Higher final speed in 30-15 intermittent fitness tests correlates with soccer's locomotor demands, not heart rate responses in small-sided soccer games.

This study aimed to achieve two objectives: firstly, to analyze the relationships between aerobic fitness, as represented by the VIFT, and the heart rate and locomotor responses of youth male soccer players across various teams; and secondly, to compare players with lower and higher VIFT in terms of performance outcomes extracted during small-sided games (SSGs). A total of twenty-six youth male soccer players, aged 16.5 ± 0.32 years, with 3.4 ± 1.1 years of experience, voluntarily participated in the study. These players belonged to two regional-level tier 2 teams (trained/developmental). In the initial week of observation, the 30-15 Intermittent Fitness Test was implemented to measure the final velocity (VIFT) achieved by the players. Subsequently, the 5v5 format of play was conducted twice a week over two consecutive weeks, during which heart rate responses and locomotor demands were measured. The Pearson product-moment correlation test revealed a significant correlation between VIFT and the total distance covered during the 5v5 format (r = 0.471 [95% CI: 0.093; 0.721], p = 0.015). Conversely, small and non-significant correlations were identified between VIFT and mean heart rate (r = 0.280 [95% CI: - 0.126; 0.598]; p = 0.166), VIFT and peak heart rate (r = 0.237 [95% CI: - 0.170; 0.569]; p = 0.243), as well as VIFT and high-speed running (r = 0.254 [95% CI: - 0.153; 0.580]; p = 0.211). Players with higher VIFT demonstrated a significantly greater total distance, with a large effect size (+ 6.64%; p = 0.015; d = 1.033), compared to those with lower VIFT. Our findings suggest that improved performance in VIFT may lead to covering more distance in 5v5 matches. However, the lack of significant associations between VIFT and heart rate levels during SSGs suggests that they are not strongly correlated, possibly because VIFT is more closely linked to locomotor profile. As a practical implication, coaches may consider organizing players during SSGs based on their VIFT if the goal is to standardize locomotor demands.

Ultrasound-assisted complex enzyme extraction, structural characterization, and biological activity of polysaccharides from Ligustrum robustum.

Ligustrum robustum is one of the traditional teas in China with a long history of drinking and medicinal use. Through Response surface optimization, the yield of polysaccharides extracted by ultrasonic-assisted complex enzyme (UAE-EN) method was increased to 14.10 ±â€¯0.56 %. Neutral homogeneous polysaccharide (LRNP) and acidic homogeneous polysaccharide (LRAP-1, LRAP-2, LRAP-3) from L. robustum were purified. The molecular weights of them were 5894, 4256, 4621 and 3915 Da. LRNP was composed of glucose (Glc), galactose (Gal), arabinose (Ara) with molar percentage of 24.97, 42.38 and 30.80. Structure analysis revealed that the backbone of LRNP consisted of 1,5-linked α-Araf, 1,4-linked ß-Galp, 1,6-linked ß-Galp, and 1,4-linked ß-Glcp with the branches of 1,2-linked α-Araf, 1,3-linked α-Araf, 1,3-linked ß-Glcp and 1,6-linked ß-Galp residues, some terminal residues of α-Araf, ß-Glcp and α-Galp were also included. In vitro experiments showed that the four polysaccharides possessed excellent antioxidant, antitumor and hypoglycemic activities. LRNP possessed the protective effect against oxidative stress. The studies provide a basis for further exploitation of L. robustum.

Internal m 6 A and m 7 G RNA modifications in hematopoietic system and acute myeloid leukemia.

