Grifola frondosa polysaccharides: A review on structure/activity, biosynthesis and engineering strategies.

Polysaccharides are the main polymers in edible fungi Grifola frondosa, playing a crucial role in the physiology and representing the healthy benefits for humans. Recent efforts have well elucidated the fine structures and biological functions of G. frondosa polysaccharides. The recently-rapid developments and increasing availability in fungal genomes also accelerated the better understanding of key genes and pathways involved in biosynthesis of G. frondosa polysaccharides. Herein, we provide a brief overview of G. frondosa polysaccharides and their activities, and comprehensively outline the complex process, genes and proteins corresponding to G. frondosa polysaccharide biosynthesis. The regulation strategies including strain improvement, process optimization and genetic engineering were also summarized for maximum production of G. frondosa polysaccharides. Some remaining unanswered questions in describing the fine synthesis machinery were also pointed out to open up new avenues for answering the structure-activity relationship and improving polysaccharide biosynthesis in G. frondosa. The review hopefully presents a reasonable full picture of activities, biosynthesis, and production regulation of polysaccharide in G. frondosa.

Fe-doped carbon dots: a novel fluorescent nanoprobe for cellular hypochlorous acid imaging.

Real-time monitoring of hypochlorous acid (HClO) in biological systems is of great significance for exploring and regulating its pathological functions because abnormal production of HClO is closely related with many diseases, such as atherosclerosis, rheumatoid arthritis, and cancer. Herein, we developed a reliable fluorescent Fe-doped carbon dots (Fe-CDs) for the sensitive and selective detection of biological HClO using ferrocenecarboxylic acid and m-phenylenediamine as precursors through a one-step solvothermal procedure. The Fe-CDs exhibited excellent a wide HClO detection range from 20 nmol/L to 1000 nmol/L with corresponding limits of detection at 7.8 nmol/L. The sensing mechanism is based on the chemical oxidation of the hydroxyl groups on the surface of Fe-CDs by HClO. In addition, Fe-CDs also displayed high photoluminescence yield, excitation-independence emission, as well as good biocompatibility, enabling the successful imaging of endogenous and exogenous HClO in HeLa cells. These results revealed that Fe-CDs holds great promise as a robust fluorescent probe for investigating HClO-mediated biological events.

Mitoguardin 1 and 2 promote granulosa cell proliferation by activating AKT and regulating the Hippo-YAP1 signaling pathway.

Mitochondria have been identified to be involved in oxidative phosphorylation, lipid metabolism, cell death, and cell proliferation. Previous studies have demonstrated that mitoguardin (Miga), a mitochondrial protein that governs mitochondrial fusion, mitochondria-endoplasmic reticulum (ER) contacts, lipid formation, and autophagy, is crucial for ovarian endocrine and follicular development. Nevertheless, whether mammalian MIGA1 or MIGA2 (MIGA1,-2) regulates ovarian granulosa cell proliferation remains unclear. This study revealed that mammalian MIGA1,-2 promotes cell proliferation and regulates the phosphorylation and localization of Yes-associated protein 1 (YAP1) in ovarian granulosa cells. MIGA2 upregulation resulted in reduced YAP1 activity, while MIGA2 removal led to increased YAP1 activity. Further analysis indicated that MIGA1,-2 regulated YAP1 via the Hippo signaling pathway and regulated protein kinase B (AKT) activity in collaboration with YAP1. In addition, lysophosphatidic acid (LPA) regulated MIGA2 expression and AKT activity by activating YAP1. Briefly, we demonstrated that the mitochondrial MIGA1 and MIGA2, especially MIGA2, promoted cellular proliferation by activating AKT and regulating the Hippo/YAP1 signaling pathway in ovarian granulosa cells, which may contribute to the molecular pathogenesis of reproductive endocrine diseases, such as polycystic ovary syndrome (PCOS).

Biochemical and structural characterization of a glucan synthase GFGLS2 from edible fungus Grifola frondosa to synthesize ß-1, 3-glucan.

