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Extracellular vesicles (EVs) contain microRNAs (miRNAs), which are important regulators of embryonic development. Nevertheless, little is known about the precise molecular processes controlling blastocyst development and quality. In a previous study, we identified bta-miR-665 as one of the miRNAs more abundantly present in extracellular vesicles of embryo-conditioned culture media of blastocysts compared to degenerate ones. Here, we investigated the effect and regulatory roles of bta-miR-665 in blastocyst development by supplementation of bta-miR-665 mimics or inhibitors to the culture media. Supplementation of bta-miR-665 mimics improved cleavage and blastocyst rate ( P < 0.01), and blastocyst quality as indicated by increased inner cell mass rates and reduced apoptotic cell ratios ( P < 0.01). Furthermore, supplementation of bta-miR-665 inhibitors had the opposite effect on these phenotypes. Low input transcriptome analysis and RT-qPCR revealed that bta-miR-665 acts on genes linked to microtubule formation and apoptosis/cell proliferation. These insights not only elucidate the important role of bta-miR-665 in embryo development, but also underscore its potential in improving reproductive efficiency in bovine embryo culture., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guan, Fan, Six, Benedetti, Raes, Fernandez Montoro, Cui, Azari Dolatabad, Van Soom, Pavani and Peelman.)

Background: Within the follicular fluid, extracellular vesicles (EVs) guide oocyte growth through their cargo microRNAs (miRNAs). Here, we investigated the role of EVs and their cargo miRNAs by linking the miRNAs found in EVs, derived from the fluid of an individual follicle, to the ability of its oocyte to become a blastocyst (competent) or not (non-competent)., Methods: Bovine antral follicles were dissected, categorized as small (2-4 mm) or large (5-8 mm) and the corresponding oocytes were subjected to individual maturation, fertilization and embryo culture to the blastocyst stage. Follicular fluid was pooled in 4 groups (4 replicates) based on follicle size and competence of the corresponding oocyte to produce a blastocyst. Follicular fluid-derived EVs were isolated, characterized, and subjected to miRNA-sequencing (Illumina Miseq) to assess differential expression (DE) in the 4 groups. Functional validation of the effect of miR-34c on embryo development was performed by supplementation of mimics and inhibitors during in vitro maturation (IVM)., Results: We identified 16 DE miRNAs linked to oocyte competence when follicular size was not considered. Within the large and small follicles, 46 DE miRNAs were driving blastocyst formation in each group. Comparison of EVs from competent small and large follicles revealed 90 DE miRNAs. Cell regulation, cell differentiation, cell cycle, and metabolic process regulation were the most enriched pathways targeted by the DE miRNAs from competent oocytes. We identified bta-miR-34c as the most abundant in follicular fluid containing competent oocytes. Supplementation of miR-34c mimic and inhibitor during IVM did not affect embryo development. However, blastocyst quality, as evidenced by higher cell numbers, was significantly improved following oocyte IVM in the presence of miR-34c mimics, while miR-34c inhibitors resulted in the opposite effect., Conclusion: This study demonstrates the regulatory effect of miRNAs from follicular fluid-derived EVs on oocyte competence acquisition, providing a further basis for understanding the significance of miRNAs in oocyte maturation and embryonic development. Up-regulation of miR-34c in EVs from follicular fluid containing competent oocytes and the positive impact of miR-34c mimics added during IVM on the resulting blastocysts indicate its pivotal role in oocyte competence., (© 2024. The Author(s).)

Biomarkers are biomolecules used to identify or predict the presence of a specific disease or condition. They play an important role in early diagnosis and may be crucial for treatment. MicroRNAs (miRNAs), a group of small non-coding RNAs, are more and more regarded as promising biomarkers for several reasons. Dysregulation of miRNAs has been linked with development of several diseases, including many different types of cancer, and abnormal levels can be present in early stages of tumor development. Because miRNAs are stable molecules secreted and freely circulating in blood and urine, they can be sampled with little or no invasion. Here, we present an overview of the current literature, focusing on the types of cancers for which dysregulation of miR-665 has been associated with disease progression, recurrence, and/or prognosis. It needs to be emphasized that the role of miR-665 sometimes seems ambiguous, in the sense that it can be upregulated in one cancer type and downregulated in another and can even change during the progression of the same cancer. Caution is thus needed before using miR-665 as a biomarker, and extrapolation between different cancer types is not advisable. Moreover, more detailed understanding of the different roles of miR-665 will help in determining its potential as a diagnostic and prognostic biomarker.

