Coherence sidelobe suppression of laser diode by white-noise-current modulation and external cavity feedback.

A coherence sidelobe suppression method for a laser diode (LD) is proposed, based on the white-noise-current modulation and external cavity feedback. The theoretical model of the coherence of the white-noise-current-modulated external cavity laser (WECL) is established, which details the spectrum broadening mechanism and the coherence sidelobe suppression. At the noise current modulation, the coherence sidelobe induced by the internal cavity is lowered by the external cavity feedback, and the position of the coherence sidelobe induced by the external cavity is controlled with the cavity length, which can extend the coherence range without the sidelobes. The experimental results demonstrate that the 98.4% sidelobe suppression ratio (SLSR) of the WECL is achieved in dynamic interferometry, which is about 20% higher than that of the laser diode only with the white-noise-current modulation. This new, to the best of our knowledge, method can avoid the stray fringe cross talk caused by the multiple coherence sidelobes in the surface error measurements of parallel plates.

Metabolome and transcriptome integration explored the mechanism of browning in Glycyrrhiza uralensis Fisch cells.

Introduction: Glycyrrhiza uralensis Fisch, a traditional Chinese medicinal herb known for its diverse pharmacological effects including heat-clearing, detoxification, phlegm dissolving, and cough relief, has experienced an exponential increase in demand due to its expanding clinical use and development prospects. Currently, large-scale cell culture stands out as one of the most promising biotechnological approaches for producing bioactive compounds from medicinal plants. However, the problem of cell browning represents a significant bottleneck in industrial applications of cell culture. Methods: This study focuses on the Glycyrrhiza uralensis Fisch cells from the Ordos plateau, aiming to elucidate the enzymatic browning process during plant cell culture. Key substrates and genes involved in enzymatic browning were identified by metabolome and transcriptome analysis of normal and browning cells. Results: Metabolome analysis reveals significant changes in the levels of chalcone, isoflavone, imidazole-pyrimidine, purine nucleosides, organic oxides, carboxylic acids and their derivatives, benzene and its derivatives, flavonoids, 2-arylated benzofuran flavonoids, diazanaphthalenes and fatty acyls within browning cells. In particular, chalcones, isoflavones, and flavones compounds account for a higher proportion of these changes. Furthermore, these compounds collectively show enrichment in four metabolic pathways: Isoflavone biosynthesis pathway; Cutin suberine and wax biosynthesis pathway; Aminoacyl-tRNA biosynthesis pathway; Isoquinoline alkaloid biosynthesis pathway; Transcriptome analysis revealed that the MYB transcription factor is a key regulator of flavonoid synthesis during the browning process in cells. In addition, 223 differentially expressed genes were identified, including phenylpropane, shikimic acid, glycolysis, and pentose phosphate pathways. Among these genes, 23 are directly involved in flavonoid biosynthesis; qPCR validation showed that eight genes (GlPK, GlPAL, Gl24CL, Gl1PDT, Gl3CHI, GlC4H, Gl2F3'H, and Gl2CCR) were up-regulated in browning cells compared to normal cells. These findings corroborate the sequencing results and underscore the critical role of these genes in cellular browning. Discussion: Consequently, modulation of their expression offers promising strategies for effective control of cellular browning issues.

Microstructures and Rheological Properties of Short-Side-Chain Perfluorosulfonic Acid in Water/2-Propanol.

