Maternal immune activation upregulates the AU020206-IRFs-STAT1 axis in modulating cytokine production in the brain.

Maternal immune activation (MIA) is reported to increase the risk of psychiatric disorders in the offspring. However, the underlying mechanism remains unclear. Methods: We constructed a MIA mouse model by intraperitoneal injection of LPS into pregnant mice and evaluated the behaviors and gene expression profiles in the brains of the female and male offspring, respectively. Results: We found that the MIA female offspring exhibited increased anxiety and a large number of differentially expressed genes (DEGs) in the brain, which were enriched with candidate gene sets of psychiatric disorders and immune functions. In contrast, the MIA male offspring exhibited no significant abnormal behaviors and only a small number of DEGs that were not enriched with disease genes and immune functions. Therefore, we further pursued the downstream study on the molecular mechanism underlying the increased anxiety in the female offspring. We identified the lncRNA AU020206-IRFs-STAT1-cytokine axis by integrating lncRNA-protein interaction data and TF-promoter interaction data, and verified the axis in vitro and in vivo. Conclusion: This study illustrates that MIA upregulates the AU020206-IRFs-STAT1 axis in controlling the brain immunity linked to abnormal behaviors, providing a basis for understanding the role of MIA in psychiatric disorders.

Recent advances in circularly polarized luminescence of planar chiral organic compounds.

Circularly polarized luminescence (CPL), as an important chiroptical phenomenon, can not only directly characterize excited-state structural information about chiroptical materials but also has great application prospects in 3D optical displays, information storage, biological probes, CPL lasers and so forth. Recently, chiral organic small molecules with CPL have attracted a lot of research interest because of their excellent luminescence efficiency, clear molecular structures, unique flexibility and easy functionalization. Planar chiral organic compounds make up an important class of chiral organic small molecular materials and often have rigid macrocyclic skeletons, which have important research value in the field of chiral supramolecular chemistry (e.g., chiral self-assembly and chiral host-guest chemistry). Therefore, research into planar chiral organic compounds has become a hotspot for CPL. It is time to summarize the recent developments in CPL-active compounds based on planar chirality. In this feature article, we summarize various types of CPL-active compounds based on planar chirality. Meanwhile, we overview recent research in the field of planar chiral CPL-active compounds in terms of optoelectronic devices, asymmetric catalysis, and chiroptical sensing. Finally, we discuss their future research prospects in the field of CPL-active materials. We hope that this review will be helpful to research work related to planar chiral luminescent materials and promote the development of chiral macrocyclic chemistry.

Fabrication of well-aligned Co-MOF arrays through a controlled and moderate process for the development of a flexible tetrabromobisphenol A sensor.

Tetrabromobisphenol A (TBBPA) has attracted a great deal of attention due to its side effects and potential bioaccumulation properties. It is of great importance to construct and develop novel electrochemical sensors for the sensitive and selective detection of TBBPA. In the present study, cobalt (Co) based metal-organic frameworks (MOFs) were synthesized on carbon cloth (CC) by using cobalt nitrate hexahydrate and 2-methylimidazole. The morphological characterization was carried out by transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). The results showed that Co-MOFs/CC have a leaf-like structure and abundant surface functional groups. The electrochemical properties of the sensor were investigated by differential pulse voltammetry (DPV). The effects of different ratios of metal ions to organic ligands, reaction temperature, time, concentration, pH value of the electrolyte, and incubation time on the oxidation peak current of TBBPA were studied. Under the optimal conditions, the linear range of the designed sensor was 0.1 µM-100 µM, and the limit of detection was 40 nM. The proposed sensor is simple, of low cost and efficient, which can greatly facilitate the detection tasks of environmental monitoring workers.

Increased NMDARs in neurons and glutamine synthetase in astrocytes underlying autistic-like behaviors of Gabrb1-/- mice.

