The correlation of the liquidus curves and valence electron structures of a ternary lithium halide molten-salt electrolyte for liquid metal batteries.

Liquid metal batteries have received considerable attention owing to their excellent properties. However, an electrolyte with low melting temperature is required to decrease operating temperature for the safety of liquid metal batteries and for saving energy. For revealing the mechanism of low liquefaction temperature, an empirical electron theory of solid molecules was used to study the thermal properties of pure lithium halides and their ternary-phase systems systematically. The theoretical bond lengths, melting points, liquefaction temperatures and mixed energies of pure lithium halides and their ternary phases match the experimental values well. The mechanism of liquefaction temperature for ternary lithium halides depends on their valence electron structures. The liquefaction temperature can be stabilized on a liquidus line or curve through the modulation of the constant number of covalent electrons (nc) and lattice electrons (nl). The liquefaction temperatures on various liquidus lines and curves are positively related to the linear density of valence electron pairs on the strong Li-X bond, bonding factor, and number of valence electrons in the s orbital but are negatively related to the number of valence electrons in the p orbital. With an increase in the linear density of the valence electron pair number and bonding factor, bond strength is enhanced, which increases the resistance of the strong Li-X bond against the break force induced by thermal phonon vibrations, and more thermal phonons with high vibrating energy are required for breaking the strongest Li-X bond at a higher temperature; therefore, the liquefaction temperature increases.

Clinical-proteomic classification and precision treatment strategy of chordoma.

Chordoma is a rare and heterogeneous mesenchymal malignancy, with distinct clinical and biological behaviors. Till now, its comprehensive clinical-molecular characteristics and accurate molecular classification remain obscure. In this research, we enroll 102 patients with chordoma and describe their clinical, imageological, and histopathological features. Through tandem mass tag-based proteomic analysis and nonnegative matrix factorization clustering, we classify chordoma into three molecular subtypes: bone microenvironment-dominant, mesenchymal-derived, and mesenchymal-to-epithelial transition-mediated pattern. The three subtypes exhibit discrete clinical prognosis and distinct biological attributes of osteoclastogenesis and immunogenicity, oxidative phosphorylation, and receptor tyrosine kinase activation, suggesting targeted therapeutic strategies of denosumab, S-Gboxin, and anlotinib, respectively. Notably, these approaches demonstrate positive treatment outcomes for each subtype in vitro and in vivo. Altogether, this work sheds light on the clinical-proteomic characteristics of chordoma and provides a candidate precision treatment strategy for chordoma according to molecular classification, underscoring their potential for clinical application.

Inhibition of TREM-1 ameliorates angiotensin II-induced atrial fibrillation by attenuating macrophage infiltration and inflammation through the PI3K/AKT/FoxO3a signaling pathway.

Inflammation and infiltration of immune cells are intricately linked to the pathogenesis of atrial fibrillation (AF). Triggering receptor expressed on myeloid cells-1 (TREM-1), an enhancer of inflammation, is implicated in various cardiovascular disorders. However, the precise role and potential mechanisms of TREM-1 in the development of AF remain ambiguous. Atrial samples from patients with AF were used to assess the expression levels of TREM-1. An angiotensin II (Ang II)-induced AF mouse model was established to assess the functionality of TREM-1. Cardiac function and AF inducibility were assessed through echocardiography, programmed transvenous cardiac pacing, and atrial electrophysiological mapping. Peripheral blood and atrial inflammatory cells were assessed using flow cytometry. Using histology, bulk RNA sequencing, biochemical analyses, and cell cultures, the mechanistic role of TREM-1 in AF was elucidated. TREM-1 expression was upregulated and co-localized with macrophages in the atria of patients with AF. Pharmacological inhibition of TREM-1 decreased Ang II-induced atrial enlargement and electrical remodeling. TREM-1 inhibition also ameliorated Ang II-induced NLRP3 inflammasome activation, inflammatory factor release, atrial fibrosis, and macrophage infiltration. Transcriptomic analysis revealed that TREM-1 modulates Ang II-induced inflammation through the PI3K/AKT/FoxO3a signaling pathway. In vitro studies further supported these findings, demonstrating that TREM-1 activation exacerbates Ang II-induced inflammation, while overexpression of FoxO3a counteracts this effect. This study discovered the critical role of TREM-1 in the pathogenesis of AF and its underlying molecular mechanisms. Inhibition of TREM-1 provides a new therapeutic strategy for the treatment of AF.