The viscosity and viscoelasticity of polyelectrolyte solutions with a single electrostatic interaction have been carefully studied experimentally and theoretically. Despite some theoretical models describe experimental results well, the influence of multiple interactions (electrostatic and hydrophobic) on rheological scaling is not yet fully resolved. Herein, we systematically study the microstructures and rheological properties of short-side-chain perfluorosulfonic acid (S-PFSA), the most promising candidate of a proton exchange membrane composed of a hydrophobic backbone with hydrophilic side-chains, in water/2-propanol. Small-angle X-ray scattering confirms that semiflexible S-PFSA colloidal particles with a length of ~38 nm and a diameter of 1-1.3 nm are formed, and the concentration dependence of the correlation length (ξ) obeys the power law ξ~c-0.5 consistent with the prediction of Dobrynin et al. By combining macrorheology with diffusing wave spectroscopy microrheology, the semidilute unentangled, semidilute entangled, and concentrated regimes corresponding to the scaling relationships ηsp~c0.5, ηsp~c1.5, and ηsp~c4.1 are determined. The linear viscoelasticity indicates that the entanglement concentration (ce) obtained from the dependence of ηsp on the polymer concentration is underestimated owing to hydrophobic interaction. The true entanglement concentration (cte) is obtained by extrapolating the plateau modulus (Ge) to the terminal modulus (Gt). Furthermore, Ge and the plateau width, τr/τe (τr and τe denote reptation time and Rouse time), scale as Ge~c2.4 and τr/τe~c4.2, suggesting that S-PFSA dispersions behave like neutral polymer solutions in the concentrated regime. This work provides mechanistic insight into the rheological behavior of an S-PFSA dispersion, enabling quantitative control over the flow properties in the process of solution coating.

A novel nomogram and survival analysis for different lymph node status in breast cancer based on the SEER database.

INTRODUCTION: The axillary lymph node status (ALNS) and internal mammary lymph nodes (IMLN) expression associated with breast cancer are closely linked to prognosis. This study aimed to establish a nomogram to predict survival at 3, 5, and 10 years in patients with various lymph node statuses. METHODS: We obtained data from patients with breast cancer between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER database). Chi-square analysis was performed to test for differences in the pathological characteristics of the groups, and Kaplan-Meier analysis and the log-rank test were used to plot and compare the correlation between overall survival (OS) and breast cancer specific survival (BCSS). The log-rank test was used for the univariate analysis, and statistically significant characteristics were included in the multivariate and Cox regression analyses. Finally, Independent factor identification was included in constructing the nomogram using R studio 4.2.0; area under curve (AUC) values were calculated, and receiver operating characteristic (ROC) curve, calibration, and decision curve analysis (DCA) curves were plotted for evaluation. RESULTS: A total of 279,078 patients were enrolled and analysed, demonstrating that the isolated tumour cells (ITC) group had clinicopathological characteristics similar to those of micrometastases (Mic). Multivariate analysis was performed to identify each subgroup's independent risk factors and construct a nomogram. The AUC values were 74.7 (95% CI 73.6-75.8), 72.8 (95% CI 71.9-73.8), and 71.2 (95% CI 70.2-72.2) for 3-, 5-, and 10-year OS, respectively, and 82.2 (95% CI 80.9-83.6), 80.1 (95% CI 79.0-81.2), and 75.5 (95% CI 74.3-76.8) for BCSS in overall breast cancer cases, respectively. AUC values for 3-, 5-, and 10-year OS in the ITC group were 64.8 (95% CI 56.5-73.2), 67.7 (95% CI 62.0-73.4), and 65.4 (95% CI 60.0-70.7), respectively. For those in the Mic group, AUC values for 3-, 5-, and 10-year OS were 72.9 (95% CI 70.7-75.1), 72.4 (95% CI 70.6-74.1), and 71.3 (95% CI 69.6-73.1), respectively, and AUC values for BCSS were 77.8 (95% CI 74.9-80.7), 75.7 (95% CI 73.5-77.9), and 70.3 (95% CI 68.0-72.6), respectively. In the IMLN group, AUC values for 3-, 5-, and 10-year OS were 75.2 (95% CI 71.7-78.7), 73.4 (95% CI 70.0-76.8), and 74.0 (95% CI 69.6-78.5), respectively, and AUC values for BCSS were 76.6 (95% CI 73.0-80.3), 74.1 (95% CI 70.5-77.7), and 74.7 (95% CI 69.8-79.5), respectively. The ROC, calibration, and DCA curves verified that the nomogram had better predictability and benefits. CONCLUSION: This study is the first to investigate the predictive value of different axillary lymph node statuses and internal mammary lymph node metastases in breast cancer, providing clinicians with additional aid in treatment decisions.