Mutations of the GABA-A receptor subunit ß1 (GABRB1) gene are found in autism patients. However, it remains unclear how mutations in Gabrb1 may lead to autism. We generated Gabrb1-/- mouse model, which showed autistic-like behaviors. We carried out RNA-seq on the hippocampus and found glutamatergic pathway may be involved. We further carried out single-cell RNA sequencing on the whole brain followed by qRT-PCR, immunofluorescence, electrophysiology, and metabolite detection on specific cell types. We identified the up-regulated Glul/Slc38a3 in astrocytes, Grin1/Grin2b in neurons, glutamate, and the ratio of Glu/GABA in the hippocampus. Consistent with these results, increased NMDAR-currents and reduced GABAAR-currents in the CA1 neurons were detected in Gabrb1-/- mice. NMDAR antagonist memantine or Glul inhibitor methionine sulfoximine could rescue the abnormal behaviors in Gabrb1-/- mice. Our data reveal that upregulation of the glutamatergic synapse pathway, including NMDARs at neuronal synapses and glutamine exported by astrocytes, may lead to autistic-like behaviors.

A pillar[5]arene-based planar chiral charge-transfer dye with enhanced circularly polarized luminescence and multiple responsive chiroptical changes.

The fabrication of circularly polarized luminescent (CPL) organic dyes based on macrocyclic architecture has become an importantly studied topic in recent years because it is of great importance to both chiral science and supramolecular chemistry, where pillar[n]arenes are emerging as a promising class of planar chiral macrocyclic hosts for CPL. We herein synthesized an unusual planar chiral charge-transfer dye (P5BB) by covalent coupling of triarylborane (Ar3B) as an electron acceptor to parent pillar[5]arene as an electron donor. The intramolecular charge transfer (ICT) nature of P5BB not only caused a thermally responsive emission but also boosted the luminescence dissymmetry factor (g lum). Interestingly, the specific binding of fluoride ions changed the photophysical properties of P5BB, including absorption, fluorescence, circular dichroism (CD), and CPL, which could be exploited as an optical probe for multi-channel detection of fluoride ions. Furthermore, the chiroptical changes were observed upon addition of 1,4-dibromobutane as an achiral guest.

Dynamic B/N Lewis Pairs: Insights into the Structural Variations and Photochromism via Light-Induced Fluorescence to Phosphorescence Switching.

Ultralong afterglow emissions due to room-temperature phosphorescence (RTP) are of paramount importance in the advancement of smart sensors, bioimaging and light-emitting devices. We herein present an efficient approach to achieve rarely accessible phosphorescence of heavy atom-free organoboranes via photochemical switching of sterically tunable fluorescent Lewis pairs (LPs). LPs are widely applied in and well-known for their outstanding performance in catalysis and supramolecular soft materials but have not thus far been exploited to develop photo-responsive RTP materials. The intramolecular LP M1BNM not only shows a dynamic response to thermal treatment due to reversible N→B coordination but crystals of M1BNM also undergo rapid photochromic switching. As a result, unusual emission switching from short-lived fluorescence to long-lived phosphorescence (rad-M1BNM, τRTP =232 ms) is observed. The reported discoveries in the field of Lewis pairs chemistry offer important insights into their structural dynamics, while also pointing to new opportunities for photoactive materials with implications for fast responsive detectors.

Applying the B/N Lewis Pair Approach to Access Fusion-Expanded Binaphthyl-Based Chiral Analogues.

We herein describe the synthesis of two axially chiral systems (HBN and BBN) by the incorporation of B centers into binaphthyl derivatives (HPy and BPy). Heteroatom-doped chiral polycyclic aromatic hydrocarbons were thus formed by fusion of the azaboroles to binaphthyls with the formation of B-N dative bonds. The resulting B-N Lewis pairs that serve as attractive fluorophores enabled modulation of the chiroptical properties both in solution and in the solid state.

Combined Exposure to 33 Trace Elements and Associations With the Risk of Oral Cancer: A Large-Scale Case-Control Study.

