Nrf2-mediated ferroptosis inhibition: a novel approach for managing inflammatory diseases.

Inflammatory diseases, including psoriasis, atherosclerosis, rheumatoid arthritis, and ulcerative colitis, are characterized by persistent inflammation. Moreover, the existing treatments for inflammatory diseases only provide temporary relief by controlling symptoms, and treatments of unstable and expensive. Therefore, new therapeutic solutions are urgently needed to address the underlying causes or symptoms of inflammatory diseases. Inflammation frequently coincides with a high level of (reactive oxygen species) ROS activation, serving as a fundamental element in numerous physiological and pathological phenotypes that can result in serious harm to the organism. Given its pivotal role in inflammation, oxidative stress, and ferroptosis, ROS represents a focal node for investigating the (nuclear factor E2-related factor 2) Nrf2 pathway and ferroptosis, both of which are intricately linked to ROS. Ferroptosis is mainly triggered by oxidative stress and involves iron-dependent lipid peroxidation. The transcription factor Nrf2 targets several genes within the ferroptosis pathway. Recent studies have shown that Nrf2 plays a significant role in three key ferroptosis-related routes, including the synthesis and metabolism of glutathione/glutathione peroxidase 4, iron metabolism, and lipid processes. As a result, ferroptosis-related treatments for inflammatory diseases have attracted much attention. Moreover, drugs targeting Nrf2 can be used to manage inflammatory conditions. This review aimed to assess ferroptosis regulation mechanism and the role of Nrf2 in ferroptosis inhibition. Therefore, this review article may provide the basis for more research regarding the treatment of inflammatory diseases through Nrf2-inhibited ferroptosis.

Room-Temperature Self-Healing Glassy Luminescent Hybrid Film.

The self-healing of glassy polymer materials on site has always been a huge challenge due to their frozen polymer network. We herein report self-repairable glassy luminescent film by assembling a lanthanide-containing polymer with randomly hyperbranched polymers possessing multiple hydrogen (H) bonds. Because of multiple H bonds, the hybrid film exhibits enhanced mechanical strength, with high glass transition temperature (Tg) of 40.3 °C and high storage modulus of 3.52 GPa, meanwhile, dynamic exchange of multiple H bonds enables its rapid room-temperature self-healing ability. This research provides new insights in preparing mechanical robust yet repairable polymeric functional materials.

Integrated fecal microbiome and metabolome analysis explore the link between polystyrene nanoplastics exposure and male reproductive toxicity in mice.

Microplastics (MPs) and nanoplastics (NPs) are novel environmental pollutants that are ubiquitous in the environment and everyday life. NPs can easily enter the tissues and have more significant potential health risks due to their smaller diameter. Previous studies have shown that NPs can induce male reproductive toxicity, but the detailed mechanisms remain uncertain. In this study, intragastric administration treated mice with polystyrene NPs (PS-NPs, 50, and 90 nm) at 3 and 15 mg/mL/day doses for 30 days. Then, the fresh fecal samples were collected from those mice that the exposure doses of 50 nm PS-NPs at 3 mg/mL/day and 90 nm at 15 mg/mL/day for subsequent investigations of 16S rRNA and metabolomics according to significant toxicological effects (Sperm number, viability, abnormality, and testosterone level). The conjoint analysis findings indicated that PS-NPs disrupted the homeostasis of the gut microbiota, metabolism, and male reproduction, suggesting that abnormal gut microbiota-metabolite pathways may be important in PS-NPs-induced male reproductive toxicity. Meanwhile, the common differential metabolites such as 4-deoxy-Erythronic acid, 8-iso-15-keto-PGE2, apo-10'-violaxanthin, beta-D-glucosamine, isokobusone, oleamide, oxoadipic acid, sphingosine induced by 50 and 90 nm PS-NPs might be used as biomarkers to explore PS-NPs-induced male reproductive toxicity. In addition, this study systematically demonstrated that nano-scale PS-NPs induced male reproductive toxicity via the crosstalk of gut microbiota and metabolites. It also provided valuable insights into the toxicity of PS-NPs, which was conducive to reproductive health risk assessment for public health prevention and treatment.