LncRNA SH3BP5-AS1 promotes hepatocellular carcinoma progression by sponging miR-6838-5p and activation of PTPN4.

BACKGROUND: Long noncoding RNAs (LncRNAs) have been demonstrated to have significant roles in the carcinogenesis of hepatocellular carcinoma (HCC). In this work, we sought to determine LncRNA SH3BP5-AS1's function and mechanism in the emergence of HCC. RESULTS: First, we discovered that the advanced tumor stage was strongly correlated with high levels of LncRNA SH3BP5-AS1 expression in HCC. MiR-6838-5p expression was down-regulated and inversely correlated with SH3BP5-AS1 expression. Additionally, overexpression of SH3BP5-AS1 boosted cell invasion, migration, and proliferation. The oncogenic effects of the inhibitor of miR-6838-5p were eliminated when PTPN4 was suppressed, following the identification of PTPN4 as a direct target of miR-6838-5p. In addition, SH3BP5-AS1 promoted cellular glycolysis via miR-6838-5p sponging and PTPN4 activation. Lastly, by directly interacting to the promoter of SH3BP5-AS1, HIF-1α could control the transcription of the gene. CONCLUSIONS: Our research suggests that SH3BP5-AS1 controls miR-6838-5p/PTPN4 in order to act as a new carcinogenic LncRNA during the growth of HCC cells. METHODS: The expression levels of SH3BP5-AS1, miR-6838-5p and PTPN4 were detected by qRT-PCR and Western blot. The effects of LncRNA SH3BP5-AS1/miR-6838-5p/PTPN4 on the proliferation, metastasis and glycolysis of HCC cells were clarified by experimental cellular functionality assays, cell derived xenograft and Glycolysis assay.

Biocompatible aggregation-induced emission active polyphosphate-manganese nanosheets with glutamine synthetase-like activity in excitotoxic nerve cells.

Glutamine synthetase (GS) is vital in maintaining ammonia and glutamate (Glu) homeostasis in living organisms. However, the natural enzyme relies on adenosine triphosphate (ATP) to activate Glu, resulting in impaired GS function during ATP-deficient neurotoxic events. To date, no reports demonstrate using artificial nanostructures to mimic GS function. In this study, we synthesize aggregation-induced emission active polyP-Mn nanosheets (STPE-PMNSs) based on end-labeled polyphosphate (polyP), exhibiting remarkable GS-like activity independent of ATP presence. Further investigation reveals polyP in STPE-PMNSs serves as phosphate source to activate Glu at low ATP levels. This self-feeding mechanism offers a significant advantage in regulating Glu homeostasis at reduced ATP levels in nerve cells during excitotoxic conditions. STPE-PMNSs can effectively promote the conversion of Glu to glutamine (Gln) in excitatory neurotoxic human neuroblastoma cells (SH-SY5Y) and alleviate Glu-induced neurotoxicity. Additionally, the fluorescence signal of nanosheets enables precise monitoring of the subcellular distribution of STPE-PMNSs. More importantly, the intracellular fluorescence signal is enhanced in a conversion-responsive manner, allowing real-time tracking of reaction progression. This study presents a self-sustaining strategy to address GS functional impairment caused by ATP deficiency in nerve cells during neurotoxic events. Furthermore, it offers a fresh perspective on the potential biological applications of polyP-based nanostructures.

A Ferroptosis-Inducing Arsenene-Iridium Nanoplatform for Synergistic Immunotherapy in Pancreatic Cancer.