Background: Trace elements exist widely in the natural environment and mostly enter the human body through drinking water or various types of food, which has raised increasing health concerns. Exposure to a single or a few trace elements has been previously reported to be associated with oral cancer risk, but studies on other elements and combined effects are limited. This study aimed to comprehensively evaluate the independent and joint effects of 33 trace elements on oral cancer risk. Methods: The concentrations of 33 trace elements from the serum samples of 463 cases and 1,343 controls were measured using inductively coupled plasma mass spectrometry (ICP-MS). Propensity score matching was used to minimize the impact of potential confounders. Conditional logistic regression was utilized to evaluate the association of each element individually with oral cancer risk. Quantile g-computation and Bayesian kernel machine regression (BKMR) models were used to assess the joint effect of the overall element mixture and interactions. Results: In single-element models, essential elements (Cu, Se, Zn, Sr, and Cr) and non-essential elements (As, Li, Th, Ce, Ti, and Sc) showed significant association with oral cancer risk. In multiple-element models, a quartile increase in overall non-essential elements was observed for a significant inverse association with oral cancer risk (ß = -3.36, 95% CI: -4.22 to -2.51). The BKMR analysis revealed a potential beneficial joint effect of essential metals on the risk of oral cancer. Among these, higher levels of serum Zn and V exhibited an adverse effect, while serum Sr, Se, and Cu displayed favorable effects when all other essential elements were fixed at 25th or 50th percentiles. Of note, Se performed complex interactions among essential metals. As for non-essential elements, there were greater effect estimates for serum Th, Li, and Y when all other elements were held at the 75th percentile. Conclusion: This study provides supportive evidence that the overall mixture effect of essential and non-essential elements might be associated with oral cancer risk, especially for serum Zn, V, Cu, Sr, Se, Th, Li, and Y. Extensive prospective studies and other experiments are warranted to confirm our findings.

U-Shaped Relationship of Rare Earth Element Lanthanum and Oral Cancer Risk: A Propensity Score-Based Study in the Southeast of China.

As an important rare earth element (REE) extensively applied to industry, agriculture, and medicine, lanthanum (La) has attracted a host of health concerns. This study aimed to explore the relationship between La exposure and the risk of developing oral cancer through a case-control study with a large sample size. Serum La levels of 430 oral cancer patients and 1,118 healthy controls were detected by inductively coupled plasma mass spectrometry (ICP-MS). The association of La level with the risk of oral cancer was assessed in two ways: (1) as a continuous scale based on restricted cubic splines (RCS); (2) as a priori defined centile categories using multivariate logistic regression model, based on propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). The RCS revealed a non-linear U-shaped relationship between serum La and oral cancer risk. Serum La deficiency or excess was associated with an increased risk of oral cancer. When the La level was analyzed as a categorical variable, a similar U-shaped association was observed. Of note, compared to those with La concentrations of 0.243-0.341 µg/L (reference quantiles, 41st-60th), the risk was increased in those with the lower or higher quantiles (0.132-0.242 µg/L vs. 0.243-0.341 µg/L: OR = 1.80, 95%CI: 1.07-3.02; 0.342-0.497 µg/L vs. 0.243-0.341 µg/L: OR = 2.30, 95%CI: 1.38-3.84). The results were generally consistent with the PSM and IPTW analyses. This preliminary study provides strong evidence that there was a U-shaped relationship between serum La levels and oral cancer risk. Much additional work is warranted to confirm our findings.

Enhanced Cancer Starvation Therapy Enabled by an Autophagy Inhibitors-Encapsulated Biomimetic ZIF-8 Nanodrug: Disrupting and Harnessing Dual Pro-Survival Autophagic Responses.

