Thickness- and Field-Dependent Magnetic Domain Evolution in van der Waals Fe3GaTe2.

The discovery of room-temperature ferromagnetism in van der Waals (vdW) materials opens new avenues for exploring low-dimensional magnetism and its applications in spintronics. Recently, the observation of the room-temperature topological Hall effect in the vdW ferromagnet Fe3GaTe2 suggests the possible existence of room-temperature skyrmions, yet skyrmions have not been directly observed. In this study, real-space imaging was employed to investigate the domain evolution of the labyrinth and skyrmion structure. First, Néel-type skyrmions can be created at room temperature. In addition, the influence of flake thickness and external magnetic field (during field cooling) on both labyrinth domains and the skyrmion lattice is unveiled. Due to the competition between magnetic anisotropy and dipole interactions, the specimen thickness significantly influences the density of skyrmions. These findings demonstrate that Fe3GaTe2 can host room-temperature skyrmions of various sizes, opening up avenues for further study of magnetic topological textures at room temperature.

Mitochondrial energy metabolism in diabetic cardiomyopathy: Physiological adaption, pathogenesis, and therapeutic targets.

ABSTRACT: Diabetic cardiomyopathy is defined as abnormal structure and function of the heart in the setting of diabetes, which could eventually develop heart failure and leads to the death of the patients. Although blood glucose control and medications to heart failure show beneficial effects on this disease, there is currently no specific treatment for diabetic cardiomyopathy. Over the past few decades, the pathophysiology of diabetic cardiomyopathy has been extensively studied, and an increasing number of studies pinpoint that impaired mitochondrial energy metabolism is a key mediator as well as a therapeutic target. In this review, we summarize the latest research in the field of diabetic cardiomyopathy, focusing on mitochondrial damage and adaptation, altered energy substrates, and potential therapeutic targets. A better understanding of the mitochondrial energy metabolism in diabetic cardiomyopathy may help to gain more mechanistic insights and generate more precise mitochondria-oriented therapies to treat this disease.

Antifungal Activity and Mechanism of 4-Propylphenol Against Fusarium graminearum, Agent of Wheat Scab, and Its Potential Application.

Fusarium head blight (FHB), caused by Fusarium graminearum, is a predominant disease of wheat. Due to the lack of disease-resistant germplasm, chemical control is an important means to control wheat scab. Volatile substances produced in near-isogenic wheat lines were detected after inoculation with F. graminearum, and 4-propylphenol, which appears in FHB-resistant lines, was identified. In vitro and in vivo antifungal activity tests demonstrate that 4-propylphenol effectively inhibits the mycelial growth of F. graminearum. Metabolomics analysis showed changes in glutathione metabolism, indicating that 4-propylphenol triggered reactive oxygen species (ROS) stress. This was consistent with the increasing ROS levels in Fusarium cells treated with 4-propylphenol. Further results demonstrated that excessive accumulation of ROS induced DNA and cell membrane damage in the mycelium. Moreover, 4-propylphenol showed different degrees of inhibition against other soil-borne pathogens (fungi and oomycetes). These findings illustrated that 4-propylphenol has broad spectrum and high antifungal activity and should be considered for use as an ecological fungicide.

Application of NIRS for hay evaluation at different degrees of sample preparation.

Objective: A study compared the performance of the NIRS (Near-Infrared Spectroscopy) calibration models developed with different degrees of hay sample preparations. Methods: Spectral data of 1-mm ground or whole hay samples were regressed against wet chemistry results of moisture, NDF (neutral detergent fiber), ADF (acid detergent fiber), CP (crude protein), and IVDMD (in vitro dry matter digestibility). A total of 227 imported alfalfa (Medicago sativa L.) and another 360 timothy (Phleum pratense L.) hay samples were used to develop the calibration models. The models developed with ground hay samples were more robust and accurate than whole hay based on cross-validation's R2 (coefficient of determination), standard error, and RPD (ratio percentage deviation). Results: The R2 of cross-validation ranged from 0.61 (moisture of alfalfa) to 0.95 (CP prediction of timothy). Although R2 of calibration models was mainly greater than 0.90, the R2 of cross-validations remained marginal. Conclusion: Estimation of nutrient concentrations in imported hay can be achieved by calibrated NIRS. The NIRS calibration models must be improved by including more imported hay samples from different years and origins. Although the analysis accuracy of NIRS was substantially higher when calibration models were developed with ground samples, less sample preparation will be more advantageous for achieving rapid delivery of hay sample analysis results. Therefore, further research warrants investigating the level of sample preparation inputs compromising analysis accuracy by NIRS.

