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Circulating concentration of insulin-like growth factor (IGF)-1 in patients with polycystic ovary syndrome (PCOS) is still unclear. Therefore, we aimed to investigate the association of IGF-1 with PCOS through this meta-analysis.Literature search was conducted through PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure (up to July 2022). A manual search was performed on the references of related original research. Then, we applied the random-effects model to evaluate the overall effect size by calculating the standard mean difference and its 95% CI. Subgroup analyses were used to explore the sources of heterogeneity. In addition, a sensitivity analysis was performed and publication bias was assessed.Twenty studies were included in this meta-analysis involving 657 individuals: 362 patients with PCOS and 295 normal controls. The results of meta-analysis showed that serum IGF-1 levels were significantly higher in patients with PCOS than in controls (standard mean difference, 0.89; 95% CI, 0.34-1.45; P = .002). The final pooled data were determined by the random-effects model because a significant high heterogeneity (IThese data suggest that elevated serum IGF-1 levels may not be a major cause of PCOS pathogenesis. Body mass index may be a major determinant of serum IGF-1.

With the continuous advancement of the modernization of the national governance system and governance capacity, industry associations, as an important part of social governance, play an increasingly important role in social life, which also poses greater challenges to the autonomy of industry associations. However, due to the complex and changeable industry environment and the influence of the industry association's own characteristics, the industry association has passive autonomy behaviors such as arbitrary fees, overcharging, and organizational monopoly in the actual performance of its responsibilities, which not only damages the reputation and autonomy of the industry association itself, but also seriously affects the healthy development of the industry as a whole. Therefore, this paper studies the problem of poor autonomy of industry associations, in order to provide valuable strategic suggestions for promoting the effective autonomy of industry associations and improving the autonomy level of industry associations.

Background: Methotrexate (MTX) is a common folic acid antagonist in clinical medicine, easily inducing a common adverse side effect of liver and kidney injury. It has been found that the expression of Folylpolyglutamate Synthetase (FPGS) and gamma-Glutamyl Hydrolase (GGH) may be closely related to that of related proteins to affect the intracellular metabolism of MTX. Objective: The relationship between FPGS/GGH and MTXPGs accumulation in liver and kidney cells was explored by adjusting the expression of FPGS and GGH in cells using UPLC-MS/MS quantitative technology. Method: Based on UPLC-MS/MS quantitative techniques, the relationship between MTXPGs accumulation and FPGS/GGH in hepatocytes and embryonic kidney cells was explored by adjusting the expression of FPGS and GGH, and the effect of FPGS/GGH on the intracellular toxicity of MTX was comprehensively analyzed. Result: The results showed that the difference in methotrexate polyglutamates (MTXPGs) accumulation in liver and kidney cells was related to the difference in FPGS and GGH expression. The expression of FPGS interacted with that of GGH. These results suggest that the protein abundance ratio of FPGS to GGH (FPGS/GGH) has more potential to be used as a predictor of MTX efficacy than the FPGS or GGH single protein index. This can effectively avoid liver and kidney damage caused by MTX and guides the rational use of drugs in MTX. Conclusion: The results prove that there is a positive correlation between the FPGS/GGH and the accumulation of MTXPGS in liver and kidney cells. Summarily, the FPGS/GGH is expected to be a predictor for MTXPGs accumulation and provides an effective method to evaluate the toxicity caused by MTX.

Gold nanoparticles (AuNPs) have attracted extensive attention in the past few years due to their unique properties and great potential application in catalysis. However, the application of AuNPs remains a significant challenge due to the lack of high efficiency and stability caused by aggregation. Immobilization of AuNPs on appropriate support shows promising results in avoiding aggregation and improving catalytic activity. In this work, reduced graphene oxide/chitosan/gold nanoparticles (rGO/CHS/AuNPs) composites were prepared using chitosan with different molecular weights (MW) as a reducing agent and stabilizer, and characterized by FT-IR, XRD, XPS, SEM, FESEM, EDS, TEM, HRTEM, and TGA. The preparation conditions of rGO/CHS/AuNPs composites, including chitosan MW, CHS/GO mass ratio, reaction temperature and time, and HAuCl

Benefiting from the structure and interface engineering, the electrocatalyst of Co/CoSe2@CNx presents superior ORR/UOR bifunctional performance with high stability and high energy conversion efficiency for urea-assisted rechargeable Zn–air batteries.

