Desulfonylative Functionalization of Organosulfones via Inert (Hetero)Aryl C(sp2)-SO2 Bond Cleavage.

As "chemical chameleons," organosulfones have been widely applied in various desulfonylative functionalization reactions. However, the desulfonylative functionalization of (hetero)arylsulfones through the cleavage of inert C(sp2)-SO2 bonds remains a challenging and underexplored task. Over the past twenty years, the use of (hetero)arylsulfones as arylation reagents has gradually gained attention in diverse cross-coupling reactions under specific catalytic conditions, especially in transition metal-catalysis and photocatalysis chemistry. In this review, we discuss the representative accomplishments and mechanistic insights achieved in desulfonylative reactions of inactive C(sp2)-SO2 bonds in (hetero)arylsulfones, including: (i) transition-metal-catalyzed desulfonylative cross-coupling reactions and (ii) photo-/electrocatalytic radical desulfonylative coupling reactions. We anticipate that this review will provide an overall perspective in this area to a general audience of researchers and stimulate further innovative strategies for desulfonylative functionalization of inert arylsulfones.

Optical directional differential operation enabled visual chirality detection.

Directional differential operation can extract the changes of directional information from complex signals, and plays an important role in target recognition and texture image processing. Here, we propose an optical directional differential operation based on large cross-polarization rotation, and realize the visual detection of chiral enantiomers. By using cross-polarization rotation in a specified direction, we design a corresponding directional spatial spectral transfer function whose transmission efficiency increases as the incident angle approaches the Brewster angle. The differential direction can be adjusted by changing the initial polarization state, and can be used to detect the concentration of chiral solutions. Finally, we apply the directional differential operation to achieve the visual detection of chiral enantiomers.

Endoscopic dacryocystorhinostomy in acute dacryocystitis: a multicenter study in China.

AIM: To report the clinical profile, endoscopic dacryocystorhinostomy (En-DCR) management, and acute dacryocystitis (AD) outcomes in China. METHODS: Clinical data of 554 adult AD patients (554 eyes) who presented in 7 tertiary eye care centers for 10y from Jan 2010 to Mar 2020 were retrospectively analyzed. Clinical profile, En-DCR management, and outcomes of all cases were recorded. The anatomical and functional success were evaluated for 12mo post-operation. RESULTS: The analysis included 149 males and 368 females with a median age of 55.2y (range: 18-84y). There were 459 eyes with a history of epiphora or purulent secretion. The time between a symptom of lacrimal duct obstruction and acute onset was 1 to 540 (66.1±58.2)mo. Fifty-nine eyes had a history of the previous acute attack. Seventy-four eyes developed a cutaneous fistula, while 11 eyes had post septal cellulitis pre-operation. En-DCR with an anatomical success of 91.7% and functional success of 90.1%. The success rate of the patients with a history of acute episodes and the preoperative fistula was lower than the overall success rates. CONCLUSION: En-DCR can be performed during an acute episode in AD with a success rate of over 90%.

Diagnostic accuracy of hemodynamic assessment of intracranial atherosclerotic stenosis from a single angiographic view: a validation study.

BACKGROUND: The aim of this study is to assess the feasibility of identifying the hemodynamic status of intracranial atherosclerotic stenosis (ICAS) using angio-based fractional flow (FF) calculated from a single angiographic view, with wire-based FF as the reference standard. METHOD: The study retrospectively recruited 100 ICAS patients who underwent pressure wire measurement and digital subtraction angiography. The AccuICAD software was used to calculate angio-based FF, with the wire-measured value serving as the reference standard for evaluating the accuracy, consistency, and diagnostic performance of angio-based FF. RESULTS: The mean±SD value of wire-based FF was 0.77±0.18, while the mean value of angio-based FF was 0.77±0.19. A good correlation between angio-based FF and wire-based FF was evident (r=0.90, P<0.001), with good agreement (mean difference 0.00±0.08). The diagnostic accuracy of angio-based FF and percent diameter stenosis (DS%) were 93.23% versus 72.18%, 91.73% versus 72.93%, and 89.47% versus 78.95% for predicted wire-based FF thresholds of 0.70, 0.75, and 0.80, respectively. The area under the curve (AUC) values for angio-based FF and DS% were 0.975 versus 0.822, 0.970 versus 0.814, and 0.943 versus 0.826 at the respective thresholds, respectively. CONCLUSION: The FF calculated from a single angiographic view can be considered an effective tool for functional assessment of cerebral arterial stenosis.