Acute Aerobic Exercise Intensity on Working Memory and Vigilance After Nap Deprivation: Effects of Low-Intensity Deserve Attention.

Background: Napping deprivation in habitual nappers leads to cognitive impairment. The ameliorative effect of acute aerobic exercise has been demonstrated for this post-cognitive impairment. However, it is still unclear which intensity of aerobic exercise is the most effective and how long this improvement can be sustained. Methods: Fifty-eight healthy adults with a chronic napping habit were randomly assigned to four intervention groups after undergoing nap deprivation: a sedentary control group, a low-intensity exercise group (50-59% maximum heart rate, HRmax), a moderate-intensity exercise group (60-69% HRmax), and a high-intensity exercise group (70-79% HRmax). Working memory (N-back task), vigilance (Psychomotor Vigilance Task, PVT), and response inhibitory capacity (Go/NoGo task) were measured. Results: Regression analyses showed a quadratic trend between exercise intensity and working memory reaction time and accuracy (F =3.297-5.769, p < 0.05, R2 =10.7-18.9%). The effects of exercise were optimal at low-intensity. There was a significant quadratic trend between exercise intensity and PVT lapse (F =4.314, p =0.042, R² =7.2%). The effect of exercise increased with higher intensity. Prolonged observation found that the effect of low-intensity exercise on working memory was maintained for 2 hours. Conclusion: The effect of low-intensity exercise might be underestimated. Low-intensity exercise significantly improved working memory performance, and the effects could be maintained throughout the afternoon. In contrast, the effects of high-intensity exercise were unlikely to be maintained and might even have negative effects. Future researchers can broaden the categories of participants to enhance the external validity and collect diverse physiological indicators to explore related physiological mechanisms.

A novel online calculator based on inflammation-related endotypes and clinical features to predict postoperative pulmonary infection in patients with cervical spinal cord injury.

BACKGROUND: Postoperative pulmonary infection (POI) of patients with cervical spinal cord injury (CSCI) is highly heterogeneous, while the potential endotypes and related risk factors remain unclear. METHODS: A retrospective collection of 290 CSCI patients was conducted from January 2010 to July 2024 using 1:1 propensity score matching to compare POI (n = 145) and non-POI (n = 145) groups. We generated laboratory examination data from admission patients and identified endotypes using unsupervised consensus clustering and machine learning. CSCI patients were randomly assigned to the training set (n = 203) and internal validation set (n = 87). A separate cohort comprising 245 CSCI patients were used for external validation. Independent predictors for POI were identified using univariate and multivariate logistic regression. A nomogram and an online calculator were developed and validated, both internally and externally. RESULTS: Two inflammation-related endotypes were identified: high inflammation endotype (endotype C1) and low inflammation endotype (endotype C2). Eight predictors for POI were identified (including age, operation duration, number of surgical segments, time between injury and surgery, preoperative steroid pulse, American Spinal Injury Association (ASIA) grade, smoking history, and inflammation-related endotype). A nomogram integrating the risk factors showed excellent discrimination in the training set (AUC, 0.976; 95% CI 0.956-0.996), internal validation set (AUC, 0.993; 95% CI 0.981-1.000), and external validation set (AUC, 0.799; 95%CI 0.744-0.854). Calibration curves demonstrated excellent fit, and decision curves highlighted its favorable clinical value. An online calculator (https://tjspine.shinyapps.io/dynnomapp/) was constructed to improve the convenience and efficiency of our prediction model. CONCLUSIONS: We identified inflammation-related endotype and constructed a web-based calculator for predicting POI in patients with CSCI, exhibiting excellent clinical utility.

sEV-mediated Lipid Droplets Transferred from Bone Marrow Adipocytes promote ferroptosis and impair Osteoblast Function.