Due to multidrug resistance and the high risk of recurrence, effective and less toxic alternative pancreatic cancer treatments are urgently needed. Pancreatic cancer cells are highly resistant to apoptosis but sensitive to ferroptosis. In this study, an innovative nanoplatform (AsIr@PDA) was developed by electrostatic adsorption of a cationic iridium complex (IrFN) onto two-dimensional (2D) arsenene nanosheets. This nanoplatform exhibits superior ferroptosis-inducing effects with high drug loading capacity and, importantly, excellent anti-cancer immune activation function, leading to efficient elimination of pancreatic tumors with no observable side effects. Interestingly, AsIr@PDA significantly prevents the recurrence of pancreatic cancer in vivo when compared with a cisplatin-loaded nanoplatform. This designed nanoplatform demonstrated superior therapeutic efficacy by synergistic ferroptosis-induced chemotherapy with immunotherapy via an all-in-one strategy, providing new insights for future pancreatic cancer therapy.

A New Biocontrol Agent Bacillus velezensis SF334 against Rubber Tree Fungal Leaf Anthracnose and Its Genome Analysis of Versatile Plant Probiotic Traits.

Natural rubber is an important national strategic and industrial raw material. The leaf anthracnose of rubber trees caused by the Colletotrichum species is one of the important factors restricting the yields of natural rubber. In this study, we isolated and identified strain Bacillus velezensis SF334, which exhibited significant antagonistic activity against both C. australisinense and C. siamense, the dominant species of Colletotrichum causing rubber tree leaf anthracnose in the Hainan province of China, from a pool of 223 bacterial strains. The cell suspensions of SF334 had a significant prevention effect for the leaf anthracnose of rubber trees, with an efficacy of 79.67% against C. siamense and 71.8% against C. australisinense. We demonstrated that SF334 can lead to the lysis of C. australisinense and C. siamense mycelia by causing mycelial expansion, resulting in mycelial rupture and subsequent death. B. velezensis SF334 also harbors some plant probiotic traits, such as secreting siderophore, protease, cellulase, pectinase, and the auxin of indole-3-acetic acid (IAA), and it has broad-spectrum antifungal activity against some important plant pathogenic fungi. The genome combined with comparative genomic analyses indicated that SF334 possesses most genes of the central metabolic and gene clusters of secondary metabolites in B. velezensis strains. To our knowledge, this is the first time a Bacillus velezensis strain has been reported as a promising biocontrol agent against the leaf anthracnose of rubber trees caused by C. siamense and C. australisinense. The results suggest that B. velezensis could be a potential candidate agent for the leaf anthracnose of rubber trees.

Immediate Pose Recovery Method for Untracked Frames in Feature-Based SLAM.

In challenging environments, feature-based visual SLAM encounters frequent failures in frame tracking, introducing unknown poses to robotic applications. This paper introduces an immediate approach for recovering untracked camera poses. Through the retrieval of key information from elapsed untracked frames, lost poses are efficiently restored with a short time consumption. Taking account of reconstructed poses and map points during local optimizing, a denser local map is constructed around ambiguous frames to enhance the further SLAM procedure. The proposed method is implemented in a SLAM system, and monocular experiments are conducted on datasets. The experimental results demonstrate that our method can reconstruct the untracked frames in nearly real time, effectively complementing missing segments of the trajectory. Concurrently, the accuracy and robustness for subsequent tracking are improved through the integration of recovered poses and map points.

Ultrathin 2D As2Se3 Nanosheets for Photothermal-Triggered Cancer Immunotherapy.