Background: Frozen shoulder is a common disorder that can lead to long-lasting impairment in shoulder-related daily activities. Traditional Chinese medicine (TCM) has played an important role in the effort to manage frozen shoulder., Purpose: We aimed to develop an evidence-based guideline for treating frozen shoulder with traditional Chinese medicine., Study Design: Evidence-based guideline., Methods: We developed this guideline based on internationally recognized and accepted guideline standards. The guideline development group used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to rate the certainty of evidence and the strength of recommendations. The benefits and harms, resources, accessibility, and other factors were fully taken into account, and the GRADE grid method was used to reach consensus on all recommendations., Results: We established a multidisciplinary guideline development panel. Based on a systematic literature search and a face-to-face meeting, nine clinical questions were identified. Finally, twelve recommendations were reached by consensus, comprehensively considering the balance of benefits and harms, certainty of evidence, costs, clinical feasibility, accessibility, and clinical acceptability., Conclusion: This guideline panel made twelve recommendations, which covered the use of manual therapy, acupuncture, needle knife, Cheezheng Xiaotong plaster, Gutong plaster, exercise therapy and integrated TCM and Western medicine, such as combined modalities and corticosteroid injections. Most of them were weakly recommended or consensus based. The users of this guideline are most likely to be clinicians and health administrators., (© 2023 The Authors. Journal of Evidence-Based Medicine published by Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

SARS-CoV-2 neutralizing antibodies have excellent application prospects in the prevention and treatment of COVID-19. This study established a competitive colloidal gold immunochromatography assay (GICA) to detect neutralizing antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 in postvaccination serum. The sensitivity, stability, and specificity of GICA were evaluated using neutralizing antibody solution reference material and positive serum. The consistency and correlation between GICA, pseudovirus neutralization (PN) assay, and ELISA were compared. Consistency analysis of serum neutralizing antibody and specific IgG antibody titers was conducted, and changes in neutralizing antibodies and specific IgG antibodies in serum after inoculation with the homologous booster inactivated vaccine and recombinant vaccine were noted. The sensitivity of the reagent was 20.66 IU/L, and the specificity was 100%. There was a strong consistency and correlation between GICA and PN (κ = 0.886, n = 165; r = 0.918, P < 0.001). The correlation coefficient of serum anti-RBD antibody and specific IgG antibody titers was 0.5253 ( P < 0.001). The specific IgG antibody titers in serum after (W4) inoculation with homologous booster inactivated vaccine were 10.80 (S/CO).The anti-RBD antibody titers were 28.33. The anti-RBD omicron variant (B.1.1.529) antibody titers were 11.67. After inoculation with the recombinant vaccine, the specific IgG antibody titers in the serum of W4 were 10.68. The serum anti-RBD antibody titers of W4 were 103.30. The serum anti-RBD omicron variant (B.1.1.529) antibody titers of W4 were 56.67. Therefore, vaccination of the third dose of the homologous booster inactivated vaccine and recombinant vaccine can enhance the level of neutralizing antibodies against the omicron variant (B.1.1.529). This study demonstrates that a GICA kit for neutralizing antibodies against the RBD of SARS-CoV-2 can be used for COVID-19 vaccine evaluation. Changes in titers enable long-term monitoring of a population's immunity and guide interventions when their immunity declines., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Background: At present, the progression mechanism of knee osteoarthritis (KOA) has not been fully elucidated, and there is a clinical need for late KOA-specific diagnostic markers to provide reference for preventive treatment. This study aimed to analyze the sequencing results of early- and late-stage KOA synovial tissue based on the key genes of late-stage KOA in combination with a machine learning algorithm., Methods: The whole transcriptome sequencing results of synovial tissue from KOA patients (GSE176223 and GSE32317) were downloaded from the gene expression omnibus (GEO) database. Thirty-nine early KOA synovial tissue samples and 31 late KOA synovial tissue samples were included in this study. The diagnostic criteria and baseline data balance of early and late KOA were referred to the data source literature, and the two groups of data had good baseline data balance. R software (V3.5.1) and R packages were used for screening and enrichment analysis of differentially expressed genes (DEGs). The key genes were screened by weighted correlation network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression analysis. A receiver operating characteristic curve (ROC) curve was used to evaluate the diagnostic efficacy of key genes for advanced KOA., Results: A total of 211 DEGs related to knee arthritis were screened out. Compared with synovial tissue of early knee arthritis, 111 genes were upregulated and 100 genes were downregulated in the synovial tissue of late knee arthritis. Sixty-six key genes were screened out through WGCNA and 34 key genes were screened out in the LASSO analysis. The genes obtained by the two algorithms combined with three overlapping genes, namely interleukin- 6 (IL-6), C-X-C chemokine ligand 12 (CXCL12), and macrophage migration inhibitor factor (MIF). The areas under the ROC curves of CXCL12 , IL-6 , and MIF were 0.96, 0.944, and 0.961, respectively (P<0.001)., Conclusions: IL-6 , CXCL12 , and MIF are the key pathogenic genes of KOA, which have good diagnostic efficacy for advanced KOA., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-3863/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