Osteoporosis is linked to increased bone marrow adipocyte (BMAd) proliferation, which displaces bone-forming cells and alters the local environment. The impact of BMAd lipid droplets on bone health and osteoblast function remains unclear. This study investigates the interplay between BMAd-derived lipid droplets and osteoblast functionality, focusing on ferroptosis pathways. Osteoblast cultures were treated with conditioned media from adipocytes to simulate in vivo conditions. High-throughput mRNA sequencing and Western blot analysis were used to profile changes in gene expression and protein levels related to ferroptosis, oxidative phosphorylation, and osteogenic markers. Cellular assays assessed the direct impact of lipid droplets on osteoblast activity. Results showed that osteoblasts exposed to adipocyte-conditioned media had increased intracellular lipid droplet accumulation, upregulation of ferroptosis-related genes and proteins, and downregulation of oxidative phosphorylation and osteoblast differentiation markers. Treatment with ferroptosis inhibitors reversed the detrimental effects on osteoblasts, indicating the functional relevance of this pathway in osteoporosis. BMAd-derived lipid droplets contribute to osteoblast dysfunction through ferroptosis induction. Inhibiting ferroptosis could preserve osteoblast function and combat osteoporosis-related bone issues, suggesting that modulating lipid metabolism and redox balance in bone cells may be promising for future treatments.

XPO1 serves as a prognostic marker involving AKT/MAPK/TGFBR1 pathway in OSCC.

BACKGROUND: Exportin 1 (XPO1) is a nuclear export protein that facilitates the transportation of various substances. XPO1 promotes tumor development as a poor prognostic factor in a variety of tumors and is a therapeutic target for screening inhibitors. However, the role of XPO1 in oral squamous cell carcinoma (OSCC) has yet to be determined. METHODS: The expression patterns of XPO1 mRNA in OSCC were investigated using bioinformatics tools, and the expression levels of XPO1 protein in OSCC specimens were confirmed by immunohistochemical assays. Survival analysis was conducted to evaluate the impact of XPO1 on prognosis. GO and KEGG enrichment analyses were utilized to uncover the signaling pathways mediated by XPO1. Additionally, we examined the association between XPO1 and AKT/MAPK/TGFBR1 and immune infiltration. RESULTS: XPO1 mRNA and protein expression levels were significantly enhanced in OSCC and associated with OSCC severity. Enhanced XPO1 expression was indicative of poor survival. Functional analysis showed that XPO1 mediated pathways associated with cell cycle and DNA replication and reduced immune infiltration in OSCC. Additionally, XPO1 mRNA and protein expression levels had significant positive relationships with AKT/MAPK/TGFBR1. CONCLUSIONS: XPO1, as a marker of poor prognosis in OSCC, can promote OSCC through AKT/MAPK/TGFBR1.

Causal relationships between GLP1 receptor agonists, blood lipids, and heart failure: a drug-target mendelian randomization and mediation analysis.