Arsenic trioxide (As2O3) has achieved groundbreaking success in the treatment of acute promyelocytic leukemia (APL). However, its toxic side effects seriously limit its therapeutic application in the treatment of solid tumors. To detoxify the severe side effects of arsenic, herein we synthesized innovative 2D ultrathin As2Se3 nanosheets (As2Se3 NSs) with synergistic photothermal-triggered immunotherapy effects. As2Se3 NSs are biocompatible and biodegradable under physiological conditions and can release As(III) and Se(0). Furthermore, selenium increases the immunomodulatory efficacy of arsenic treatments, facilitating reprogramming of the tumor microenvironment by As2Se3 NSs by enhancing the infiltration of natural killer cells and effector tumor-specific CD8+ T cells. The synergistic combination of photothermal therapy and immunotherapy driven by As2Se3 NSs via a simple but effective all-in-one strategy achieved efficient anticancer effects, addressing the key limitations of As2O3 for solid tumor treatment. This work demonstrates not only the great potential of selenium for detoxifying arsenic but also the application of 2D As2Se3 nanosheets for cancer therapy.

S100A8/A9 promotes endometrial fibrosis via regulating RAGE/JAK2/STAT3 signaling pathway.

Intrauterine adhesion (IUA) is characterized by endometrial fibrosis. S100A8/A9 plays an important role in inflammation and fibroblast activation. However, the role of S100A8/A9 in IUA remains unclear. In this study, we collect normal and IUA endometrium to verify the expression of S100A8/A9. Human endometrial stromal cells (hEnSCs) are isolated to evaluate fibrosis progression after S100A8/A9 treatment. A porcine IUA model is established by electrocautery injury to confirm the therapeutic effect of menstrual blood-derived stromal cells (MenSCs) on IUA. Our study reveals increased S100A8/A9 expression in IUA endometrium. S100A8/A9 significantly enhances hEnSCs proliferation and upregulates fibrosis-related and inflammation-associated markers. Furthermore, S100A8/A9 induces hEnSCs fibrosis through the RAGE-JAK2-STAT3 pathway. Transplantation of MenSCs in a porcine IUA model notably enhances angiogenesis, mitigates endometrial fibrosis and downregulates S100A8/A9 expression. In summary, S100A8/A9 induces hEnSCs fibrosis via the RAGE-JAK2-STAT3 pathway, and MenSCs exhibit marked effects on endometrial restoration in the porcine IUA model.

Body Weight Correlates with Molecular Variances in Patients with Cancer.

Overweight and obesity are identified by a high body mass index (BMI) and carry significant health risks due to associated comorbidities. Although epidemiologic data connect overweight/obesity with 13 cancer types, a better understanding of the molecular mechanisms underlying this correlation is needed to improve prevention and treatment strategies. In this study, we conducted a comprehensive analysis of molecular differences between overweight or obese patients and normal weight patients across 14 different cancer types from The Cancer Genome Atlas. Using the propensity score weighting algorithm to control for confounding factors, obesity-specific mutational features were identified, such as higher mutation burden in rectal cancer and biased mutational signatures in other cancers. Differentially expressed genes (DEG) in tumors from patients with overweight/obesity were predominantly upregulated and enriched in inflammatory and hormone-related pathways. These DEGs were significantly associated with survival rates in various cancer types, highlighting the impact of elevated body fat on gene expression profiles and clinical outcomes in patients with cancer. Interestingly, while high BMI seemed to have a negative impact on most cancer types, the normal weight-biased mutational and gene expression patterns indicated overweight/obesity may be beneficial in endometrial cancer, suggesting the presence of an "obesity paradox" in this context. Body fat also significantly impacted the tumor microenvironment by modulating immune cell infiltration, underscoring the importance of understanding the interplay between weight and immune response in cancer progression. Together, this study systematically elucidates the molecular differences corresponding to body weight in multiple cancer types, offering potentially critical insights for developing precision therapy for patients with cancer. SIGNIFICANCE: Elucidation of the complex interplay between body weight and the molecular landscape of cancer could potentially guide tailored therapies and improve patient management amid the global obesity crisis.

Co(III)-Catalyzed C6-Selective C-H Activation/Pyridine Migration of 2-Pyridones with Propiolates.

