Lipid biomarkers indicate the dynamics of particulate organic carbon and its carbon sequestration effects during the degradation of Ulva prolifera.

Millions of tons of Ulva prolifera sink to the seafloor and gradually degrade after green tide occurred annually in the Yellow Sea, releasing substantial amounts of particulate organic carbon (POC) into marine environments. However, monitoring the dynamics of macroalgae-derived POC and its carbon sequestration effects is challenging due to severe environmental disturbances. Here, we conducted a long-term simulated degradation experiment with U. prolifera in the laboratory. During degradation, 86-90 % of U. prolifera-derived POC was readily degraded by microorganisms, while 10-14 % was stabilized in seawater as bio-recalcitrant POC. Microbial community structure underwent significant succession, driving the degradation of U. prolifera and the release and transformation of POC. 28-isofucosterol and POC concentrations changed concurrently and showed a significant positive correlation throughout the degradation. Hence, we propose that lipid biomarkers, i.e. 28-isofucosterol, can be used to track the release of U. prolifera-derived POC and to potentially reveal its carbon sequestration in marine environments.

Polymorphospora lycopeni sp. nov., a lycopene-producing actinomycetes isolated from lakeside soil sample of Baiyangdian.

A novel actinomycetes producing lycopene, designated HBU208002T, was isolated from a lakeside soil sample collected in Baiyangdian, located in Xiong'an New Area of China, and its taxonomic position was investigated by a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that the strain HBU208002T fell within the genus Polymorphospora and was closely related to Polymorphospora rubra JCM 14904T (99.73% identity). However, the average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH) and average amino acid identity (AAI) values between the strain HBU208002T and P. rubra JCM 14904T were 91.78, 44.7 and 91.6%, respectively, which were lower than the ANI (95-96%), DDH (>70%) and AAI (>95%) thresholds of prokaryotic microbial defined species. The predominant fatty acids of the strain HBU208002T were iso-C16:0, C17:1 ω8c. The menaquinones of the strain HBU208002T were MK-8(H8) and MK9(H4), while those of P. rubra JCM 14904T were MK-10(H6), MK-10(H4), MK-9(H6) and MK-9(H4). Meanwhile, some phenotypic characterizations and antibacterial activities distinguished the strain HBU208002T from P. rubra JCM 14904T. The strain HBU208002T exhibited inhibitory effects on Fusarium graminearum, Fusarium verticillioides and Botrytis cinerea, but P. rubra JCM 14904T had no activity. Therefore, the strain HBU208002T should be assigned as representing a novel species of the genus Polymorphospora, for which the name Polymorphospora lycopeni was proposed. The type strain is HBU208002T (=KCTC49833T = GDMCC4.236T).

Prenylated Dihydroflavonol from Sophora flavescens Regulate the Polarization and Phagocytosis of Macrophages In Vitro.

As an important member of innate immunity, macrophages show remarkable plasticity and heterogeneity, and play an important role in immune regulation, tissue development, homeostasis of the internal environment and injury repair. However, the excessive activation of macrophages is closely related to the occurrence and development of many diseases. The prenylated flavonoid structure is one of the characteristic structures isolated from Sophora flavescens, with anti-inflammatory, anti-tumor, anti-allergy and other effects. In this study, the effects of (2R)-3ß,7,4'-trihydroxy-5-methoxy-8-prenylflavanone (TMP), a prenylated dihydroflavonol, on the polarization and phagocytosis of macrophages were systematically studied. In LPS-induced M1-type macrophages, TMP dose-dependently inhibited the expression of COX-2, iNOS and the secretion of NO, IL-1ß, IL-6 and IL-18, showing an inhibitory effect on M1 polarization. Further experiments revealed that it was related to the inhibition of TLR4-related AKT/mTOR, MAPK and NF-κB signaling pathways; in IL-4-induced M2-type macrophages, TMP down-regulated the expression of M2-related Arg1, IL-10, TGF-ß, CD206 and CD163, as well as the phosphorylation levels of AKT1 and STAT6. For macrophages in a physiological state, it was very important for cells to return from a stress state to a phenotypic stability in the M0 state. These results indicated that TMP negatively regulated the M1/M2 polarization of macrophages, and made them tend to M0 homeostasis, which might provide new theoretical and data support for explaining the anti-inflammatory immunoregulatory activity of Sophora flavescens.

