High-quality on-chip entangled photon source with broad tunable range based on coupling compensation.

This paper introduces a tunable and high-quality photon source that utilizes evanescent-wave coupling phase matching. By adjusting the coupling gap, the signal light can be tuned from 1307 nm to 1493.9 nm, and the idler light can be tuned from 1612.8 nm to 1907 nm. Throughout the entire tuning range, the purity of the photon pairs remains above 92%. In specific tuning ranges (signal photons from 1307 nm to 1421.7 nm and idler photons from 1706.4 nm to 1907 nm), the purity exceeds 99% and the full width at half-maximum of the generated photon spectra is less than 1.85 nm. The photon source is designed using a silicon-organic hybrid waveguide, which effectively minimizes the impact of two-photon absorption and achieves a 15 dB enhancement in four-wave mixing conversion efficiency compared to a strip waveguide. This design may promote efficient and precise generation of high-quality photons at desired frequencies, offering promising potential for various applications in quantum technologies.

Effective enhancement of the non-Hermitian corner skin effect in reciprocal photonic crystals.

With the rich physical phenomena arising from non-Hermitian systems, the non-Hermitian skin effect (NHSE) has become a current research hotspot. Nowadays, the corner skin effect based on non-reciprocal photonic crystals has been proposed. Considering the complexity of realizing non-reciprocity, the corner skin effect based on reciprocal photonic crystals is well worth investigating. In this Letter, a non-Hermitian reciprocal geometry-dependent corner skin effect based on two-dimensional photonic crystals is presented, which is manifested as the distribution of eigenstates on the corners of a particular geometry by applying open boundary conditions in both directions of photonic crystals. For the better application of the NHSE in the future, such as highly sensitive sensors and lasers, a new, to the best of our knowledge, method that can effectively enhance the performance of the NHSE in photonic crystals is proposed. The method introduces both gain and loss in an ideal photonic crystal to enhance the non-Hermitian specificity of the system, which improves the performance of the non-Hermitian corner skin effect of photonic crystals by 64.5%. Furthermore, this geometry-dependent corner skin effect is corroborated with the spectral topology.

Bioaccumulation and thyroid endcrione disruption of 2-ethylhexyl diphenyl phosphate at environmental concentration in zebrafish larvae.

2-ethylhexyl diphenyl phosphate (EHDPP) strongly binds to transthyretin (TTR) and affects the expression of genes involved in the thyroid hormone (TH) pathway in vitro. However, it is still unknown whether EHDPP induces endocrine disruption of THs in vivo. In this study, zebrafish (Danio rerio) embryos (< 2 h post-fertilization (hpf)) were exposed to environmentally relevant concentrations of EHDPP (0, 0.1, 1, 10, and 100 µg·L-1) for 120 h. EHDPP was detected in 120 hpf larvae at concentrations of 0.06, 0.15, 3.71, and 59.77 µg·g-1 dry weight in the 0.1, 1, 10, and 100 µg·L-1 exposure groups, respectively. Zebrafish development and growth were inhibited by EHDPP, as indicated by the increased malformation rate, decreased survival rate, and shortened body length. Exposure to lower concentrations of EHDPP (0.1 and 1 µg·L-1) significantly decreased the whole-body thyroxine (T4) and triiodothyronine (T3) levels and altered the expressions of genes and proteins involved in the hypothalamic-pituitary-thyroid axis. Downregulation of genes related to TH synthesis (nis and tg) and TH metabolism (dio1 and dio2) may be partially responsible for the decreased T4 and T3 levels, respectively. EHDPP exposure also significantly increased the transcription of genes involved in thyroid development (nkx2.1 and pax8), which may stimulate the growth of thyroid primordium to compensate for hypothyroidism. Moreover, EHDPP exposure significantly decreased the gene and protein expression of the transport protein transthyretin (TTR) in a concentration-dependent manner, suggesting a significant inhibitory effect of EHDPP on TTR. Molecular docking results showed that EHDPP and T4 partly share the same mode of action of binding to the TTR protein, which might result in decreased T4 transport due to the binding of EHDPP to the TTR protein. Taken together, our findings indicate that EHDPP can cause TH disruption in zebrafish and help elucidate the mechanisms underlying EHDPP toxicity.

Screening of differentially methylated genes in skeletal fluorosis of rats with different types and involvement of aberrant methylation of Cthrc1.