Reproducibility and stability are important indicators for the evaluation of quantitative sensing methods based on surface-enhanced Raman scattering (SERS) technology. Developing a SERS substrate with self-calibration capabilities is vital for effectively quantifying targets. In this work, a competitive ratiometric SERS aptasensor was developed. 4-Aminothiophenol as an internal standard (IS) was embedded in the substrate followed by gradually loading with the aptamer and methylene blue functionalizing of the complementary sequences of the aptamer (MB-cDNA). Recognition and binding of the target to the aptamer resulted in the shedding of MB-cDNA after magnetic separation reducing the SERS signal of MB, allowing for the ratiometric determination of the target based on the constant intensity from the IS. For the selective detection of okadaic acid (OA), a good negative correlation was achieved between the SERS ratiometric intensity and OA concentration in the range of 0.5-100 ng/mL. The magnetic separation strategy effectively simplifies the production steps of the aptasensor, and the ratiometric strategy effectively improved the reproducibility and stability of the OA sensing. This ratiometric aptasensor has been successfully employed to detect OA in food and environmental samples and is expected to be extended to detect other targets.

Fabrication, arrangement, and controllable composition of ordered organometallic films are critical for designing a highly active catalyst and investigating the catalytic mechanism. In this paper, an organometallic terpyridine Pd(II)/Ni(II) monolayer linked on the silicon substrate surface (denoted as Si-Tpy-Pd1/Ni1) was prepared and characterized using water contact angle, ultraviolet spectra, X-ray diffraction, scanning electron microscopy, and X-ray photoelectron microscopy. Si-Tpy-Pd1/Ni1 exhibited high catalytic activity, substrate applicability, and reusability after 5 runs. During recycling, the deactivation was induced by the aggregation of active Pd/Ni nanoparticles. The catalytic mechanism was heterogeneous and occurred on the Si-Tpy-Pd1/Ni1 monolayer surface; the mechanism was confirmed using hot filtrate, poison test, and a three-phase experiment. The real active center was Pdδ–/Niδ+ and was formed in situ on the organometallic monolayer surface, which acted as a precursor with a synergistic effect between Pd and Ni. The electron density of Pd became more negative because of electron transfer from Ni to Pd, which facilitated the oxidative addition reaction.

We introduce a graded homology theory for graded \'etale groupoids. For $\mathbb Z$-graded groupoids, we establish an exact sequence relating the graded zeroth-homology to non-graded one. Specialising to the arbitrary graph groupoids, we prove that the graded zeroth homology group with constant coefficients $\mathbb Z$ is isomorphic to the graded Grothendieck group of the associated Leavitt path algebra. To do this, we consider the diagonal algebra of the Leavitt path algebra of the covering graph of the original graph and construct the group isomorphism directly. Considering the trivial grading, our result extends Matui's on zeroth homology of finite graphs with no sinks (shifts of finite type) to all arbitrary graphs. We use our results to show that graded zeroth-homology group is a complete invariant for eventual conjugacy of shift of finite types and could be the unifying invariant for the analytic and the algebraic graph algebras., Comment: 23 pages

Plants have evolved delicate systems for stimulating or inhibiting inorganic phosphate (Pi) uptake in response to the fluctuating Pi availability in soil. However, the negative regulators inhibiting Pi uptake at the transcriptional level are largely unexplored. Here, we functionally characterized a transcription factor in rice (Oryza sativa), OsWRKY10. OsWRKY10 encodes a nucleus-localized protein and showed preferential tissue localization. Knockout of OsWRKY10 led to increased Pi uptake and accumulation under Pi-replete conditions. In accordance with this phenotype, OsWRKY10 was transcriptionally induced by Pi, and a subset of PHOSPHATE TRANSPORTER 1 (PHT1) genes were up-regulated upon its mutation, suggesting that OsWRKY10 is a transcriptional repressor of Pi uptake. Moreover, rice plants expressing the OsWRKY10–VP16 fusion protein (a dominant transcriptional activator) accumulated even more Pi than oswrky10. Several lines of biochemical evidence demonstrated that OsWRKY10 directly suppressed OsPHT1;2 expression. Genetic analysis showed that OsPHT1;2 was responsible for the increased Pi accumulation in oswrky10. Furthermore, during Pi starvation, OsWRKY10 protein was degraded through the 26S proteasome. Altogether, the OsWRKY10–OsPHT1;2 module represents a crucial loop in the Pi signaling network in rice, inhibiting Pi uptake when there is ample Pi in the environment.