Predictive effect of lipopolysaccharide-stimulated inflammatory cytokines on symptoms of generalized anxiety disorder.

BACKGROUND: Generalized anxiety disorder (GAD) is a relatively common mental disorder. Recently, inflammation, an important factor for the development of depression, has attracted increasing attention. Several studies have shown that inflammatory cytokines can affect the pathophysiological processes of several nervous system diseases. We hypothesized that there is a correlation between the levels of lipopolysaccharide (LPS)-stimulated inflammatory cytokines and the clinical symptoms of GAD. AIM: To investigate the predictive effect of LPS-stimulated inflammatory cytokines on symptoms of GAD. METHODS: This was a cross-sectional study in which 89 patients with GAD diagnosed at The First Hospital of Hebei Medical University from January 2022 to December 2022 and 70 individuals without anxiety and depression (controls) during the same period were included. Fasting venous blood was collected from all the subjects in heparin tubes, and another 3 ml of blood was supplemented with LPS (10 ng/ml). The plasma levels of 12 cytokines [Interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-17A, IL-12p70, and IFN-α] were detected. RESULTS: Post-LPS stimulation, the levels of IL-1ß, IL-6, IL-8, IL-10, and TNF-α in both the control and GAD groups were significantly elevated above those in the nonstimulated groups, with IL-6 and IL-8 showing marked increases. Increases in IL-8 and TNF-α were statistically significant in the GAD group (P < 0.05). IL-1ß, IL-6, IL-8, IL-10, and TNF-α were found to be significantly correlated with Hamilton Anxiety Rating Scale (HAMA) scores (P < 0.05). A negative correlation was observed between IL-10 levels and HAMA scores. Further analysis revealed that TNF-α was associated with mental anxiety, whereas IL-1ß, IL-8, and IL-10 were associated with physical anxiety symptoms, with IL-10 showing a negative correlation with physical anxiety. IL-6 was associated with both mental and physical aspects of anxiety. CONCLUSION: The physical symptoms of GAD are related to inflammatory factors. IL-1ß, IL-8, IL-10, and TNF-a can be used as predictors of physical or mental anxiety in patients with GAD.

A transcription-independent role for HIF-1α in modulating microprocessor assembly.

Microprocessor is an essential nuclear complex responsible for the initial RNase-mediated cleavage of primary miRNA, which is a tightly controlled maturation process that requires the proper assembly of Drosha and DGCR8. Unlike previously identified mechanisms directly targeting the enzymatic subunit Drosha, current knowledge about the biological ways of controlling miRNA nuclear maturation through DGCR8 is less addressed. In this study, we unveiled that the microprocessor assembly is governed by a master gene regulator HIF-1α irrespective of its canonical transcriptional activity. First, a widespread protein binding of HIF-1α with DGCR8 instead of Drosha was observed in response to biological stimulations. Similar protein interactions between their corresponding orthologues in model organisms were also observed. After dissecting the essential protein domains, we noticed that HIF-1α suppresses microprocessor assembly via binding to DGCR8. Furthermore, our results showed that HIF-1α hijacks monomeric DGCR8 thus reducing its dimer formation prior to microprocessor assembly, and consequently, the suppressed microprocessor formation and nuclear processing of primary miRNA were demonstrated. In conclusion, here we unveiled the mechanism of how microprocessor assembly is regulated by HIF-1α, which not only demonstrates a non-transcriptional function of nuclear HIF-1α but also provides new molecular insights into the regulation of microprocessor assembly through DGCR8.