Autophagy is an important protective mechanism in maintaining or restoring cell homeostasis under physiological and pathological conditions. Nanoparticles (NPs) with certain components and morphologies can induce autophagic responses in cancer cells, providing a new perspective for establishing cancer therapy strategies. Herein, a novel nanodrug system, cell membranes-coated zeolitic imidazolate framework-8 (ZIF-8) NPs encapsulating chloroquine (CQ) and glucose oxidase (GOx) (defined as mCG@ZIF), is designed to achieve an enhanced anticancer effect with the combination of starvation therapy and an autophagy regulation strategy. It is found that ZIF-8 as a nanocarrier can induce autophagy to promote survival of cancer cells via the upstream Zn2+-stimulated mitochondrial reactive oxygen species (ROS) so that the anticancer effect is directly achieved by inhibiting this pro-survival autophagy using CQ released from mCG@ZIF under a tumor acidic microenvironment. Moreover, a cancer cell under starvation caused by GOx harnesses autophagy to maintain intracellular ATP levels and resist starvation therapy. The released CQ further inhibits the starvation-induced pro-survival autophagy and cuts off the protective pathway of cancer cells, enhancing the anticancer efficiency of GOx-based starvation therapy. Significantly, the cell membrane coating endows mCG@ZIF with excellent in vivo homotypic targeting ability. Both in vitro and in vivo results have confirmed the enhanced anticancer effect achieved by mCG@ZIF with a negligible side effect.

Pillar[5]arene-based Neutral Radicals with Doublet Red Emissions and Stable Chiroptical Properties.

Stable organic radicals with unique luminescence show great importance in photoelectromagnetic materials. We herein report two unusual radical-based systems (P5N-TTM and P5B-TTM) using the concerted effects of planar chiral pillar[5]arenes and tris(2,4,6-trichlorophenyl)methyl (TTM) radicals. The steric effect and electronic doublet-spin character of these radicals allowed the optical resolution and the first red emissions (∼650 nm) for pillar[5]arene derivatives. Notably, cross-coupling with macrocyclic pillar[5]arene, in turn, considerably enhanced the configurational stability of TTM radicals.

Upregulated NMDAR-mediated GABAergic transmission underlies autistic-like deficits in Htr3a knockout mice.

Mutations in serotonin pathway genes, especially the serotonergic receptor subunit gene HTR3A, are associated with autism. However, the association of HTR3A deficiency with autism and the underlying mechanisms remain unknown. Methods: The Htr3a knockout (KO) mice were generated using transcription activator-like effector nuclease technology. Various behavior tests, including social interaction, social approach task, olfactory habituation/dishabituation, self-grooming, novel object recognition, contextual fear conditioning, elevated plus maze, open field and seizure susceptibility, were performed to assess the phenotypes. Transcriptome sequencing was carried out to search for molecular network and pathways underlying the phenotypes. Electrophysiological recordings, immunoblotting, immunofluorescence staining, immunoprecipitation, and quantitative real-time PCR were performed to verify the potential mechanisms. The N-methyl-D-aspartate receptor (NMDAR) antagonist memantine was used to treat the KO mice for rescuing the phenotypes. Results: The Htr3a KO mouse model showed three phenotypic domains: autistic-like behaviors (including impaired social behavior, cognitive deficits, and increased repetitive self-grooming), impaired memory, and attenuated susceptibility to pentylenetetrazol-induced seizures. We observed enhanced action potential-driven γ-aminobutyric acid-ergic (GABAergic) transmission in pyramidal neurons and decreased excitatory/inhibitory (E/I) ratio using the patch-clamp recording. Transcriptome sequencing on the hippocampus revealed the converged pathways of the dysregulated molecular networks underlying three phenotypic domains with upregulation of NMDAR. We speculated that Htr3a KO promotes an increase in GABA release through NMDAR upregulation. The electrophysiological recordings on hippocampal parvalbumin-positive (PV+) interneuron revealed increased NMDAR current and NMDAR-dependent excitability. The NMDAR antagonist memantine could rescue GABAergic transmission in the hippocampus and ameliorate autistic-like behaviors of the KO mice. Conclusion: Our data indicated that upregulation of the NMDAR in PV+ interneurons may play a critical role in regulating GABAergic input to pyramidal neurons and maybe involve in the pathogenesis of autism associated with HTR3A deficiency. Therefore, we suggest that the NMDAR system could be considered potential therapeutic target for autism.