Improving physical and mental health in women with breast cancer undergoing anthracycline-based chemotherapy through wearable device-based aerobic exercise: a randomized controlled trial.

Purpose: Aimed to assess the impact of wearable device-based aerobic exercise on the physical and mental well-being of women with breast cancer (BC) undergoing chemotherapy. Methods: Forty adult women with BC who underwent anthracycline-based chemotherapy were randomly allocated to the exercise group (n = 21) or the control group (n = 19). Both groups received standard health education and oncology care. In addition, the exercise group wore wearable devices to engage in moderate to high-intensity (50-90% HRmax) aerobic exercise during chemotherapy, while the control group did not carry out exercise intervention. Health-related physical fitness level, physical activity energy expenditure (PAEE), anxiety and depression scores, sleep quality, cancer-related fatigue, and overall quality of life (QoL), were assessed both before (prior to the first chemotherapy session) and after (prior to the fifth chemotherapy session) the exercise intervention. Exercise-related adverse events, exercise compliance, number and severity of gastrointestinal reactions and myelosuppression occurred were recorded during the exercise intervention. Results: After the intervention, compared to the control group, the exercise group (1) had significantly higher relative VO2peak (p = 0.003) and handgrip strength (p < 0.001); (2) had significantly higher PAEE (p < 0.001); (3) had a significantly lower scores in anxiety (p = 0.007), depression (p = 0.028), sleep quality in domains of subjective sleep quality (p = 0.010), sleep disturbances (p = 0.004), daytime dysfunction (p = 0.007), cancer-related fatigue in domains of physical (p < 0.001) and affective (p < 0.001); and (4) had a significantly lower scores in QoL in domains of physical well-being (p < 0.001) and emotional well-being (p = 0.019), while a significantly higher scores in functional well-being (p < 0.001). Patients in the exercise group experienced less severe gastrointestinal reactions (p = 0.028) and myelosuppressive symptoms (p < 0.001) than that in the control group. Patients in the exercise group had no serious exercise-related adverse events, with a mean exercise adherence of 81.8%. Conclusion: Wearable device-based aerobic exercise during chemotherapy can be an effective adjunctive therapy to improve physical and mental health in BC patients. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=200247, Identifier: ChiCTR2300073667.

Morphology Control and Spectral Study of the 2D and Hierarchical Nanostructures Self-Assembled by the Chiral Alanine-Decorated Perylene Bisimides.

Tailoring the morphologies and optical properties of the 2D and hierarchical nanostructures self-assembled by the π-conjugated molecules is both interesting and challenging. Herein, a series of 2D ribbon-like nanostructures with single or multiple H-aggregated perylene bisimides (PBI) monolayer and hierarchical nanostructures (including straw-like, dumbbell-shaped, and rod-like nanostructures) are fabricated by solution self-assembly of three chiral alanine-decorated PBI. The influence of the solvent's dissolving capacity, the chirality of alanine, and the preparation methods on the morphologies and optical properties of the nanostructures were extensively studied. It was observed that the hierarchical nanostructures are formed by the reorganization of the 2D ribbon-like nanostructures. The size of the 2D ribbon-like nanostructures and the amount of the hierarchical nanostructures increase with the decrease in the solvent's dissolving capacity. The small chiral alanine moiety is unable to induce chirality in the nanostructures, owing to its low steric hindrance and the dominant strong π-π stacking interaction of the PBI skeleton. A weaker π-π stacking interaction and better H-aggregated arrangement of the PBI skeleton could reduce the low-wavelength fluorescence intensity. The process of heating, cooling, and aging promotes the formation of H-aggregation in the PBI skeleton. The region of spectral overlap of the PBI solutions increases with the decrease in the dissolving capacity of the solvent and the steric hindrance of the chiral alanine. This study supplies a view to tailor the morphologies and optical properties of the nanostructures, which could be used as sensors and photocatalysts.