Zinc/Iron-Regulated Transporter-like Protein CsZIP4 Enhances Zinc and Nitrogen Uptake and Alleviates Zinc Stresses with Nitrogen Supply in Camellia sinensis.

Zinc (Zn) and nitrogen (N) are the two crucial nutrients for tea plant growth and development and contribute to the quality formation of tea fresh leaves. In this study, a zinc/iron-regulated transporter-like protein 4 gene (i.e., CsZIP4) was functionally characterized. Expression profiling showed that CsZIP4 could be induced by Zn stresses and a N deficiency. Heterologous expression of CsZIP4 in yeast revealed that CsZIP4 possessed the capacity for Zn transport but not ammonium. Moreover, CsZIP4 overexpression in Arabidopsis thaliana promoted Zn and N uptake and transport and contributed to alleviate Zn stresses by collaborating with N supply, which might be interrelated to the expression of N or Zn metabolism-related genes, such as AtNRT1.1 and AtZIP4. Additionally, CsZIP4 was localized in the plasma membrane and chloroplast, which was helpful in maintaining cellular homeostasis under a Zn excess. Furthermore, silencing of CsZIP4 in tea plants by virus-induced gene silencing increased the chlorophyll content but decreased the Zn content. Finally, the yeast one-hybrid assay demonstrated that CsbZIP2 bound to the CsZIP4 promoter. These results will shed light on the functions of CsZIP4 in the N and Zn interaction in tea plants.

Single-cell sequencing reveals the heterogeneity of pancreatic neuroendocrine tumors under genomic instability and histological grading.

Histological grading is the key factors affecting the prognosis and instructive in guiding treatment and assessing recurrence in non-functional pancreatic neuroendocrine tumor (NF-Pan-NET). Approximately one-third of patients without copy number variation (CNV) alteration and the prognosis of these patients are better than that of patients with CNV alteration. However, the difference between CNV and histological grading is unclear. Here, we analyzed the heterogeneity of tumor cells according to two classification criteria, genomic instability (including CNV alteration and tumor mutation burden) and histological grading. We revealed that the activated core pathways of tumor cells were significantly different under different histological grading's and genomic instability patterns. We also found that tip cells, lymphatic endothelial cells, macrophages, CD1A + dendritic cell, Treg, MAIT, ILC, and CAFs might participate in the process of hepatic metastases, which will facilitate the understanding of the patterns to decode the malignant potential and of NF-Pan-NET.

Racial stereotype and Black adolescents' math achievement: Unpacking the socio-cognitive mechanisms.

Racial stereotypes are salient to Black adolescents and to the academic domain of mathematics; however, few studies have examined the socio-cognitive mechanisms through which racial stereotypes impact math achievement. This 2-year longitudinal study (N = 790 Grade 6, 8, and 10 students during Year 1; 50.7% girls and 49.3% boys) investigated (a) the extent to which the endorsement of positively and negatively biased racial stereotypes predicted Black adolescents' math performance through their cognitive engagement and ability mindset and (b) whether gender and ethnic-racial identity moderated these links. Results suggested that endorsement of negatively biased stereotypes was associated with diminished cognitive engagement and lower math scores across 2 years (p < .05). Additionally, adolescents' ethnic-racial identity commitment moderated the negative links between stereotype endorsement and math cognitive engagement in Year 2 (p < .05). When considering the mediating role of math ability mindsets, the endorsement of both positively and negatively biased racial stereotypes operated on math performance via its links to stronger fixed ability mindset beliefs in both years (p < .05). Gender also moderated the effects of racial stereotype endorsement on math mindset beliefs in Year 1 (p < .01). This study's findings advance the field's understanding of the psychosocial mechanisms through which racial stereotypes operate, thus enabling educators to develop tailored practices that facilitate equitable access to math learning opportunities.

Specific ion effects on the soil shear strength and clay surface properties of collapsing wall in Benggang.

