Development and validation of a random survival forest model for predicting long-term survival of early-stage young breast cancer patients based on the SEER database and an external validation cohort.

Young breast cancer (YBC) patients often face a poor prognosis, hence it's necessary to construct a model that can accurately predict their long-term survival in early stage. To realize this goal, we utilized data from the Surveillance, Epidemiology, and End Results (SEER) databases between January 2010 and December 2020, and meanwhile, enrolled an independent external cohort from Tianjin Medical University Cancer Institute and Hospital. The study aimed to develop and validate a prediction model constructed using the Random Survival Forest (RSF) machine learning algorithm. By applying the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, we pinpointed key prognostic factors for YBC patients, which were used to create a prediction model capable of forecasting the 3-year, 5-year, 7-year, and 10-year survival rates of YBC patients. The RSF model constructed in the study demonstrated exceptional performance, achieving C-index values of 0.920 in the training set, 0.789 in the internal validation set, and 0.701 in the external validation set, outperforming the Cox regression model. The model's calibration was confirmed by Brier scores at various time points, showcasing its excellent accuracy in prediction. Decision curve analysis (DCA) underscored the model's importance in clinical application, and the Shapley Additive Explanations (SHAP) plots highlighted the importance of key variables. The RSF model also proved valuable in risk stratification, which has effectively categorized patients based on their survival risks. In summary, this study has constructed a well-performed prediction model for the evaluation of prognostic factors influencing the long-term survival of early-stage YBC patients, which is significant in risk stratification when physicians handle YBC patients in clinical settings.

Ambient polycyclic aromatic hydrocarbon exposure and breast cancer risk in a population-based Canadian case-control study.

PURPOSE: Polycyclic aromatic hydrocarbons (PAHs) represent a class of ubiquitous pollutants recognized as established human carcinogens and endocrine-disrupting chemicals. PAHs have seldom been modeled at the population-level in epidemiological studies. Fluoranthene is a prevalent PAH in urban settings and correlates with the occurrence of other PAHs. The purpose of this study was to evaluate associations between long-term residential exposure to ambient PAHs and breast cancer risk, both pre- and post-menopausal, in Canada. METHODS: Using the National Enhanced Cancer Surveillance System (NECSS), a national-scale Canadian population-based case-control study, annual fluoranthene exposures were estimated using the GEM-MACH-PAH chemical transport model on the basis of geocoded residential histories throughout a 20-year exposure window. Odds ratios (ORs) and 95% confidence intervals (CIs) controlling for potential confounders were estimated using logistic regression. Separate analyses were conducted for Ontario and national samples given a finer-resolution exposure surface and additional risk factor information available for Ontario. RESULTS: Positive associations were observed between fluoranthene exposure and premenopausal breast cancer, with inconsistent findings for postmenopausal breast cancer. For premenopausal breast cancer, adjusted ORs of 2.48 (95% CI: 1.29, 4.77) and 1.59 (95% CI: 1.11, 2.29) were observed when comparing the second highest category of exposure to the lowest, among the Ontario and national samples, respectively. For postmenopausal breast cancer, adjusted ORs were 1.10 (95% CI: 0.67, 1.80) and 1.33 (95% CI: 1.02, 1.73). Associations for the highest level of exposure, across both samples and menopausal strata, were non-significant. CONCLUSION: This study provides support for the hypothesis that ambient PAH exposures increase the risk of premenopausal breast cancer.

[Research progress on structures, activities, and biosynthesis of blazeispirol compounds from Agaricus blazei].