BACKGROUND: Glucagon-like peptide-1 receptor (GLP1R) agonists have been shown to reduce major cardiovascular events in diabetic patients, but their role in heart failure (HF) remains controversial. Recent evidence implies their potential benefits on cardiometabolism such as lipid metabolism, which may contribute to lowering the risk of HF. Consequently, we designed a Mendelian randomization (MR) study to investigate the causal relationships of circulating lipids mediating GLP1R agonists in HF. METHODS: The available cis-eQTLs for GLP1R target gene were selected as instrumental variables (IVs) of GLP1R agonism. Positive control analyses of type 2 diabetes mellitus (T2DM) and body mass index (BMI) were conducted to validate the enrolled IVs. Two-sample MR was performed to evaluate the associations between GLP1R agonism and HF as well as left ventricular ejection fraction (LVEF). Summary data for HF and LVEF were obtained from two genome-wide association studies (GWASs), which included 977,323 and 40,000 individuals of European ancestry, respectively. The primary method employed was the random-effects inverse variance weighted, with several other methods used for sensitivity analyses, including MR-Egger, MR PRESSO, and weighted median. Additionally, multivariable MR and mediation MR were applied to identify potentially causal lipid as mediator. RESULTS: A total of 18 independent IVs were included. The positive control analyses showed that GLP1R agonism significantly reduced the risk of T2DM (OR = 0.79, 95% CI = 0.75-0.85, p < 0.0001) and decreased BMI (OR = 0.95, 95% CI = 0.93-0.96, p < 0.0001), ensuring the effectiveness of selected IVs. We found favorable evidence to support the protective effect of GLP1R agonism on HF (OR = 0.75, 95% CI = 0.71-0.79, p < 0.0001), but there was no obvious correlation with increased LVEF (OR = 1.01, 95% CI = 0.95-1.06, p = 0.8332). Among the six blood lipids, only low-density lipoprotein cholesterol (LDL-C) was both associated with GLP1R agonism and HF. The causal effect of GLP1R agonism on HF was partially mediated through LDL-C by 4.23% of the total effect (95% CI = 1.04-7.42%, p = 0.0093). CONCLUSIONS: This study supported the causal relationships of GLP1R agonists with a reduced risk of HF. LDL-C might be the mediator in this association, highlighting the cardiometabolic benefit of GLP1R agonists on HF.

The severity of preoperative bone marrow oedema negatively influences short-term clinical outcomes following arthroscopic bone marrow stimulation for osteochondral lesions of the talus.

PURPOSE: The purpose of this study was to study the effects of the severity of preoperative bone marrow oedema (BME) on the postoperative short-term outcomes following bone marrow stimulation (BMS) for osteochondral lesions of the talus (OLTs) and to propose a new metric that combines volume and signal density to evaluate BME. METHODS: Sixty-five patients with symptomatic OLTs (<100 mm2) and preoperative BME, who received BMS in our institution from April 2017 to July 2021 with follow-ups of 3, 6 and 12 months, were analysed retrospectively. The area, volume and signal value of the BME were collected on preoperative magnetic resonance imaging. The enroled patients were divided into two groups according to the BME index (BMEI), which was defined as the product of oedema relative signal intensity and the relation of oedema volume to total talar volume. Visual analogue scale, American Orthopedic Foot and Ankle Society (AOFAS), Tegner, Foot and Ankle Ability Measure (FAAM)-activities of daily living (ADL) and Sports scores were assessed before surgery and at each follow-up. The relationship between the scores and the volume, relative signal intensity and BMEI was explored. RESULTS: Sixty-five patients with preoperative BME were divided into the mild (n = 33) and severe (n = 32) groups based on the BMEI. A significant difference was found for each score with the general linear model for repeated measures through all follow-up time points (p < 0.001). For the preoperative and 12-month postoperative changes of the enroled patients, 53 patients (81.5%) exceeded the minimal clinically important difference of AOFAS and 26 (40.0%) exceeded that of FAAM-sports in this study. The mild group showed significantly more improvement in AOFAS scores at 12 months (89.6 ± 7.0 vs. 86.2 ± 6.2) and FAAM-ADL scores at 6 months (83.6 ± 7.6 vs. 79.7 ± 7.7) and 12 months (88.5 ± 8.5 vs. 84.4 ± 7.7) than the severe group (p < 0.05). No significant difference of all the scores between the groups was found at 3 months. No significant correlation was found in each group between BMEI and clinical outcomes. CONCLUSION: The severity of the preoperative BME negatively affected short-term clinical outcomes following arthroscopic BMS for OLTs. Worse clinical outcomes were shown at postoperative 6 and 12 months in patients with a high preoperative BMEI, which could be a favourable parameter for assessing the severity of BME and assist in developing personalised rehabilitation plans and determining the approach and timing of surgery. LEVEL OF EVIDENCE: Level III.

Subfunctionalisation and self-repression of duplicated E1 homologues finetunes soybean flowering and adaptation.