Benggangs are a special type of soil erosion in the hilly granite regions of the tropical and subtropical areas of Southern China. They cause severe soil and water loss, which can severely deteriorate soil quality and threat to the local ecological environment. Soils (red soil, sandy soil and detritus soil) were collected from collapsing wall of a typical Benggang in Changting County of Fujian Province, and their physicochemical and mineralogical properties were analyzed. Five different monovalent cations were used to saturate the soil samples to examine the specific ion effects on the shear strength and clay surface properties. Red soil had a higher clay content, plastic limit, liquid limit and shear strength than sandy soil and detritus soil. The studied soils mainly consisted of kaolinite, hydroxy-interlayer vermiculite, illite and gibbsite clay minerals. The soils saturated with K+, NH4 +and Cs+ had greater cohesion than the Li+- and Na+-saturated soils, e.g., the cohesion of the red soil saturated with Li+, K+, NH4 + and Cs+ cations were 1.05, 1.23, 1.45 and 1.20 times larger than that of the Na+-saturated soil, respectively. While the internal friction angle was slightly different, which indicated that different monovalent cations affected the shear strength differently. K+-, NH4 +- and Cs+-saturated clay particles had higher zeta potentials and thinner shear plane thicknesses than Li+- and Na+-saturated clay particles and showed strong specific ion effects on the clay surface properties. The changes in clay surface properties strongly affected the soil mechanical properties. Soils saturated with K+, NH4 + and Cs+ could increase the shear strength, and then increase the stability of the collapsing wall, thus might decrease the erosion intensity of Benggang. The results provide a scientific basis for the interpretation of and practical treatment of Benggang.

Returning from the afterlife? Sotorasib treatment for advanced KRAS mutant lung cancer: A case report.

BACKGROUND: Lung cancer is increasing in incidence worldwide, and targeted therapies are developing at a rapid pace. Furthermore, the KRAS specific gene is strongly associated with non-small cell lung cancer (NSCLC). Adult patients with locally advanced or metastatic NSCLC who have tested positive for the KRAS G12C mutation and have progressed after at least one systemic treatment are treated with sotorasib. CASE SUMMARY: In this study, we report on an advanced NSCLC with a KRAS G12C mutation. The histological diagnosis indicates stage IVB left lung adenocarcinoma with pelvic and bone metastases, identified as cT4N2bM1c. Using circulating tumor DNA analysis, it was possible to determine the mutation abundance of the KRAS gene exon 2, c.34G>Tp.G12C, which was 32.3%. The patient was advised to take sotorasib as part of their treatment. The imaging data were compared before and after treatment. Furthermore, clinical reassessments and regular serial blood testing were conducted. We found that the patient's clinical symptoms significantly improved after receiving sotorasib medication, and there were no notable side effects, such as liver toxicity, during the treatment. CONCLUSION: Sotorasib has shown promising clinical efficacy in patients with the KRAS G12c mutation and has no apparent toxic side effects.

When ethnic-racial discrimination from math teachers spills over and predicts the math adjustment of nondiscriminated adolescents: The mediating role of math classroom climate perceptions.

Ethnic-racial discrimination is a pernicious experience that affects discriminated adolescents' healthy human development, but the spillover consequences of discrimination on the nondiscriminated adolescent population are less clear. Adolescents who vicariously witness their classmates experience ethnic-racial discrimination from educators may question their educators' authority and classroom rules, and educators who perpetuate discrimination may engage in other practices that disadvantage the entire classroom. Thus, we posed three research questions: Did classmates' ethnic-racial discrimination from teachers predict adolescents' classroom adjustment outcomes (e.g., class grades, test scores, and engagement), did classroom climate mediate the link between classmates' ethnic-racial discrimination and adolescents' classroom adjustment outcomes, and did the results differ between early versus middle adolescents? To answer these research questions, the present study leveraged longitudinal data among 1,539 adolescents (Mage = 13.81, SDage = 1.49; 60% Black, 30% White, 9% other, 1% Asian; 49% female, 51% male) nested in 104 math classrooms, as math is a subject domain with pervasive ethnic-racial stereotypes about students' abilities and opportunities to succeed in class. Results illustrated that direct and vicarious ethnic-racial discrimination from math educators in the fall semester predicted worse math course grades, state-administered standardized test scores, and classroom engagement across the fall and spring semesters. Math classroom climate perceptions mediated the longitudinal relations between ethnic-racial discrimination and their math adjustment outcomes, and the role of ethnic-racial discrimination varied across different developmental stages of adolescence. Implications for the measurement of ethnic-racial discrimination in the classroom context and the social contagion linked to ethnic-racial disadvantage are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Weight Loss Blockbuster Development: A Role for Unimolecular Polypharmacology.

