Chemopreventive effects of atractylenolide-III on mammary tumorigenesis via activation of the Nrf2/ARE pathway through autophagic degradation of Keap1.

The incidence of breast cancer is increasing annually, making it a major health threat for women. Chemoprevention using natural, dietary, or synthetic products has emerged as a promising approach to address this growing burden. Atractylenolide-III (AT-III), a sesquiterpenoid present in various medicinal herbs, has demonstrated potential therapeutic effects against several diseases, including tumors, nonalcoholic fatty liver disease, and cerebral ischemic injury. However, its impact on breast cancer chemoprevention remains unexplored. In this study, we used an N-methyl-N-nitrosourea (NMU)-induced rat breast cancer model and 17ß-estradiol (E2)-treated MCF-10A cells to evaluate the chemopreventive potential of AT-III on mammary tumorigenesis. AT-III inhibited mammary tumor progression, evidenced by reduced tumor volume and multiplicity, prolonged tumor latency, and the reversal of NMU-induced weight loss. Furthermore, AT-III suppressed NMU-induced inflammation and oxidative stress through the Nrf2/ARE pathway in breast cancer tissues. In vitro, AT-III effectively suppressed E2-induced anchorage-independent growth and cell migration in MCF-10A cells. Nrf2 knockdown attenuated the protective effects of AT-III, highlighting the pivotal role of Nrf2 in AT-III-mediated suppression of tumorigenesis. The mechanism involves the induction of Nrf2 expression by AT-III through the autophagic degradation of Kelch-like ECH-associated protein 1 (Keap1). Overall, the results of this study indicate that AT-III is a promising candidate for breast cancer chemoprevention and provide valuable insights into its molecular interactions and signaling pathways.

Advanced subject-specific neck musculoskeletal modeling unveils sex differences in muscle moment arm and cervical spine loading.

Neck pain and injuries are growing healthcare burdens with women having a higher incidence rate and poorer treatment outcomes than males. A better understanding of sex differences in neck biomechanics, foundational for more targeted, effective prevention or treatment strategies, calls for more advanced subject-specific musculoskeletal modeling. Current neck musculoskeletal models are based on generic anatomy, lack subject specificity beyond anthropometric scaling, and are unable to accurately reproduce neck strengths exhibited in vivo without arbitrary muscle force scaling factors or residual torque actuators. In this work, subject-specific neck musculoskeletal models of 23 individuals (11 male, 12 female) were constructed by integrating multi-modality imaging and biomechanical measurements. Each model simulated maximal voluntary neck static exertions in three postures: neck flexion in a neutral posture, flexion in a 40° extended posture, and extension in a 40° flexed posture. Quantitative model validation showed close agreement between model-predicted muscle activation and EMG measurement. The models unveiled that (1) males have greater moment arms in one flexor muscle group and five extensor muscle groups, (2) females exhibited higher cervical spinal compression per unit exertion force in the flexed posture, and (3) the variability of compression force was much greater in females in all three exertions but most notably in the extension with a flexed "dropped head" position. These insights illuminated a plausible pathway from sex differences in neck biomechanics to sex disparities in the risk and prevalence of neck pain.

The minimum mass ratio of W UMa-type contact binaries-a new calculation.

A model is developed to establish the relationship between the critical gyration radius k of the primary component and the mass ratio (q) by considering the different dimensionless gyration radii of main-sequence stars with varying masses. The next step involves obtaining the low mass ratio limit ( q min = 0.038 ∼ 0.041 for overcontact degree f = 0 ~ 1) of W UMa-type contact binaries. Furthermore, the radial density distributions are estimated within the range of 0.3 M ⊙ ∼ 4.0 M ⊙ , based on the mass-radius relationship of main-sequence stars. Subsequently, the physical meaning of the minimum k value is proposed, which leads to an explanation for the cause of the minimum mass ratio. Finally, a stability criterion is proposed, which is based on both the mass ratio (q) and the total mass of the two components ( M tot ).

Residual learning-based robotic image analysis model for low-voltage distributed photovoltaic fault identification and positioning.