Metformin ameliorates polycystic ovary syndrome in a rat model by decreasing excessive autophagy in ovarian granulosa cells via the PI3K/AKT/mTOR pathway.

Polycystic ovary syndrome (PCOS) is a common gynecological disease accompanied by a variety of clinical features, including anovulation, hyperandrogenism, and ovarian abnormalities, resulting in infertility. PCOS affects approximately 6%-15% of all reproductive-age women worldwide. Metformin, a popular drug used to treat PCOS in patients, has beneficial effects in reducing hyperandrogenism and inducing ovulation; however, the mechanisms by which metformin ameliorates PCOS are not clear. Hence, we aimed to explore the mechanisms of metformin in treating PCOS. In the present study, we first treated a letrozole-induced PCOS rat model with metformin, detected the pathological recovery of PCOS, and then assessed the effects of metformin on H2O2-induced autophagy in ovarian granulosa cells (GCs) by detecting the level of oxidative stress and the expression of autophagy-associated proteins and key proteins in the PI3K/AKT/mTOR pathway. We demonstrated that metformin ameliorated PCOS in a rat model by downregulating autophagy in GCs, and metformin decreased the levels of oxidative stress and autophagy in H2O2-induced GCs and affected the PI3K/AKT/mTOR signaling pathway. Taken together, our results indicate that metformin ameliorates PCOS in a rat model by decreasing excessive autophagy in GCs via the PI3K/AKT/mTOR pathway, and this study provides evidence for targeted reduction of excessive autophagy of ovarian granulosa cells and improvement of PCOS.

A Caffeic Acid Matrix Improves In Situ Detection and Imaging of Proteins with High Molecular Weight Close to 200,000 Da in Tissues by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging.

To our knowledge, this was the first study in which caffeic acid (CA) was successfully evaluated as a matrix to enhance the in situ detection and imaging of endogenous proteins in three biological tissue sections (i.e., a rat brain and Capparis masaikai and germinating soybean seeds) by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Our results show several properties of CA, including strong ultraviolet absorption, a super-wide MS detection mass range close to 200,000 Da, micrometer-sized matrix crystals, uniform matrix deposition, and high ionization efficiency. More high-molecular-weight (HMW) protein ion signals (m/z > 30,000) could be clearly detected in biological tissues with the use of CA, compared to two commonly used MALDI matrices, i.e., sinapinic acid (SA) and ferulic acid (FA). Notably, CA shows excellent performance for HMW protein in situ detection from biological tissues in the mass range m/z > 80,000, compared to the use of SA and FA. Furthermore, the use of a CA matrix also significantly enhanced the imaging of proteins on the surface of selected biological tissue sections. Three HMW protein ion signals (m/z 50,419, m/z 65,874, and m/z 191,872) from a rat brain, two sweet proteins (mabinlin-2 and mabinlin-4) from a Capparis masaikai seed, and three HMW protein ion signals (m/z 94,838, m/z 134,204, and m/z 198,738) from a germinating soybean seed were successfully imaged for the first time. Our study proves that CA has the potential to become a standard organic acid matrix for enhanced tissue imaging of HMW proteins by MALDI-MSI in both animal and plant tissues.

Lead contamination alters enzyme activities and microbial composition in the rhizosphere soil of the hyperaccumulator Pogonatherum crinitum.