Soybean is a photoperiod-sensitive staple crop. Its photoperiodic flowering has major consequences for latitudinal adaptation and grain yield. Here, we identify and characterise a flowering locus named Time of flower 4b (Tof4b), which encodes E1-Like b (E1Lb), a homologue of the key soybean floral repressor E1. Tof4b protein physically associates with the promoters of two FLOWERING LOCUS T (FT) genes to repress their transcription and delay flowering to impart soybean adaptation to high latitudes. Three E1 homologues undergo subfunctionalisation and show differential subcellular localisation. Moreover, they all possess self-repression capability and each suppresses the two homologous counterparts. Subfunctionalisation and the transcriptional regulation of E1 genes collectively finetune flowering time and high-latitude adaptation in soybean. We propose a model for the functional fate of the three E1 genes after the soybean whole-genome duplication events, refine the molecular mechanisms underlying high-latitude adaption, and provide a potential molecular-breeding resource.

Alleviation of Salt Stress and Changes in Glycyrrhizic Acid Accumulation by Dark Septate Endophytes in Glycyrrhiza glabra Grown under Salt Stress.

This study aimed to investigate the mechanisms by which dark septate endophytes (DSE) regulate salt tolerance and the accumulation of bioactive constituents in licorice. First, the salt stress tolerance and resynthesis with the plant effect of isolated DSE from wild licorice were tested. Second, the performance of licorice inoculated with DSE, which had the best salt-tolerant and growth-promoting effects, was examined under salt stress. All isolated DSE showed salt tolerance and promoted plant growth, withCurvularia lunata D43 being the most effective. Under salt stress, C. lunata D43 could promote growth, increase antioxidant enzyme activities, enhance glycyrrhizic acid accumulation, improve key enzyme activities in the glycyrrhizic acid synthesis pathway, and induce the expression of the key enzyme gene and salt tolerance gene of licorice. The structural equation model demonstrated that DSE alleviate the negative effects of salt stress through direct and indirect pathways. Variations in key enzyme activities, gene expression, and bioactive constituent concentration can be attributed to the effects of DSE. These results contribute to revealing the value of DSE for cultivating medicinal plants in saline soils.

Recovery of Metal Ions (Cd2+, Co2+, and Ni2+) from Nitrate and Sulfate on Laser-Induced Graphene Film Using Applied Voltage and Its Application.

The urgent removal of Cd, Co, and Ni from nitrate and sulfate is essential to mitigate the potential risk of chemical pollution from large volumes of industrial wastewater. In this study, these metal ions were rapidly recovered through applying voltage on nitrate and sulfate, utilizing laser-induced graphene/polyimide (LIG/PI) film as the electrode. Following the application of external voltage, both the pH value and conductivity of the solution undergo changes. Compared to Co2+ and Ni2+, Cd2+ exhibits a lower standard electrode potential and stronger reducibility. Consequently, in both nitrate and sulfate solutions, the reaction sequence follows the order of Cd2+ > Co2+ > Ni2+, with the corresponding electrode adsorption quantities in the order of Cd2+ > Co2+ ~ Ni2+. Additionally, using the recovered Co(OH)2 as the raw material, a LiCoO2 composite was prepared. The assembled battery with this composite exhibited a specific capacity of 122.8 mAh g-1, meeting practical application requirements. This research has significance for fostering green development.

Unsupervised domain adaptation based on feature and edge alignment for femur X-ray image segmentation.

The gold standard for diagnosing osteoporosis is bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry (DXA). However, various factors during the imaging process cause domain shifts in DXA images, which lead to incorrect bone segmentation. Research shows that poor bone segmentation is one of the prime reasons of inaccurate BMD measurement, severely affecting the diagnosis and treatment plans for osteoporosis. In this paper, we propose a Multi-feature Joint Discriminative Domain Adaptation (MDDA) framework to improve segmentation performance and the generalization of the network in domain-shifted images. The proposed method learns domain-invariant features between the source and target domains from the perspectives of multi-scale features and edges, and is evaluated on real data from multi-center datasets. Compared to other state-of-the-art methods, the feature prior from the source domain and edge prior enable the proposed MDDA to achieve the optimal domain adaptation performance and generalization. It also demonstrates superior performance in domain adaptation tasks on small amount datasets, even using only 5 or 10 images. In this study, MDDA provides an accurate bone segmentation tool for BMD measurement based on DXA imaging.