ABSTRACT: Epitranscriptomics focuses on the RNA-modification-mediated post-transcriptional regulation of gene expression. The past decade has witnessed tremendous progress in our understanding of the landscapes and biological functions of RNA modifications, as prompted by the emergence of potent analytical approaches. The hematopoietic system provides a lifelong supply of blood cells, and gene expression is tightly controlled during the differentiation of hematopoietic stem cells (HSCs). The dysregulation of gene expression during hematopoiesis may lead to severe disorders, including acute myeloid leukemia (AML). Emerging evidence supports the involvement of the mRNA modification system in normal hematopoiesis and AML pathogenesis, which has led to the development of small-molecule inhibitors that target N6-methyladenosine (m 6 A) modification machinery as treatments. Here, we summarize the latest findings and our most up-to-date information on the roles of m 6 A and N7-methylguanine in both physiological and pathological conditions in the hematopoietic system. Furthermore, we will discuss the therapeutic potential and limitations of cancer treatments targeting m 6 A.

Does artistic training affect color perception? A study of ERPs and EROs in experiencing colors of different brightness.

Color is a visual cue that can convey emotions and attract attention, and there is no doubt that brightness is an important element of color differentiation. To examine the impact of art training on color perception, 44 participants were assigned to two groups-one for those with and one for those without art training-in an EEG experiment. While the participants had their electroencephalographic data recorded, they scored their emotional responses to color stimuli of different brightness levels based on the Munsell color system. The behavioral results revealed that in both groups, high-brightness colors were rated more positively than low-brightness colors. Furthermore, event-related potential results for the artist group showed that high-brightness colors enhanced P2 and P3 amplitudes. Moreover, non-artists had longer N2 latency than artists, and there was a significant Group × Brightness interaction separately for the N2 and P3 components. Simple effect analysis showed that N2 and P3 amplitudes were substantially higher for high-brightness stimuli than for lower-brightness stimuli in the artistic group, but this was not the case in the non-artist group. Additionally, evoked event-related oscillation results showed that in both groups, high-brightness stimuli also elicited large delta, theta, and alpha as well as low gamma responses. These results indicate that high-brightness color stimuli elicit more positive emotions and stronger neurological reactions and that artistic training may have a positive effect on top-down visual perception.

A novel pectin polysaccharide from vinegar-baked Radix Bupleuri absorbed by microfold cells in the form of nanoparticles.

Polysaccharides of vinegar-baked Radix Bupleuri (VBCP) have been reported to exhibit liver-targeting and immunomodulatory activities through oral administration, but the absorption behavior and mechanism of VBCPs have not been extensively studied. In this study, a novel HG type pectin polysaccharide, VBCP1-4, with a high molecular weight of 2.94 × 106 Da, was separated from VBCP. VBCP1-4 backbone was contained 1,4-α-D-GalpA, 1,4-α-D-GalpA6OMe, 1,3,4-α-D-GalpA and 1,2,4-α-D-Rhap. The branches were mainly contained 1,5-α-L-Araf, 1,3,5-α-L-Araf, t-α-L-Araf and t-α-D-Galp, which linked to the 3 position of 1,3,4-α-D-GalpA and the 4 position of 1,2,4-α-D-Rhap. VBCP1-4 could self-assemble to nanoparticles in water, with CMC values of 106.41 µg/mL, particle sizes of 178.20 ± 2.82 nm and zeta potentials of -23.19 ± 1.44 mV. The pharmacokinetic study of VBCP1-4, which detected by marking with FITC, revealed that it could be partially absorbed into the body through Peyer's patches of the ileum. In vitro absorption study demonstrated that VBCP1-4 was difficult to be absorbed by Caco-2 cell monolayer, but could be absorbed by M cells in a time and concentration dependent manner. The absorption mechanism was elucidated that VBCP1-4 entered M cells through clathrin-mediated endocytosis in the form of nanoparticles. These findings provide valuable insights into the absorption behavior of VBCP and contribute to its further development.

Supervised Offseason Training Programs are able to mitigate the Effects of Detraining in Youth Men Soccer Players Physical Fitness: A Randomized Parallel Controlled Study.