Pogonatherum crinitum is a promising lead (Pb) hyperaccumulator; however, the effects of Pb contamination on P. crinitum rhizosphere soil enzymatic activities and microbial composition remain largely unexplored. Thus, an indoor experiment was conducted by cultivating P. crinitum seedlings and exposing them to four Pb concentrations (0, 1,000, 2000 and 3000 mg/kg Pb). Protease, urease, acid phosphatase and invertase activities were determined using standard methods while soil bacterial composition was determined by 16 S rDNA sequencing. The results showed that rhizosphere soil acid phosphatase activity significantly increased with increasing Pb concentration, while urease activity was significantly greater in rhizosphere soil contaminated with 1000 and 2000 mg/kg than in the control. There was a clear shift in bacterial composition during phytoremediation by P. crinitum. Compared to the control, Bacteroidetes was more abundant in all Pb-contaminated soils, Actinobacteria was more abundant in 1000 mg/kg Pb-treated soil, and Firmicutes was more abundant in 3000 mg/kg Pb-treated soil. Positive correlations were observed between dominant bacterial phyla and soil enzyme activities. Metabolic pathways, such as ABC transporter, quinine reductase, and ATP-binding protein were significantly increased in rhizosphere soil bacteria with Pb contamination. In conclusion, Pb contamination differentially influenced the activities of rhizosphere soil enzymes, specifically increasing acid phosphatase and urease activities, and alters the dominance of soil bacteria through up-regulation of genes related to some metabolic pathways. The strong correlations between dominant bacterial phyla and enzymatic activities suggest synergetic effects on the growth of P. crinitum during Pb contamination.

Di-(2-ethylhexyl) phthalate exposure induces female reproductive toxicity and alters the intestinal microbiota community structure and fecal metabolite profile in mice.

Di-(2-ethylhexyl) phthalate (DEHP) is one of the most commonly used plasticizers, and it is widely applied in various plastic products. DEHP is an endocrine-disrupting chemical (EDC) that has been shown to disrupt the function of reproductive system in females. Although many studies have shown that DEHP potentially causes female reproductive toxicity, including depletion of the primordial follicle and decreased sex hormone production, the specific mechanisms by which DEHP affects female reproduction remain unknown. In recent years, research focused on the intestinal flora has provided an idea to eliminate our confusion, and gut bacterial dysbiosis may contribute to female reproductive toxicity. In the present study, the feces of DEHP-exposed mice were collected and analyzed using 16S rRNA amplicon sequencing and untargeted global metabolite profiling of metabolomics. DEHP obviously causes reproductive toxicity, including the ovarian organ coefficient, estradiol level, histological features of the ovary and estrus. Furthermore, DEHP exposure alters the structure of the intestinal microbiota community and fecal metabolite profile in mice, suggesting that the reproductive toxicity may be caused by gut bacterial dysbiosis and altered metabolites, such as changes in the levels of short-chain fatty acid (SCFA). Additionally, it is well known that changes in gut microbiota and fecal metabolites cause inflammation and tissue oxidative stress, expectedly, we found oxidative stress in the ovary and systemic inflammation in DEHP exposed mice. Thus, based on our findings, DEHP exposure may cause gut bacterial dysbiosis and altered metabolite profiles, particularly SCFA profiles, leading to oxidative stress in the ovary and systemic inflammation to ultimately induce female reproductive toxicity.

Construction and application of a composite model for acid mine drainage quality evaluation based on analytic hierarchy process, factor analysis and fuzzy comprehensive evaluation: Guizhou Province, China, as a case.

The process of mining activities often causes the formation of acid mine drainage (AMD). Through rock fractures and underground rivers, AMD can easily enter the groundwater environment near mines and cause serious pollution to water quality. In order to effectively evaluate the quality of polluted mine water and to understand its threat to the ecosystem around the mine. In this study, four AMD pollution distribution areas, Guiyang City, Bijie City, Qianxinan Prefecture, and Qiandongnan Prefecture in Guizhou Province, were used as the study area. A composite model for mine water quality evaluation was constructed using factor analysis (FA), analytic hierarchy process (AHP), and fuzzy comprehensive evaluation (FCE). Furthermore, by introducing the weighted average method and the level characteristic value (J), the water quality type and the water body environmental quality were evaluated comprehensively, respectively. Compared with the traditional evaluation model, the AHP-FA-FCE model has obvious advantages in the selection of evaluation indicators, the determination of indicator weights, and the comprehensive evaluation of water quality types, and the evaluation results obtained are more reasonable and accurate. Three common factors mainly controlled by mineral oxidation factor, human activity factor, and mineral dissolution factor were extracted by dimension reduction of the original hydrochemical data by FA. The water quality of the mine water samples was evaluated using SO4 2- , Fe, Al, Mn, Na, and F- as evaluation indicators, and the results showed that the mine water samples in the study area as a whole were dominated by class V water, which accounted for 77.78% of the total. Based on the statistical analysis of the original data, it was found that influenced by the water-rock interactions in the study area and the AMD pollution components, the hydrochemical type of the mine water is mainly SO4 2- -Ca-Mg type. The water body environmental quality of mine water in four areas, Guiyang City, Qianxinan Prefecture, Bijie City, and Qiandongnan Prefecture, is from excellent to poor. The average level characteristic value of all the areas is more than 3, and the overall environmental quality of the water body is poor. The strong water-rock interaction and mining activities in the study area may be the main cause of AMD pollution. The results of this study may provide some theoretical reference for the water quality evaluation of AMD-polluted areas. PRACTITIONER POINTS: A composite model for mine water quality evaluation was constructed. A factor analysis-based evaluation indicator selection method is proposed. This study improved the weighting process of the traditional fuzzy comprehensive evaluation. A water quality discriminant based on the weighted average method is proposed. The water environmental quality of various types of mine water was evaluated.