With the fast development of large-scale Photovoltaic (PV) plants, the automatic PV fault identification and positioning have become an important task for the PV intelligent systems, aiming to guarantee the safety, reliability, and productivity of large-scale PV plants. In this paper, we propose a residual learning-based robotic (UAV) image analysis model for low-voltage distributed PV fault identification and positioning. In our target scenario, the unmanned aerial vehicles (UAVs) are deployed to acquire moving images of low-voltage distributed PV power plants. To get desired robustness and accuracy of PV image detection, we integrate residual learning with attention mechanism into the UAV image analysis model based on you only look once v4 (YOLOv4) network. Then, we design the sophisticated multi-scale spatial pyramid fusion and use it to optimize the YOLOv4 network for the nuanced task of fault localization within PV arrays, where the Complete-IOU loss is incorporated in the predictive modeling phase, significantly enhancing the accuracy and efficiency of fault detection. A series of experimental comparisons in terms of the accuracy of fault positioning are conducted, and the experimental results verify the feasibility and effectiveness of the proposed model in dealing with the safety and reliability maintenance of low-voltage distributed PV systems.

Bioengineered Artificial Extracellular Vesicles Presenting PD-L1 and Gal-9 Ameliorate New-onset Type 1 Diabetes.

An important factor in the development of Type 1 diabetes (T1D) is the deficiency of inhibitory immune checkpoint ligands, specifically programmed cell death ligand 1 (PD-L1) and Galectin-9 (Gal-9), in ß-cells. Hence, modulation of the pancreas infiltrated T lymphocytes by exogenous PD-L1 or Gal-9 is an ideal approach for treating the new-onset T1D. Herein, we genetic engineered the macrophage cells to generate artificial extracellular vesicles (aEVs) overexpressing PD-L1 and Gal-9, which could restrict the islets autoreactive T lymphocytes and protect ß-cells from destruction. Intriguingly, overexpressing Gal-9 spurred macrophage polarization to M2 phenotype with immune suppressive attribute. Alternatively, both of PD-L1 and Gal-9 presenting aEVs (PD-L1-Gal-9 aEVs) favorably adhere to T cells via the interaction of programmed cell death protein 1 (PD-1)/PD-L1 or T cell immunoglobulin mucin 3 (TIM-3)/Gal-9. Moreover, PD-L1-Gal-9 aEVs prominently promoted effector T cell apoptosis and splenic regulatory T cells (Treg) cells differentiation in vitro. Virtually, PD-L1-Gal-9 aEVs efficaciously reversed the new-onset hyperglycemia in the NOD mice, prevented T1D progress, and declined the proportion and activation of CD4+ and CD8+ T cells infiltrating the pancreas notably, which together contributed to preserving the residual ß-cells survival and mitigating the hyperglycemia.

Ageing microenvironment mediates lymphocyte carcinogenesis and lymphoma drug resistance: From mechanisms to clinical therapy (Review).

Cellular senescence has a complex role in lymphocyte carcinogenesis and drug resistance of lymphomas. Senescent lymphoma cells combine with immunocytes to create an ageing environment that can be reprogrammed with a senescence­associated secretory phenotype, which gradually promotes therapeutic resistance. Certain signalling pathways, such as the NF­κB, Wnt and PI3K/AKT/mTOR pathways, regulate the tumour ageing microenvironment and induce the proliferation and progression of lymphoma cells. Therefore, targeting senescence­related enzymes or their signal transduction pathways may overcome radiotherapy or chemotherapy resistance and enhance the efficacy of relapsed/refractory lymphoma treatments. Mechanisms underlying drug resistance in lymphomas are complex. The ageing microenvironment is a novel factor that contributes to drug resistance in lymphomas. In terms of clinical translation, some senolytics have been used in clinical trials on patients with relapsed or refractory lymphoma. Combining immunotherapy with epigenetic drugs may achieve better therapeutic effects; however, senescent cells exhibit considerable heterogeneity and lymphoma has several subtypes. Extensive research is necessary to achieve the practical application of senolytics in relapsed or refractory lymphomas. This review summarises the mechanisms of senescence­associated drug resistance in lymphoma, as well as emerging strategies using senolytics, to overcome therapeutic resistance in lymphoma.