Agaricus blazei is a rare medicinal and edible fungus with a crispy taste and delicious flavor. Both fruiting body and mycelium are rich in polysaccharides, sterols, terpenoids, peptides, lipids, polyphenols, and other active ingredients, which have strong pharmacological activities such as anti-tumor, lipid-lowering, glucose-lowering, immunomodulation, optimization of intestinal flora, and anti-oxidation. Therefore, it is a kind of fungal resource with a great prospect of edible and medicinal development. Among the reported chemical components of A. blazei, blazeispirol is a series of sterol compounds unique to A. blazei, which has a spiral structure and is different from classical steroids. It is an important active ingredient found in the mycelium of A. blazei and has significant hepatoprotective activity. It can be used as a phylogenetic and chemotaxonomic marker of A. blazei strains and is considered an excellent lead compound for drug development. According to the skeleton structure characteristics, the 17 discovered blazeispirol compounds can be divided into two types: blazeispirane and problazeispirane. In order to further explore the resource of blazeispirol compounds of A. blazei, the discovery, isolation, structure, biological activity, and biosynthetic pathways of blazeispirol compounds of A. blazei were systematically reviewed. Besides, the metabolic regulation strategies related to the fermentation synthesis of blazeispirol A by A. blazei were discussed. This review could provide a reference for the efficient synthesis and development of blazeispirol compounds, the research and development of related drugs and functional foods, and the quality improvement of A. blazei and other medicinal and edible fungi resources and derivatives.

Acevaltrate promotes apoptosis and inhibits proliferation by suppressing HIF-1α accumulation in cancer cells.

Acevaltrate is a natural product isolated from the roots of Valeriana glechomifolia F.G.Mey. (Valerianaceae) and has been shown to exhibit anti-cancer activity. However, the mechanism by which acevaltrate inhibits tumor growth is not fully understood. We here demonstrated the effect of acevaltrate on hypoxia-inducible factor-1α (HIF-1α) expression. Acevaltrate showed a potent inhibitory activity against HIF-1α induced by hypoxia in various cancer cells. This compound markedly decreased the hypoxia-induced accumulation of HIF-1α protein dose-dependently. Further analysis revealed that acevaltrate inhibited HIF-1α protein synthesis and promoted degradation of HIF-1α protein, without affecting the expression level of HIF-1α mRNA. Moreover, the phosphorylation levels of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), and eIF4E binding protein-1 (4E-BP1) were significantly suppressed by acevaltrate. In addition, acevaltrate promoted apoptosis and inhibited proliferation, which was potentially mediated by suppression of HIF-1α. We also found that acevaltrate administration inhibited tumor growth in mouse xenograft model. Taken together, these results suggested that acevaltrate was a potent inhibitor of HIF-1α and provided a new insight into the mechanisms of acevaltrate against cancers.

Cost-effectiveness comparison of dalpiciclib and abemaciclib combined with an aromatase inhibitor as first-line treatment for HR+/HER2- advanced breast cancer.

OBJECTIVES: CDK4/6 inhibitors dalpiciclib and abemaciclib have been approved by the Chinese National Medical Products Administration as first-line treatment for postmenopausal females with hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer (ABC). We aimed to assess the cost-effectiveness of dalpiciclib plus letrozole/anastrozole (non-steroidal aromatase inhibitor [NSAI]) compared with abemaciclib plus NSAI as a first-line treatment for HR+/HER2- ABC in China. METHODS: We constructed a Markov model with three health states to evaluate health and economic outcomes of first-line treatment with dalpiciclib plus NSAI and abemaciclib plus NSAI for HR+/HER2- ABC. Efficacy data was obtained from MONARCH3 and DAWNA-2 trials. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. RESULTS: Compared with abemaciclib plus NSAI, dalpiciclib plus NSAI resulted in 4.27 additional QALYs, with an ICER of $14827.4/QALY. At a willingness-to-pay threshold of 3 times gross domestic product per capita in China for 2023 ($37721.5/QALY), the cost-effectiveness probability of dalpiciclib plus NSAI was 77.42%. CONCLUSIONS: From the perspective of Chinese payers, dalpiciclib plus NSAI appears to be a cost-effective strategy compared with abemaciclib plus NSAI for the first-line treatment of patients with HR+/HER2- ABC in China. CLINICAL TRIAL REGISTRATION: MONARCH3, www.clinicaltrials.gov, identifier is NCT02246621 and DAWNA-2, www.clinicaltrials.gov, identifier is NCT03966898.

Novel noninvasive indices for the assessment of liver fibrosis in primary biliary cholangitis.