N6-methyladenosine mRNA methylation positively regulated the response of poplar to salt stress.

As the most abundant form of methylation modification in messenger RNA (mRNA), the distribution of N6-methyladenosine (m6A) has been preliminarily revealed in herbaceous plants under salt stress, but its function and mechanism in woody plants were still unknown. Here, we showed that global m6A levels increased during poplar response to salt stress. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) revealed that m6A significantly enriched in the coding sequence region and 3'-untranslated regions in poplar, by recognising the conserved motifs, AGACU, GGACA and UGUAG. A large number of differential m6A transcripts have been identified, and some have been proved involving in salt response and plant growth and development. Further combined analysis of MeRIP-seq and RNA-seq revealed that the m6A hypermethylated and enrich in the CDS region preferred to positively regulate expression abundance. Writer inhibitor, 3-deazaneplanocin A treatment increased the sensitivity of poplar to salt stress by reducing mRNA stability to regulate the expression of salt-responsive transcripts PagMYB48, PagGT2, PagNAC2, PagGPX8 and PagARF2. Furthermore, we verified that the methyltransferase PagFIP37 plays a positively role in the response of poplar to salt stress, overexpressed lines have stronger salt tolerance, while RNAi lines were more sensitive to salt, which relied on regulating mRNA stability in an m6A manner of salt-responsive transcripts PagMYB48, PagGT2, PagNAC2, PagGPX8 and PagARF2. Collectively, these results revealed the regulatory role of m6A methylation in poplar response to salt stress, and revealed the importance and mechanism of m6A methylation in the response of woody plants to salt stress for the first time.

Efficacy and Safety of Oral Propranolol or Topical Timolol for the Treatment of Superficial Infantile Hemangiomas.

Infantile hemangiomas (IHs) are the most common benign soft tissue tumors of infancy. Oral propranolol has become a first-line treatment option since the unexpected discovery of its surprising efficacy in the treatment of IHs in 2008. However, oral propranolol causes systemic complications, including hypotension, bradycardia, and hypoglycemia. To minimize systemic adverse effects of oral propranolol, timolol maleate, a nonselective ß-blocker similar to propranolol, has been used as a topical agent to treat superficial IHs. The authors evaluated the efficacy and safety of oral propranolol or topical timolol in 60 patients with IHs. Of the 60 patients recruited, 30 patients were treated using orally administrated propranolol and an additional 30 patients received topical timolol. The efficacy rate of the oral propranolol and topical timolol was 96.7% and 93.3%, respectively. There were no significant differences between the two treatment patterns for the efficacy rate. The incidence of systemic adverse effects for patients treated with oral propranolol was significantly higher than that for cases received topically timolol treatment. Topical timolol maleate is effective and well-tolerated in the treatment of IHs. It could be considered as the first-line treatment choice, especially for superficial IHs.

Kisspeptin-10 binding to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated dephosphorylation of Src.