SignificanceHatching from the zona pellucida is a prerequisite for embryo implantation and is less likely to occur in vitro for reasons unknown. Extracellular vesicles (EVs) are secreted by the embryo into the culture medium. Yet the role that embryonic EVs and their cargo microRNAs (miRNAs) play in blastocyst hatching has not been elucidated, partially due to the difficulties of isolating them from low amounts of culture medium. Here, we optimized EV-miRNA isolation from medium conditioned by individually cultured bovine embryos and subsequently showed that miR-378a-3p, which was up-regulated in EVs secreted by blastocysts, plays a crucial role in promoting blastocyst hatching. This demonstrates the regulatory effect of miR-378-3p on hatching, which is an established embryo quality parameter linked with implantation.

Background: Knee osteoarthritis (KOA) is more common in middle-aged and elderly people, and seriously affects the quality of life of those affected. Traditional Chinese medicine (TCM) treatment of KOA has been widely recognized. In recent years, warm needling acupuncture (WNA) has been used to treat KOA and has achieved good results. However, there is a lack of comparison of the efficacy of WNA and other TCM treatments for KOA., Methods: We conducted a search for reports of WNA and/or TCM treatment of KOA in English- and Chinese-language databases. The data was retrieved from inception of the database until October 2021. The Cochrane risk of bias tool was used to evaluate the quality of the included studies, and the network meta-analysis was performed using the software RevMan 5.20., Results: A total of 8 articles met the inclusion criteria, including 399 patients treated with WNA (WNA group), and 396 patients treated with other TCM (TCM group). The results of meta-analysis showed that compared with patients in the TCM group, the effective rate [relative risk (RR)] was 1.18, 95% confidence interval (CI): 1.06 to 1.33, the last follow-up osteoarthritis index [mean difference (MD)] was -6.93, 95% CI: -12.14 to -1.72, and the last follow-up knee pain visual analogue scale (VAS) MD was -1.06, 95% CI: -1.61 to -0.51, which were all statistically significant. However, the difference in daily activities (MD: -4.31, 95% CI: -10.90 to 2.28) was not statistically significant., Discussion: Compared with other TCM treatments for KOA, WNA has better overall patient efficacy. However, further randomized controlled studies are needed to compare WNA and other TCM treatments individually to confirm the efficacy of WNA.