High-intensity interval training vs. yoga in improving binge eating and physical fitness in inactive young females.

Yoga is effective in binge eating disorder (BED) treatment, but it does not seem effective enough to improve low physical fitness. In contrast, high-intensity interval training (HIIT) is effective in improving physical fitness but has never been studied in the context of BED. In the study, 47 young inactive females with mild to moderate BED were recruited and randomly assigned to a HIIT group (HIIT), a Yoga group (YG), or a control group (CG; age, 19.47 ± 0.74, 19.69 ± 0.874, and 19.44 ± 0.63 years; BMI, 21.07 ± 1.66, 21.95 ± 2.67, and 20.68 ± 2.61 kg/m2, respectively). The intervention groups participated in 8-week specific exercises, while the CG maintained their usual daily activity. Before and after the training, participants were evaluated for BED using the binge eating scale (BES) and for physical fitness. The obtained data were compared within groups and between groups, and a correlation analysis between BES and physical fitness parameters was performed. After the training, the YG presented significant improvements in BES (- 20.25%, p = 0.006, ηp2 = 0.408), fat mass (FM, - 3.13%, p = 0.033, ηp2 = 0.269), and maximal oxygen consumption (VO2max, 11.51%, p = 0.000, ηp2 = 0.601), whereas the HIIT showed significant improvements in body weight (BW, - 1.78%, p = 0.006, ηp2 = 0.433), FM (- 3.94%, p = 0.033, ηp2 = 0.285), and BMI (- 1.80%, p = 0.006, ηp2 = 0.428), but not in BES. Comparisons between groups revealed that both HIIT and YG had significantly higher VO2max levels than CG (HIIT 12.82%, p = 0.006, ηp2 = 0.088; YG: 11.90%, p = 0.009, ηp2 = 0.088) with no difference between HIIT and YG. Additionally, YG presented significantly lower BES than both HIIT (15.45%, p = 0.02, ηp2 = 0.03) and CG (11.91%, p = 0.022, ηp2 = 0.03). In conclusion, Yoga is an effective treatment for BED, but HIIT is not, despite its high efficacy in improving physical fitness.

Early emergence and determinants of human-induced Walker circulation weakening.

The Walker circulation is projected to slow down in response to greenhouse gas warming. However, detecting the impact of human activities on changes in the Walker circulation is challenging due to the significant influence of internal variability. Here, based on ensembles of multiple climate models from the Coupled Model Intercomparison Project Phase 6 (CMIP6), we show evidence that the emergence of the human-induced weakening of Walker circulation tends to occur earlier in the middle-upper troposphere than at the surface. This earlier emergence is attributed to a more pronounced initial weakening response of the middle-upper tropospheric Walker circulation to atmospheric CO2 radiative forcing. We further reveal that the emergence time of a weaker Walker circulation varies across models. This intermodel spread is governed by an ocean thermostat that operates by modulating the zonal sea surface temperature gradient over the tropical Indo-Pacific region. Our findings address the key question of whether and how to detect human-induced large-scale atmospheric circulation changes and provide valuable insights for assessing the associated risks.

Recent clinical researches and technological development in TIL therapy.