Pillararenes: fascinating planar chiral macrocyclic arenes.

Chiral macrocycles possess significant value in chiral science and supramolecular chemistry. Pillararenes, as a class of relatively young supramolecular macrocyclic hosts, have been widely used for host-guest recognition and self-assembly. Since the position of substituents on the benzene rings breaks the molecular symmetry (symmetric plane and symmetric center), pillararenes possess planar chirality. However, it is a great challenge to synthesize stable and resolvable enantiomers because of the easy rotation of the phenylene group. In this review, we summarize the construction methods of resolvable chiral pillararenes. We also focus on their applications in enantioselective recognition, chiral switches, chirality sensing, asymmetric catalysis, circularly polarized luminescence, metal-organic frameworks, and highly permeable membranes. Finally, we discuss the future research perspectives in this field of pillararene-based planar chiral materials. We hope that this review will encourage more researchers to work in this exciting field.

Pillar[5]arene-Based Dual Chiral Organoboranes with Allowed Host-Guest Chemistry and Circularly Polarized Luminescence.

We first describe two examples of highly luminescent organoboranes (NP5BN1 and NP5BN2) with dual chirality that were achieved by molecular functionalization of planar chiral pillar[5]arenes with naphthyls. Sufficiently strong steric effects are imposed by triarylamine (Ar3N) and triarylborane (Ar3B) moieties and further enhanced by the proximity of the chiral building blocks, leading to the isolation of multiple enantiomers via chiral high-performance liquid chromatography. The intramolecular charge transfer from N-donor to B-acceptor across both chiral subunits enabled the circularly polarized luminescence and thermally robust colorimetric responses in their emissions. Furthermore, their remarkable host-guest chemistry was allowed at no expense in the pursuit of advanced chiroptical properties using pillar[5]arene-based supramolecular scaffolds.

Association Between Rare Earth Element Cerium and the Risk of Oral Cancer: A Case-Control Study in Southeast China.

Cerium (Ce), the most abundant of rare earth elements in the earth's crust, has received much health concerns due to its wide application in industry, agriculture, and medicine. The current study aims to evaluate whether there is an association between Ce exposures and the risk of developing oral cancer. Serum Ce level of 324 oral cancer patients and 650 matched healthy controls were measured by inductively coupled plasma mass spectrometry. Association between Ce level and the risk of oral cancer was estimated with an unconditional logistic regression model. Serum Ce concentrations in the oral cancer patients and controls were 0.57 (0.21-3.02) µg/L and 2.27 (0.72-4.26) µg/L, respectively. High level of Ce was associated with a decreased risk of oral cancer (OR: 0.60, 95% CI: 0.43-0.84). Stronger inverse associations between high level of Ce and oral cancer risk were observed among those with smoking (OR: 0.46, 95% CI: 0.27-0.79), drinking (OR: 0.50, 95% CI: 0.26-0.96), limited intake of leafy vegetables (OR: 0.40, 95% CI: 0.22-0.71) and fish (OR: 0.52, 95% CI: 0.33-0.83). There were significant multiplicative interactions between Ce level and alcohol drinking or intake of leafy vegetables and fish (all Pinteraction <0.05). This preliminary case-control study suggests an inverse association between high serum Ce level and the risk of oral cancer. Further prospective studies with a larger sample size are needed to confirm the findings.

[Study on the correlation between the content of bone morphogenetic protein 2 in demineralized bone matrix and its osteogenic activity in vitro and in vivo].