Understanding the impact of valproate on male fertility: insights from preclinical and clinical meta-analysis.

BACKGROUND: Valproic acid (VPA) is a widely used antiepileptic drug (AED) often prescribed as a first-line treatment for many idiopathic and symptomatic generalized epilepsies. Several studies have highlighted the side effects of VPA on male fertility and reproductive factors in males, although the specific underlying etiology of these abnormalities is not clear. The present systematic review and meta-analysis aimed to assess the preclinical and clinical evidence concerning the impact of VPA on male fertility and reproductive factors. METHODS: The scientific literature was reviewed for eligibility using PubMed, Web of Science, and PsycINFO, encompassing preclinical and clinical studies. Factors related to male fertility and reproduction, such as differences in sperm count, sperm motility, and the percentage of abnormal sperm, were compared between the experimental groups treated with VPA (in both preclinical and clinical) and the control groups using the Standardized Mean Difference (SMD) with 95% confidence intervals (CIs). Additionally, differences in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were explicitly assessed in clinical studies. RESULTS: Male fertility data were extracted from 7 preclinical studies (112 animals) and 5 clinical studies (274 male individuals). The results of animal studies found that the sperm count (SMD = -2.28, 95% CI: -3.39 to -1.18, P = 0.335) and sperm motility (SMD = -2.32, 95% CI: -3.34 to -1.30, P = 0.368) were decreased in the treated groups compared to the control groups. The percentage of abnormal sperm (SMD = 3.27, 95% CI: 1.98 to 4.56, P = 0.019) was significantly increased, while a non-significant reduction was revealed in the weight of the testis (SMD = -2.73, 95% CI: -4.23 to -1.23, P = 0.673) in treated groups. The outcomes of clinical studies indicated a non-significant decrease in sperm count (SMD = -0.78, 95% CI: -1.58 to 0.03, P = 0.286) among patients with epilepsy treated with VPA compared to control subjects. However, a significant reduction in sperm motility (SMD = -1.62, 95% CI: -2.81 to -0.43, P = 0.033 was observed. The percentage of abnormal sperm showed a non-significant increase (SMD = 0.93, 95% CI: -0.97 to 2.84, P = 0.616) after being treated with VPA. Furthermore, there was a non-significant reduction in the levels of FSH (SMD = -1.32, 95% CI: -2.93 to 0.29, P = 0.198) and LH (SMD = -0.96, 95% CI: -1.95 to 0.04, P = 0.211) observed in clinical participants. CONCLUSION: This meta-analysis of both preclinical and clinical studies revealed that VPA causes a significant reduction in male fertility and reproductive factors among male patients with epilepsy. Clinical neurologists should be more cautious when prescribing VPA, especially to young male adult patients with epilepsy.

Nrf2-mediated ferroptosis of spermatogenic cells involved in male reproductive toxicity induced by polystyrene nanoplastics in mice. / Nrf2ä»‹å¯¼çš„ç”Ÿç²¾ç»†èƒžé“æ­»äº¡å‚ä¸Žäº†èšè‹¯ä¹™çƒ¯çº³ç±³å¡‘æ–™å¯¼è‡´çš„å°é¼ é›„æ€§ç”Ÿæ®–æ¯’æ€§.