This study aimed to analyze the effects of three off-season training programs on the aerobic capacity, countermovement jump (CMJ), and linear sprint performance of young male soccer players. The study employed a randomized multi-arm design, consisting of three experimental groups: i) a high-intensity interval training (HIIT) group; (ii) a plyometric jump training (PJT) group; and (iii) a HIIT+PJT group; and an inactive control group. Fifty-eight under-19 male soccer players (aged 17.6 ±0.6 years) were randomly assigned to participate in a 3-week offseason training program exclusively performing HIIT, PJT, or a combination of both, while the fourth group remained inactive. Players underwent assessments twice, using the Yo-Yo Intermittent Recovery Test - Level 1 (YYIRT), CMJ, and 30-meter linear sprint. Significant interactions between time and groups were found in CMJ (p<0.001), YYIRT (p<0.001), and 30-m sprint (p<0.001). Group*time interaction revealed that the control group was significantly different from HIIT (p<0.001), PJT (p<0.001), and HIIT+PJT (p<0.001) considering the CMJ. Moreover, the control group was significantly different from HIIT (p=0.037) in YYIRT. Finally, the control group was significantly different from HIIT (p=0.024), PJT (p<0.001), and HIIT+PJT (p=0.021) considering the 30-m sprint. In conclusion, off-season training programs are effective in significantly reducing declines in CMJ and sprint performance compared to maintaining training cessation. However, in the YYIRT, only HIIT seems to be significantly superior to maintaining inactivity. To mitigate aerobic performance declines, incorporating HIIT sessions twice weekly during the offseason is advisable. To enhance or maintain jump performance, integrating at least one session of PJT weekly is beneficial.

The combination of IL-2 nanoparticles and Palbociclib enhances the anti-tumor immune response for colon cancer therapy.

Immunotherapy of tumors plays a pivotal role in the current treatment of cancer. While interleukin 2 (IL-2) demonstrated its efficacy as an immunotherapeutic drug in the early days, its short blood circulation time poses challenges in maintaining effective therapeutic concentrations. Additionally, IL-2's activation of regulatory T cells can counteract its anti-cancer effects. Therefore, the primary goal of this study was to formulate IL-2-carrying nanoparticles via boron-nitrogen coordination between methoxy poly (ethylene glycol) block poly-[(N-2-hydroxyethyl)-aspartamide]phenylboronic acid (mPEG-b-PHEA-PBA, P-PBA) and poly (L-lysine) (PLL). These nanoparticles are intended to be used in combination with CDK4/6 inhibitors to address the short blood circulation time of IL-2, reduce its immunosuppressive effects, and enhance the overall immune response. The envisaged outcome is a sustained and potent therapeutic effect, offering a novel and promising combination therapy strategy for tumor immunotherapy.

Single-cell transcriptomics reveals the role of antigen presentation in liver metastatic breast cancer.

Liver metastasis (LM) is the primary cause of cancer-related mortality in late-stage breast cancer (BC) patients. Here we report an in-depth analysis of the transcriptional landscape of LM of 11 patients with secondary hepatic carcinoma at single-cell resolution. Our study reveals that terminally exhausted CD4+ and dysfunctional CD8+ T cells were enriched in LM along with low antigen presentation. We also found that macrophages were associated with the tumor infiltrating CD4+ T cells, while FCN3+ macrophages, type 1 conventional dendritic cells (cDC1) and LAMP3+ DC regulated T cell functions, probably via antigen processing and presentation. Major histocompatibility complex expression in FCN3+ macrophage, cDC1 and LAMP3+ DC was reduced in LM compared to those in normal tissues and primary BC. Malfunctioned antigen presentation in these cells is linked to a worse prognosis in invasive BC and hepatocellular carcinoma. Our results provide valuable insights into the role of tumor infiltrating T cells in LM.

N-doped carbon dots for the determination of Al3+ and Fe3+ using aggregation-induced emission.