BACKGROUND: Grifola frondosa is a Basidiomycete fungus belonging to the family of Grifolaceae and the order of Polyporales. ß-Glucans are the main polymers in G. frondosa, playing a crucial role in the physiology and representing the healthy benefits for humans. The membrane-integrated ß-1, 3-glucan synthase (GLS) is responsible for glucan synthesis, cell wall assembly, differentiation and growth of the edible fungi. However, the structural/catalytic characteristics and mechanisms of ß-1, 3-glucan synthases in G. frondosa are still unknown due to their extremely complex structures with multi-transmembranes and large molecular masses. RESULTS: Herein, a ß-1, 3-glucan synthase (GFGLS2) was purified and identified from the cultured mycelia with a specific activity of 60.01 pmol min-1 µg-1 for the first time. The GFGLS2 showed a strict specificity to UDP-glucose with a Vmax value of 1.29 ± 0.04 µM min-1 at pH 7.0 and synthesized ß-1, 3-glucan with a maximum degree of polymerization (DP) of 62. Sequence Similarity Network (SSN) analysis revealed that GFGLS2 has a close relationship with others in Ganoderma sinense, Trametes coccinea, Polyporus brumalis, and Trametes pubescens. With the assistance of 3D structure modelling by AlphaFold 2, molecular docking and molecular dynamics simulations, the central hydrophilic domain (Class III) in GFGLS2 was the main active sites through binding the substrate UDP-glucose to 11 amino acid residues via hydrogen bonds, π-stacking and salt bridges. CONCLUSIONS: The biochemical, 3D structural characterization and potential catalytic mechanism of a membrane-bound ß-1, 3-glucan synthase GFGLS2 from cultured mycelia of G. frondosa were well investigated and would provide a reasonable full picture of ß-1, 3-glucan synthesis in fungi.

Scalable Multipartite Entanglement Created by Spin Exchange in an Optical Lattice.

Ultracold atoms in optical lattices form a competitive candidate for quantum computation owing to the excellent coherence properties, the highly parallel operations over spins, and the ultralow entropy achieved in qubit arrays. For this, a massive number of parallel entangled atom pairs have been realized in superlattices. However, the more formidable challenge is to scale up and detect multipartite entanglement, the basic resource for quantum computation, due to the lack of manipulations over local atomic spins in retroreflected bichromatic superlattices. In this Letter, we realize the functional building blocks in quantum-gate-based architecture by developing a cross-angle spin-dependent optical superlattice for implementing layers of quantum gates over moderately separated atoms incorporated with a quantum gas microscope for single-atom manipulation and detection. Bell states with a fidelity of 95.6(5)% and a lifetime of 2.20±0.13 s are prepared in parallel, and then connected to multipartite entangled states of one-dimensional ten-atom chains and two-dimensional plaquettes of 2×4 atoms. The multipartite entanglement is further verified with full bipartite nonseparability criteria. This offers a new platform toward scalable quantum computation and simulation.

Changes in body weight and cardiovascular risk factors in a Chinese population with type 2 diabetes mellitus: a longitudinal study.

Introduction: The primary care management of blood glucose, blood pressure, lipid profiles, and body weight is important among patients with type 2 diabetes mellitus (T2DM) to prevent disease progression. Information on how weight changes would improve or deteriorate cardiovascular (CV) risk factors is warranted for making primary care recommendations. We aimed to investigate the changes in body weight and CV risk factors and to analyse their association in a Chinese population with T2DM. Methods: We retrieved longitudinal data between 2020 and 2021 from 1,758 adult primary care patients enrolled in a diabetic retinopathy (DR) screening programme. Linear associations of changes in body weight with CV risk factors were explored. Multivariable logistic regression analysis was performed to examine associations between different weight change categories and the worsening of CV risk factors. Results: The mean age of all the participants was 63.71 years, and over half of participants were females. During a one-year follow-up period, 24.7% of patients had a weight loss of ≥3%, while 22.2% of patients had a weight gain of ≥3%. Patients who had a weight loss of ≥3% were more likely to prevent the worsening of haemoglobin A1c (HbA1c) and triglycerides, while those who had a weight gain of ≥3% tended to have worsened HbA1c, lipid profiles, and blood pressure. Conclusion: Results from this real-world investigation suggested the concurrent need for weight loss intervention among patients who are overweight or obese and weight gain prevention among patients whose body weight falls within the normal range in the context of community-based diabetes management.