Osteoclasts are over-activated as we age, which results in bone loss. Src deficiency in mice leads to severe osteopetrosis due to a functional defect in osteoclasts, indicating that Src function is essential in osteoclasts. G-protein-coupled receptors (GPCRs) are the targets for ∼35% of approved drugs but it is still unclear how GPCRs regulate Src kinase activity. Here, we reveal that GPR54 activation by its natural ligand Kisspeptin-10 (Kp-10) causes Dusp18 to dephosphorylate Src at Tyr 416. Mechanistically, Gpr54 recruits both active Src and the Dusp18 phosphatase at its proline/arginine-rich motif in its C terminus. We show that Kp-10 binding to Gpr54 leads to the up-regulation of Dusp18. Kiss1, Gpr54 and Dusp18 knockout mice all exhibit osteoclast hyperactivation and bone loss, and Kp-10 abrogated bone loss by suppressing osteoclast activity in vivo. Therefore, Kp-10/Gpr54 is a promising therapeutic target to abrogate bone resorption by Dusp18-mediated Src dephosphorylation.

mRNA-Laden Lipid-Nanoparticle-Enabled in Situ CAR-Macrophage Engineering for the Eradication of Multidrug-Resistant Bacteria in a Sepsis Mouse Model.

Sepsis, which is the most severe clinical manifestation of acute infection and has a mortality rate higher than that of cancer, represents a significant global public health burden. Persistent methicillin-resistant Staphylococcus aureus (MRSA) infection and further host immune paralysis are the leading causes of sepsis-associated death, but limited clinical interventions that target sepsis have failed to effectively restore immune homeostasis to enable complete eradication of MRSA. To restimulate anti-MRSA innate immunity, we developed CRV peptide-modified lipid nanoparticles (CRV/LNP-RNAs) for transient in situ programming of macrophages (MΦs). The CRV/LNP-RNAs enabled the delivery of MRSA-targeted chimeric antigen receptor (CAR) mRNA (SasA-CAR mRNA) and CASP11 (a key MRSA intracellular evasion target) siRNA to MΦs in situ, yielding CAR-MΦs with boosted bactericidal potency. Specifically, our results demonstrated that the engineered MΦs could efficiently phagocytose and digest MRSA intracellularly, preventing immune evasion by the "superbug" MRSA. Our findings highlight the potential of nanoparticle-enabled in vivo generation of CAR-MΦs as a therapeutic platform for multidrug-resistant (MDR) bacterial infections and should be confirmed in clinical trials.

Charting Single Cell Lineage Dynamics and Mutation Networks via Homing CRISPR.

Single cell lineage tracing, essential for unraveling cellular dynamics in disease evolution is critical for developing targeted therapies. CRISPR-Cas9, known for inducing permanent and cumulative mutations, is a cornerstone in lineage tracing. The novel homing guide RNA (hgRNA) technology enhances this by enabling dynamic retargeting and facilitating ongoing genetic modifications. Charting these mutations, especially through successive hgRNA edits, poses a significant challenge. Our solution, LINEMAP, is a computational framework designed to trace and map these mutations with precision. LINEMAP meticulously discerns mutation alleles at single-cell resolution and maps their complex interrelationships through a mutation evolution network. By utilizing a Markov Process model, we can predict mutation transition probabilities, revealing potential mutational routes and pathways. Our reconstruction algorithm, anchored in the Markov model's attributes, reconstructs cellular lineage pathways, shedding light on the cell's evolutionary journey to the minutiae of single-cell division. Our findings reveal an intricate network of mutation evolution paired with a predictive Markov model, advancing our capability to reconstruct single-cell lineage via hgRNA. This has substantial implications for advancing our understanding of biological mechanisms and propelling medical research forward.

Global burden of diabetes mellitus from 1990 to 2019 attributable to dietary factors: An analysis of the Global Burden of Disease Study 2019.