Fluoride is a widespread pollutant in the environment. There is a high risk of developing skeletal fluorosis from excessive fluoride exposure. Skeletal fluorosis has different phenotypes (including osteosclerotic, osteoporotic and osteomalacic) under the same fluoride exposure and depends on dietary nutrition. However, the existing mechanistic hypothesis of skeletal fluorosis cannot well explain the condition's different pathological manifestations and their logical relation with nutritional factors. Recent studies have shown that DNA methylation is involved in the occurrence and development of skeletal fluorosis. DNA methylation is dynamic throughout life and may be affected by nutrition and environmental factors. We speculated that fluoride exposure leads to the abnormal methylation of genes related to bone homeostasis under different nutritional statuses, resulting in different skeletal fluorosis phenotypes. The mRNA-Seq and target bisulfite sequencing (TBS) result showed differentially methylated genes in rats with different skeletal fluorosis types. The role of the differentially methylated gene Cthrc1 in the formation of different skeletal fluorosis types was explored in vivo and in vitro. Under normal nutritional conditions, fluoride exposure led to hypomethylation and high expression of Cthrc1 in osteoblasts through TET2 demethylase, which promoted osteoblast differentiation by activating Wnt3a/ß-catenin signalling pathway, and participated in the occurrence of osteosclerotic skeletal fluorosis. Meanwhile, the high CTHRC1 protein expression also inhibited osteoclast differentiation. Under poor dietary conditions, fluoride exposure led to hypermethylation and low expression of Cthrc1 in osteoblasts through DNMT1 methyltransferase, and increased the RANKL/OPG ratio, which promoted the osteoclast differentiation and participated in the occurrence of osteoporotic/osteomalacic skeletal fluorosis. Our study expands the understanding of the role of DNA methylation in regulating the formation of different skeletal fluorosis types and provides insights into new prevention and treatment strategies for patients with skeletal fluorosis.

Let-7c-5p Regulates CyclinD1 in Fluoride-Mediated Osteoblast Proliferation and Activation.

Endemic fluorosis is caused by the intake of high environmental fluoride, which causes dental and skeletal fluorosis. Osteoblast proliferation and activation is closely related to skeletal fluorosis and is tightly regulated by the cell cycle. Several biological processes, including bone metabolism and osteoblast proliferation and activation, are regulated by a type of noncoding RNA called microRNAs (miRNAs). However, the understanding of miRNA functions in skeletal fluorosis is limited. Based on our previous miRNA sequencing results and bioinformatics analysis, we investigated the function of the miRNA let-7c-5p to regulate CyclinD1 in fluoride-induced osteoblast proliferation and activation. We designed population experiments as well as in vitro studies using 5-Ethynyl-2'-deoxyuridine (EdU), flow cytometry, immunofluorescence, dual-luciferase reporters, and chromatin immunoprecipitation. The population-based analysis showed a decrease in let-7c-5p expression as fluoride exposure increased. In addition, let-7c-5p levels were negatively correlated with CyclinD1 and Wnt9a (another let-7c-5p target). We verified in vitro that let-7c-5p participates in the fluoride-induced proliferation and activation of human osteoblasts by directly targeting CyclinD1. Furthermore, we demonstrated that let-7c-5p regulates CyclinD1 expression via the Wnt/ß-catenin signaling pathway. This study demonstrated the participation of let-7c-5p in fluoride-induced proliferation and activation of human osteoblasts by regulation of CyclinD1 expression at the post-transcriptional and transcriptional levels.

Downregulation of miR-4755-5p promotes fluoride-induced osteoblast activation via tageting Cyclin D1.

BACKGROUND: Endemic fluorosis remains a major public health issue in many countries. Fluoride can cause abnormalities in osteoblast proliferation and activation, leading to skeletal fluorosis. However, its detailed molecular mechanism remains unclear. Based on a previous study, the aim of this study is to explore the role of miRNA in osteoblast activation of skeletal fluorosis via targeting of Cyclin D1. METHODS: A population study of coal-burning fluorosis and in vitro experiments were performed in this study. Urine fluoride (UF) concentrations of the participants were determined using a national standardized ion selective electrode approach. Based on our previous miRNA sequence results, bioinformatic analysis was used to predict miR-4755-5p targeting Cyclin D1. Quantitative real-time PCR (qRT-PCR) was used to verify the expression of miR-4755-5p. The expression of Cyclin D1 mRNA was detected by qRT-PCR. The expression of Cyclin D1 protein was detected by enzyme-linked immunosorbent assay (ELISA) and Western blotting, respectively. Cell viability was detected by CCK-8 method. The distribution of the cell cycle was analyzed by flow cytometry. The alkaline phosphatase (ALP) activity and bone Gla protein (BGP) content were detected by micronutrient enzymes standard method and ELISA. The target binding between miR-4755-5p and Cyclin D1 was verified using dual-luciferase reporter assay. RESULTS: In the fluoride-exposed population, the results showed that with the increase in UF content, the expression of miR-4755-5p decreased gradually, while the mRNA transcription and protein expression of Cyclin D1 increased gradually. The relative miR-4755-5p expression showed a negative correlation with Cyclin D1 expression. Subsequently, in human osteoblasts treated with sodium fluoride (NaF), the results also showed that NaF caused low expression of miR-4755-5p and increased expression of Cyclin D1. Further, the results of miR-4755-5p mimic transfection confirmed that under the action of NaF, miR-4755-5p overexpression reduced Cyclin D1 protein expression within osteoblasts and further inhibited cell proliferation and activation. Simultaneously, luciferase reporter assays verified that Cyclin D1 was the miR-4755-5p direct target. CONCLUSION: The results demonstrate that fluoride exposure induced the downregulation of miR-4755-5p and downregulated miR-4755-5p promoted fluoride-induced osteoblast activation by increasing Cyclin D1 protein expression. This study sheds new light on biomarkers and potential treatment for endemic fluorosis.