New portable hydrogel sensors for Al3+ and Fe3+ detection were designed based on the aggregation-induced emission (AIE) and color change of N-doped carbon dots (N-CDs). N-CDs with yellow fluorescence were prepared by a one-pot hydrothermal method from 2,5-dihydroxyterephthalic acid and acrylamide. The fluorescence of N-CDs was enhanced by Al3+ about 20 times and quenched by Fe3+. It was interesting that although Fe3+ showed obvious quenching on the fluorescence of N-CDs it did not cause a noticeable change in the fluorescence of N-CDs + Al3+. The colorless solution of N-CDs appeared blue in the presence of Fe3+ without the influence of Al3+. Therefore, the turn-on fluorometry and colorimetry systems based on N-CDs were constructed for the simultaneous detection of Al3+ and Fe3+. Furthermore, the portable sensing of Al3+ and Fe3+ was realized with the assistance of hydrogel, filter paper, cellulose acetate, and cellulose nitrate film. The proposed approach was successfully applied to the detection of Al3+ and Fe3+ in food samples and cell imaging.

REDH: A database of RNA editome in hematopoietic differentiation and malignancy.

BACKGROUND: The conversion of adenosine (A) to inosine (I) through deamination is the prevailing form of RNA editing, impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species. Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases, providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets. However, the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking. METHODS: We downloaded RNA sequencing (RNA-seq) data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used. We performed sequence alignment, identified RNA editing sites, and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases. RESULTS: We established a new database, "REDH", represents RNA editome in hematopoietic differentiation and malignancy. REDH is a curated database of associations between RNA editome and hematopoiesis. REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts (human). Through the Differentiation, Disease, Enrichment, and knowledge modules, each A-to-I editing site is systematically integrated, including its distribution throughout the genome, its clinical information (human sample), and functional editing sites under physiological and pathological conditions. Furthermore, REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control. CONCLUSIONS: REDH is accessible at http://www.redhdatabase.com/ . This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies. It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.

Efficacy of roxadustat in maintenance hemodialysis patients with erythropoietin-hyporesponsive anemia.

OBJECTIVE: To investigate the efficacy of roxadustat in hemodialysis patients with erythropoietin (EPO) hypo-responsive anemia. MATERIALS AND METHODS: This retrospective study included 55 hemodialysis patients with erythropoietin hypo-responsive anemia at the First Affiliated Hospital of Chongqing Medical University from January to December 2020. We observed their hemoglobin (Hb) changes, inflammatory factors, and adverse reactions before and after 12 weeks of roxadustat treatment. RESULTS: Among the 55 patients, the average age was 60.75 ± 13.96 years old, and the median dialysis age was 48 months. All patients were taken off EPO and switched to roxadustat during the follow-up period. Compared with baseline, patients' Hb was significantly increased (90.64 ± 20.01 g/L, 98.52 ± 15.89 g/L, 104.34 ± 19.15 g/L, and 107.02 ± 20.54 g/L, respectively) (p < 0.05). At 12 weeks of roxadustat treatment, 34 patients (61.82%) met the target Hb levels (100 - 130 g/L). The multivariate logistic analysis showed that Hb response positively correlated with the Hb level before roxadustat treatment (p = 0.046), while responding well to roxadustat negatively correlated with blood platelet-to-lymphocyte ratio (PLR) and duration of dialysis (p = 0.029 and p = 0.046) in patients with EPO hypo-responsive anemia. CONCLUSION: Roxadustat could effectively improve anemia; the PLR and dialysis age were independent predictors of roxadustat efficacy in dialysis patients with EPO hypo-responsive anemia.

Immunoswitch Nanomodulators Enable Active Targeting and Selective Proliferation of Regulatory T Cells for Multiple Sclerosis Therapy.