The present study aimed to investigate the accuracy of new noninvasive markers in predicting liver fibrosis among individuals with primary biliary cholangitis (PBC). This retrospective analysis included subjects with PBC who had liver biopsies. Scheuer's classification was used to determine the fibrosis stage. The bilirubin to albumin (Alb) ratio (BAR), fibrosis index based on the four factors (FIB-4), γ-glutamyl transpeptidase to platelet (PLT) ratio (GPR), red cell distribution width to PLT ratio (RPR), aspartate aminotransferase (AST) to alanine aminotransferase ratio (AAR), AST to PLT ratio index (APRI) and total bilirubin to PLT ratio (TPR) were calculated based on the laboratory parameters. A novel index called BARP was conceived as BAR x RPR. A total of 78 individuals with PBC were included in the study, 84.6% of whom had significant fibrosis, 30.8% had advanced fibrosis and 15.4% had cirrhosis. In the multivariate analysis, Alb was determined to be an independent predictor of advanced fibrosis (odds ratio=0.823, P=0.034). The area under the receiver operating characteristic curves (AUROCs) of the BAR, GPR, TPR and BARP were statistically significant in predicting severe fibrosis (P<0.05) and were 0.747, 0.684, 0.693 and 0.696, respectively. In assessing advanced fibrosis, the AUROCs for the AAR, APRI, BAR, FIB-4, RPR, TPR and BARP were 0.726, 0.650, 0.742, 0.716, 0.670, 0.735 and 0.750, respectively. The AUROCs for the APRI, BAR, FIB-4, RPR, TPR and BARP for cirrhosis prediction were 0.776, 0.753, 0.821, 0.819, 0.808 and 0.832, respectively. By comparing the AUROCs, it was demonstrated that the diagnostic capabilities of the BARP (P=0.021) and TPR (P=0.044) were superior to those of the APRI in predicting advanced fibrosis. In conclusion, the BAR, BARP and TPR were of predictive value for the grade of liver fibrosis in PBC and Alb had a diagnostic value in identifying early fibrosis. The aforementioned noninvasive indices may be used for predicting histologic stages of PBC.

Transcriptome identification of differential mammary genes of Kazakh horses during early pregnancy.

Kazakh mares have attracted widespread attention with their outstanding lactation traits. Lactation is a complex dynamic process regulated by multiple factors. The extensive application of transcriptome sequencing technology enables researchers to further explore this biological issue. This study selected three pregnant and three non-pregnant Kazakh mares as the research subject. Their mammary glands were taken for transcriptome sequencing. The results show that there are 9 lncRNAs and 122 mRNAs differentially expressed between the two groups. GO enrichment analysis shows that there are 175 molecular functions, 59 cellular components, and 555 biological processes, including cellular hormone metabolic process, hormone catabolic process, and I-kappaB kinase/NF-kappaB signaling. KEGG enrichment analysis exhibits that these differential genes are mainly enriched in the NF-kappa B signaling pathway, steroid hormone biosynthesis, breast cancer, ECM-receptor interaction, and MAPK signaling pathway. WNT4, DPP4, and NFKBIA are key nodes regulating breast activation. Conclusions: Through the comparative analysis of the transcriptome data of mammary tissues of pregnant and non-pregnant mares, relevant differentially expressed genes are screened and analyzed. This study provides valuable fundamental data for investigating candidate genes related to the lactation regulation and mammogenesis of Kazakh horses.

miPEPPred-FRL: A Novel Method for Predicting Plant MiRNA-Encoded Peptides Using Adaptive Feature Representation Learning.

MicroRNAs (miRNAs) are an essential type of small molecule RNAs that play significant regulatory roles in organisms. Recent studies have demonstrated that small open reading frames (sORFs) harbored in primary miRNAs (pri-miRNAs) can encode small peptides, known as miPEPs. Plant miPEPs can increase the abundance and activity of cognate miRNAs by promoting the transcription of their corresponding pri-miRNAs, thereby modulating plant traits. Biological experiments are the most effective way to accurately identify miPEPs; however, they are time-consuming and expensive. Hence, an efficient computational method for the identification of miPEPs on a large scale is highly desirable. Up to now, there have been no specialized computational tools for identifying miPEPs. In this work, a novel predictor named miPEPPred-FRL based on an adaptive feature representation learning framework that consists of the feature transformation module and the cascade architecture has been proposed. The feature transformation module integrating a newly designed feature selection method and classifier selection rule is developed to convert sequence-based features into primary class and probabilistic features, which are then fed into the improved cascade architecture to obtain more stable and discriminative augmented features. Finally, the augmented features are utilized to construct the final predictor. Cross-validation experiments illustrate that the novel feature selection method and classifier selection rule contribute to boosting the feature representation ability of the framework. Furthermore, the high accuracy of miPEPPred-FRL on independent testing data suggests that it is a trustworthy and valuable tool for the identification of miPEPs.