Histone Deacetylation in the Promoter of p16 Is Involved in Fluoride-Induced Human Osteoblast Activation via the Inhibition of Sp1 Binding.

Chronic fluorosis is a systemic condition which principally manifests as defects in the skeleton and teeth. Skeletal fluorosis is characterized by aberrant proliferation and activation of osteoblasts, however, the underlying mechanisms of osteoblast activation induced by fluoride are not fully understood. Therefore, we investigated the pathogenic mechanism of human primary osteoblast proliferation and activation in relation to histone acetylation of the promoter p16, a well-known cell cycle regulation-related gene. The results showed that sodium fluoride (NaF) induced deacetylation and decreased expression of the p16 gene via inhibition of specificity protein 1 (Sp1) binding to its response element, which accounts for NaF increasing cell viability and promoting proliferation in human primary osteoblasts. These results reveal the regulatory mechanism of histone acetylation of the p16 gene on osteoblast activation in skeletal fluorosis.

Modifications of H3K9me2, H3K36me3 and H4K20me2 may be involved in arsenic-induced genetic damage.

Endemic arsenic poisoning is a worldwide disease and many studies show that arsenic has obvious genetic toxicity. However, the mechanism of arsenic-induced genetic damage is unclear. In this study, coal-fired arsenic poisoning patients in the Guizhou Province, China, were selected as research subjects. Through an analysis of the relationship between genetic damage and histone modification levels and by comparing the control and arsenic poisoning groups, further analysis of their relationship was carried out, the aim being to explore the role of histone modification in arsenic-induced genetic damage. The result shows that arsenic may inhibit the modification level of H4K20me2 and H3K9me2, and increase the modification of H3K36me3, involved in the repair of DNA damage induced by arsenic. This study could provide a new pathway for studies of the genetic toxicity of arsenic.

[Relationship between changes of genetic damage and development of disease in patients with arsenism caused by coal-burning].