This study built an electrochemical label-free progesterone aptasensor to detect progesterone (P4) levels in environmental water samples. The truncated aptamer-modified sulfhydryl adopted self-assembly as a way to stably immobilize at the electrode surface modified by gold nanoparticles (AuNPs). When progesterone combines with the aptamer, the complexes will inhibit electrode surface electron transfer, which reduces the redox peak current value of [Fe(CN)6]3−/4−. As a result, the amount of progesterone combined with the aptamer on the electrode reacted to the electric current’s response values. We have established the relationship between the concentration of progesterone and the current change by a standard curve that is ΔI (μA) = 11.78log CP4 (nM)+48.98. The coefficient of association was 0.9358. The test ranges were from 0.5 nM to 1000 nM. At the same time, other molecules with a similar structure, such as testosterone, estradiol, and 17α-hydroxyl progesterone, had lower response interference than P4. In conclusion, the aptasensor, which had outstanding repeatability and stability, could be applied to determine P4. Food hygiene and clinical diagnosis can be made easier with this newly developed electrochemical biosensor based on aptamers.

The liver plays a key role in keeping the homeostasis of glucose and lipid metabolism. Insulin resistance of the liver induced by extra glucose and lipid ingestion contributes greatly to chronic metabolic disease, which is greatly threatening to human health. The small peptide, VLPVPQK, originating from casein hydrolysates of milk, shows various health-promoting functions. However, the effects of VLPVPQK on metabolic disorders of the liver are still not fully understood. Therefore, in the present study, the effects and regulatory mechanism of VLPVPQK on insulin-resistant HepG2 cells was further investigated. The results showed that VLPVPQK exerted strong scavenging capacities against various free radicals, including oxygen radicals, hydroxyl radicals, and cellular reactive oxygen species. In addition, supplementation of VLPVPQK (62.5, 125, and 250 μM) significantly reversed the high glucose and fat (30 mM glucose and 0.2 mM palmitic acid) induced decrement of glucose uptake in HepG2 cells without affecting cell viability. Furthermore, VLPVPQK intervention affected the transcriptomic profiling of the cells. The differentially expressed (DE) genes (FDR < 0.05, and absolute fold change (FC) > 1.5) between VLPVPQK and the model group were mostly enriched in the carbohydrate metabolism-related KEGG pathways. Interestingly, the expression of two core genes (HKDC1 and G6PC1) involved in the above pathways was dramatically elevated after VLPVPQK intervention, which played a key role in regulating glucose metabolism. Furthermore, supplementation of VLPVPQK reversed the high glucose and fat-induced depression of AKR1B10. Overall, VLPVPQK could alleviate the metabolic disorder of hepatocytes by elevating the glucose uptake and eliminating the ROS, while the HKDC1 and AKR1B10 genes might be the potential target genes and play important roles in the process.

MCM8 and MCM9 form a functional helicase complex (MCM8/9) that plays an essential role in DNA homologous recombination repair for DNA double-strand break. However, the structural characterization of MCM8/9 for DNA binding/unwinding remains unclear. Here, we report structures of the MCM8/9 complex using cryo-electron microscopy single particle analysis. The structures reveal that MCM8/9 is arranged through a three-fold symmetry axis to form a heterohexamer with a central channel to accommodate DNA. Multiple characteristic hairpins from the N-terminal oligosaccharide/oligonucleotide (OB) domains of MCM8/9 protrude into the central channel and serve to unwind the duplex DNA. When activated by HROB, the structure of MCM8/9’s N-tier ring converts its symmetry fromC3toC1with a conformational change that expands the MCM8/9’s trimer interface. Moreover, structural dynamic analyses revealed that the flexible C-tier ring exhibited rotary motions relative to the N-tier ring, which is required for the unwinding ability of MCM8/9. In summary, our structural and biochemistry study provide a basis for the DNA unwinding mechanism of MCM8/9 helicase in homologous recombination.

Aqueous zinc anodes have attracted the attention of many researchers owing to their high safety, low cost, and high theoretical specific capacity. However, its practical application is severely limited by the dendrite growth on zinc anode. Herein, we develop an intrinsically zincophobic barium-titanate protective layer with a porous structure to suppress the zinc dendrite formation by homogenizing the ion distribution on the anode surface, increasing the nucleation sites, and limiting the irregular zinc growth. Based on these synergistic effects, the coated zinc anode can exhibit long cycle life (840 h at 0.5 mA/cm2 for 0.5 mAh/cm2) and low voltage hysteresis (36 mV). This work can provide a feasible direction for the design of intrinsically zincophobic coating materials to uniformize the zinc stripping and plating.