Interleukin-2 (IL-2) used in multiple sclerosis (MS) therapy modulates the balance between regulatory T (Treg) cells and effector T (Teff) cells. However, the off-target activation of Teff cells by IL-2 limits its clinical application. Therefore, a rapidly prepared immunoswitch nanomodulator termed aT-IL2C NPs was developed, which specifically recognized Treg cells with high TIGIT expression thanks to the presence of an anti-TIGIT and an IL-2/JES6-1 complex (IL2C) being delivered to Treg cells but not to Teff cells with low TIGIT expression. Then, IL2C released IL-2 due to the specific expression of the high-affinity IL-2 receptor on Treg cells, thus enabling the active targeting and selective proliferation of Treg cells. Moreover, the anti-TIGIT of aT-IL2C NPs selectively inhibited the proliferation of Teff cells while leaving the proliferation of Treg cells unaffected. In addition, since the IL-2 receptor on Teff cells had medium-affinity, the IL2C hardly released IL-2 to Teff cells, thus enabling the inhibition of Teff cell proliferation. The treatment of experimental autoimmune encephalomyelitis (EAE) mice with aT-IL2C NPs ameliorated the severity of the EAE and restored white matter integrity. Collectively, this work described a potential promising agent for effective MS therapy.

Conjoint analysis of clinical, imaging, and pathological features of schistosomiasis and colorectal cancer.

This study aims to examine and compare clinical, radiological, and pathological data between colorectal cancer (CRC) patients with and without schistosomiasis and uncover distinctive CRC characteristics when accompanied by schistosomiasis. This retrospective study is based on data collected from 341 patients diagnosed with CRC post-surgery and pathology. Of these patients, 101 (Group A) were diagnosed with colorectal cancer co-occurring with schistosomiasis (CRC-S), while 240 patients (Group B) were diagnosed with colorectal cancer without concurrent schistosomiasis (CRC-NS). Both groups were compared and analyzed based on their clinical data, imaging-based TNM staging, lymph node metastasis, nerve invasion, vascular cancer thrombus, and histopathological differentiation. A Chi-squared test revealed a significant difference in gender distribution between the patients with CRC-S (Group A) and CRC-NS (Group B), with a p -value of 0.043 and χ2 = 4.115. Specifically, a higher incidence rate was observed among males in Group A. There was a difference in the overall distribution of TNM staging between the two groups (p = 0.034, χ2 = 6.764). After pairwise comparison, a statistically significant difference was observed in the T3 stage (p <0.05). The proportion of the T3 stage in Group A was significantly higher than that in Group B, indicating certain advantages. There was a difference in postoperative histopathological grading between the two groups (p = 0.005, χ2 = 10.626). After pairwise comparison, a statistically significant difference was observed between the well-differentiated adenocarcinoma and the moderately and poorly differentiated adenocarcinoma (p <0.05), with a higher proportion of welldifferentiated patients in Group A compared to Group B. There was no significant difference in age, lymph node metastasis, nerve invasion, and vascular invasion between the two groups of patients (p > 0.05). Among the 101 patients with CRC-S, 87 (86%) showed linear calcification on CT imaging. Patients with CRC-S are mainly male, with tumor staging mostly in the middle stage, high tumor differentiation, and low malignancy. CT imaging can help identify the presence of lumps and linear calcification indicative of schistosome deposits. MRI can early clarify TNM staging and determine the presence of lymph node metastasis and nerve and vascular invasion.

Deciphering the Functional Long Non-Coding RNAs Derived from MicroRNA Loci.

Albeit the majority of eukaryotic genomes can be pervasively transcribed to a diverse population of lncRNAs and various subtypes of lncRNA are discovered. However, the genome-wide study of miRNA-derived lncRNAs is still lacking. Here, it is reported that over 800 miRNA gene-originated lncRNAs (molncRNAs) are generated from miRNA loci. One of them, molnc-301b from miR-301b and miR-130b, functions as an "RNA decoy" to facilitate dissociation of the chromatin remodeling protein SMARCA5 from chromatin and thereby sequester transcription and mRNA translation. Specifically, molnc-301b attenuates erythropoiesis by mitigating the transcription of erythropoietic and translation-associated genes, such as GATA1 and FOS. In addition, a useful and powerful CRISPR screen platform to characterize the biological functions of molncRNAs at large-scale and single-cell levels is established and 29 functional molncRNAs in hematopoietic cells are identified. Collectively, the focus is on miRNA-derived lncRNAs, deciphering their landscape during normal hematopoiesis, and comprehensively evaluating their potential roles.

