGROUND: SIRPB1 expression is upregulated in various tumor types, including gliomas, and is known to contribute to tumor progression; nevertheless, its function in the immune milieu of gliomas is still mainly unknown. METHODS: This study, we analyzed 1152 normal samples from the GTEx database and 670 glioma samples from the TCGA database to investigate the relationship between the expression of SIRPB1 and clinicopathological features. Moreover, SIRPB1 gene knockout THP-1 cell lines were constructed using CRISPR/Cas9 and were induced into a co-culture of macrophages and glioma cells in vitro to learn more about the role of SIRPB1 in the glioma immune milieu. Lastly, we established a prognostic model to predict the effect of SIRPB1 on prognosis. RESULTS: Significantly higher levels of SIRPB1 expression were found in gliomas, which had an adverse effect on the immune milieu and correlated poorly with patient survival. SIRPB1 activation with certain antibodies results in SYK phosphorylation and the subsequent activation of calcium, MAPK, and NF-κB signaling pathways. This phenomenon is primarily observed in myeloid-derived cells as opposed to glioma cells. In vitro co-culture demonstrated that macrophages with SIRPB1 knockout showed decreased IL1RA, CCL2, and IL-8, which were recovered upon ectopic expression of SIRPB1 but reduced again following treatment with SYK inhibitor GS9973. Critically, a lower overall survival rate was linked to increased SIRPB1 expression. Making use of SIRPB1 expression along with additional clinicopathological variables, we established a nomogram that showed a high degree of prediction accuracy. CONCLUSIONS: Our study demonstrates that glioma cells can be activated by macrophages via SIRPB1, subsequently reprogramming the TME, suggesting that SIRPB1 could serve as a promising therapeutic target for gliomas.

Carboxymethylated Desmodium styracifolium polysaccharide reduces the risk of calcium oxalate kidney stone formation by inhibiting crystal adhesion and promoting crystal endocytosis.

The inhibition of cell surface crystal adhesion and an appropriate increase in crystal endocytosis contribute to the inhibition of kidney stone formation. In this study, we investigated the effects of different degrees of carboxymethylation on these processes. An injury model was established by treating human renal proximal tubular epithelial (HK-2) cells with 98.3 ± 8.1 nm calcium oxalate dihydrate (nanoCOD) crystals. The HK-2 cells were protected with carboxy (-COOH) Desmodium styracifolium polysaccharides at 1.17% (DSP0), 7.45% (CDSP1), 12.2% (CDSP2), and 17.7% (CDSP3). Changes in biochemical indexes and effects on nanoCOD adhesion and endocytosis were detected. The protection of HK-2 cells from nanoCOD-induced oxidative damage by carboxymethylated Desmodium styracifolium polysaccharides (CDSPs) is closely related to the protection of subcellular organelles, such as mitochondria. CDSPs can reduce crystal adhesion on the cell surface and maintain appropriate crystal endocytosis, thereby reducing the risk of kidney stone formation. CDSP2 with moderate -COOH content showed the strongest protective activity among the CDSPs.

Biofortified Rice Provides Rich Sakuranetin in Endosperm.

Sakuranetin plays a key role as a phytoalexin in plant resistance to biotic and abiotic stresses, and possesses diverse health-promoting benefits. However, mature rice seeds do not contain detectable levels of sakuranetin. In the present study, a transgenic rice plant was developed in which the promoter of an endosperm-specific glutelin gene OsGluD-1 drives the expression of a specific enzyme naringenin 7-O-methyltransferase (NOMT) for sakuranetin biosynthesis. The presence of naringenin, which serves as the biosynthetic precursor of sakuranetin made this modification feasible in theory. Liquid chromatography tandem mass spectrometry (LC-MS/MS) validated that the seeds of transgenic rice accumulated remarkable sakuranetin at the mature stage, and higher at the filling stage. In addition, the panicle blast resistance of transgenic rice was significantly higher than that of the wild type. Specially, the matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging was performed to detect the content and spatial distribution of sakuranetin and other nutritional metabolites in transgenic rice seeds. Notably, this genetic modification also did not change the nutritional and quality indicators such as soluble sugars, total amino acids, total flavonoids, amylose, total protein, and free amino acid content in rice. Meanwhile, the phenotypes of the transgenic plant during the whole growth and developmental periods and agricultural traits such as grain width, grain length, and 1000-grain weight exhibited no significant differences from the wild type. Collectively, the study provides a conceptual advance on cultivating sakuranetin-rich biofortified rice by metabolic engineering. This new breeding idea may not only enhance the disease resistance of cereal crop seeds but also improve the nutritional value of grains for human health benefits.

Initial nutrient condition determines the recovery speed of quiescent cells in fission yeast.

Most of microbe cells spend the majority of their times in quiescence due to unfavorable environmental conditions. The study of this dominant state is crucial for understanding the basic cell physiology. Retained recovery ability is a critical property of quiescent cells, which consists of two features: how long the cells can survive (the survivability) and how fast they can recover (the recovery activity). While the survivability has been extensively studied under the background of chronological aging, how the recovery activity depends on the quiescent time and what factors influence its dynamics have not been addressed quantitatively. In this work, we systematically quantified both the survivability and the recovery activity of long-lived quiescent fission yeast cells at the single cell level under various nutrient conditions. It provides the most profound evolutionary dynamics of quiescent cell regeneration ability described to date. We found that the single cell recovery time linearly increased with the starvation time before the survivability significantly declined. This linearity was robust under various nutrient conditions and the recovery speed was predetermined by the initial nutrient condition. Transcriptome profiling further revealed that quiescence states under different nutrient conditions evolve in a common trajectory but with different speed. Our results demonstrated that cellular quiescence has a continuous spectrum of depths and its physiology is greatly influenced by environmental conditions.