OBJECTIVE: To investigate the changes of genetic damage in patients with arsenism caused by coal-burning in 9 years. To analyze the relationship between the changes of genetic damage and disease progression and provide a basis for condition monitoring. METHODS: Of 206 arsenism patients from the area with endemic arsenism in Guizhou province were tracking surveyed in February 1998 and divided into 4 groups, including suspicious, mild, moderate and severe poisoning group. Another 67 healthy residents from a neighbour township 12 km away where arsenic was not prevalent were surveyed. Over a 9-year follow-up, 131 arsenism patients and 45 controls with the complete biochemical indexes among them were selected as subjects in December 2006. Arsenic (As) concentration of urine and hair were detected by silver diethyldithiocarbamate spectrophotometry (Ag-DDC). Micronucleis (MN) and chromosome aberrations (CA) were analyzed by conventional methods. DNA single-strand breaks of peripheral blood were measured by single cell gel electrophoresis (SCGE), and the tail lengths of comet were used to measure DNA damage. RESULTS: Among the control, suspicious, mild, moderate and severe arsenic poisoning group, the As contents of urine and hair were respectively (34.16 ± 10.25), (52.35 ± 22.41), (62.26 ± 31.13), (71.43 ± 49.92), (78.45 ± 50.64) µg/L and (1.37 ± 0.56), (3.69 ± 1.78), (4.88 ± 3.49), (5.21 ± 3.10), (6.25 ± 4.04) µg/g in 2006, which were lower than that 9 years before (urine as contents were (36.07 ± 20.70), (73.65 ± 41.33) , (90.92 ± 82.14) , (126.55 ± 107.31) and (139.44 ± 90.90) µg/L, and hair As contents were (1.41 ± 1.18), (4.85 ± 4.20), (5.72 ± 4.07) , (6.43 ± 4.32) and (7.19 ± 4.68) µg/g, respectively, F value was 10.63, 7.72, 14.66, 11.00 respectively, all P values were < 0.05). Except for suspicious poisoning group, the differences of urine As contents in the other groups all showed significance (P < 0.05). The incidences of MN were (0.238 ± 0.130) %, (0.268 ± 0.192) %, (0.283 ± 0.157) % and (0.391 ± 0.233)%; the incidences of CA were (14.36 ± 5.44) %, (18.09 ± 6.49) %, (19.38 ± 5.63)% and (19.83 ± 5.84) %; the tail lengths of comet were (29.88 ± 13.81) , (29.84 ± 12.80) , (34.50 ± 9.88) and (41.58 ± 12.98) µm respectively in 2006 for all poisoning groups; which were higher than that 9 years before(the incidences of MN were (0.163 ± 0.051) %, (0.186 ± 0.117) %, (0.196 ± 0.104) % and (0.273 ± 0.142) %; the incidences of CA were (13.18 ± 5.17)%, (14.48 ± 6.61)%, (15.67 ± 8.49) % and (16.90 ± 8.38) %; the tail lengths of comet were (15.07 ± 12.93) , (19.57 ± 8.80) , (27.03 ± 10.77) and (34.71 ± 14.95) µm) , except for the incidences of MN and CA in suspicious poisoning group and of MN in mild poisoning group , the differences of the three indexes in the other groups were significant (P < 0.05) . The state of illness of arsenic poisoning patients aggravated 9 years later. With the increase of urine and hair As contents and the development of arsenism, the incidences of MN, CA and the tail lengths of comet of all poisoning groups increased. There were positive correlations among them (r values were respectively 0.212, 0.316, 0.232, 0.263, 0.321, 0.654 and 0.760) (P < 0.05). CONCLUSION: The exacerbation of genetic damage was related to constantly high arsenic loads. The accumulation of genetic damage and its irreversibility might be one of the important reasons of the development of arsenism and cancer.

Unventilated indoor coal-fired stoves in Guizhou province, China: cellular and genetic damage in villagers exposed to arsenic in food and air.

BACKGROUND: Inorganic arsenic (iAs) is a well-known human carcinogen recognized by the World Health Organization and the International Agency for Research on Cancer. Currently, most iAs studies in populations are concerned with drinking water and occupational arsenicosis. In Guizhou province, arsenicosis caused by the burning of coal in unventilated indoor stoves is an unusual type of exposure. Because the poisoning mechanism involved in arsenicosis is as yet unknown and no effective therapy exists, progress has been slow on the prevention and therapy of arsenicosis. OBJECTIVES: We examined the relationship between arsenic (As) exposure from the burning of coal in unventilated indoor stoves and genetic damage in humans, using cellular and molecular indices. We selected villagers from Jiaole township, Guizhou province, China, who had been exposed to milligram levels of As daily via food and air contaminated by the burning of As-containing coal in unventilated indoor stoves. RESULTS: The As-exposed subjects from Jiaole were divided into four groups according to skin lesion symptoms: nonpatients, mild, intermediate, and severe arsenicosis. Another 53 villagers from a town 12 km from Jiaole were recruited as the external control group. In the four groups of exposed subjects, As concentrations in urine and hair were 76-145 microg/L and 5.4-7.9 microg/g, respectively. These values were higher than those in the external control group, which had As concentrations of 46 microg/L for urine and 1.6 microg/g for hair. We measured sister chromatid exchange and chromosomal aberrations to determine human chromosome damage, and for DNA damage, we measured DNA single-strand breaks and DNA-protein cross-links. All measurements were higher in the four exposed groups compared with the external control group. DNA repair was impaired by As exposure, as indicated by the mRNA of O-6-methylguanine-DNA methyltransferase (MGMT), X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1), and, to a lesser extent, by the mismatch repair gene hMSH2 mRNA. The expression of mutant-type p53 increased with aggravation of arsenicosis symptoms, whereas the expression of p16-INK4(p16) decreased. p53 mutated at a frequency of 30-17% in the carcinoma (n = 10) and precarcinoma (n = 12) groups. No mutation was found in p16, although deletion was evident. Deletion rates were 8.7% (n = 23) and 38.9% (n = 18) in noncarcinoma and carcinoma groups, respectively. CONCLUSIONS: The results showed that long-term As exposure may be associated with damage of chromosomes and DNA, gene mutations, gene deletions, and alterations of DNA synthesis and repair ability.