The role of circular RNAs in regulating resistance to cancer immunotherapy: mechanisms and implications.

Cancer immunotherapy has rapidly transformed cancer treatment, yet resistance remains a significant hurdle, limiting its efficacy in many patients. Circular RNAs (circRNAs), a novel class of non-coding RNAs, have emerged as pivotal regulators of gene expression and cellular processes. Increasing evidence indicates their involvement in modulating resistance to cancer immunotherapy. Notably, certain circRNAs function as miRNA sponges or interact with proteins, influencing the expression of immune-related genes, including crucial immune checkpoint molecules. This, in turn, shapes the tumor microenvironment and significantly impacts the response to immunotherapy. In this comprehensive review, we explore the evolving role of circRNAs in orchestrating resistance to cancer immunotherapy, with a specific focus on their mechanisms in influencing immune checkpoint gene expression. Additionally, we underscore the potential of circRNAs as promising therapeutic targets to augment the effectiveness of cancer immunotherapy. Understanding the role of circRNAs in cancer immunotherapy resistance could contribute to the development of new therapeutic strategies to overcome resistance and improve patient outcomes.

Balancing Bioresponsive Biofilm Eradication and Guided Tissue Repair via Pro-Efferocytosis and Bidirectional Pyroptosis Regulation during Implant Surgery.

There is an increasingly growing demand to balance tissue repair guidance and opportunistic infection (OI) inhibition in clinical implant surgery. Herein, we developed a nanoadjuvant for all-stage tissue repair guidance and biofilm-responsive OI eradication via in situ incorporating Cobaltiprotoporphyrin (CoPP) into Prussian blue (PB) to prepare PB-CoPP nanozymes (PCZs). Released CoPP possesses a pro-efferocytosis effect for eliminating apoptotic and progressing necrotic cells in tissue trauma, thus preventing secondary inflammation. Once OIs occur, PCZs with switchable nanocatalytic capacity can achieve bidirectional pyroptosis regulation. Once reaching the acidic biofilm microenvironment, PCZs possess peroxidase (POD)-like activity that can generate reactive oxygen species (ROS) to eradicate bacterial biofilms, especially when synergized with the photothermal effect. Furthermore, generated ROS can promote macrophage pyroptosis to secrete inflammatory cytokines and antimicrobial proteins for biofilm eradication in vivo. After eradicating the biofilm, PCZs possess catalase (CAT)-like activity in a neutral environment, which can scavenge ROS and inhibit macrophage pyroptosis, thereby improving the inflammatory microenvironment. Briefly, PCZs as nanoadjuvants feature the capability of all-stage tissue repair guidance and biofilm-responsive OI inhibition that can be routinely performed in all implant surgeries, providing a wide range of application prospects and commercial translational value.

Isolated fracture of the coronoid process following a molar extraction: A rare case report.

Isolated coronoid process fractures are uncommon, and iatrogenic isolated fractures are extremely rare. This case describes a displaced fracture of an isolated coronoid process thought to be due to excessive force applied by a dentist that had been overlooked and left untreated for about a month. The patient was a woman in her late 50's and she had undergone a molar extraction. Her dentist had confused her symptoms of trismus, pain, and facial oedema with the complex tooth extraction procedure. Following a cone-beam computed tomography (CBCT) scan we showed that the mandibular coronoid process on her right side had suffered a longitudinal fracture, and the fractured fragment had rotated upwards and inwards. Following successful surgical elimination of the fragmented coronoid process, the patient received targeted physiotherapy sessions that yielded excellent results. At the five-month follow-up, the ability of the patient to open her mouth had improved enormously, and her facial appearance almost recovered to its original state.

Radiomic features at Contrast-enhanced CT Predict Virus-driven Liver Fibrosis: A Multi-institutional Study.