Combined exposure to manganese and iron decreases oxidative stress-induced nerve damage by increasing Nrf2/HO-1/NQO1 expression.

BACKGROUND: Manganese (Mn) and iron (Fe) are essential trace elements for humans, yet excessive exposure to Mn or Fe can accumulate in the central nervous system (CNS) and cause neurotoxicity. The purpose of this study was to investigate the effects of Mn and Fe exposure, alone or in combination, on inducing oxidative stress-induced neurological damage in rat cortical and SH-SY5Y cells, and to determine whether combined exposure to these metals increases their individual toxicity. METHODS: SH-SY5Y cells and male Sprague-Dawley rats were used to observe the effects of oxidative stress-induced neurological damage induced by exposure to manganese and iron alone or in combination. To detect the expression of anti-oxidative stress-related proteins, Nrf2, HO-1, and NQO1, and the apoptosis-related proteins, Bcl2 and Bax, and the neurological damage-related protein, α-syn. To detect reactive oxygen species generation and apoptosis. To detect the expression of the rat cortical protein Nrf2. To detect the production of proinflammatory cytokines. RESULTS: We demonstrate that juvenile developmental exposure to Mn and Fe and their combination impairs cognitive performance in rats by inducing oxidative stress causing neurodegeneration in the cortex. Mn, Fe, and their combined exposure increased the expression of ROS, Bcl2, Bax, and α-syn, activated the inflammatory factors IL-6 and IL-12, inhibited the activities of SOD and GSH, and induced oxidative stress-induced neurodegeneration both in rats and SH-SY5Y cells. Combined Mn-Fe exposure attenuated the oxidative stress induced by Mn and Fe exposure alone by increasing the expression of antioxidant factors Nrf2, HO-1, and NQO1. CONCLUSION: In both in vivo and in vitro studies, manganese and iron alone or in combination induced oxidative stress, leading to neuronal damage. In contrast, combined exposure to manganese and iron mitigated the oxidative stress induced by exposure to manganese and iron alone by increasing the expression of antioxidant factors. Therefore, studies to elucidate the main causes of toxicity and establish the molecular mechanisms of toxicity should help to develop more effective therapeutic modalities in the future.

Combined application of biochar and sulfur alleviates cadmium toxicity in rice by affecting root gene expression and iron plaque accumulation.

Biochar and sulfur are considered useful amendments for soil cadmium (Cd) contamination remediation. However, there is still a gap in the understanding of how combined biochar and sulfur application affects Cd resistance in rice, and the role of the accumulation of iron plaque and the expression of Cd efflux transporter-related genes are still unclear in this type of treatment. In this study, we screened an effective combination of biochar and sulfur (0.75 % biochar, 60 mg/kg sulfur) that significantly reduced the Cd content of rice roots (32.9 %) and shoots (12.3 %); significantly reduced the accumulation of amino acids and their derivatives, organic acids and their derivatives and flavonoids in rice roots; and altered secondary metabolite production and release. This combined biochar and sulfur application alleviated the toxicity of Cd to rice, in which the enhancement of iron plaque (24.8 %) formation and upregulated expression of heavy metal effector genes (NRAMP3, MTP3, ZIP1) were important factors. These findings show that iron plaque and heavy metal transport genes are involved in the detoxification of rice under the combined application of biochar and sulfur, which provides useful information for the combined treatment of soil Cd pollution.

Modified interproximal tunneling technique with customized sub-epithelial connective tissue graft for gingival papilla reconstruction: report of three cases with a cutback incision on the palatal side.