Soybean hypocotyl elongation is regulated by a MYB33-SWEET11/21-GA2ox8c module involving long-distance sucrose transport.

The length of hypocotyl affects the height of soybean and lodging resistance, thus determining the final grain yield. However, research on soybean hypocotyl length is scarce, and the regulatory mechanisms are not fully understood. Here, we identified a module controlling the transport of sucrose, where sucrose acts as a messenger moved from cotyledon to hypocotyl, regulating hypocotyl elongation. This module comprises four key genes, namely MYB33, SWEET11, SWEET21 and GA2ox8c in soybean. In cotyledon, MYB33 is responsive to sucrose and promotes the expression of SWEET11 and SWEET21, thereby facilitating sucrose transport from the cotyledon to the hypocotyl. Subsequently, sucrose transported from the cotyledon up-regulates the expression of GA2ox8c in the hypocotyl, which ultimately affects the length of the hypocotyl. During the domestication and improvement of soybean, an allele of MYB33 with enhanced abilities to promote SWEET11 and SWEET21 has gradually become enriched in landraces and cultivated varieties, SWEET11 and SWEET21 exhibit high conservation and have undergone a strong purified selection and GA2ox8c is under a strong artificial selection. Our findings identify a new molecular pathway in controlling soybean hypocotyl elongation and provide new insights into the molecular mechanism of sugar transport in soybean.

Mechanistic analyses reveal that Pueraria montana var. lobata (Willd.) is effective in inhibiting ovarian cancer progression.

Ovarian cancer (OC) is a common malignancies of the female genitalia. P. montana var. lobata (Willd.), a herb with anti-tumor effects, is widely used in the clinical treatment of ovarian cancer (OC), but the ingredients and molecular mechanism of action remains to be explored. In this study, we extracted the main active ingredients of P. montana var. lobata (Willd.) from the TCMSP database, and predicted its potential targets of action against OC from the DisGeNET and GeneCards databases. Protein-protein interaction (PPI) was constructed using the STRING database, while pathway enrichment analyses were performed using the DAVID database. Next, we generated an Ingredient-Target-Pathway network using Cytoscape 3.7.2, then processed the key targets of action and main active ingredients for molecular docking. The results showed that seven active ingredients of P montana var. lobata (Willd.) were associated with treating for OC, namely beta-sitosterol, coumestrol, daidzein, formononetin, genistein, puerarin and scoparone, two important targets Casp3 and Jun, and signaling pathways of P. montana var. lobata (Willd.) against the progression of OC. TUNEL staining, enzyme-linked immunosorbent assay (ELISA), and Western blot assays, the pharmacodynamic effect of puerarin in the treatment of OC and the major targets were verified. Animal experiment demonstrated that application of puerarin at different times of modeling not only upregulated expression of Casp3, Smac, and c-jun proteins, but also promoted apoptosis in tumor cells, hence inhibiting progression of OC. This study demonstrates that P. montana var. lobata (Willd.) can thereby induce apoptosis in tumor cells and inhibit malignant progression through activating expression of Casp3, smac, and c-jun proteins to regulate related apoptosis pathways, as validated by network pharmacology predictions and animal experiments, and can be verifed by large-scale clinical trials in the future. This study also provides theoretical support and new research perspectives for this disease.

Analysis of chemoresistance characteristics and prognostic relevance of postoperative gemcitabine adjuvant chemotherapy in pancreatic cancer.