Due to the presence of peptidase and protease in the gastrointestinal tract, peptides are subjected to digestion and inactivation when administrated orally. To avoid degradation and maintain the desired efficacy of peptide drugs, there is a demand to develop transdermal and intradermal delivery systems. This requires efficient and specific analytical methods to separate and quantify the peptide drugs from the formulation and the skin matrix in the early stages of pharmaceutical development. A high-performance liquid chromatography (HPLC) system equipped with a fluorometric detector was used to quantify enfuvirtide, which is the first fusion inhibitor for HIV treatment. The HPLC method was developed and validated according to the ICH Q2(R1) guidelines. The viability of the method was demonstrated during in vitro studies, where samples were analysed following intradermal administration of a thermosensitive in situ forming gel. Compared with previously reported methods, this assay proved efficient, sensitive and accurate, with a detection limit of 0.74 μg/mL and a run time of 9 min, mitigating the use of any internal standards and detergents. The addition of an organic solvent to the samples successfully solved the problem of low recovery caused by the adsorption of the drug to the plastic consumables in the sample treatment process. The amount of enfuvirtide releasing from the in situ gel through skin after 7 hours was 16.25 ± 7.08 μg, which was significantly lower than the reconstituted FUZEON® itself (26.68 ± 10.45 μg), showing a longer release profile. The results may be beneficial as a constructive input for future enfuvirtide quantification within a preclinical setting through in vitro release studies across the skin. Graphical Abstract

Powdery mildew is a devastating disease that affects wheat yield and quality. Despite wheat wild relatives being a valuable source of resistance genes, their incorporation into wheat improvement is constrained by their adverse effects on agronomic traits, difficulty in isolating genes and poor understanding of the resistance mechanisms. Here, we report cloning of Pm57, the first gene isolated from Aegilops searsii. It encodes an unusual wheat tandem kinase (WTK) protein with putative kinase-pseudokinase domains followed by a von Willebrand factor A (vWA) domain, designated WTK7-vWA. The resistance function of Pm57 was validated by independent mutants, gene silencing, and transgenic assays. Stable Pm57 transgenic wheat lines showed high levels and all-stage resistance against diverse isolates of Bgt fungus with no adverse effects on agronomic traits. Our findings highlight the emerging role of kinase fusion proteins in plant disease resistance and provide a powerful gene for wheat breeding.

Wheat powdery mildew is one of the most destructive diseases threatening global wheat production. The wild relatives of wheat comprise rich sources of diversity for powdery mildew resistance. Here, we report map-based cloning of broad-spectrum powdery mildew resistance gene Pm13 from wild wheat species Aegilops longissima. Pm13 encodes a novel mixed lineage kinase domain-like (MLKL) protein which contains an N-terminal HeLo domain and a C-terminal authentic serine/threonine kinase (STK) domain, a unique domain architecture that has not been reported in plant disease-resistance genes. The resistance function of Pm13 was validated by loss-of-function mutants, gene silencing, transgenic assay, and allelic association analyses. Thus, Pm13 represents a special class of plant resistance genes revealing a novel aspect of host-pathogen interactions. Though introgressed into wheat ~30 years ago it was hardly exploited due to linkage drag. The new lines with small Ae. longissima Pm13 segment will lead to wide-scale deployment in wheat cultivars.

Cadmium is a common reproductive toxin in aquatic systems. Cd exposure of fish species at high concentrations can severely affect the reproductive function of fish. However, the underlying toxicity of cadmium exposure at low concentrations on the reproductive function in parental fish remains unclear. To investigate the impacts of cadmium exposure on reproductive capability, eighty-one male and eighty-one female rare minnows (Gobiocypris rarus) were exposed to cadmium at 0 (control group), 5 and 10 μg/L for 28 days, and then transferred into clean water to pair spawn. The results showed that cadmium exposure at 5 or 10 μg/L for 28 days in rare minnows could reduce the success rates of pair spawning in parent rare minnows, lessen no-spawning activities, and prolong the time for first spawning. Furthermore, the mean egg production of the cadmium exposure group increased. The fertility rate of the control group was significantly higher than that of the 5 μg/L cadmium exposure group. Anatomical and histological data further revealed that the intensity of atretic vitellogenic follicles significantly increased and spermatozoa vacuolated after cadmium exposure (p < 0.05), but slightly increased the condition factor (CF), and relatively stable gonadosomatic index (GSI) values were also observed in the cadmium exposure groups. These observed results indicated that cadmium exposure at 5 or 10 μg/L affected the reproductive activity of paired rare minnow by accumulating Cd in the gonads, and the effect diminished over time. The reproductive risk of low-dose cadmium exposure to fish species remains a cause for concern.