AIMS: To analyse spatial and temporal changes in the global burden of diabetes mellitus (DM) attributable to dietary factors from 1990 to 2019. MATERIALS AND METHODS: The burden of DM was analysed in terms of age-standardized disability-adjusted life-year (DALY) rates and age-standardized death rates (ASDRs), which were obtained from the Global Burden of Disease Study 2019, and their corresponding estimated annual percentage changes (EAPCs). RESULTS: The ASDR exhibited a decreasing trend (EAPC = -0.02), while the age-standardized DALY rate exhibited an increasing trend (EAPC = 0.65). Forty-four percent of the burden of DM was attributable to dietary factors, with the three largest contributors being high intake of red meat, high intake of processed meat, and low intake of fruit. Residence in a region with a high sociodemographic index (SDI) was associated with a diet low in whole grains and high in red meat and processed meat, while residence in a low-SDI region was associated with a diet low in whole grains and fruits, and high in red meat. CONCLUSIONS: The age-standardized DALYs of DM attributable to dietary factors increased between 1990 and 2019 but differed among areas. The three largest dietary contributors to the burden of DM were high intake of red meat, high intake of processed meat, and low intake of fruit.

Effects of 2-Phenylethanol on Controlling the Development of Fusarium graminearum in Wheat.

Applying plant-derived fungicides is a safe and sustainable way to control wheat scab. In this study, volatile organic compounds (VOCs) of wheat cultivars with and without the resistance gene Fhb1 were analyzed by GC-MS, and 2-phenylethanol was screened out. The biocontrol function of 2-phenylethanol on Fusarium graminearum was evaluated in vitro and in vivo. Metabolomics analysis indicated that 2-phenylethanol altered the amino acid pathways of F. graminearum, affecting its normal life activities. Under SEM and TEM observation, the mycelial morphology changed, and the integrity of the cell membrane was destroyed. Furthermore, 2-phenylethanol could inhibit the production of mycotoxins (DON, 3-ADON, 15-ADON) by F. graminearum and reduce grain contamination. This research provides new ideas for green prevention and control of wheat FHB in the field.

Grouping motivational interviewing is only effective for younger patients with alcohol dependence in the rehabilitation stage.

Alcohol dependence (AD) is a risk factor for death and disability. Relapse prevention for AD has been exclusively dominated by psychotherapy intervention for many years. Our study aimed to investigate the efficacy of group motivational interviewing (MI) on the psychological craving for alcohol and depressive symptoms in AD patients in the rehabilitation phase, as well as the impact of age. The participants included 108 individuals with AD in the rehabilitation phase. All participants were assigned to the MI intervention group or the control group and were treated for 6 weeks. The severity of psychological craving for alcohol was assessed by the Penn Alcohol Craving Scale (PACS), and psychological status was evaluated by the Hamilton Depression Rating Scale (HAMD). We found that group MI significantly reduced the psychological craving for alcohol in patients with AD in the rehabilitation phase (p < 0.05). In addition, when patients were divided into two groups according to their ages, we found that group MI interventions tended to be effective only in younger patients with AD, but not in older patients. Our findings provide further evidence that the efficacy of group MI interventions was influenced by the age of patients with AD in the rehabilitation stage.

Nicorandil Regulates Ferroptosis and Mitigates Septic Cardiomyopathy via TLR4/SLC7A11 Signaling Pathway.

This study mainly explored the role of nicorandil in regulating ferroptosis and alleviating septic cardiomyopathy through toll-like receptor (TLR) 4/solute carrier family 7 member 11 (SLC7A11) signaling pathway. Twenty-four male SD rats were randomly divided into control, Nic (nicorandil), LPS (lipopolysaccharide), and LPS + Nic groups and given echocardiography. A detection kit was applied to measure the levels of lactic dehydrogenase (LDH), cardiac troponin I (cTnI), and creatine kinase-MB (CK-MB); HE staining and the levels of glutathione (GSH), malondialdehyde (MDA), total iron, and Fe2+ of myocardial tissues were detected. Moreover, the expression of TLR4 and SLC7A11 were measured by qRT-PCR and the proteins regulating ferroptosis (TLR4, SLC7A11, GPX4, ACSL4, DMT1, Fpn, and TfR1) were checked by western blot. Myocardial cells (H9C2) were induced with lipopolysaccharide (LPS) and transfected with si-TLR4 or SLC7A11-OE. Then, the viability, ferroptosis, and TLR4/SLC7A11 signaling pathway of cells were examined. Nicorandil could significantly increase left ventricular (LV) ejection fraction (LVEF) while reduce LV end-diastolic volume (LVEDV) and LV end-systolic volume (LVESV). Also, it greatly reduced the levels of LDH, cTnI, and CK-MB; alleviated the pathological changes of myocardial injury; notably decreased MDA, total iron, and Fe2+ levels in myocardial tissues; and significantly increased GSH level. Besides, nicorandil obviously raised protein levels of GPX4, Fpn, and SLC7A11, and decreased protein levels of ACSL4, DMT1, TfR1, and TLR4. After knockdown of TLR4 or overexpression of SLC7A11, the inhibition effect of nicorandil on ferroptosis was strengthened in LPS-induced H9C2 cells. Therefore, nicorandil may regulate ferroptosis through TLR4/SLC7A11 signaling, thereby alleviating septic cardiomyopathy.