Microplastics (MPs) and nanoplastics (NPs) have become hazardous materials due to the massive amount of plastic waste and disposable masks, but their specific health effects remain uncertain. In this study, fluorescence-labeled polystyrene NPs (PS-NPs) were injected into the circulatory systems of mice to determine the distribution and potential toxic effects of NPs in vivo. Interestingly, whole-body imaging found that PS-NPs accumulated in the testes of mice. Therefore, the toxic effects of PS-NPs on the reproduction systems and the spermatocytes cell line of male mice, and their mechanisms, were investigated. After oral exposure to PS-NPs, their spermatogenesis was affected and the spermatogenic cells were damaged. The spermatocyte cell line GC-2 was exposed to PS-NPs and analyzed using RNA sequencing (RNA-seq) to determine the toxic mechanisms; a ferroptosis pathway was found after PS-NP exposure. The phenomena and indicators of ferroptosis were then determined and verified by ferroptosis inhibitor ferrostatin-1 (Fer-1), and it was also found that nuclear factor erythroid 2-related factor 2 (Nrf2) played an important role in spermatogenic cell ferroptosis induced by PS-NPs. Finally, it was confirmed in vivo that this mechanism of Nrf2 played a protective role in PS-NPs-induced male reproductive toxicity. This study demonstrated that PS-NPs induce male reproductive dysfunction in mice by causing spermatogenic cell ferroptosis dependent on Nrf2.

Two new megastigmane glycosides from the leaves of Nicotiana tabacum and their anti-inflammatory activities.

Two new megastigmane glycosides, (6 R,7E,9R)-3-oxo-α-ionyl-9-O-α-L-rhamnopyranosyl-(1''→4')-ß-D-glucopyranoside (1) and (6 R,7E,9R)-3-oxo-α-ionyl-9-O-ß-D-glucopyranosyl-(1''→6')-ß-D-glucopyranoside (2), together with six known analogues (3-8) were isolated from the leaves of Nicotiana tabacum. The structures of all metabolites were determined by comprehensive analysis of NMR and MS spectroscopic data as well as by comparison with those of previously reported. The in vitro anti-inflammatory activity of all isolates was evaluated using a lipopolysaccharide (LPS)-induced RAW264.7 cell inflammatory model, and the compounds 1, 3, 7, and 8 exhibited inhibition of LPS-induced NO production in RAW264.7 macrophage cells with IC50 values of 42.3-61.7 µM (positive control, dexamethasone, IC50 = 21.3 ± 1.2 µM).

Integrated transcriptomic and metabolomic analysis reveals the underlying mechanisms for male reproductive toxicity of polystyrene nanoplastics in mouse spermatocyte-derived GC-2spd(ts) cells.

BACKGROUND: Polystyrene nanoplastics (PS-NPs), are ubiquitous pollution sources in human environments, posing significant biosafety and health risks. While recent studies, including our own, have illustrated that PS-NPs can breach the blood-testis barrier and impact germ cells, there remains a gap in understanding their effects on specific spermatogenic cells such as spermatocytes. METHODS AND RESULTS: Herein, we employed an integrated approach encompassing phenotype, metabolomics, and transcriptomics analyses to assess the molecular impact of PS-NPs on mouse spermatocyte-derived GC-2spd(ts) cells. Optimal exposure conditions were determined as 24 h with 50 nm PS-NPs at 12.5 µg/mL and 90 nm PS-NPs at 50 µg/mL for subsequent multi-omics analysis. Our findings revealed that PS-NPs significantly influenced proliferation and viability, causing alterations in transcriptome and metabolome profiles. Transcriptomics analysis of GC-2spd(ts) cells exposed to PS-NPs indicated the pivotal involvement of cell proliferation and cycle, autophagy, ferroptosis, and redox reaction pathways in PS-NP-induced effects on the proliferation and viability of GC-2spd(ts) cells. Furthermore, metabolomics analysis identified major changes in amino acid metabolism, cyanoamino acid metabolism, and purine and pyrimidine metabolism following PS-NP exposure. CONCLUSION: Our integrated approach, combining metabolomics and transcriptomics profiles with phenotype data, enhances our understanding of the adverse effects of PS-NPs on germ cells.