BACKGROUND: Liver fibrosis is a major cause of morbidity and mortality among in chronic hepatitis patients. Radiomics, particularly of the spleen, may improve diagnostic accuracy and treatment strategies. External validations are necessary to ensure reliability and generalizability. METHODS: In this retrospective study, we developed three radiomics models using contrast-enhanced CT scans from 167 patients with liver fibrosis (training group) between January 2020 and December 2021. Radiomic features were extracted from arterial venous, portal venous, and equilibrium phase images. Recursive feature selection random forest (RFS-RF) and the least absolute shrinkage and selection operator (LASSO) logistic regression were used for feature selection and dimensionality reduction. Performance was assessed by area under the curve, C-index, calibration plots and decision curve analysis. External validation was performed on 114 patients from two institutions. RESULTS: Twenty-five radiomic features were significantly associated with fibrosis stage, with 80% of the top 10 features originating from portal venous phase spleen images. The radiomics models showed good performance in the validation cohort (C-indices: 0.723-0.808) and excellent calibration. Decision curve analysis indicated clinical benefits, with machine learning-based radiomics models (RFR-score and SVMR-score) providing more significant advantages. CONCLUSION: Radiomic features offer significant benefits over existing serum indices for staging virus-driven liver fibrosis, underscoring the value of radiomics in enhancing diagnostic accuracy. Specifically, radiomics analysis of the spleen presents additional noninvasive options for assessing fibrosis, highlighting its potential in improving patient management and outcomes.

Crizotinib enhances PARP inhibitor efficacy in ovarian cancer cells and xenograft models by inducing autophagy.

Poly (ADP-ribose) polymerase inhibitors (PARPi) can encounter resistance through various mechanisms, limiting their effectiveness. Our recent research showed that PARPi alone can induce drug resistance by promoting autophagy. Moreover, our studies have revealed that anaplastic lymphoma kinase (ALK) plays a role in regulating the survival of ovarian cancer cells undergoing autophagy. Here, we explored whether the ALK-inhibitor crizotinib could enhance the efficacy of PARPi by targeting drug-induced autophagic ovarian cancer cell and xenograft models. Our investigation demonstrates that crizotinib enhances the anti-tumor activity of PARPi across multiple ovarian cancer cells. Combination therapy with crizotinib and olaparib reduced cell viability and clonogenic growth in two-olaparib resistant cell lines. More importantly, this effect was consistently observed in patient-derived organoids. Furthermore, combined treatment with crizotinib and olaparib led to tumor regression in human ovarian xenograft models. Mechanistically, the combination resulted in increased levels of reactive oxygen species (ROS), induced DNA damage, and decreased the phosphorylation of AKT, mTOR, and ULK-1, contributing to increased olaparib-induced autophagy and apoptosis. Notably, pharmacologic, or genetic inhibition or autophagy reduced the sensitivity of ovarian cancer cell lines to olaparib and crizotinib treatment, underscoring the role of autophagy in cell death. Blocking ROS mitigated olaparib/crizotinib-induced autophagy and cell death while restoring levels of phosphorylated AKT, mTOR and ULK-1. These findings suggest that crizotinib can improve the therapeutic efficacy of olaparib by enhancing autophagy. Implications: The combination of crizotinib and PARPi presents a promising strategy, that could provide a novel approach to enhance outcomes for patients with ovarian cancer.

Multi-stimulus perception and visualization by an intelligent liquid metal-elastomer architecture.

Multi-stimulus responsive soft materials with integrated functionalities are elementary blocks for building soft intelligent systems, but their rational design remains challenging. Here, we demonstrate an intelligent soft architecture sensitized by magnetized liquid metal droplets that are dispersed in a highly stretchable elastomer network. The supercooled liquid metal droplets serve as microscopic latent heat reservoirs, and their controllable solidification releases localized thermal energy/information flows for enabling programmable visualization and display. This allows the perception of a variety of information-encoded contact (mechanical pressing, stretching, and torsion) and noncontact (magnetic field) stimuli as well as the visualization of dynamic phase transition and stress evolution processes, via thermal and/or thermochromic imaging. The liquid metal-elastomer architecture offers a generic platform for designing soft intelligent sensing, display, and information encryption systems.