Identification of the methotrexate resistance-related diagnostic markers in osteosarcoma via adaptive total variation netNMF and multi-omics datasets.

Osteosarcoma is one of the most common malignant bone tumors with high chemoresistance and poor prognosis, exhibiting abnormal gene regulation and epigenetic events. Methotrexate (MTX) is often used as a primary agent in neoadjuvant chemotherapy for osteosarcoma; However, the high dosage of methotrexate and strong drug resistance limit its therapeutic efficacy and application prospects. Studies have shown that abnormal expression and dysfunction of some coding or non-coding RNAs (e.g., DNA methylation and microRNA) affect key features of osteosarcoma progression, such as proliferation, migration, invasion, and drug resistance. Comprehensive multi-omics analysis is critical to understand its chemoresistant and pathogenic mechanisms. Currently, the network analysis-based non-negative matrix factorization (netNMF) method is widely used for multi-omics data fusion analysis. However, the effects of data noise and inflexible settings of regularization parameters affect its performance, while integrating and processing different types of genetic data is also a challenge. In this study, we introduced a novel adaptive total variation netNMF (ATV-netNMF) method to identify feature modules and characteristic genes by integrating methylation and gene expression data, which can adaptively choose an anisotropic smoothing scheme to denoise or preserve feature details based on the gradient information of the data by introducing an adaptive total variation constraint in netNMF. By comparing with other similar methods, the results showed that the proposed method could extract multi-omics fusion features more effectively. Furthermore, by combining the mRNA and miRNA data of methotrexate (MTX) resistance with the extracted feature genes, four genes, Carboxypeptidase E (CPE), LIM, SH3 protein 1 (LASP1), Pyruvate Dehydrogenase Kinase 1 (PDK1) and Serine beta-lactamase-like protein (LACTB) were finally identified. The results showed that the gene signature could reliably predict the prognostic status and immune status of osteosarcoma patients.

Assessment of growing condition variables on alfalfa productivity.

This study was conducted to assess the impact of growing condition variables on alfalfa (Medicago sativa L.) productivity. A total of 197 alfalfa yield results were acquired from the alfalfa field trials conducted by the South Korean National Agricultural Cooperative Federation or Rural Development Administration between 1983 and 2008. The corresponding climate and soil data were collected from the database of the Korean Meteorological Administration. Twenty-three growing condition variables were developed as explaining variables for alfalfa forage biomass production. Among them, twelve variables were chosen based on the significance of the partial-correlation coefficients or potential agricultural values. The selected partial correlation coefficients between the variables and alfalfa forage biomass ranged from -0.021 to 0.696. The influence of the selected twelve variables on yearly alfalfa production was summarized into three dominant factors through factor analysis. Along with the accumulated temperature variables, the loading scores of the daily mean temperature higher than 25°C were over 0.88 in factor 1. The sunshine duration at temperature between 0°C-25°C was 0.939 in factor 2. Precipitation days were 0.82, which was the greatest in factor 3. Stepwise regression applied with the three dominant factors resulted in the coefficients of factors 1, 2, and 3 for 0.633, 0.485, and 0.115, respectively, and the R-square of the model was 0.602. The environmental conditions limiting alfalfa growth, such as daily temperature higher than 25°C or daily mean temperature affected annual alfalfa production most substantially among the growing condition variables. Therefore, future cultivar selection should consider the capability of alfalfa to be tolerant to extreme summer weather along with biomass production potential.