A Self-Powered, Skin Adhesive, and Flexible Human-Machine Interface Based on Triboelectric Nanogenerator.

Human-machine interactions (HMIs) have penetrated into various academic and industrial fields, such as robotics, virtual reality, and wearable electronics. However, the practical application of most human-machine interfaces faces notable obstacles due to their complex structure and materials, high power consumption, limited effective skin adhesion, and high cost. Herein, we report a self-powered, skin adhesive, and flexible human-machine interface based on a triboelectric nanogenerator (SSFHMI). Characterized by its simple structure and low cost, the SSFHMI can easily convert touch stimuli into a stable electrical signal at the trigger pressure from a finger touch, without requiring an external power supply. A skeleton spacer has been specially designed in order to increase the stability and homogeneity of the output signals of each TENG unit and prevent crosstalk between them. Moreover, we constructed a hydrogel adhesive interface with skin-adhesive properties to adapt to easy wear on complex human body surfaces. By integrating the SSFHMI with a microcontroller, a programmable touch operation platform has been constructed that is capable of multiple interactions. These include medical calling, music media playback, security unlocking, and electronic piano playing. This self-powered, cost-effective SSFHMI holds potential relevance for the next generation of highly integrated and sustainable portable smart electronic products and applications.

A rapid self-healing glassy polymer/metal-organic-framework hybrid membrane at room temperature.

The development of repairable MOF-polymer hybrid materials will greatly extend their service life by repairing fractured parts on the spot; however, it is difficult for robust glassy polymers to self-heal below the glass transition temperature (Tg) as the polymer network is frozen. We herein report glassy polyMOF-RHP hybrid membranes by integrating lanthanide polyMOF (polyLnMOF) with randomly hyperbranched polymers (RHP) bearing a high density of hydrogen bonds. Since crystalline lanthanide MOFs act as multiconnected cross-linking agents and cross-link the interpenetrating polymer network, the obtained polyLnMOF-polymer membrane shows enhanced mechanical strength with a storage modulus of 3.09 GPa and a Tg up to 49 °C. Meanwhile, the high intersegment migration ability of the polyLnMOF-polymer network facilitates the exchange of hydrogen-bonded pairs even in the glassy state, leading to an instantaneous room-temperature self-healing ability. The polyLnMOF-polymer membranes inherit the ratiometric temperature-sensing behavior of pristine lanthanide MOFs, resulting in more processable temperature-sensing membranes. This work provides an appealing strategy for the design of mechanically robust, yet self-healing, MOF-polymer functional materials.

Acetate accumulation and regulation by process parameters control in Chinese hamster ovary cell culture.

Chinese hamster ovary (CHO) cells represent a group of predominantly used mammalian hosts for producing recombinant therapeutic proteins. Known for their rapid proliferation rates, CHO cells undergo aerobic glycolysis that is characterized by fast glucose consumption, that ultimately gives rise to a group of small-molecule organic acids. However, only the function of lactate has been extensively studied in CHO cell culture. In this study, we observed the accumulation of acetate from the late exponential phase to harvest day, potentially contributing to the pH decline in late culture stage regardless of lactate consumption. In addition, we evaluated the acidification of the fresh media and the cell culture suspension, and the data revealed that acetate presented a lower acidification capacity compared to lactate and exhibited limited inhibitory effect on cells with less than 20 mM supplemented in the media. This study also explored the ways to control acetate accumulation in CHO cell culture by manipulating the process parameters such as temperature, glucose, and pH control. The positive correlation between the specific glucose consumption rate and acetate generation rate provides evidence of the endogenous acetate generation from overflow metabolism. Reducing these parameters (temperature, glucose consumption) and HCl-controlled low pH ultimately suppress acetate build-up. In addition, the specific acetate generation rate and relevant glucose consumption rate are found to be a metabolic trait associated with specific cell lines. Taken together, the results presented in these experiments provide a means to advance industrial CHO cell culture process control and development.