Background: Coronavirus disease 2019 (COVID-19) 2 has emerged as a global pandemic. However, as effective treatments for this disease are still unclear, safe and efficient therapies are urgently needed. Qingfei Paidu decoction (QPD) 3 is strongly recommended in the Chinese Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (Provisional 6th Edition). However, clinical research data on the effects of QPD on COVID-19 are scarce. Our study aimed to explore the effects of combined treatment with QPD and Western medicine on COVID-19., Methods: In this study, 63 patients with confirmed COVID-19 were analyzed. During the first 14 days of hospitalization, patients with deteriorating symptoms were administered QPD along with Western medicine therapy (the antiviral medicine selected from interferon, lopinavir, or arbidol). The clinical characteristics and blood laboratory indices (blood routine, inflammatory factors, and multi-organ biochemical indices) were examined, and the total lung severity scores were evaluated in each patient by reviewing chest computed tomography before treatment and at the end of treatment., Results: Before QPD treatment, the combined treatment group showed higher blood C-reactive protein levels and more severe pulmonary inflammation and clinical symptoms than the Western medicine treatment group. Both groups met the discharge criteria after a similar length of hospitalization. At the end of treatment, circulating white blood cells, total lymphocyte count, and glutamic-oxaloacetic transaminase levels improved dramatically in both groups (P <  0.05). In contrast, C-reactive protein, creatine kinase, creatine kinase-myocardial band, lactate dehydrogenase, and blood urea nitrogen levels were improved only in the combined treatment group (P <  0.05), and C-reactive protein and creatine kinase were the most pronounced (P <  0.01). Compared with baseline, at the end of treatment, the proportion of patients with normal values of C-reactive protein, total lymphocyte count, and lactate dehydrogenase were increased in the combined treatment group (P < 0.05), whereas no significant difference was observed in the Western medicine treatment group (P >  0.05)., Conclusion: The combination of QPD with Western medicine demonstrated significant anti-inflammatory effects compared with those of only Western medicine in patients with mild and moderate COVID-19; however, neither mortality nor length of hospitalization was affected. Moreover, the combined treatment tended to mitigate the extent of multi-organ impairment. Long-term randomized controlled trials with follow-up evaluations are required to confirm the results presented here., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Urbanization processes have accelerated over recent decades, prompting efforts to model land use change (LUC) patterns for decision support and urban planning. Cellular automata (CA) are extensively employed given their simplicity, flexibility, and intuitiveness when simulating dynamic LUC. Previous research, however, has ignored the spatial heterogeneity among sub-regions, instead applying the same transition rules across entire regions; moreover, most existing methods extract neighborhood effects with only one data time slice, which is inconsistent with the nature of neighborhood interactions as a long-term process exhibiting obvious spatiotemporal dependency. Accordingly, we propose a hybrid cellular automata model coupling area partitioning and spatiotemporal neighborhood features learning, named PST-CA. We use a machine-learning-based partitioning strategy, self-organizing map (SOM), to divide entire regions into several homogeneous sub-regions, and further apply a spatiotemporal three-dimensional convolutional neural network (3D CNN) to extract the spatiotemporal neighborhood features. An artificial neural network (ANN) is then built to create a conversion probability map for each sub-region using both spatiotemporal neighborhood features and factors that drive the LUC. Finally, the dynamic simulation results of entire study area are generated by fusing these probability maps, constraints and stochastic factors. Land use data collected from 2000 to 2015 in Shanghai were selected to verify our proposed method. Four traditional models were implemented for comparison, including logistic regression (LR)-CA, support vector machine (SVM)-CA, random forest (RF)-CA and conventional ANN-CA. Results illustrate that the proposed PST-CA outperformed four traditional models, with overall accuracy increased by 4.66%~6.41%. Moreover, three distinctly different "coverage rate-growth rate" composite patterns of built-up areas are shown in the SOM partitioning results, which verifies SOM's ability to address spatial heterogeneity; while the optimal time steps in 3D CNN generally maintained a positive correlation with the growth rate of built-up areas, which implies longer temporal dependency should be captured for rapidly developing areas., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript. The manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described is original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Breast cancer is a heterogeneous disease with increasing incidence and mortality and represents one of the most common cancer types worldwide. Low-density lipoprotein (LDL) is a complex particle composed of several proteins and lipids, which carries cholesterol into peripheral tissues and also affects the metabolism of fatty acids. Recent reports have indicated an emerging role of LDL in breast cancer, affecting cell proliferation and migration, thereby facilitating disease progression. However, controversy still exists among distinct types of breast cancer that can be affected by LDL. Classical therapeutic approaches, such as radiotherapy, chemotherapy, and lipid-lowering drugs were also reported as affecting LDL metabolism and content in breast cancer patients. Therefore, in this review we summarized and discussed the role of LDL in the development and treatment of breast cancer.

We report on the fabrication of Cu2+-sensing thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) microgels labeled with metal-chelating acceptor and fluorescent reporter moieties. Cu2+ detection sensitivity can be considerably enhanced via thermo-induced collapse of the sensing matrix, which can easily optimize the relative spatial distribution of Cu2+-binding sites and fluorescence readout functionalities. A novel picolinamine-containing monomer with Cu2+-binding capability, N-(2-(2-oxo-2-(pyridine 2-yl-methylamino)ethylamino)ethyl)acrylamide (PyAM, 3), was synthesized at first. Nearly monodisperse Cu2+-sensing microgels were prepared via emulsion polymerization of N-isopropylacrylamide (NIPAM) in the presence of a nonionic surfactant, N,N'-Methylene-bis(acrylamide) (BIS), PyAM (3), and fluorescent dansylaminoethyl- acrylamide (DAEAM, 5) monomers at around neutral pH and 70 degrees C. At 20 degrees C, as-synthesized microgels in their swollen state can selectively bind Cu2+ over other metal ions (Hg2+, Mg2+, Zn2+, Pb2+, Ag+, and Al3+), leading to prominent quenching of fluorescence emission intensity. Above the volume phase transition temperature, P(NIPAM-co-PyAM-co-DAEAM) microgels exhibit increased fluorescence intensity. It was observed that Cu2+ detection sensitivity can be dramatically enhanced via thermo-induced microgel collapse at elevated temperatures. At a microgel concentration of 3.0x10(-6) g/mL, the detection limit drastically improved from approximately 46 nM at 20 degrees C to approximately 8 nM at 45 degrees C. The underlying mechanism for this novel type of sensor with thermotunable detection sensitivity was tentatively proposed.