Hearing intervention for decreasing risk of developing dementia in elders with mild cognitive impairment: study protocol of a multicenter randomized controlled trial for Chinese Hearing Solution for Improvement of Cognition in Elders (CHOICE).

BACKGROUND: Age-related hearing loss (ARHL) signifies the bilateral, symmetrical, sensorineural hearing loss that commonly occurs in elderly individuals. Several studies have suggested a higher risk of dementia among patients diagnosed with ARHL. Although the precise causal association between ARHL and cognitive decline remains unclear, ARHL has been recognized as one of the most significant factors that can be modified to reduce the risk of developing dementia potentially. Mild cognitive impairment (MCI) typically serves as the initial stage in the transition from normal cognitive function to dementia. Consequently, the objective of our randomized controlled trial (RCT) is to further investigate whether the use of hearing aids can enhance cognitive function in older adults diagnosed with ARHL and MCI. METHODS AND DESIGN: This study is a parallel-arm, randomized controlled trial conducted at multiple centers in Shanghai, China. We aim to enlist a total of 688 older adults (age ≥ 60) diagnosed with moderate-to-severe ARHL and MCI from our four research centers. Participants will be assigned randomly to either the hearing aid fitting group or the health education group using block randomization with varying block sizes. Audiometry, cognitive function assessments, and other relevant data will be collected at baseline, as well as at 6, 12, and 24 months post-intervention by audiologists and trained researchers. The primary outcome of our study is the rate of progression to dementia among the two groups of participants. Additionally, various evaluations will be conducted to measure hearing improvement and changes in cognitive function. Apart from the final study results, we also plan to conduct an interim analysis using data from 12-month follow-up. DISCUSSION: In recent years, there has been a notable lack of randomized controlled trials (RCTs) investigating the possible causal relationship between hearing fitting and the improvement of cognitive function. Our findings may demonstrate that hearing rehabilitation can be a valuable tool in managing ARHL and preventing cognitive decline, which will contribute to the development of a comprehensive framework for the prevention and control of cognitive decline. TRIAL REGISTRATION: Chinese Clinical Trial Registry chictr.org.cn ChiCTR2000036139. Registered on 21 August 2020.

ABCB1 Regulates Immune Genes in Breast Cancer.

Background: Resistance to standard chemotherapy is a critical problem for breast cancer patients. The ATP-binding cassette (ABC) superfamily transporters actively pump out drugs and play an important role in chemoresistance. ABCB1 (ABC subfamily B, member 1, also named as multidrug resistance protein 1, MDR1) and suppressive myeloid-derived suppressor cells (MDSCs) potentially involve in chemoresistance of breast cancer. The relationship between ABCB1 and immune genes in breast cancer has not been widely studied. Methods: Microarray and RNA sequencing data were obtained from The Cancer Genome Atlas Breast Invasive Carcinoma in Genomic Data Commons Data Portal and Gene Expression Omnibus database. A patient-derived xenograft (PDX) model of HER2+ breast cancer was established to investigate the association between ABCB1 and immune genes in breast cancer. Results: Expression of ABCB1 increased in doxorubicin-selected MCF-7/ADR cells. High expression of ABCB1 mRNA is correlated with lymph-node metastasis and worse overall survival in patients with breast cancer. ABCB1 is positively correlated with IL6, CSF1, CSF3, and PTGS2. In the HER2+ stage IIA breast cancer PDX model, both doxorubicin and paclitaxel suppressed growth of P2 tumors. IL6, CSF1, CSF3, and PTGS2 expression were suppressed by paclitaxel but not doxorubicin. Intrasplenic MDSCs, including CD11b+Ly6G+ and CD11b+Ly6C+ cells, were more abundant than intratumor MDSCs in PDX-carrying nude mice. Clinically, the patient developed cancer recurrence after adjuvant chemotherapy with doxorubicin-based regimen and was well controlled after paclitaxel-trastuzumab combined therapy. Conclusion: ABCB1 was a poor predictor of HER2+ LN- breast cancer. Regulation of immune genes by ABCB1 contributed to cancer recurrence and treatment effect. The PDX model was suitable for investigation the expression of target genes and expansion of immune cells.