Comparative Study on Anti-Inflammatory Effect of Polysaccharides from Vinegar-Baked Radix Bupleuri Using Different Methods.

The impact of the extraction method on the physiochemical characteristics and anti-inflammatory effect of polysaccharides from vinegar-baked Radix Bupleuri (VBCPs) was studied. Five extraction methods were employed to obtain the VBCPs: hot water extraction (HW), ultrasound-assisted extraction (UA), enzyme-assisted extraction (EA), citric acid-assisted extraction (CA), and ammonia-assisted extraction (KA). The results showed that the extraction method affects the yield, characteristics, and anti-inflammatory effect of the polysaccharides significantly. KA produced the highest yield, Ara content, and the strongest effect of enhancing IL-10 secretion. VBCP-EA exhibited the largest molecular weight (Mw), the highest Man content, and the poorest effect on inhibiting NO, VBCP-UA possessed more Gal than other VBCPs, the lowest Mw, and a comparable effect on inhibiting NO and TNF-α with VBCP-KA and VBCP-CA. All VBCP self-assembled into nanoparticles in solutions, and VBCP-KA presented the lowest particle size. The structure-activity analysis showed that Mw and Man content are negatively correlated and Ara content is positively correlated with the NO inhibition and IL-10 secretion effects; Rha and Gal A content are positively correlated and Glu is negatively correlated with the TNF-α inhibiting effect. The above results indicated that KA is an efficient method for obtaining anti-inflammatory VBCP, which provides new insight into the extraction of VBCP.

Preparation of an Ultrahigh-DAR PDL1 monoclonal antibody-polymeric-SN38 conjugate for precise colon cancer therapy.

Antibody-drug conjugates (ADCs) are the most potent active tumor-targeting agents used clinically. However, the preparation of ADCs with high drug-to-antibody ratios (DARs) remains a major challenge. Herein, a Fab-nondestructive SN38-loaded antibody-polymeric-drug conjugate (APDC), aPDL1-NPLG-SN38, was prepared that had a DAR as high as 72 for the first time, by increased numbers of payload binding sites via the carboxyl groups of poly (l-glutamic acid) (PLG). The bonding of Fc-III-4C peptide with PLG-graft-mPEG/SN38 (Fc-NPLG-SN38) was achieved using a click reaction between azide and DBCO groups. The aPDL1-NPLG-SN38 conjugate was then synthesized by the high-affinity interaction between the Fc-III-4C peptide in Fc-NPLG-SN38 and the crystallizable fragment (Fc) of PDL1 monoclonal antibody (aPDL1). This approach avoided the potential deleterious effects on the Fab structure of the monoclonal antibody. The aqueous environment used in its preparation helped maintain monoclonal antibody recognition capability. Through the specific recognition by aPDL1 of PDL1 that is highly expressed on MC38 tumors, the accumulation of aPDL1-NPLG-SN38 in the tumors was 2.8-fold greater than achieved with IgG-NPLG-SN38 that had no active tumor-targeting capability. aPDL1-NPLG-SN38 exhibited excellent therapeutic properties in both medium-sized and large MC38 tumor animal models. The present study provides the details of a novel preparation strategy for SN38-loaded ADCs having a high DAR.

Light-driven biohybrid system utilizes N2 for photochemical CO2 reduction.

Attempting to couple photochemical CO2 reduction with N2 fixation is usually difficult, because the reaction conditions for these two processes are typically incompatible. Here, we report that a light-driven biohybrid system can utilize abundant, atmospheric N2 to produce electron donors via biological nitrogen fixation, to achieve effective photochemical CO2 reduction. This biohybrid system is constructed by incorporating molecular cobalt-based photocatalysts into N2-fixing bacteria. It is found that N2-fixing bacteria can convert N2 into reductive organic nitrogen and create a localized anaerobic environment, which allows the incorporated photocatalysts to continuously perform photocatalytic CO2 reduction under aerobic conditions. Specifically, the light-driven biohybrid system displays a high formic acid production rate of over 1.41 × 10-14 mol h-1 cell-1 under visible light irradiation, and the organic nitrogen content undergoes an over-3-fold increase within 48 hours. This work offers a useful strategy for coupling CO2 conversion with N2 fixation under mild and environmentally benign conditions.