Roles of follicle stimulating hormone and sphingosine 1-phosphate co-administered in the process in mouse ovarian vitrification and transplantation.

Some major challenges of ovarian tissue vitrification and transplantation include follicle apoptosis induced by cryopreservation and ischemia-reperfusion injury, as well as ovarian follicle loss during post-transplantation. This research aimed to investigate the protective effects and underlying mechanisms of follicle-stimulating hormone (FSH) and Sphingosine-1-phosphate (S1P) on vitrified and post-transplantation ovaries. Ovaries from 21-day-old mice were cryopreservation by vitrification with 0.3 IU/mL FSH, 2 µM S1P, and 0.3 IU/mL FSH + 2 µM S1P, respectively, for follicle counting and detection of apoptosis-related indicators. The results demonstrated that FSH and S1P co-intervention during the vitrification process could preserve the primordial follicle pool and inhibit follicular atresia by suppressing cell apoptosis. The thawed ovaries were transplanted under the renal capsule of 6-8 week-old ovariectomized mice and removed 24 h or 7 days after transplantation. The results indicated that FSH and S1P co-intervention can inhibit apoptosis and autophagy in ovaries at 24 h after transplantation, and promote follicle survival by up-regulating Cx37 and Cx43 expression, enhanced angiogenesis in transplanted ovaries by promoting VEGF expression, as well as increased the E2 levels to restore ovarian endocrine function at 7 days after transplantation. The hypoxia and ischemia cell model was established by CoCl2 treatment for hypoxia in human granulosa-like tumor cell line (KGN), as well as serum-free culture system was used for ischemia. The results confirmed that ischemia-hypoxia-induced apoptosis in ovarian granulosa cells was reduced by FSH and S1P co-intervention, and granulosa cell autophagy was inhibited by up-regulating the AKT/mTOR signaling pathway. In summary, co-administration of FSH and S1P can maintain ovarian survival during ovarian vitrification and increase follicle survival and angiogenesis after transplantation.

Physiological and transcriptome analyses reveal the response of Ammopiptanthus mongolicus to extreme seasonal temperatures in a cold plateau desert ecosystem.

Ammopiptanthus mongolicus is the only evergreen broad-leaved shrub present in arid areas of Northwest China and plays an important role in maintaining the stability of the local desert ecosystem. It can survive under extreme temperatures (e.g., extreme low temperature: - 24.8 °C and extreme high temperature: 37.7 °C). To understand the gene expression-physiological regulation network of A. mongolicus in extreme temperature environments, we monitored the changes in gene expression and photosynthetic traits of the leaves. The results showed that at low temperatures, the net photosynthetic rates (A), Fv'/Fm' and electron transport rate (ETR) decreased, the Fv/Fm ratio was only 0.32, and the proportion of nonregulatory heat dissipation Y(NO) increased. Based on a KEGG analysis of the differentially expressed genes, 15 significantly enriched KEGG pathways were identified, which were mainly related to circadian rhythm, photosynthesis, lipid metabolism, carbohydrate metabolism, plant hormones and other life activities. At high temperatures, the A value increased, and the proportion of regulatory energy dissipation Y(NPQ) increased. The KEGG analysis identified 24 significantly enriched KEGG pathways, which are mainly related to circadian rhythm, carbon sequestration of photosynthesis, carotenoid biosynthesis, secondary metabolites, cofactors and vitamin metabolism. In general, at the expense of photosynthesis, A. mongolicus can ensure the survival of leaves by increasing Y(NO) levels, regulating the circadian rhythm, increasing the synthesis of unsaturated fatty acids and changing the role of plant hormones. Under high-temperature stress, a high photosynthetic capacity was maintained by adjusting the stomatal conductance (gsw), increasing Y(NPQ), consuming excess light energy, continuously assembling and maintaining PSII, and changing the production of antioxidants.

Lack of phenotypic plasticity in leaf hydraulics for 10 woody species common to urban forests of North China.