CHRNA9 as a New Prognostic Marker and Potential Therapeutic Target in Glioma.

Background: The nicotinic acetylcholine receptor (nAChR) subunit alpha-9 (CHRNA9) is a unique cholinergic receptor, which is involved in tumor proliferation, apoptosis, metastasis and chemotherapy resistance. However, the correlation between the expression level of CHRNA9 in glioma and the clinical features and prognosis of glioma patients has not been clarified. The aim of this study was to verify the expression level of CHRNA9 in glioma and its effect on prognosis by bioinformatics methods. Methods: The RNA-seq data of glioma and normal samples were obtained from the TCGA and GTEx databases. Bioinformatics methods were utilized to analyze the differential expression of CHRNA9 between tumor samples and normal samples. The potential association between CHRNA9 and the clinicopathological features of glioma patients was also investigated. The Kaplan-Meier method and Cox regression were utilized to analyze the relationship between CHRNA9 expression level and survival time and prognostic value of glioma patients. Enrichment analysis was applied to predict gene function and signaling pathways associated with CHRNA9. Experimental verification was performed using tumor tissues and paracancerous tissues from glioma patients. Results: The results of bioinformatics analysis showed that the expression of CHRNA9 was increased in glioma tissues, correlating with poor prognosis and reduced patient survival time. Enrichment analysis suggested that CHRNA9 may interact with the JAK/STAT pathway. CHRNA9 was also found to be abnormally expressed in various other tumors and associated with the expression levels of numerous immune checkpoints in glioma. The findings from the analysis of clinical samples revealed that the expression levels of both mRNA and protein of CHRNA9 in glioma tissues were higher than those in paracancerous tissues. Similarly, the mRNA expression levels of STAT3, IL-6, and TNF-α, which are crucial factors in the STAT3 pathway, were elevated in glioma tissues compared to paracancerous tissues. Conclusion: CHRNA9 is a potential prognostic marker and immunotherapy target for glioma, with its mechanism of action potentially linked to the STAT3 pathway.

Combined simultaneous transsphenoidal and transcranial regimen improves surgical outcomes in complex giant pituitary adenomas: A longitudinal retrospective cohort study.

BACKGROUND: Surgical treatment of complex giant pituitary adenomas (GPAs) presents significant challenges. The efficacy and safety of combining transsphenoidal and transcranial approaches for these tumors remain controversial. In this largest cohort of patients with complex GPAs, we compared the surgical outcomes between those undergoing a combined regimen and a non-combined regimen. We also examined the differences in risks of complications, costs, and logistics between the two groups, which might offer valuable information for the appropriate management of these patients. MATERIALS AND METHODS: This was a multicenter retrospective cohort study conducted at 13 neurosurgical centers. Consecutive patients who received a combined or non-combined regimen for complex GPAs were enrolled. The primary outcome was gross total resection, while secondary outcomes included complications, surgical duration, and relapse. A propensity score-based weighting method was used to account for differences between the groups. RESULTS: Out of 647 patients (298 [46.1%] women, mean age: 48.5 ± 14.0 years) with complex GPAs, 91 were in the combined group and 556 were in the non-combined group. Compared with the non-combined regimen, the combined regimen was associated with a higher probability of gross total resection (50.5% vs. 40.6%, odds ratio [OR]: 2.18, 95% confidence interval [CI]: 1.30-3.63, P = 0.003). The proportion of patients with life-threatening complications was lower in the combined group than in the non-combined group (4.4% vs. 11.2%, OR: 0.25, 95% CI: 0.08-0.78, P = 0.017). No marked differences were found between the groups in terms of other surgical or endocrine-related complications. However, the combined regimen exhibited a longer average surgery duration of 1.3 h (P < 0.001) and higher surgical costs of 22,000 CNY (approximate 3,000 USD, P = 0.022) compared with the non-combined approach. CONCLUSIONS: The combined regimen offered increased rates of total resection and decreased incidence of life-threatening complications, which might be recommended as the first-line choice for these patients.

Comparison of Nutritional Diversity in Five Fresh Legumes Using Flavonoids Metabolomics and Postharvest Botrytis cinerea Defense Analysis of Peas Mediated by Sakuranetin.

Legumes possess several bioactive nutrients, including flavonoids, and the study of the flavonoid profile of legumes is of great significance to human health. Using widely targeted metabolomics, we revealed the flavonoid profiles of five popular fresh legumes: cowpea, soybean, pea, fava bean, and kidney bean. A total of 259 flavonoids were identified, and the flavonoid accumulation patterns of the five legumes were remarkably different. In addition to analyzing common and species-specific flavonoids in the five legumes, we also generalized representative flavonoids of various subclasses. We related these to the health-promoting effects of legumes. Furthermore, legumes' total flavonoid content and antioxidant system activity were also detected. Intriguingly, sakuranetin, the sole flavonoid phytoalexin that can be induced by UV radiation, was detected only in the peas by metabolomics. Meanwhile, we found that UV treatment could significantly increase the sakuranetin content and the postharvest Botrytis cinerea resistance of pea pods. This study provides clues for the target diet, industrial development of legumes, and a new idea for the postharvest preservation of peas.