BACKGROUND: Gingival papilla defects, which cause an unpleasant appearance and involve the upper anterior teeth, may be triggered by several factors. Several noninvasive and invasive techniques have been proposed for gingival papilla reconstruction. The combination of interproximal tunneling and customized connective tissue grafts (CTGs) has shown promise in papilla augmentation. However, due to the narrowness and limited blood supply of the gingival papilla, the long-term outcomes of these techniques remain unpredictable. Therefore, achieving tension-free coronal advancement of the interdental papilla and proper placement of the CTG is crucial for successful long-term outcomes and could provide widely applicable methods for papilla augmentation. CASE REPORT: In this study, we enrolled three patients with gingival papilla defects in the maxillary anterior teeth. For reconstruction, we proposed a modified interproximal tunneling (MIPT) technique combined with a CTG. A crucial modification based on previous studies involved adding a cutback incision to the base of the palatal vertical incision, resulting in tension-free healing. Additionally, the CTG was sutured upright to further enhance the height of the gingiva papilla. To evaluate the efficacy of the MIPT technique, the clinical parameters-including the Jemt papilla index and the distance from the tip of the papilla to the interproximal contact point-were examined using a periodontal probe (UNC15, Hu-friedy) at baseline and 12 months after surgery. All three patients achieved satisfactory papilla reconstruction 12 months after the surgery. These three cases were used to evaluate the efficacy of the MIPT technique combined with the customized CTG. An average increase in the Jemt papilla score from 1.6 to 2.8 and a reduction in the distance from the papilla tip to the contact point of adjacent teeth from 2 mm to 0.08 mm were observed 12 months after surgery. CONCLUSION: The preliminary results confirmed that this technique holds promise for gingival papilla augmentation between tooth/tooth or tooth/implant.

Multi-rod posterior correction only with halo-femoral traction for the management of adult neuromuscular scoliosis (> 100°) with severe pelvic obliquity: a minimum 5-year follow-up.

BACKGROUND: Many patients with neuromuscular scoliosis (NMS) experience a variety of difficult medical problems that aggravate the development effects of progressive scoliosis and pelvic obliquity (PO). The objective of the current study was to assess the safety and effectiveness of multi-rod posterior correction only (MRPCO) with halo-femoral traction (HFT) for the management of adult NMS (> 100°) with severe PO. METHODS: From 2012 to 2017, 13 adult patients who suffered from NMS (> 100°) with severe PO underwent MRPCO with HFT. The radiography parameters in a sitting position, such as the coronal Cobb angle of the main curve, the PO and the trunk shift (TS), were measured at the preoperative, postoperative and final follow-up stages. The preoperative and final follow-up assessment of the Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) was taken. RESULTS: The average follow-up span was 68.15 ± 6.78 months. There was decreased postoperative coronal Cobb angle with an average mean of 125.24° ± 11.78° to 47.55° ± 12.10°, with a correction rate of 62.43%; the PO was reduced to 6.25° ± 1.63° from 36.93° ± 4.25° with a correction rate of 83.07%; the TS was reduced to 2.41 cm ± 1.40 cm from 9.19 cm ± 3.07 cm. There was significant improvement in all parameters compared to the preoperative data. The VAS score reduced from 4.77 ± 0.93 to 0.69 ± 0.75, and the ODI score reduced from 65.38 ± 16.80 to 28.62 ± 12.29 at the final follow-up. CONCLUSIONS: Treatment of adult NMS (> 100°) with severe PO could be safe and effective with MRPCO with HFT. In order to obtain the optimum sitting balance, this could reduce the prevalence of complications and rectify the curvature and the correction of PO.

Hepatitis B reactivation in cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis.