Predicting the potential mechanism of radix chimonanthi pracecocis in treating osteoarthritis by network pharmacology analysis combined with experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Chimonanthi Pracecocis (RCP), also known as Tiekuaizi, widely used by the Miao community in Guizhou, exhibits diverse biological activities and holds promise for the treatment of osteoarthritis (OA). However, there is a lack of contemporary pharmacological research in this area. AIMS OF THE STUDY: This study aims to explore the potential of targets and mechanisms of RCP in the treatment of OA. MATERIALS AND METHODS: The chemical components of RCP were identified using UPLC-MS/MS, and active components were determined based on the Lipinski rule. RCP and OA-related targets were retrieved from public databases such as TCMSP and GeneCards. Network pharmacology approaches were employed to identify key genes. The limma package (version 3.40.2) in R 4.3.2 was used to screen for differentially expressed genes (DEGs) between OA and healthy individuals in GSE82107. DEGs were analyzed using an independent sample t-test and receiver operating characteristic analysis in GraphPad Prism 9.5.1. Additionally, molecular docking (SYBYL2.1.1) was used to analyze the binding interactions between the active components and target proteins. Finally, we established a papain-induced osteoarthritis (OA) rat model and treated it with RCP aqueous extract by gavage. We validated relevant indicators using real-time fluorescence quantitative polymerase chain reaction, Western blot, immunohistochemistry, and enzyme-linked immunosorbent assays. RESULTS: Seven active components and 53 targets were identified. The results of GO and KEGG enrichment analyses confirmed the significant role of RCP in the regulation of pyroptosis. Hypoxia-inducible factor-1α (HIF-1α) was identified as a key gene involved in the main biological functions. Molecular docking analysis revealed that Praecoxin, Isofraxidin, Esculin, and Naringenin can bind to the nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) (T-Score >5). Additionally, Praecoxin can bind to HIF-1α (T-Score >5). In vivo experiments demonstrated that RCP significantly affects the NLRP3 inflammasome, which is regulated by the HIF-1α pathway. RCP inhibited pyroptosis and reduced synovial inflammation. CONCLUSIONS: This study confirmed the efficacy of RCP aqueous extract in the treatment of OA and identified seven active components (esculin, dihydrokaempferol, naringenin, praecoxin, carnosol, hydroxyvalerenic acid, isofraxidin) that may play an anti-pyroptosis role in the treatment of OA by downregulating the expression of HIF-1α and NLRP3 inflammasome.

In Situ Synthesis of an Immune-Checkpoint Blocker from Engineered Bacteria Elicits a Potent Antitumor Response.

Immune-checkpoint blockade (ICB) reinvigorates T cells from exhaustion and potentiates T-cell responses to tumors. However, most patients do not respond to ICB therapy, and only a limited response can be achieved in a "cold" tumor with few infiltrated lymphocytes. Synthetic biology can be used to engineer bacteria as controllable bioreactors to synthesize biotherapeutics in situ. We engineered attenuated Salmonella VNP20009 with synthetic gene circuits to produce PD-1 and Tim-3 scFv to block immunosuppressive receptors on exhausted T cells to reinvigorate their antitumor response. Secreted PD-1 and Tim-3 scFv bound PD-1+ Tim-3+ T cells through their targeting receptors in vitro and potentiated the T-cell secretion of IFN-γ. Engineered bacteria colonized the hypoxic core of the tumor and synthesized PD-1 and Tim-3 scFv in situ, reviving CD4+ T cells and CD8+ T cells to execute an antitumor response. The bacteria also triggered a strong innate immune response, which stimulated the expansion of IFN-γ+ CD4+ T cells within the tumors to induce direct and indirect antitumor immunity.

Fibroblast-localized lncRNA CFIRL promotes cardiac fibrosis and dysfunction in dilated cardiomyopathy.