Mitoguardin2 Is Associated With Hyperandrogenism and Regulates Steroidogenesis in Human Ovarian Granulosa Cells.

Polycystic ovary syndrome (PCOS) is an endocrinopathy characterized by hyperandrogenism, anovulation, and polycystic ovaries, in which hyperandrogenism manifests by excess androgen and other steroid hormone abnormalities. Mitochondrial fusion is essential in steroidogenesis, while the role of mitochondrial fusion in granulosa cells of hyperandrogenic PCOS patients remains unclear. In this study, mRNA expression of mitochondrial fusion genes mitoguardin1, -2 (MIGA 1, -2) was significantly increased in granulosa cells of hyperandrogenic PCOS but not PCOS with normal androgen levels, their mRNA expression positively correlated with testosterone levels. Dihydrotestosterone (DHT) treatment in mice led to high expression of MIGA2 in granulosa cells of ovulating follicles. Testosterone or forskolin/ phorbol 12-myristate 13-acetate treatments increased expression of MIGA2 and the steroidogenic acute regulatory protein (StAR) in KGN cells. MIGA2 interacted with StAR and induced StAR localization on mitochondria. Furthermore, MIGA2 overexpression significantly increased cAMP-activated protein kinase A (PKA) and phosphorylation of AMP-activated protein kinase (pAMPK) at T172 but inhibited StAR protein expression. However, MIGA2 overexpression increased CYP11A1, HSD3B2, and CYP19A1 mRNA expression. As a result, MIGA2 overexpression decreased progesterone but increased estradiol synthesis. Besides the androgen receptor, testosterone or DHT might also regulate MIGA2 and pAMPK (T172) through LH/choriogonadotropin receptor-mediated PKA signaling. Taken together, these findings indicate that testosterone regulates MIGA2 via PKA/AMP-activated protein kinase signaling in ovarian granulosa cells. It is suggested mitochondrial fusion in ovarian granulosa cells is associated with hyperandrogenism and potentially leads to abnormal steroidogenesis in PCOS.

Cytochrome†P450 Catalyzes Benzene Ring Formation in the Biosynthesis of Trialkyl-Substituted Aromatic Polyketides.

Lorneic acid and related natural products are characterized by a trialkyl-substituted benzene ring. The formation of the aromatic core in the middle of the polyketide chain is unusual. We characterized a cytochrome P450 enzyme that can catalyze the hallmark benzene ring formation from an acyclic polyene substrate through genetic and biochemical analysis. Using this P450 as a beacon for genome mining, we obtained 12 homologous type I polyketide synthase (PKS) gene clusters, among which two gene clusters are activated and able to produce trialkyl-substituted aromatic polyketides. Quantum chemical calculations were performed to elucidate the plausible mechanism for P450-catalyzed benzene ring formation. Our work expands our knowledge of the catalytic diversity of cytochrome P450.

Element sulfur-based autotrophic denitrification constructed wetland as an efficient approach for nitrogen removal from low C/N wastewater.

Constructed wetlands (CWs) integrated with sulfur autotrophic denitrification to stimulate high-rate nitrogen removal from carbon-limited wastewater holds particular application prospect due to no excessive carbon source addition, high efficiency, and good stability. In this study, we conducted elemental sulfur-based constructed wetland (SCW) and traditional constructed wetland (CW) under different C/N (2, 1, and 0.5) to explore the feasibility and mechanisms for nitrogen removal from low C/N wastewater. Compared with CW, SCW was demonstrated more robust in nitrogen removal in the case of low C/N influent. When the influent C/N control was at 0.5, SCW observed total nitrogen (TN) and nitrate removal efficiency of 69.36 ± 3.96% and 81.71 ± 3.96%, with the corresponding removal rate of 1.18 ± 0.66 and 1.70 ± 0.92 g-N·m-2·d-1, which were 2.11 and 10.03 times of CW, respectively. The nitrate removal rate constant k in the SCW was 1.05, 3.83, and 10.33 times higher than the CW with C/N of 2, 1 and 0.5. Furthermore, 14.40, 54.51, and 79.82% of nitrogen were removed by the sulfur autotrophic denitrification (SAD) in SCW, which also contributed 43.89, 73.68, and 71.70% of sulfate production. Moreover, the combined system of CW-SCW is proved be an efficient operation mode for simultaneously removing total ammonia nitrogen (TAN) and nitrate. In the SCW, the richness of the microbial community was improved and sulfur-oxidizing genera (e.g. Thiobacillus, Sulfurimonas) was selectively enriched, which affect the performance the elemental sulfur-based denitrification process. The nitrate reduction pathway was overwhelmed by denitrification and the dissimilatory nitrate reduction process. These findings offer elemental sulfur-based autotrophic denitrification constructed wetland has excellent potential to enhance nitrogen removal from carbon-limited wastewater.