Tumor-infiltrating lymphocyte (TIL) therapy represents a groundbreaking advancement in the solid cancer treatment, offering new hope to patients and their families with high response rates and long overall survival. TIL therapy involves extracting immune cells from a patient's tumor tissue, expanding them ex vivo, and infusing them back into the patient to target and eliminate cancer cells. This revolutionary approach harnesses the power of the immune system to combat cancers, ushering in a new era of T cell-based therapies along with CAR-T and TCR-therapies. In this comprehensive review, we aim to elucidate the remarkable potential of TIL therapy by delving into recent advancements in basic and clinical researches. We highlight on the evolving landscape of TIL therapy as a prominent immunotherapeutic strategy, its multifaceted applications, and the promising outcomes. Additionally, we explore the future horizons of TIL therapy, next-generation TILs, and combination therapy, to overcome the limitations and improve clinical efficacy of TIL therapy.

DKK3 promotes adipogenic differentiation of stem cells by inhibiting Wnt/ß-catenin signaling pathway related gene expression and mitochondrial autophagy function.

Mesenchymal stem cells can differentiate into adipocyte precursor cells, and the balance of stem cell differentiation determines the quantity of adipocytes. Early-stage adipose tissue expression profiling revealed abnormal expression of DKK3 in the high-fat group. Moreover, DKK3 is enriched in the Wnt/ß-catenin signaling pathway, and studies have shown that DKK3 can serve as a gene involved in early regulation of adipogenesis. Therefore, this study focuses on exploring how DKK3 regulates the molecular mechanism of adipocyte differentiation through the Wnt/ß-catenin signaling pathway. In this experiment, the role of DKK3 in the differentiation of bone marrow mesenchymal stem cells into adipocyte precursors was validated using in vitro cultured chicken bone marrow mesenchymal stem cells. The results showed that overexpression of DKK3 led to a significant downregulation of Wnt/ß-catenin signaling pathway-related marker gene expression (P < 0.05), a significant upregulation of adipogenic differentiation-related genes (P < 0.05), an increase in lipid droplet content, a significant increase in OD value (P < 0.05), a significant upregulation of mitochondrial oxidative respiratory-related marker gene expression (P < 0.05), and a significant downregulation of mitochondrial autophagy-related marker genes (P < 0.05). Conversely, the results were opposite after interfering with DKK3 gene expression. In this study, 4 SNP sites, including g.8419139, g.8419556, g.8419560, and g.8419598, were detected in the 7th exon of DKK3, among which the g.8419598 (C > T) site was significantly correlated with abdominal fat weight and abdominal fat rate in 100-day-old Ma Huang chickens (P < 0.001).

Efficacy and Safety of Pioglitazone/Metformin Fixed-Dose Combination Versus Uptitrated Metformin in Patients with Type 2 Diabetes without Adequate Glycemic Control: A Randomized Clinical Trial.

INTRODUCTION: We aim to evaluate the efficacy and safety of pioglitazone/metformin fixed-dose combination (FDC) versus uptitrated metformin in patients with type 2 diabetes mellitus (T2DM) without adequate glycemic control. METHODS: A total of 304 patients were recruited from 15 hospitals in China and randomly assigned (1:1) to the test group (pioglitazone/metformin FDC, 15/500 mg) or the control group (uptitrated metformin, 2000-2500 mg/day). The primary endpoint was the proportion of patients with glycated hemoglobin A1c (HbA1c) ≤ 6.5% and ≤ 7.0% at week 16. The secondary outcomes included the change from baseline in glucose, serum lipids, and liver function. Full analysis set (FAS) and per-protocol set (PPS) were used for analyses. RESULTS: In the test group, 103 (69.59%) patients reached HbA1c ≤ 7.0% (FAS, P = 0.009), with 68 (45.95%) patients achieved HbA1c ≤ 6.5 (FAS, P = 0.043). More reduction in HbA1c, homeostatic model assessment for insulin resistance, and diastolic pressure was found. Bodyweight, body mass index, and high-density lipoprotein cholesterol increased markedly. The changes of triglycerides, alanine transaminase, aspartate aminotransferase, and high-sensitivity C-reactive protein decreased noticeably. There were no significant differences in rates of adverse events between the two groups. CONCLUSIONS: Pioglitazone/metformin FDC was superior to uptitrated metformin among patients with T2DM without adequate glycemic control. TRIAL REGISTRATION NUMBER: This trial is registered with the Chinese Clinical Trial Registry (ChiCTR1900028606).