BACKGROUND: Immunotherapy shows promise as a treatment option for various cancers. However, there is growing concern over potential complications from hepatitis B virus (HBV) reactivation after checkpoint blockade immunotherapy. Although most of the previous clinical trials on immune checkpoint inhibitors (ICIs) excluded patients with HBV, a few case reports and retrospective studies of HBV reactivation have been published. The aim of this study is to assess the risk of hepatitis B virus reactivation (HBVr) in patients receiving ICIs for advanced cancer. METHODS: English and Chinese language literature published prior to April 30, 2023, was searched in PubMed, EMBASE, Web of Science, Cochrane, SinoMed, CNKI and Wanfang Data for studies reporting HBVr rates in cancer patients treated with ICIs. A pooled risk estimate was calculated for HBVr rates with 95% confidence intervals (CI). RESULTS: Data from 34 studies including 7126 patients were retrieved and analyzed. The pooled HBVr rate in cancer patients treated with ICIs was 1.3% (I2 = 90.44%, 95% CI: 0.2-2.9%, P < 0.001). Subgroup analysis revealed that patients diagnosed with hepatocellular carcinoma (HCC), HBV carriers, and patients from Asian regions or in developing countries have a higher rate of HBVr. CONCLUSIONS: Our meta-analysis demonstrated a low risk of HBVr in patients treated with ICIs for advanced cancer. ICI treatment may be safely used in patients with existing HBV infection or chronic hepatitis B, accompanied by regular monitoring and appropriate antiviral prophylaxis if necessary.

Coupled sorptive and oxidative antimony(III) removal by iron-modified biochar: Mechanisms of electron-donating capacity and reactive Fe species.

Sorption and oxidation are two potential pathways for the decontamination of trivalent antimony (Sb(III))-bearing water, using iron (Fe)-modified biochar (FeBC). Here we investigated the sorption and oxidation behavior of FeBC for Sb(III) in aqueous solutions. Results revealed that Sb(III) removal by FeBC was significantly improved showing the maximum Sb(III) sorption (64.0 mg g-1). Density functional theory (DFT) calculations indicated that magnetite (Fe3O4) in FeBC offered a sorption energy of -0.22 eV, which is 5 times that of non-modified biochar. With the addition of peroxymonosulfate (PMS), the sorption of Sb(III) on FeBC was 7 times higher than that on BC, indicating the sorption capacity of FeBC for Sb(III) could be substantially increased by adding oxidizing agents. Electrochemical analysis showed that Fe modification imparted FeBC higher electron-donating capacity than that of BC (0.045 v. s. 0.023 mmol e- (g biochar)-1), which might be the reason for the strong Sb(III) oxidation (63.6%) on the surface of FeBC. This study provides new information that is key for the development of effective biochar-based composite materials for the removal of Sb(III) from drinking water and wastewater. The findings from this study have important implications for protecting human health and agriculture.

Novel Dual-Mode NIR-II/MRI Nanoprobe Targeting PD-L1 Accurately Evaluates the Efficacy of Immunotherapy for Triple-Negative Breast Cancer.

Background: Durable responses to immune-checkpoint blocking therapy (ICT) targeting programmed cell death protein-1/ligand-1 (PD-1/PD-L1) have improved outcomes for patients with triple negative breast cancer (TNBC). Unfortunately, only 19-23% of patients benefit from ICT. Hence, non-invasive strategies evaluating responses to therapy and selecting patients who will benefit from ICT are critical issues for TNBC immunotherapy. Methods: We developed a novel nanoparticle-Atezolizumab (NPs-Ate) consisting of indocyanine green (ICG), gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA), human serum albumin (HSA), and Atezolizumab. The efficiency of Gd-DTPA linking was verified using mass spectrometry, and the size of NPs-Ate was characterized using Nano-flow cytometry. The synthesized NPs-Ate were evaluated for fluorescence stability, penetration depth, and target specificity. TNBC cell lines and tumor-bearing mice models were used to identify the feasibility of this dual-modal second near-infrared/magnetic resonance imaging (NIR-II/MRI) system. Additionally, ICT combination with chemotherapy or radiotherapy in TNBC tumor-bearing mice models were used to assess dynamic changes of PD-L1 and predicted therapeutic responses with NPs-Ate. Results: Atezolizumab, a monoclonal antibody, was successfully labeled with ICG and Gd-DTPA to generate NPs-Ate. This demonstrated strong fluorescence signals in our NIR-II imaging system, and relaxivity (γ1) of 9.77 mM-1 s-1. In tumor-bearing mice, the NIR-II imaging signal background ratio (SBR) reached its peak of 11.51 at 36 hours, while the MRI imaging SBR reached its highest as 1.95 after 12 hours of tracer injection. NPs-Ate specifically targets cells and tumors expressing PD-L1, enabling monitoring of PD-L1 status during immunotherapy. Combining therapies led to inhibited tumor growth, prolonged survival, and increased PD-L1 expression, effectively monitored using the non-invasive NPs-Ate imaging system. Conclusion: The NIR-II/MRI NPs-Ate effectively reflected PD-L1 status during immunotherapy. Real-time and non-invasive immunotherapy and response/prognosis monitoring under NIR-II/MRI imaging guidance in TNBC is a promising and innovative technology with potential for extensive clinical applications in the future.