The survival and performance of urban forests are increasingly challenged by urban drought, consequently compromising the sustainability and functionality of urban vegetation. Plant-water relations largely determine species drought tolerance, yet little is known about the hydraulics of urban forest species. Here, we report the leaf hydraulic and carbon traits that govern plant growth and drought resistance, including vulnerability to embolism, hydraulic conductivity and leaf gas exchange characteristics, as well as morphological traits that are potentially linked with these physiological attributes, with the aim of guiding species selection and management in urban forests. Plant materials were collected from mature shrubs and trees on our university campus in Beijing, representing 10 woody species common to urban forests in north China. We found that the leaf embolism resistance, represented by the water potential inducing 50% loss of hydraulic conductivity (P50), as well as the hydraulic safety margin (HSM) defined by P50 and the water potential threshold at the inception of embolism (P12), varied remarkably across species, but was unrelated to growth form. Likewise, stem and leaf-specific hydraulic conductivity (Kstem and kl) was also highly species-specific. Leaf P50 was positively correlated with hydraulic conductivity. However, neither P50 nor hydraulic conductivity was correlated with leaf gas exchange traits, including maximum photosynthetic rate (Amax) and stomatal conductance (gs). Plant morphological and physiological traits were not related, except for specific leaf area, which showed a negative relationship with HSM. Traits influencing plant-water transport were primarily correlated with the mean annual precipitation of species climatic niche. Overall, current common woody species in urban forest environments differed widely in their drought resistance and did not have the capacity to modify these characteristics in response to a changing climate. Species morphology provides limited information regarding physiological drought resistance. Thus, screening urban forest species based on plant physiology is essential to sustain the ecological services of urban forests.

A novel anticancer property of Lycium barbarum polysaccharide in triggering ferroptosis of breast cancer cells.

Breast cancer is one of the most malignant tumors and is associated with high mortality rates among women. Lycium barbarum polysaccharide (LBP) is an extract from the fruits of the traditional Chinese herb, L. barbarum. LBP is a promising anticancer drug, due to its high activity and low toxicity. Although it has anticancer properties, its mechanisms of action have not been fully established. Ferroptosis, which is a novel anticancer strategy, is a cell death mechanism that relies on iron-dependent lipid reactive oxygen species (ROS) accumulation. In this study, human breast cancer cells (Michigan Cancer Foundation-7 (MCF-7) and MD Anderson-Metastatic Breast-231 (MDA-MB-231)) were treated with LBP. LBP inhibited their viability and proliferation in association with high levels of ferroptosis. Therefore, we aimed to ascertain whether LBP reduced cell viability through ferroptosis. We found that the structure and function of mitochondria, lipid peroxidation, and expression of solute carrier family 7 member 11 (SLC7A11, also known as xCT, the light-chain subunit of cystine/glutamate antiporter system Xc-) and glutathione peroxidase 4 (GPX4) were altered by LBP. Moreover, the ferroptosis inhibitor, Ferrostatin-1 (Fer-1), rescued LBP-induced ferroptosis-associated events including reduced cell viability and glutathione (GSH) production, accumulation of intracellular free divalent iron ions and malondialdehyde (MDA), and down-regulation of the expression of xCT and GPX4. Erastin (xCT inhibitor) and RSL3 (GPX4 inhibitor) inhibited the expression of xCT and GPX4, respectively, which was lower after the co-treatment of LBP with Erastin and RSL3. These results suggest that LBP effectively prevents breast cancer cell proliferation and promotes ferroptosis via the xCT/GPX4 pathway. Therefore, LBP exhibits novel anticancer properties by triggering ferroptosis, and may be a potential therapeutic option for breast cancer.

Highly Stereoselective Intramolecular Carbofluorination of Internal α,ß-Ynones Promoted by Selectfluor.

Herein, we report a metal-free intramolecular carbofluorination protocol for the synthesis of tetrasubstituted monofluoroalkenes from internal α,ß-ynones and Selectfluor with both high stereoselectivity and broad functional group tolerance. The chelation between tetrafluoroborate anion and the oxygen present in the aldehyde group rendered the reaction highly stereoselective, with the tetrafluoroborate serving as the direct fluorine source. Therefore, with addition of sodium tetrafluoroborate, Selectfluor could be reused several times without sacrificing reactivity.