A series of DNA targeted Cu (II) complexes containing 1,8-naphthalimide ligands: Synthesis, characterization and in vitro anticancer activity.

Copper(II) complexes are very promising candidates for platinum-based anticancer agents. Herein, three Cu (II) complexes (1-3) containing 1,8-naphthalimide ligands were synthesized and characterized by FT-IR, elemental analysis, ESI-MS and single crystal X-ray diffraction (complex 3). In addition, a control compound (complex 4) without 1,8-naphthalimide ligand was synthesized and characterized. The in vitro anticancer activity of the synthesized complexes against five cancer cell lines and one normal cell line was evaluated by MTS assay. The results displayed the antitumor activity of complexes 1-3 was controlled by the aliphatic chain length of ligands, their cytotoxicity was in the order 3 > 2 > 1, giving the IC50 values ranging from 2.874 ± 0.155 µM to 31.47 ± 0.29 µM against five cancer cell lines. Complex 4 showed less activity in comparison with complex 1-3. Notably, complexes 1-3 displayed much higher selectivity (SI = 2.65 to 10.16) compared to complex 4 (SI = 1.0), indicated that the introduction of 1,8-naphthalimide group not only increased the activity of this series of compounds but also enhanced their specific selectivity to cancer cells. Compound 3 induced apoptosis in cancer cells and blocked the S-phase and G2/M of cancer cells. The interaction with DNA of complexes 3 and 4 was studied by UV/Vis spectroscopic titrations, competitive DNA-binding experiment, viscometry and CD spectra. The results showed that complex 3 interacted with DNA in an intercalating mode, but the interaction mode of compound 4 with DNA was electrostatic interaction.

Sesquiterpenoids from the roots and rhizomes of Valeriana officinalis var. latifolia.

The genus Valeriana is used in traditional Chinese medicine to treat nervous disorders, sleep disorders, epilepsy and skin diseases. A large number of sesquiterpenoids from this genus have been found to exhibit anti-inflammatory, antiproliferative, anti-influenza virus and neuroprotective activities. In order to discover more sesquiterpenoids with structural diversity and bioactivity from Valeriana plants, fifteen sesquiterpenoids, including ten undescribed ones, valernaenes A-J (1, 5-7, 9-11 and 13-15), were isolated from the roots and rhizomes of Valeriana officinalis var. latifolia. Their structures were elucidated by extensive spectroscopic techniques (1D, 2D NMR and HRESIMS) and electronic circular dichroism (ECD) calculation. Structurally, valernaenes C (6) and D (7) were two caryophyllane-type norsesquiterpenoids. In addition, valernaenes A (1) and F (10) exhibited anti-influenza virus activity with EC50 values of 38.76 ± 1.44 and 23.01 ± 4.89 µM, respectively. Furthermore, caryophyllenol A (2) showed promoting effect on nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells with differentiation rate of 12.26% at a concentration of 10 µM. This study not only enriched the structural diversity of sesquiterpenoids in the genus Valeriana, but also provided theoretical basis for the discovery of anti-influenza virus and neuroprotective agents from this genus.

[Guidelines for traditional dietary care in autumn and winter].