CFIRL is a long noncoding RNA (lncRNA), we previously identified as the most significantly upregulated lncRNA in the failing hearts of patients with dilated cardiomyopathy (DCM). In this study, we determined the function of CFIRL and its role in DCM. Real-time polymerase chain reaction and in situ hybridization assays revealed that CFIRL was primarily localized in the nucleus of cardiac fibroblasts and robustly increased in failing hearts. Global knockdown or fibroblast-specific knockout of CFIRL attenuated transverse aortic constriction (TAC)-induced cardiac dysfunction and fibrosis in vivo. Overexpression of CFIRL in vitro promoted fibroblast proliferation and aggravated angiotensin II-induced differentiation to myofibroblasts. CFIRL knockdown attenuated these effects. Mechanistically, RNA pull-down assay and gene expression profiling revealed that CFIRL recruited ENO1, a newly identified noncanonical transcriptional factor, to activate IL-6 transcription. IL-6 exerted a paracrine effect on cardiomyocytes to promote cardiac hypertrophy, which can be prevented by CFIRL knockdown. These findings uncover the critical role of CFIRL, a fibroblast-associated lncRNA, in heart failure by facilitating crosstalk between fibroblasts and cardiomyocytes. CFIRL knockdown might be a potent strategy to prevent cardiac remodeling in heart failure, particularly in DCM.

Utilization of home- and community-based services among older adults worldwide: A systematic review and meta-analysis.

OBJECTIVE: To identify and categorize home- and community-based services used by older adults and the distribution of their utilization, and to examine their utilization patterns in terms of region, time trends, and older adults' characteristics. DESIGN: Systematic review and meta-analysis. METHODS: We conducted a systematic search of six databases for studies published up to January 12, 2023, and performed meta-analyses and subgroup analyses to identify the utilization of home- and community-based services and analyze utilization patterns concerning region, time trends, and individual characteristics. RESULTS: We included 42 studies from 10 countries worldwide, involving a total of 2,942,069 older adults. Home- and community-based services were grouped into three categories: health services, social services, and family caregiver services. Regional differences were consistently evident across all three categories of services, reflecting diverse patterns of home- and community-based service adoption worldwide. Notably, there was a significant increase in the utilization of social services, as distinct from health services and family caregiver services, during the post-2010 period (2010-2018) in comparison with the pre-2010 period (before 2010). In addition, age and cognitive function also played an important role in the utilization of home- and community-based services. CONCLUSION: These findings highlight the importance of tailoring home- and community-based services to specific populations and understanding the needs of older adults over time. Further research should be undertaken to gain a deeper understanding of the reasons behind these variations and differences and to provide more targeted and effective services to older adults worldwide.

PD-1-CD28-enhanced receptor and CD19 CAR-modified tumor-infiltrating T lymphocytes produce potential anti-tumor ability in solid tumors.

The limited expansion ability and functional inactivation of T cells within the solid tumor microenvironment are major problems faced during in the application of using tumor-infiltrating lymphocytes (TILs) in vivo. We sought to determine whether TILs carrying a PD-1-CD28-enhanced receptor and CD19 CAR could overcome this limitation and mediate tumor regression. First, anti-tumor effects of PD-1-CD28-enhanced receptor or CD19 CAR modified NY-ESO-1-TCR-T cells to mimic the TILs function (hereafter "PD-1-CD28-TCR-T" or "CD19 CAR-TCR-T" cells, respectively) were tested using the NY-ESO-1 over-expressed tumor cell line in vitro and in a tumor-bearing model. Furthermore, the safety and anti-tumor ability of S-TILs (TILs modified through transduction with a plasmid encoding the PD-1-CD28-T2A-CD19 CAR) were evaluated in vivo. PD-1-CD28-TCR-T cells showed a formidable anti-tumor ability that was not subject to PD-1/PD-L1 signaling in vivo. CD19 CAR-TCR-T cells stimulated with CD19+ B cells exhibited powerful expansion and anti-tumor abilities both in vitro and in vivo. Three patients with refractory solid tumors received S-TILs infusion. No treatment-related mortality was observed, and none of the patients experienced serious side effects. One patient with melanoma achieved a partial response, and two patients with colon or kidney cancer achieved long-term stable disease following S-TILs therapy. To the best of our knowledge, this is the first study describing the safety and efficacy of the adoptive transfer of autologous S-TILs to control disease in patients with advanced cancers, suggesting that S-TILs may be a promising alternative therapy for cancer.