OBJECTIVE: To investigate the correlation between the content of bone morphogenetic protein 2 (BMP-2) in demineralized bone matrix (DBM) and its osteogenic activity in vitro and in vivo, in order to choose a simple and convenient method to evaluate the osteogenic activity of DBM. METHODS: The left mid-femoral tissues of 9 donors were taken, and DBMs (S1-S9) were prepared by dynamic decalcification process, and inactivated DBM (control group) was prepared at the same time. Protease inhibitor method, collagenase method, guanidine hydrochloride/ethylene diamine tetraacetic acid (EDTA) method, and RIPA lysate method were used to extract BMP-2 in S1-S9 and inactivated DBMs. The BMP-2 content was measured and the differences between DBMs were compared. Then the S1-S9 and inactivated DBMs were co-cultured with mouse embryonic osteoblasts MC3T3-E1, respectively. The cell proliferation was detected by MTT method and fluorescence staining, and alkaline phosphatase (ALP) activity was detected at the same time. Thirty BALB/c male nude mice were divided into 10 groups, namely S1-S9 DBM groups (S1-S9 groups) and inactivated DBM group (control group), with 3 mice in each group. Muscle pockets of the middle thighs were prepared on both hindlimbs of mice in each group, and implanted corresponding DBM materials. At 4 weeks after operation, the samples were taken for HE staining observation and semi-quantitative evaluation, and the new bone formation score was calculated. RESULTS: The BMP-2 content of DBM derived from different donor bones was distinct. The BMP-2 content obtained by different extraction methods for DBM prepared from the same donor bone was also different, and the extraction efficiency of the guanidine hydrochloride/EDTA method was the highest. In vitro cell experiments, MTT test displayed that cell proliferations and ALP activity were significantly higher in S4 and S6 groups than in other groups at each time point after co-cultivation ( P<0.05). Moreover, the cell proliferation of S4 group was the most significant at 7 days ( P<0.05); fluorescence staining demonstrated that the osteoblasts of each group was in good condition, but the osteoblasts of S1, S2, S3, S4, and S6 groups were significantly more than other groups. In vivo ectopic osteogenesis experiments, the cartilage and new bone formation could be seen in the bone graft area of S1-S6 groups at 4 weeks after operation, and with the increase of BMP-2 content, the more new bone formation induced by the material, the higher the score of new bone formation of the material ( P<0.05). Among them, S4 and S6 groups contained a large number of chondrocytes and osteoblasts in the osteogenesis area. CONCLUSION: The osteogenic activity of DBM can be evaluated through BMP-2 quantitative detection combined with in vitro osteoblast proliferation and differentiation experiments.

Planar Chiral Organoboranes with Thermoresponsive Emission and Circularly Polarized Luminescence: Integration of Pillar[5]arenes with Boron Chemistry.

Enantiopure molecules based on macrocyclic architecture are unique for applications in enantioselective host-guest recognition, chiral sensing and asymmetric catalysis. Taking advantage of the chiral transfer from the intrinsically planar chirality of pillar[5]arenes, we herein present an efficient and straightforward approach to achieve early examples of highly luminescent chiral systems (P5NN and P5BN). The optical resolution of their enantiomers has been carried out via preparative chiral HPLC, which was ascribed to the molecular functionalization of pillar[5]arenes with π-conjugated, sterically bulky triarylamine (Ar3 N) as an electron donor and triarylborane (Ar3 B) as an acceptor. This crucial design enabled investigations of the chiroptical properties, including circular dichroism (CD) and circularly polarized luminescence (CPL) in the solid state. The intramolecular charge transfer (ICT) nature in P5BN afforded an interesting thermochromic shift of the emission over a wide temperature range.

Comparison of the neurotoxicity associated with cobalt nanoparticles and cobalt chloride in Wistar rats.