The National Nutrition Plan(2017-2030) and the Healthy China Action Plan(2019-2030) propose to vigorously develop traditional dietary care services, fully leverage the role of traditional dietary care in modern nutrition, and guide citizens to develop dietary habits that are in line with the dietary characteristics of different regions in China. Traditional dietary care has a long history in China and is one of the brilliant treasures of Chinese cuisine and traditional Chinese medicine(TCM) culture. It has played an important role in disease prevention, treatment, and health preservation and longevity. To promote the traditional culture of TCM, and guide and standardize the application and promotion of dietary care, it is necessary to develop a dietary care guideline with TCM characteristics. Based on the theories and practices of TCM, the China Academy of Chinese Medical Sciences(CACMS) has developed this guideline, which is tailored to local conditions and combined with modern nutrition, and targets people with different physical constitutions. According to the principles of dialectical diet, tailored to people, times, and local conditions, reinforcing healthy qi, correction, the combination of meat and vegetables, and the combination of four qi and five flavors, suitable ingredients are recommended(including TCM materials that are both food and medicinal materials). By promoting the popularization and development of traditional dietary care, this guideline contributes to integrating the strength of TCM into a unique nutritional and health model with Chinese characteristics.

A low-swelling alginate hydrogel with antibacterial hemostatic and radical scavenging properties for open wound healing.

Development of a low-cost and biocompatible hydrogel dressing with antimicrobial, antioxidant, and low swelling properties is important for accelerating wound healing. Here, a multifunctional alginate hydrogel dressing was fabricated using the D-(+)-gluconic acidδ-lactone/CaCO3system. The addition of hyaluronic acid and tannic acid (TA) provides the alginate hydrogel with anti-reactive oxygen species (ROS), hemostatic, and pro-wound healing properties. Notably, soaking the alginate hydrogel in a poly-ϵ-lysine (EPL) aqueous solution enables the alginate hydrogel to be di-crosslinked with EPL through electrostatic interactions, forming a dense network resembling 'armor' on the surface. This simple one-step soaking strategy provides the alginate hydrogel with antibacterial and anti-swelling properties. Swelling tests demonstrated that the cross-sectional area of the fully swollen multifunctional alginate hydrogel was only 1.3 times its initial size, thus preventing excessive wound expansion caused by excessive swelling. After 5 h ofin vitrorelease, only 7% of TA was cumulatively released, indicating a distinctly slow-release behavior. Furthermore, as evidenced by the removal of 2,2-diphenyl-1-picrylhydrazyl free radicals, this integrated alginate hydrogel systems demonstrate a notable capacity to eliminate ROS. Full-thickness skin wound repair experiment and histological analysis of the healing site in mice demonstrate that the developed multifunctional alginate hydrogels have a prominent effect on extracellular matrix formation and promotion of wound closure. Overall, this study introduces a cost-effective and convenient multifunctional hydrogel dressing with high potential for clinical application in treating open wounds.

Widely Targeted Metabolomic Analysis Reveals Dynamic Metabolic Changes in Yanbian Cattle during Dry-Aging Process.

Dry-aging is a postmortem process that can substantially enhance the texture and flavour of beef. This study entailed suspending Yanbian cattle M. gluteus medius in the aging cabinet, maintained at a temperature of 2-4 °C and a relative humidity of 85 ± 5% for 35 days. Throughout this period, samples were systematically collected every 7 days. The widely targeted metabolomic analysis has been used in this investigation to analyse the dynamic changes in Yanbian cattle metabolites during dry-aging. A total of 883 metabolites were identified, with amino acids and their metabolites representing the largest proportion. Multivariate statistical analysis showed that 373 metabolites were identified as differential metabolites that changed significantly during the dry-aging process, including metabolites of amino acids, glycerophospholipids, and nucleotides and their metabolites. Additionally, 308 metabolites exhibited various increasing trends with time in dry-aging. The analysis of KEGG pathway analysis showed that ABC transporters, glycerophospholipid, and arachidonic acid metabolism are the most important metabolic pathways during dry-aging. These findings can guide technological developments in the meat processing sector and provide valuable insights into the metabolic traits and pathways of Yanbian cattle during the dry-aging process.

Effect of Alloying on Microstructure and Mechanical Properties of AlCoCrFeNi2.1 Eutectic High-Entropy Alloy.