Baicalin suppress the development of polycystic ovary syndrome via regulating the miR-874-3p/FOXO3 and miR-144/FOXO1 axis.

CONTEXT: Polycystic ovary syndrome (PCOS) is a common and complex disease caused by endocrine and metabolic dysfunction in women of reproductive age. Baicalin is reported to ameliorate PCOS. OBJECTIVE: This study determines whether baicalin could affect the progression of PCOS. MATERIALS AND METHODS: To establish an animal model of PCOS, female Sprague-Dawley (SD) rats were subcutaneously injected with dehydroepiandrosterone (DHEA, 60 mg/kg) for 20 days. Next, normal and PCOS mice were divided into 3 groups: control, PCOS, PCOS + Baicalin (20 mg/kg) groups. In addition, the levels of microRNA-874-3p (miR-874-3p) and microRNA-144 (miR-144) in ovarian tissues were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). RESULTS: Compared to the PCOS group, baicalin treatment significantly declined free testosterone (33.71 pg/mL vs. 56.05 pg/mL) and luteinizing hormone (LH; 3971.73 pg/mL vs. 5201.50 pg/mL) levels in rats with PCOS. Additionally, compared to the control group, 100 µM baicalin lessened miR-874-3p and miR-144 levels in human ovarian granulosa cells (KGN cells) by 36.87% and 32.57%, respectively. Furthermore, forkhead box O (FOXO) proteins FOXO1 and FOXO3 are the direct targets of miR-144 and miR-874-3p, respectively. Meanwhile, baicalin induced G0-G1 phase arrest (69.56 ± 3.7% at baicalin with 100 µM vs. 51.24 ± 3.2%, control) in KGN cells correlating with decreased p27 Kip1 (FOXO proteins downstream effector gene) expression by 55.5%; however, miR-874-3p or miR-144 overexpression could abolish this effect. CONCLUSIONS: Baicalin could alleviate the symptoms of PCOS via regulating miR-874-3p/FOXO3 and miR-144/FOXO1 axis, demonstrating its potential utility in PCOS treatment.

An MMAE-loaded PDL1 active targeting nanomedicine for the precision treatment of colon cancer.

Tumor-active-targeting drugs such as antibody-drug conjugates have emerged as promising accurate therapeutic agents. However, their complex preparations risk compromising the targeting ability of the fragment antigen binding (Fab) region and promote aggregation over long-term storage. Here, we propose a tumor-active-targeting nanomedicine, aPDL1-PLG-MMAE, that effectively targets programmed death-ligand 1 (PDL1) high-expressing tumors and delivers monomethyl auristatin E (MMAE). aPDL1-PLG-MMAE consists of an anti-PDL1 monoclonal antibody (aPDL1) and poly(L-glutamic acid) (PLG) grafted Fc-III-4C peptide/Val-Cit-PAB-MMAE (Fc-PLG-MMAE). Fc-PLG-MMAE was obtained by conjugating the Fc-III-4C peptide and Val-Cit-PAB-MMAE to PLG via amide condensation. The strong affinity between the fragment crystallizable (Fc) region of aPDL1 and the Fc-III-4C peptide enabled aPDL1 and Fc-PLG-MMAE to self-assemble into aPDL1-PLG-MMAE after four hours of coincubation in PBS. As this nanomedicine can be quickly prepared for immediate use, the required antibodies can be stored separately from the Fc-PLG-MMAE portion for extended periods, which also facilitates transport. Moreover, aPDL1-PLG-MMAE demonstrated robust tumor recognition and targeting effects on MC38 colon cancer cells, resulting in potent therapeutic efficacy without significant toxicities.