Cobalt nanoparticles (CoNPs) have been widely used in industry given their physical, chemical and magnetic properties; however, CoNPs may cause neurological symptoms and diseases in human, yet their mechanisms of toxicity remain unknown. Here, we used male Wistar rats to investigate differences in the toxic effects associated with CoNPs and CoCl2. Upon exposure to CoCl2, and 96 nm or 123 nm CoNPs at the same concentration, the Co2+ content in CoCl2 group was significantly higher than that in either the CoNPs groups in brain tissues and blood, but lower in liver. Significant neural damage was observed in both hippocampus and cortex of the temporal lobe. Increase malondialdehyde (MDA) content and CASPASE 9 protein level were associated both with CoCl2 and CoNPs treatments, consistent with lipid perioxidation and apoptosis. Heme oxygenase-1 and (NF-E2) p45-related factor-2 protein levels were elevated in response to 96 nm CoNPs exposure. In PC12 cells, NRF2 downregulation led to reduced cell viability and increased apoptotic rate. In conclusion, both CoNPs and CoCl2 cause adverse neural effects, with nanoparticles showing greater neurotoxic potency. In addition, NRF2 protects neural cells from damage induced by CoCl2 and CoNPs by activating downstream antioxidant responses.

High copper levels in follicular fluid affect follicle development in polycystic ovary syndrome patients: Population-based and in vitro studies.

Although the adverse effects of copper overexposure on the liver, kidney, spleen and intestinal organs are well known, information about the impact of copper toxicity on human reproduction is limited. A total of 348 infertile patients were enrolled in our present study, including 89 with polycystic ovary syndrome (PCOS), 145 with fallopian tube obstruction and 114 controls. The follicular fluid concentrations of 22 trace elements were measured by inductively coupled plasma mass spectrometry (ICP-MS). Principal component analysis was used to identify trace element profile alterations in different groups. The mRNA levels of steroidogenesis-related genes were measured by real-time PCR. Our results showed that the trace element profile in follicular fluid was obviously altered in PCOS patients. Copper concentrations were significantly (p < .05) higher in the PCOS group than in the other two groups. Increased copper levels in follicular fluid were associated with a higher number of retrievable oocytes in the PCOS group (B = 1.785, p = .001) but a lower rate of high-quality embryos (B = -6.360, p = .050). Moreover, follicular fluid copper levels were positively correlated with follicular fluid progesterone levels (r = 0.275, p = .010) and testosterone levels (r = 0.250, p = .022). Cultured human granulosa cells overexposed to copper showed significantly (p < .05) increased estradiol secretion and decreased testosterone levels. Real-time quantitative PCR revealed a significant (p < .05) increase in CYP19A1 and HSD3b mRNA expression. Our results indicate that increased copper levels in follicular fluid could affect follicle development in PCOS patients, and the mechanism may be related to copper-induced abnormalities in steroidogenesis.

Serum copper and zinc levels and the risk of oral cancer: A new insight based on large-scale case-control study.

OBJECTIVE: Limited evidence exists on the roles of serum copper (Cu) and zinc (Zn) in oral cancer risk. We aimed to preliminarily explore the association between serum Cu and Zn levels and oral cancer risk with relatively large-scale samples. METHODS: Serum Cu and Zn levels of 344 oral cancer patients and 1,122 matched healthy controls in this case-control study were measured by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Restricted cubic spline revealed the U-shaped relationship between serum Cu or Zn levels and the risk of oral cancer. Serum deficient or elevated levels of Cu were significantly associated with the risk of oral cancer: The ORs were 1.38 (95% CI: 1.01-1.89) and 2.82 (95% CI: 1.60-4.98), respectively. The positive association of serum low or high levels of Zn with oral cancer risk was also observed: The ORs were 2.72 (95% CI: 1.60-4.62) and 12.41 (95% CI: 9.09-16.93), respectively. Additionally, there were multiplicative interactions between the aforementioned trace elements and smoking. CONCLUSIONS: This preliminary study suggests that both serum excess and deficient levels of Cu or Zn were significant correlation with oral cancer risk, which may provide a new insight on the roles of serum Cu and Zn in oral cancer.