A versatile Co(III)-catalyzed C6-selective C-H activation/pyridine migration of 2-pyridones with available propiolates as coupling partners was demonstrated. This method features high atom economy, excellent regioselectivity, and good functional group tolerance by employing an inexpensive Co(III) catalyst under mild reaction conditions. Moreover, gram-scale synthesis and late-stage modifications of pharmaceuticals were performed to prove the effectiveness of these synthetic approaches.

Altered expression of the L-arginine/nitric oxide pathway in ovarian cancer: metabolic biomarkers and biological implications.

MOTIVATION: Ovarian cancer (OC) is a highly lethal gynecological malignancy. Extensive research has shown that OC cells undergo significant metabolic alterations during tumorigenesis. In this study, we aim to leverage these metabolic changes as potential biomarkers for assessing ovarian cancer. METHODS: A functional module-based approach was utilized to identify key gene expression pathways that distinguish different stages of ovarian cancer (OC) within a tissue biopsy cohort. This cohort consisted of control samples (n = 79), stage I/II samples (n = 280), and stage III/IV samples (n = 1016). To further explore these altered molecular pathways, minimal spanning tree (MST) analysis was applied, leading to the formulation of metabolic biomarker hypotheses for OC liquid biopsy. To validate, a multiple reaction monitoring (MRM) based quantitative LCMS/MS method was developed. This method allowed for the precise quantification of targeted metabolite biomarkers using an OC blood cohort comprising control samples (n = 464), benign samples (n = 3), and OC samples (n = 13). RESULTS: Eleven functional modules were identified as significant differentiators (false discovery rate, FDR < 0.05) between normal and early-stage, or early-stage and late-stage ovarian cancer (OC) tumor tissues. MST analysis revealed that the metabolic L-arginine/nitric oxide (L-ARG/NO) pathway was reprogrammed, and the modules related to "DNA replication" and "DNA repair and recombination" served as anchor modules connecting the other nine modules. Based on this analysis, symmetric dimethylarginine (SDMA) and arginine were proposed as potential liquid biopsy biomarkers for OC assessment. Our quantitative LCMS/MS analysis on our OC blood cohort provided direct evidence supporting the use of the SDMA-to-arginine ratio as a liquid biopsy panel to distinguish between normal and OC samples, with an area under the ROC curve (AUC) of 98.3%. CONCLUSION: Our comprehensive analysis of tissue genomics and blood quantitative LC/MSMS metabolic data shed light on the metabolic reprogramming underlying OC pathophysiology. These findings offer new insights into the potential diagnostic utility of the SDMA-to-arginine ratio for OC assessment. Further validation studies using adequately powered OC cohorts are warranted to fully establish the clinical effectiveness of this diagnostic test.

Loss of Ptpmt1 limits mitochondrial utilization of carbohydrates and leads to muscle atrophy and heart failure in tissue-specific knockout mice.

While mitochondria in different tissues have distinct preferences for energy sources, they are flexible in utilizing competing substrates for metabolism according to physiological and nutritional circumstances. However, the regulatory mechanisms and significance of metabolic flexibility are not completely understood. Here, we report that the deletion of Ptpmt1, a mitochondria-based phosphatase, critically alters mitochondrial fuel selection - the utilization of pyruvate, a key mitochondrial substrate derived from glucose (the major simple carbohydrate), is inhibited, whereas the fatty acid utilization is enhanced. Ptpmt1 knockout does not impact the development of the skeletal muscle or heart. However, the metabolic inflexibility ultimately leads to muscular atrophy, heart failure, and sudden death. Mechanistic analyses reveal that the prolonged substrate shift from carbohydrates to lipids causes oxidative stress and mitochondrial destruction, which in turn results in marked accumulation of lipids and profound damage in the knockout muscle cells and cardiomyocytes. Interestingly, Ptpmt1 deletion from the liver or adipose tissue does not generate any local or systemic defects. These findings suggest that Ptpmt1 plays an important role in maintaining mitochondrial flexibility and that their balanced utilization of carbohydrates and lipids is essential for both the skeletal muscle and the heart despite the two tissues having different preferred energy sources.