AIM: To investigate the relationship between chemoresistance in pancreatic cancer patients receiving postoperative gemcitabine adjuvant therapy and specific clinical/pathological characteristics, as well as its impact on patient prognosis. METHODS: From June 2018 to June 2021, clinical and pathological data of 148 pancreatic cancer patients were collected, and 101 patients were followed up for tumor recurrence/metastasis and survival status. The correlation between chemoresistance and specific clinical/pathological characteristics or patient prognosis was retrospectively analyzed. RESULTS: Of the 148 patients, 78 were in the chemoresistance group and 70 in the non-chemoresistance group. Univariate analysis showed that the development of chemoresistance may be related to patient age, combined diabetes, preoperative CA19-9 level, tumor size, AJCC stage, vascular invasion, and positive lymph node ratio. Furthermore, subsequent multivariate analysis incorporating these variables indicated that tumor size may be a key factor influencing chemoresistance (p < 0.001, OR = 1.584). Log-rank test showed patients in the chemoresistance group had worse overall survival (OS) (HR = 2.102, p = 0.018) and progression free survival (PFS) (HR = 3.208, p = 0.002) than patients in the non-chemoresistance group; and patients with smaller size tumors (diameter ≤3 cm) had significantly better OS (HR = 2.923, p < 0.001) and PFS (HR = 2.930, p = 0.003) than those with larger size tumors (diameter >3 cm). CONCLUSIONS: Patients with pancreatic cancer receiving postoperative gemcitabine adjuvant therapy are more likely to develop chemoresistance when their tumor sizes are larger (diameter >3 cm). Development of chemoresistance exacerbates the prognosis of patients with pancreatic cancer, and larger tumor size is also a risk factor for poor prognosis in these patients.

Programmably engineered stochastic RNA nanowalker for ultrasensitive miRNA detection.

A programmably engineered stochastic RNA nanowalker powered by duplex-specific nuclease (DSN) is developed. By utilizing poly-adenine-based spherical nucleic acids (polyA-SNA) to accurately regulate the densities of DNA tracks, the nanowalker showcases its capability to identify miRNA-21, miRNA-486, and miRNA-155 with quick kinetics and attomolar sensitivity, positioning it as a promising option for cancer clinical surveillance.

Effect of Cigarette Smoking on Postoperative Outcomes After Arthroscopic Bone Marrow Stimulation for Osteochondral Lesions of the Talus.

BACKGROUND: Bone marrow stimulation (BMS) is presently considered first-line surgical treatment for osteochondral lesions of the talus (OLTs); however, some patients still experience pain or dysfunction after surgery, and the reasons for success or failure remain somewhat unclear. This study aimed to investigate the effect of smoking on postoperative outcomes after arthroscopic BMS for OLTs. METHODS: Consecutive patients with OLTs who underwent BMS between January 2017 and January 2020 were included. Smokers were defined as patients who actively consumed cigarettes before surgery and postoperatively, whereas nonsmokers were patients who never smoked. Visual analog scale (VAS), American Orthopaedic Foot & Ankle Society ankle hindfoot score (AOFAS), Karlsson-Peterson, and Tegner scores were assessed preoperatively and at follow-up. Additionally, a general linear model (GLM) was performed, followed by the interaction analysis to explore the potential influence of smoking. RESULTS: The study enrolled 104 patients with a mean follow-up of 30.91 ± 7.03 months, including 28 smokers and 76 nonsmokers. There were no significant differences in patient age (35.2 ± 10.0 years vs 37.6 ± 9.7 years, P = .282) or OLT area (63.7 ± 38.7 mm2 vs 52.8 ± 37.0 mm2, P = .782). Both univariate analysis and GLM revealed that smoking was associated with worse postoperative pain levels, Karlsson-Peterson, and AOFAS scores (P < .05). The interaction analysis showed a significant interaction between smoking and OLT area for postoperative Karlsson-Peterson scores (general ankle function) (P = .031). Simple main effects analysis revealed that the negative effect of smoking on Tegner score significantly increased among patients >32 years old or with OLT area>50 mm2 (P < .05). CONCLUSION: Smoking was associated with worse clinical outcomes following BMS of OLTs. As the size of OLTs increased, the difference in general ankle function between smokers and nonsmokers also increased. Furthermore, smokers who were older than 32 years or had larger OLTs were less likely to resume participation in high-level activities.