Objective: Previous basic studies on the use of titanized polypropylene meshes in abdominal external hernia repair are not only limited, but also highly controversial. This study aims to investigate the modification effect of titanium compounds on polypropylene materials and compare the performance of two kinds of meshes both in vivo and in vitro.Methods: Human peritoneal mesothelial cells (HMrSV5), human epidermal fibroblasts (HSF), and human monocytic cells (THP-1) were cultured in vitro to simulate the abdominal external hernia environment. Titanized polypropylene meshes (Ti) and polypropylene mesh (Non-Ti) were co-cultured with the cells respectively. The effects of titanium compounds on cell growth were determined by cell activity and apoptosis, and the growth of cells on the mesh surface was assessed using a scanning electron microscope and a confocal microscope. In vivo experiments, different sizes titanized polypropylene meshes and polypropylene meshes were placed between the external oblique abdominal muscle and the internal oblique abdominal muscle, the parietal peritoneum, the serous layer of the descending colon, and the underside of the femoral nerve in rabbits. The effects of titanium compounds were evaluated by observing the anti-adhesion, anti-contraction, anti-fibrotic properties, and effects on nerves of the mesh.Results: Titanium compounds effectively reduced the effects of polypropylene material on cell growth, and improved the fixation and adhesion of HMrSV5, HSF and THP-1 (M0) on the surface of titanized polypropylene meshes. Furthermore, titanium compounds improved the adhesion, contraction and fibrosis of polypropylene material, as well as reduced nerve damage. This improvement demonstrated a regular trend with the type of titanized polypropylene meshes.Conclusion: The titanium compounds improved the biocompatibility of the polypropylene material, which was conducive to the fixation and adhesion of cells on the surface of the meshes, and alleviated the adhesion and contraction of the meshes, and the degree of tissue fibrosis, as well as the influence on nerves.

Table S3 shows the pancEts-1 and hnRNPK transcript levels in 42 NB patients

Table S1 shows primer sets used for RACE, qRT-PCR, RIP, probe, and ChIP

Figure S1 shows the schematic positions for primers; Figure S2 shows the characterization of a novel lncRNA pancEts-1; Figure S3 shows the expression and Kaplan-Meier survival curves of pancEts-1 downstream genes; Figure S4 shows the expression of β-catenin and hnRNPK in NB cells; Figure S5 shows the roles of pancEts-1 in facilitating the β-catenin activity and downstream gene expression in NB cells.

Table S6 show the univariate and multivariate analysis of prognostic factors in 88 NB patients derived from public dataset (GSE16476)

Table S5 shows the hnRNPK expression in human NB tissues

Long noncoding RNAs (lncRNA) play essential roles in tumor progression. However, the functions of lncRNAs in the tumorigenesis and aggressiveness of neuroblastoma still remain to be determined. Here, we report the identification of lncRNA pancEts-1 as a novel driver of neuroblastoma progression by using a public microarray dataset. LncRNA pancEts-1 promoted the growth, invasion, and metastasis of neuroblastoma cells in vitro and in vivo. Mechanistically, pancEts-1 bound to hnRNPK to facilitate its physical interaction with β-catenin, whereas hnRNPK stabilized the β-catenin by inhibiting proteasome-mediated degradation, resulting in transcriptional alteration of target genes associated with neuroblastoma progression. Both pancEts-1 and hnRNPK were upregulated in clinical neuroblastoma tissues, and were associated with unfavorable outcome of patients. Overall, our results define an oncogenic role of pancEts-1 in neuroblastoma progression through hnRNPK-mediated β-catenin stabilization, with potential implications for the clinical therapeutics of neuroblastoma.Significance: These findings reveal the oncogenic functions of a long noncoding RNA in neuroblastoma progression, offering a potential target for clinical therapeutics. Cancer Res; 78(5); 1169–83. ©2018 AACR.

Table S4 shows the mass spectrometry analysis of protein pulled down by biotin-labeled pancEts-1 or hnRNPK antibody in BE(2)-C cells

Supplementary Figure Legends for Figures S1-S5.