In order to explore the effect of alloying on the microstructures and mechanical properties of AlCoCrFeNi2.1 eutectic high-entropy alloys (EHEAs), 0.1, 0.2, and 0.3 at.% V, Mo, and B were added to the AlCoCrFeNi2.1 alloy in this work. The effects of the elements and contents on the phase composition, microstructures, mechanical properties, and fracture mechanism were investigated. The results showed that the crystal structures of the AlCoCrFeNi2.1 EHEAs remained unchanged, and the alloys were still composed of FCC and BCC structures, whose content varied with the addition of alloying elements. After alloying, the aggregation of Co, Cr, Al, and Ni elements remained unchanged, and the V and Mo were distributed in both dendritic and interdendritic phases. The tensile strengths of the alloys all exceeded 1000 MPa when the V and Mo elements were added, and the Mo0.2 alloy had the highest tensile strength, of 1346.3 MPa, and fracture elongation, of 24.6%. The alloys with the addition of V and Mo elements showed a mixed ductile and brittle fracture, while the B-containing alloy presented a cleavage fracture. The fracture mechanism of Mo0.2 alloy is mainly crack propagation in the BCC lamellae, and the FCC dendritic lamellae exhibit the characteristics of plastic deformation.

An Ingenane-Type Diterpene from Euphorbia kansui Promoted Cell Apoptosis and Macrophage Polarization via the Regulation of PKC Signaling Pathways.

Euphorbia kansui, a toxic Chinese medicine used for more than 2000 years, has the effect of "purging water to promote drinking" and "reducing swelling and dispersing modules". Diterpenes and triterpenes are the main bioactive components of E. kansui. Among them, ingenane-type diterpenes have multiple biological activities as a protein kinase C δ (PKC-δ) activator, which have previously been shown to promote anti-proliferative and pro-apoptotic effects in several human cancer cell lines. However, the activation of PKC subsequently promoted the survival of macrophages. Recently, we found that 13-hydroxyingenol-3-(2,3-dimethylbutanoate)-13-dodecanoate (compound A) from E. kansui showed dual bioactivity, including the inhibition of tumor-cell-line proliferation and regulation of macrophage polarization. This study identifies the possible mechanism of compound A in regulating the polarization state of macrophages, by regulating PKC-δ-extracellular signal regulated kinases (ERK) signaling pathways to exert anti-tumor immunity effects in vitro, which might provide a new treatment method from the perspective of immune cell regulation.

Monosome Stalls the Translation Process Mediated by IGF2BP in Arcuate Nucleus for Puberty Onset Delay.

Puberty onset through hypothalamic-pituitary-gonad (HPG) axis as an important reproductive event in postnatal development is initiated from hypothalamic arcuate nucleus (ARC). The growing evidence indicates that translational control also plays an essential role in the final expression of gonadotropin genes. To investigate the role of protein translation and behavior of ribosomes in pubertal onset, the global profiles of transcriptome, single ribosome (monosome), polysome, and tandem mass tag proteome were comprehensively investigated in rat hypothalamic ARCs of different pubertal stages using RNA sequencing, polyribo sequencing, and mass spectrum. Transcriptome-wide enrichments of N6-methyladenosine and IGF2BP2 were investigated using meRIP and RIP sequencing. Monosome was robustly enriched on a large proportion of mRNA in early puberty rats (postnatal day (PND)-25) compared to late puberty (PND-35 and PND-45). Monosome-enriched mRNAs, including HPG axis-related genes, had a large number of upstream ORFs (uORF, < 100 nt) and displayed translational repression in early puberty. Furthermore, insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) could particularly interact with and facilitate monosome to bind with mRNA in early puberty. Finally, ectopic over-expression of IGF2BP2 in hypothalamic ARC via lateral ventricle injection in vivo could recruit monosome to aggregate on mRNA and delay puberty onset. We uncovered a novel regulatory mechanism of IGF2BP2 and monosome for translational control in puberty onset, which shed light on the neuroendocrine regulatory network involved in HPG axis activation.