Cells are powered by mitochondria, a group of organelles that produce chemical energy in the form of molecules called ATP. This energy is derived from the breakdown of carbohydrates, fats, and proteins. The number of mitochondria in a cell and the energy source they use to produce ATP varies depending on the type of cell. Mitochondria can also switch the molecules they use to produce energy when the cell is responding to stress or disease. The heart and the skeletal muscles ­ which allow movement ­ are two tissues that require large amounts of energy, but it remained unknown whether disrupting mitochondrial fuel selection affects how these tissues work. To answer these questions, Zheng, Li, Li et al. investigated the role of an enzyme found in mitochondria called Ptpmt1. Genetically deleting Ptpmt1 in the heart and skeletal muscle of mice showed that while the development of these organs was not affected, mitochondria in these cells switched from using carbohydrates to using fats as an energy source. Over time, this shift damaged both the mitochondria and the tissues, leading to muscle wasting, heart failure, and sudden death in the mice. This suggests that balanced use of carbohydrates and fats is essential for the muscles and heart. These findings imply that long-term use of medications that alter the fuel that mitochondria use may be detrimental to patients' health and could cause heart dysfunction. This may be important for future drug development, as well as informing decisions about medication taken in the clinic.

Exosomes derived from menstrual blood stromal cells ameliorated premature ovarian insufficiency and granulosa cell apoptosis by regulating SMAD3/AKT/MDM2/P53 pathway via delivery of thrombospondin-1.

Premature ovarian insufficiency (POI) is clinically irreversible and seriously damages female fertility. We previously demonstrated that menstrual blood stromal cells (MenSCs)-derived exosomes (EXOs) effectively improved ovarian functions in the POI rat model. In this study, we investigated whether TSP1 is the key component in EXOs to ameliorate ovarian functions and further explored the molecular mechanism of EXOs in improving granulosa cell (GCs) activities. Our results demonstrated that knockdown TSP1 significantly debilitated the therapeutic effect of EXOs on estrous cyclicity, ovarian morphology, follicle numbers and pregnancy outcomes in 4-vinylcyclohexene diepoxide (VCD) induced POI rat model. In addition, EXOs treatment significantly promoted the activities and inhibited the apoptosis of VCD induced granulosa cells in vitro. Moreover, EXOs stimulation markedly activated the phosphorylation of SMAD3(Ser425) and AKT(Ser473), up-regulated the expressions of BCL2 and MDM2 as well as down-regulated the expressions of CASPASE3, CASPASE8, P53 and BAX. All these effects were supressed by SIS3, a inhibitor of TGF1/SMAD3. Our study revealed the key role of TSP1 in EXOs in improving POI pathology, restoring ovarian functions and GCs activities, andprovided a promising basis for EXOs in the treatment of ovarian dysfunction.

All-fiber orthogonal-polarized white-noise-modulated laser for short-coherence dynamic interferometry.

An all-fiber orthogonal-polarized white-noise-modulated laser (AOWL) for short-coherence dynamic interferometry is proposed. Short-coherence laser is achieved by current modulating of a laser diode with the band-limited white noise. A pair of orthogonal-polarized lights with adjustable delay for short-coherence dynamic interferometry are output by the all-fiber structure. In the non-common-path interferometry, the AOWL can significantly suppress the interference signal clutter with 73% side lobe suppression ratio, that improves the positioning accuracy of zero optical path difference. The wavefront aberrations of a parallel plate are measured with the AOWL in the common-path dynamic interferometers, avoiding the fringe crosstalk.

A Novel Three-Dimensional Follicle Culture System Decreases Oxidative Stress and Promotes the Prolonged Culture of Human Granulosa Cells.