Obesity and type 2 diabetes mellitus (T2DM) impact more than 2.5 billion adults worldwide, necessitating innovative therapeutic approaches. Unimolecular polypharmacology, which involves designing single molecules to target multiple receptors or pathways simultaneously, has revolutionized treatment strategies. Blockbuster drugs such as tirzepatide and retatrutide have shown unprecedented success in managing obesity and T2DM, demonstrating superior efficacy compared to conventional single agonists. Tirzepatide, in particular, has garnered tremendous attention for its remarkable effectiveness in promoting weight loss and improving glycemic control, while offering additional cardiovascular and renal benefits. Despite their promises, such therapeutic agents also face challenges that include gastrointestinal side effects, patient compliance issues, and body weight rebound after cessation of the treatment. Nonetheless, the development of these therapies marks a significant leap forward, underscoring the transformative potential of unimolecular polypharmacology in addressing metabolic diseases and paving the way for future innovations in personalized medicine.

Emerging trends and research hotspots in the relationship between mast cells and atopic dermatitis based on the literature from 2001 to 2024: A bibliometric and visualized analysis.

BACKGROUND: Atopic dermatitis (AD) is a prevalent chronic inflammatory and highly pruritic skin condition characterized by the infiltration of immune cells, notably eosinophils and mast cells. Mast cells (MCs) critically participate in the complex pathogenesis of AD through multiple pathways and have recently garnered growing attention in research. Despite the abundance of related studies published over the years, a comprehensive bibliometric analysis on this topic remains lacking. OBJECTIVE: Our objective was to perform an up-to-date bibliometric analysis of the literature focusing on the relationship between MCs and AD. This analysis would provide valuable insights through a thorough bibliometric review, enabling a clearer understanding of the current research landscape, pinpointing key studies, and detecting emerging trends within this field. METHODS: We searched the Web of Science Core Collection (WoSCC) database on 15 July 2024. The data retrieval strategy was structured as follows: #1: TS = ("mast cells") OR TS = ("mast cell") OR TS = ("mastocyte"); #2: TS = ("atopic dermatitis") OR TS = ("atopic eczema") Final data: (#1 AND #2). A total of 2272 items published between 2001 and 2024 were included. Several scientometric visualization tools, including VOSviewer, R-bibliometrix, CiteSpace and an online analytical platform, were utilized to conduct text mining and to visualize the bibliometric data, facilitating a comprehensive analysis of research trends and patterns. RESULTS: Out of the initial 2272 articles retrieved, 2168 were selected for analysis after applying inclusion and exclusion criteria based on publication type. The findings indicate a steady and substantial exponential growth in the annual number of publications focused on the relationship between over the years. The South Korea (547/2168), USA (465/2168) and Japan (436/2168) were the major contributors within this field, collectively constituting more than half of the total publications. To clarify the underlying mechanisms and role of MCs in the pathogenesis of AD and to make MCs prime targets for therapeutic intervention have garnered the most attention in this field. According to references analysis, the research emphasis has shifted to developing MC-related therapeutics and intervention and regulating the immune system of AD patients through modulating the activity of various immune cells. On the basis of keywords analysis, we outlined the following research frontiers and hotpots in the future: the role of oxidative stress in the pathogenesis; imbalance in the different types of T helper (Th) cells during immune response; skin barrier and barrier dysfunction; improving quality of life; sensory neurons; biological agents and small-molecule drugs. Furthermore, IL-13, IL-4, NFKB1, BCGF-1 and CD4 ranked as the top five genes that have received the most investigative attention in the intersection of MCs and AD. CONCLUSION: In a word, this analysis would greatly benefit from a thorough bibliometric review to gain a deeper understanding of the current research landscape, identify pivotal studies and pinpoint emerging trends in the field of MCs and AD. Meanwhile, our findings offered researchers a holistic perspective of ongoing developments, serving as a valuable resource for guiding future research and informing decision-making for both researchers and policymakers in this area.