Water adsorption characteristic and its impact on pore structure and methane adsorption of various rank coals.

Coalbed methane not only is a new clean energy source, but also has potential damage to ecological environment. Water and methane coexist in coal reservoir; understanding the adsorption of water on coal and its impact on pore structure and methane adsorption of coal is vital to evaluate the reserves and productivity of coalbed methane. In the paper, water adsorption characteristics of various rank coals are firstly investigated by ten mathematical models. The modified Dent model provides a best fit, followed by GAB and Dent models. For GAB model, the primary site adsorption is more difficult to reach saturation, and the contribution rate of the secondary site adsorption is surprisingly high at P/P0 approaching 0, which can be attributed to the possible overestimation of GAB monolayer adsorption capacity and secondary site adsorption. Besides, the low-rank coal sample YZG2 exhibits more prominent hysteresis than middle- to high-rank coals. The low-pressure hysteresis can be attributed to the water-water interactions over the primary site and the strengthened binding forces of water molecules in the water desorption process. In contrast, the high-pressure hysteresis largely depends on pore structure of coal such as ink-bottle pores, especially for the studied sample YZG2. Besides, pore analyses by low-temperature nitrogen adsorption method show that the pre-adsorbed water has remarkable influence on micropores smaller than 10 nm, and the micropores smaller than 4 nm almost disappear for water-equilibrated coals, which is closely related to the formed water clusters and capillary water in pore throats. This finding reveals that more methane gas can only be adsorbed in the larger pores of moist coal, and provides an explanation for water weakening methane adsorption capacity.

Lighting up of carbon dots for copper(II) detection using an aggregation-induced enhanced strategy.

Carbon dots have promising prospects for analytical and monitoring purposes, but are greatly hindered by the aggregation-induced luminescence quenching owing to the π-π interaction or the non-radiation-excited radical complex formation. Herein hydrothermally prepared orange-yellow fluorescent carbon dots (O-CDs) show an aggregation-induced fluorescence enhancement (AIFE) with Cu2+ owing to the complexation of Cu(II) and the O-CDs. Cu2+ was then sensitively and selectively detected in the linear range from 0.02 to 30 µM with the detection limit of 14 nM, making the detection of Cu2+ in fresh water and E. coli lysate successful, showing that the as-prepared O-CDs could be well applied to the environmental monitoring of heavy metals.

RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression.