Low Serum Apolipoprotein A1 Levels Impair Antitumor Immunity of CD8+ T Cells via the HIF-1α-Glycolysis Pathway.

An immunosuppressive microenvironment promotes the occurrence and development of tumors. Low apolipoprotein A1 (ApoA1) is closely related to tumor development, but the underlying mechanisms are unclear. This study investigated the association between serum ApoA1 levels and the immune microenvironment in endometrial, ovarian, and lung cancers. The serum ApoA1 level was decreased significantly in patients with endometrial and ovarian cancers compared with healthy controls. In endometrial cancer (EC) tissues, the low serum ApoA1 level group showed increased CD163+ macrophage infiltration and decreased CD8+ T-cell infiltration compared with the normal serum ApoA1 group. Compromised tumor-infiltrating CD8+ T-cell functions and decreased CD8+ T-cell infiltration also were found in tumor-bearing Apo1-knockout mice. CD8+ T-cell depletion experiments confirmed that ApoA1 exerted its antitumor activity in a CD8+ T-cell-dependent manner. In vitro experiments showed that the ApoA1 mimetic peptide L-4F directly potentiated the antitumor activity of CD8+ T cells via a HIF-1α-mediated glycolysis pathway. Mechanistically, ApoA1 suppressed ubiquitin-mediated degradation of HIF-1α protein by downregulating HIF-1α subunit α inhibitor. This regulatory process maintained the stability of HIF-1α protein and activated the HIF-1α signaling pathway. Tumor-bearing Apoa1 transgenic mice showed an increased response to anti-PD-1 therapy, leading to reduced tumor growth along with increased infiltration of activated CD8+ T cells and enhanced tumor necrosis. The data reported herein demonstrate critical roles for ApoA1 in enhancing CD8+ T-cell immune functions via HIF-1α-mediated glycolysis and support clinical investigation of combining ApoA1 supplementation with anti-PD-1 therapy for treating cancer.

Both arthroscopic one-step Broström-Gould and Lasso-loop stitch techniques achieved favourable clinical outcomes for chronic lateral ankle instability.

PURPOSE: Both the arthroscopic Broström-Gould and Lasso-loop stitch techniques are commonly used to treat chronic lateral ankle instability (CLAI). The purpose of this study is to introduce an arthroscopic one-step outside-in Broström-Gould (AOBG) technique and compare the mid-term outcomes of the AOBG technique and Lasso-loop stitch technique. METHODS: All CLAI patients who underwent arthroscopic lateral ankle stabilization surgery in our department from 2018 to 2019 were retrospectively enrolled. The patients were divided into two groups according to the surgical methods employed: the AOBG technique (Group A) and the Lasso-loop technique (Group B). The visual analogue scale pain score, American Orthopaedic Foot and Ankle Society ankle hindfoot score, Tegner activity score and Karlsson-Peterson score were evaluated preoperatively and during the follow-up from June to December 2022. The surgical duration, return to sports, sprain recurrence and surgical complications were also recorded and compared. RESULTS: A total of 74 patients (Group A, n = 42; Group B, n = 32) were included in this study with a mean follow-up of 39 months. No statistically significant differences were observed in demographic parameters or follow-up time between the two groups. Postoperative clinical scores indicated a significant improvement (all with p < 0.001) with no significant difference between the two groups (not significant [n.s.]). There was no significant difference in the surgical duration (46.1 vs. 49.7 min, n.s.), return to sports (92.9% vs. 93.8%, n.s.), or sprain recurrence (4.8% vs. 6.3%, n.s.). Only two cases in Group A reported knot irritation (4.8% vs. 0, n.s.), and one case in Group A experienced local skin numbness (0 vs. 3.1%, n.s.), with no significant difference. CONCLUSION: Both the AOBG and Lasso-loop stitch techniques yielded comparable favourable mid-term outcomes and return to sports with a low rate of surgical complications. Both procedures could be feasible strategies for CLAI patients. LEVEL OF EVIDENCE: Level III.