Meniscus root tears: what is the hype?

ABSTRACT: Meniscus root tears are increasingly being studied due to their importance in meniscus function. Meniscus root tears can increase the joint contact pressure significantly, similar to a total meniscectomy. This may cause rapid progression of joint degeneration and produce inferior clinical outcome. Historically, they were treated with partial meniscectomy, which did not change the natural history. New repair techniques such as transtibial pull-out repair and suture anchor repair have improved the clinical outcome. This review article summarises the anatomy of the meniscus, the pathology of meniscus root tears and different repair techniques with their clinical outcomes.

How do stretch rate, temperature, and solvent exchange affect elastic network rupture?

In this study, we investigate three different polymeric networks in terms of their tensile strength as a function of stretching rate, or temperature, or medium viscosity. Both an acrylate-based elastomer and a crosslinked poly(methyl acrylate) are stronger, more stretchable, and tougher at high rates. They are also much stronger at lower temperatures. Such phenomena systematically suggest that the kinetics of bond dissociation in backbones of those load-bearing strands dictate the rate and temperature dependencies. We apply Eyring's activation idea for chain scission to rationalize the influence of rate and temperature on rupture for both elastomers and hydrogels where hydrogels become much more stretchable and stronger when water is replaced by glycerol.

Oxidative lipid damage by naringenin selectively sensitizes chronic myeloid leukemia cell lines and patient samples to Bcr-Abl tyrosine kinase inhibitors.

Chronic myeloid leukemia (CML) treatment with Bcr-Abl tyrosine kinase inhibitors (TKIs) has significantly improved patient outcomes, yet challenges such as drug resistance and persistence of leukemic stem cells persist. This study explores the potential of naringenin, a natural flavonoid, to enhance the efficacy of Bcr-Abl TKIs in CML therapy. We showed that naringenin reduces viability of a panel of CML cell lines regardless of varying cellular origin and genetic mutations, and acts synergistically with dasatinib and ponatinib. Importantly, naringenin is effective in targeting blast crisis CML CD34+ cells by decreasing their colony formation, self-renewal and viability. Compared to CML, naringenin is significantly less effective against normal bone marrow (NBM) counterparts. In addition, naringenin significantly enhances the inhibitory effects of dasatinib in CML but not NBM CD34+ cells. Mechanism studies showed that naringenin's inhibitory effects were associated with the induction of oxidative stress and lipid damage, as evidenced by increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Notably, naringenin upregulated genes related to mitochondrial biogenesis while downregulating antioxidant defense genes. Pretreatment with α-tocopherol, which inhibits lipid-mediated ROS production, completely abolished the ROS increase and restored cell viability, indicating that lysosomal lipid peroxidation plays a crucial role in naringenin's mechanism of action. In a CML xenograft mouse model, the combination of naringenin and dasatinib resulted in remarkably more tumor growth suppression compared to single drug alone. Importantly, this combination was well-tolerated, with no adverse effects on body weight observed. These findings suggest that naringenin, by inducing oxidative lipid damage, enhances the anti-leukemic effects of Bcr-Abl TKIs, offering a promising therapeutic strategy for CML.

PGC-based cryobanking, regeneration through germline chimera mating, and CRISPR/Cas9-mediated TYRP1 modification in indigenous Chinese chickens.