Comparison of the incidence of wound complications with preoperative and postoperative radiotherapy in patients with extremity soft tissue sarcoma resection: A meta-analysis.

We performed a meta-analysis to compare the effect of preoperative and postoperative radiotherapy on wound complications after resection of extremity soft tissue sarcoma (ESTS). A comprehensive computerised search of the PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang databases was conducted from their inception to August 2023 to identify studies comparing the effect of preoperative and postoperative radiotherapy on wound complications after ESTS resection. Two investigators independently screened the literature, extracted the data, and assessed the quality of the articles. The meta-analysis was performed using RevMan 5.4 software. Nine studies with 1271 patients were included, with 631 and 640 patients in the preoperative and postoperative radiotherapy groups, respectively. The results showed that the incidence of postoperative wound complications after ESTS resection was significantly higher with preoperative radiotherapy than with postoperative radiotherapy (27.26% vs. 12.03%, odds ratio [OR]: 2.88, 95% confidence interval [CI]: 2.12-3.91, p < 0.001). However, the rate of local recurrence of ESTS was significantly lower with preoperative radiotherapy than with postoperative radiotherapy (8.75% vs. 14.81%, OR: 0.57, 95% CI: 0.36-0.91, p = 0.02), and the 3-year overall survival was significantly higher in the preoperative radiotherapy group than in the postoperative radiotherapy group (82.24% vs. 70.04%, OR: 1.97, 95% CI: 1.05-3.71, p = 0.03). This pooled analysis suggests that although preoperative radiotherapy increases the rate of wound complications in ESTS compared with postoperative radiotherapy, it significantly reduces the rate of local recurrence after ESTS resection and improves the overall survival of patients. Owing to the limitations in the number and quality of the included studies, additional prospective cohort studies or randomised controlled trials are required to confirm these findings.

A Graphene Oxide-based Assay for Sensitive Osteonecrosis of the Femoral Head (ONFH) related microRNA Detection via Exonuclease-III Assisted Dual Signal Cycle.

Accurate detection of circulating microRNAs (miRNAs) plays a vital role in the diagnosis of various diseases. The current miRNA detection methods, however, are widely criticized for their low sensitivity and excessive background signal. Herein, we propose a graphene oxide (GO) based fluorescent biosensor for sensitive and reliable miRNA analysis with a low background signal by utilizing exonuclease III (Exo III)-assisted target recycling and hybridization chain reaction (HCR). To initiate Exo-III-assisted dual signal cycles, a hairpin DNA probe (H probe) was developed for selective miRNA binding. Dye quenching occurred when carboxyfluorescein (FAM)-labeled hairpins (HP1 and HP1) were unable to bind to their intended target and instead adsorb onto the surface of GO via p-stacking interactions. Exo III sequentially cleaved the 3'-strand of the H probe and the S probe upon attachment of the target miRNA, resulting in the release of the miRNA and the autonomous production of a "g" sequence. The released target miRNA then hybridized with a second H probe and progressed to the subsequent reaction phase. With the help of the HP1 and HP2 probes, a lengthy dsDNA product was produced when the "g" sequence triggered HCR. The dsDNA product was not absorbed by GO, and the material instead fluoresced brightly. As a result, the amount of miRNA of interest was measured. With a LOD of only 5.6 fM, this bioassay demonstrated excellent selectivity and great sensitivity.