SARS-CoV-2 infection, vaccination and in vitro fertilization treatment: A prospective cohort study.

BACKGROUND: The impact of COVID-19 on reproductive health is controversial. The association between female SARS-CoV-2 infection and laboratory and pregnancy outcomes following subsequent in vitro fertilization (IVF) treatment remains unclear. This study aimed to investigate the relationship between IVF treatment at different time intervals after SARS-CoV-2 infection and reproductive outcomes. METHODS: A prospective cohort study of 920 IVF cycles post-SARS-CoV-2 infection was conducted. Modified Poisson regression and logistic regression models were utilized to evaluate oocyte- and embryo-related outcomes as well as clinical outcomes. Stratified analyses were also performed based on the vaccination status of the female participants. RESULTS: SARS-CoV-2 infection within three months was associated with reduced available [Adjusted RR (aRR): 0.96, 95 %CI: 0.91-1.00] and top-quality embryos (aRR: 0.90, 95 %CI: 0.83-0.98) in subsequent IVF treatment. Among patients failing to finish the three-dose vaccination, the interval between SARS-CoV-2 infection and cycle initiation of less than 90 days was associated with a lower number of oocytes retrieval (aRR: 8.81, 95 %CI: 8.24-9.41 vs aRR: 9.64, 95 %CI: 9.06-10.25), available embryos (aRR: 0.93, 95 %CI: 0.88-0.99), and top-quality embryos (aRR: 0.81, 95 %CI: 0.72-0.91) rather than among fully vaccinated women. Moreover, COVID-19 infection was not associated with biochemical pregnancy, clinical pregnancy, embryo implantation, and early abortion either in fresh embryo transfer (ET) or frozen ET. CONCLUSIONS: This study indicated that initiating IVF treatment within 90 days of SARS-CoV-2 infection might reduce the likelihood of obtaining available and top-quality embryos, especially among those who had not completed the three-dose vaccination. Nevertheless, female COVID-19 infection did not affect pregnancy or early abortion. Further rigorously designed studies are required to support these findings.

[Retracted] Propofol modulates the proliferation, invasion and migration of bladder cancer cells through the miR­145­5p/TOP2A axis.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the tumour images shown in Fig. 6B on p. 8 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes, which had either already been published or were under consideration for publication at around the same time. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 23: 439, 2021; DOI: 10.3892/mmr.2021.12078].

Deciphering the impact of circRNA-mediated autophagy on tumor therapeutic resistance: a novel perspective.

Cancer therapeutic resistance remains a significant challenge in the pursuit of effective treatment strategies. Circular RNAs (circRNAs), a class of non-coding RNAs, have recently emerged as key regulators of various biological processes, including cancer progression and drug resistance. This review highlights the emerging role of circRNAs-mediated autophagy in cancer therapeutic resistance, a cellular process that plays a dual role in cancer by promoting both cell survival and death. Increasing evidence suggests that circRNAs can modulate autophagy pathways, thereby influencing the response of cancer cells to therapeutic agents. In this context, the intricate interplay between circRNAs, autophagy, and therapeutic resistance is explored. Various mechanisms are discussed through which circRNAs can impact autophagy, including direct interactions with autophagy-related genes, modulation of signaling pathways, and cross-talk with other non-coding RNAs. Furthermore, the review delves into specific examples of how circRNA-mediated autophagy regulation can contribute to resistance against chemotherapy and radiotherapy. Understanding these intricate molecular interactions provides valuable insights into potential strategies for overcoming therapeutic resistance in cancer. Exploiting circRNAs as therapeutic targets or utilizing them as diagnostic and predictive biomarkers opens new avenues for developing personalized treatment approaches. In summary, this review underscores the importance of circRNA-mediated autophagy in cancer therapeutic resistance and proposes future directions for research in this exciting and rapidly evolving field.