Research progress on the regulation of bone marrow stem cells by noncoding RNAs in adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity in young women, but its pathogenesis remains unclear. The primary pathogenic factors contributing to its development include genetics, abnormal bone metabolism, and endocrine factors. Bone marrow stem cells (BMSCs) play a crucial role in the pathogenesis of AIS by regulating its occurrence and progression. Noncoding RNAs (ncRNAs) are also involved in the pathogenesis of AIS, and their role in regulating BMSCs in patients with AIS requires further evaluation. In this review, we discuss the relevant literature regarding the osteogenic, chondrogenic, and lipogenic differentiation of BMSCs. The corresponding mechanisms of ncRNA-mediated BMSC regulation in patients with AIS, recent advancements in AIS and ncRNA research, and the importance of ncRNA translation profiling and multiomics are highlighted.

Unveiling the secrets of non-coding RNA-encoded peptides in plants: A comprehensive review of mining methods and research progress.

Non-coding RNAs (ncRNAs) are not conventionally involved in protein encoding. However, recent findings indicate that ncRNAs possess the capacity to code for proteins or peptides. These ncRNA-encoded peptides (ncPEPs) are vital for diverse plant life processes and exhibit significant potential value. Despite their importance, research on plant ncPEPs is limited, with only a few studies conducted and less information on the underlying mechanisms, and the field remains in its nascent stage. This manuscript provides a comprehensive overview of ncPEPs mining methods in plants, focusing on prediction, identification, and functional analysis. We discuss the strengths and weaknesses of various techniques, identify future research directions in the ncPEPs domain, and elucidate the biological functions and agricultural application prospects of plant ncPEPs. By highlighting the immense potential and research value of ncPEPs, we aim to lay a solid foundation for more in-depth studies in plant science.

Hsa_circ_0007334 Promotes the Osteogenic Differentiation and Proliferation of Human Bone Marrow Mesenchymal Stem Cells by Sponging miR-144-3p.

This study aimed to identify the possible function and the molecular mechanism of hsa_circ_0007334 in human bone marrow mesenchymal stem cells (hBMSCs) osteogenic differentiation. The level of hsa_circ_0007334 was detected by means of quantitative real-time polymerase chain reaction (RT-qPCR). Alkaline phosphatase (ALP), RUNX2, osterix (OSX), and osteocalcin (OCN) were monitored to analyze the degree of osteogenic differentiation under routine culture or under the control of hsa_circ_0007334. The proliferation of hBMSCs was tested with a cell counting kit-8 (CCK-8) assay. The migration of hBMSCs was tested using the Transwell assay. Bioinformatics analysis was used to predict the possible targets of hsa_circ_0007334 or miR-144-3p. Dual-luciferase reporter assay system was used to analyze the combination between hsa_circ_0007334 and miR-144-3p. Hsa_circ_0007334 was upregulated in osteogenic differentiation of hBMSCs. Osteogenic differentiation increased by hsa_circ_0007334 in vitro was confirmed with levels of ALP and bone markers (RUNX2, OCN, OSX). hsa_circ_0007334 overexpression promoted osteogenic differentiation, proliferation, and migration of hBMSCs, and knockdown of hsa_circ_0007334 has the opposite effects. miR-144-3p was identified as the target of hsa_circ_0007334. The targeting genes of miR-144-3p are involved in osteogenic-differentia-tion-related biological processes (such as bone development, epithelial cell proliferation, and mesenchymal cell apoptotic prosess) and pathways (including FoxO and VEGF signaling pathway). Hsa_circ_0007334, therefore, presents itself as a promising biological for osteogenic differentiation.