Tissue engineering advancements have made it possible to modify biomaterials to reconstruct a similar three-dimensional structure of the extracellular matrix (ECM) for follicle development and to supply the required biological signals. We postulated that an artificial polysaccharide hydrogel modified with an ECM mimetic peptide may produce efficient irritation signals by binding to specific integrins providing a suitable environment for follicular development and influencing the behavior of human granulosa cells (hGCs). Laminin, an important component of the extracellular matrix, can modulate hGCs and oocyte growth. Specifically, follicles of mice were randomly divided into two-dimensional (2D) and three-dimensional (3D) culture systems established by a hydrogel modified with RGD or laminin mimetic peptides (IKVAV and YIGSR) and RGD (IYR). Our results showed that 3D cultured systems significantly improved follicle survival, growth, and viability. IYR peptides enhanced the oocyte meiosis competence. Additionally, we explored the effect of 3D culture on hGCs, which improved hGCs viability, increased the proportion of S- and G2/M-phase cells, and inhibited cell apoptosis of hGCs. On days 1 and 2, the secretion of progesterone was reduced in 3D-cultured hGCs. Notably, 3D-cultured hGCs exhibited delayed senescence, decreased oxidative stress, and elevated mitochondrial membrane potential. Moreover, the expression levels of cumulus expansion-related genes (COX2, HAS2, and PTX3) and integrin α6ß1 were upregulated in 3D-cultured hGCs. In conclusion, a 3D culture utilizing hydrogels modified with Laminin-mimetic peptides can provide a durable physical environment suitable for follicular development. The laminin-mimetic peptides may regulate the biological activity of hGCs by attaching to the integrin α6ß1.

Highly Strong and Tough Supramolecular Polymer Networks Enabled by Cryptand-Based Host-Guest Recognition.

Supramolecular polymer networks (SPNs) demonstrate great potential in the development of smart materials owing to their attractive dynamic properties. However, as they suffer from the inherent weak bonding of most noncovalent cross-links, it remains a significant challenge to construct SPNs with outstanding mechanical performance. Herein, we exploit the cryptand/paraquat host-guest recognition motifs as cross-links to prepare a class of highly strong and tough SPNs. Unlike those supramolecular cross-links with relatively weak binding abilities, the cryptand-based host-guest interactions have a high association constant and steady complexing structure, which effectively stabilizes the network and resists mechanical deformation under external force. Such favorable structural stability endows our SPNs with greatly enhanced mechanical performance, compared with the control-1 cross-linked by the weakly complexed crown ether/secondary ammonium salt motif (tensile strength: 21.1±0.5 vs 2.8±0.1 MPa; Young's modulus: 102.6±4.8 vs 2.1±0.3 MPa; toughness: 90.4±2.0 vs 10.8±0.6 MJ m-3 ). Moreover, our SPNs also retain abundant dynamic properties including good abilities in energy dissipation, reprocessability, and stimuli-responsiveness. These findings provide novel insights into the preparation of SPNs with enhanced mechanical properties, and promote the development of high-performance intelligent supramolecular materials.

A chiral fluorescent Ir(iii) complex that targets the GPX4 and ErbB pathways to induce cellular ferroptosis.

Ferroptosis has recently emerged as a non-apoptotic form of programmed cell death and promising target for anticancer treatment. However, it is challenging to discover ferroptosis inducers with both highly selective tumour targeting and low cytotoxicity to normal cells. Here, we report an Ir(iii) complex, Ir1, that contains a novel chiral pyridine RAS-selective lethal ligand (Py-RSL). This complex effectively inhibits glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) to induce ferroptosis in human fibrosarcoma (HT-1080) cells. Notably, metal coordination not only endows Ir1 with fluorescent properties for convenient cellular real-time tracking but also efficiently reduces the off-target toxicity of the Py-RSL ligand. Furthermore, label-free quantitative proteomic profiling revealed that Ir1 simultaneously inhibits the ErbB signalling pathway to enhance tumour suppression. Our work is the first to report a ferroptosis-inducing iridium complex with dual mechanisms of inhibition and provides a highly selective and efficient route to develop new ferroptosis-inducing metallodrugs.