Primordial germ cells (PGCs) are vital for producing sperm and eggs and are crucial for conserving chicken germplasm and creating genetically modified chickens. However, efforts to use PGCs for preserving native chicken germplasm and genetic modification via CRISPR/Cas9 are limited. Here we show that we established 289 PGC lines from eight Chinese chicken populations with an 81.6% success rate. We regenerated Piao chickens by repropagating cryopreserved PGCs and transplanting them into recipient chickens, achieving a 12.7% efficiency rate. These regenerated chickens carried mitochondrial DNA from female donor PGC and the rumplessness mutation from both male and female donors. Additionally, we created the TYRP1 (tyrosinase-related protein 1) knockout (KO) PGC lines via CRISPR/Cas9. Transplanting KO cells into male recipients and mating them with wild-type hens produced four TYRP1 KO chickens with brown plumage due to reduced eumelanin production. Our work demonstrates efficient PGC culture, cryopreservation, regeneration, and gene editing in chickens.

Activation of Follicle-Stimulating Hormone Receptor in Adrenal Zona Fasciculata Cells Promotes Cortisol Secretion: Implications for the Development of Menopause-Associated Diseases.

OBJECTIVE: Changes in postmenopausal hormone levels are associated with a variety of disorders. This study elucidated the mechanism by which follicle-stimulating hormone (FSH) increases cortisol production involved in development of menopause-related diseases. METHODS: The expression of FSH receptors (FSHRs) in murine adrenal zona fasciculata (AZF) cells and ATC7 cells was verified by immunofluorescence, western blotting and RT-PCR. The function of FSHR in promoting cortisol production was analyzed by cell culture and molecular biological methods. FSHR signaling pathways in ATC7 cells were analyzed by ELISA, qRT-PCR, and western blotting. Further, a mouse model was established by ovariectomy. Ovariectomized mice were treated with GnRHa. Ovariectomized mice initially received physiological doses of estrogen and were then injected with recombinant FSH. Then serum FSH, luteinizing hormone (LH), estradiol, and cortisol, and bone mineral density (BMD), blood pressure (BP) and heart rate (HR) were determined. RESULTS: FSHRs were expressed in murine AZF cells and ATC7 cells. FSH accelerated cortisol production through activated protein kinase A (PKA), cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB), protein kinase B (PKB/AKT) and 5' AMP-activated protein kinase (MAPK) signaling pathways by Gsα-coupled FSHRs in ATC7 cells. Serum FSH levels (P<0.001) were elevated in ovariectomized mice with concurrent increases in cortisol (P<0.01), areal BMD (aBMD) (P<0.05), volumetric BMD (vBMD) (P<0.05), systolic BP (SBP) (P<0.05), diastolic BP (DBP) (P<0.05), and HR (P<0.05). However, the administration of GnRHa suppressed the increase in FSH levels and the elevation of cortisol, aBMD, vBMD, SBP, DBP, and HR induced by ovariectomy, even in the presence of normal serum estradiol levels. CONCLUSION: The study findings indicate that elevated FSH levels stimulate cortisol secretion, through a mechanism related to FSHRs expression in AZF cells.

A cyclic shift-temperature operation method to train microbial communities of mesophilic anaerobic digestion.

Temperature is the critical factor affecting the efficiency and cost of anaerobic digestion (AD). The current work develops a shift-temperature AD (STAD) between 35 °C and 55 °C, intending to optimise microbial community and promote substrate conversion. The experimental results showed that severe inhibition of biogas production occurred when the temperature was firstly increased stepwise from 35 °C to 50 °C, whereas no inhibition was observed at the second warming cycle. When the organic load rate was increased to 6.37 g VS/L/d, the biogas yield of the STAD reached about 400 mL/g VS, nearly double that of the constant-temperature AD (CTAD). STAD promoted the proliferation of Methanosarcina (up to 57.32 %), while severely suppressed hydrogenophilic methanogens. However, when the temperature was shifted to 35 °C, most suppressed species recovered quickly and the excess propionic acid was quickly consumed. Metagenomic analysis showed that STAD also promoted gene enrichment related to pathways metabolism, membrane functions, and methyl-based methanogenesis.