BACKGROUND: The rhomboids are a family of multi-transmembrane proteins, many of which have been implicated in facilitating tumor progression. Little is yet known, however, about rhomboid-associated biomarkers in cancers. An analysis of such biomarkers could yield important insights into the role of the rhomboids in cancer pathology. METHODS: In this study, we carried out the univariate Cox regression analysis and compared gene expression patterns of several rhomboid genes in 30 types of cancers by using The Cancer Genome Atlas (TCGA) database and the methods delineated in Gene Expression Profiling Interactive Analysis (GEPIA). We then used datasets GSE47032, GSE126964, GSE68417 and 75 paired pathological specimens to verify the influences of the rhomboid genes in cancer progression. Moreover, we carried out Weighted Gene Correlation Network Analysis (WGCNA) to investigate gene-related functions and we exploited potential correlations between rhomboid genes expression and immune cell infiltration in cancer tissues. Furthermore, we constructed gene-knockdown cancer cell lines to investigate rhomboid gene functions. RESULTS: We find that kidney renal clear cell carcinoma (KIRC) disease progression is affected by fluctuations in the expression of a number of the rhomboid family of genes and, more specifically, high levels of RHBDF2 gene expression are a good indicator of poor prognosis of the disease, as patients with high RHBDF2 expression levels exhibit less favorable survival rates compared to those with low RHBDF2 levels. Silencing of the RHBDF2 gene in KIRC cell lines leads to significantly diminished cell proliferation and migration; this is in good agreement with the identification of an enhanced presence of a number of cell growth and migration promoting signaling molecules in KIRC tumors. We found that, although high level of RHBDF2 correlated with increased infiltration of lymphocytes in cancer tissues, artificially overexpressed RHBDF2 led to an inhibition of the activity of the infiltrated immune cells through sustaining PD-L1 protein level. Furthermore, we show that RHBDF2 related cell migration and PD-L1 regulation were potentially mediated by EGFR signaling pathway. CONCLUSIONS: RHBDF2 gene functions are correlated to facilitated renal clear cell carcinoma progression and may serve as a critical prognostic biomarker for the disease.

[Characteristics of Atmospheric PM2.5 Pollution and Its Influence on Visibility in Background Areas of Ji'nan].

In order to study the seasonal variations in the chemical composition of atmospheric particulate matter with diameters less than 2.5 µm (PM2.5) and its influence on visibility in background areas, atmospheric PM2.5 samples were collected in spring, summer, autumn, and winter 2016 at Qixingtai in Ji'nan. The pollution characteristics of water-soluble ions components, organic carbon (OC), and elemental carbon (EC) were analyzed, and their regional transmission contributions were studied. The results show that NH4+, SO42-, and NO3- were the main components of water-soluble ions, accounting for 90.24% of the annual total ion concentration. The secondary water soluble inorganic ions were polluted severely. NO3-/SO42- presented obvious seasonal variations of high (low) levels in winter (summer). In each season, SO42- and NH4+ existed mainly in the form of (NH4)2SO4. The value of secondary OC (SOC)/OC ranged from 21.17% to 54.21%, indicating the presence of relatively severe secondary organic pollution in this area. The sulfur oxidation ratio (SOR) value in all seasons was greater than 0.1, indicating that the secondary generation of SO42- occurs in all seasons in this region, and the value of nitrogen oxidation ratio (NOR) in all seasons was higher than the SOR value. The secondary transformation of NO2 in the Qixingtai region was stronger than that of SO2. The range of atmospheric extinction coefficient (Bext) was 172.68-320.61 Mm-1, with an annual mean of 256.48 Mm-1. The atmospheric extinction coefficient showed an obvious seasonal trend of the lowest (highest) in summer (winter). The backward airflow trajectory shows that the Qixingtai was affected mainly by the long-distance transmission from Northwest China and the ocean in spring and summer and by local sources in autumn and winter. A comparison of the characteristics of atmospheric PM2.5 pollution in Ji'nan in 2008 revealed that the influence of motor vehicles on the atmospheric environment has been significantly improved.

Ultra-low noise and high bandwidth bipolar current driver for precise magnetic field control.

Current sources with extremely low noise are significant for many branches of scientific research, such as experiments of ultra-cold atoms, superconducting quantum computing, and precision measurements. Here we construct and characterize an analog-controlled bipolar current source with high bandwidth and ultra-low noise. A precise and stable resistor is connected in series with the output for current sensing. After being amplified with an instrumentation amplifier, the current sensing signal is compared with an ultra-low noise reference, and proportional-integral (PI) calculations are performed via a zero-drift low-noise operational amplifier. The result of the PI calculation is sent to the output power operational amplifier for closed-loop control of the output current. In this way, a current of up to 16 A can be sourced to or sunk from a load with a compliance voltage of greater than ±12 V. The broadband current noise of our bipolar current source is about 0.5 µA/Hz and 1/f corner frequency is less than 1 Hz. Applications of this current source in a cold atom interferometer, as well as active compensation of a stray magnetic field, are presented. A method for measuring high-frequency current noise in a 10 A DC current with a sensitivity down to a level of 10 µA is also described.