Infiltrated 2D/3D Heterojunction with Tunable Electric Field Landscape for Robust Inverted Perovskite Solar Cells with over 24% Efficiency.

In inverted perovskite solar cells, conventional planar 2D/3D perovskite heterojunctions typically exhibit a type-II band alignment, where the electric field tends to drive the electron motion in the opposite direction to the direction of electron transfer. Here, a 2D/3D gradient heterojunction is developed by allowing the 2D perovskite to infiltrate the 3D perovskite surface along the grain boundaries using the interaction between the organic cation of the 2D perovskite and the pseudohalogen thiocyanate ion (SCN-), which has the ability to diffuse downward. The infiltrated 2D perovskite not only fills the gaps of grain boundaries with improved structural stability, but it also reconstructs the original landscape of the electric field toward the n-doped surface to enable more rapid electron transfer and weaken the adverse type-II band alignment effect. Since 2D perovskite seals the GBs, the nonvolatile SCN- can accumulate at the top and bottom dual interfaces, releasing residual stress and significantly inhibiting nonradiative recombination. The device exhibits an excellent efficiency of 24.76% (certified 24.29%) and long-term stability that is >90% of the original PCE value after 800 h of heating at 85 °C or in high humidity (≈65%).

Adulthood bisphenol A exposure induces anxiety in male mice via downregulation of alpha-1D adrenergic receptor in paraventricular thalamus.

Bisphenol A (BPA), a ubiquitous endocrine disrupting chemical, is widely used in household plastic products. Large amounts of evidence indicate prenatal and postnatal BPA exposure causes neurodevelopmental disorders such as anxiety and autism. However, the neuronal mechanisms underlying the neurotoxic effects of adulthood BPA exposure remain poorly understood. Here, we provided evidences that adult mice treated with BPA (0.45 mg/kg/day) during 3 weeks exhibited sex-specific anxiety like behaviors. We demonstrated that the BPA-induced anxiety in male mice, but not in female mice, was closely associated with hyperactivity of glutamatergic neurons in the paraventricular thalamus (PVT). Acute chemogenetic activation of PVT glutamatergic neurons caused similar effects on anxiety as observed in male mice exposed to BPA. In contrast, acute chemogenetic inhibition of PVT glutamatergic neurons reduced BPA-induced anxiety in male mice. Concomitantly, the BPA-induced anxiety was related with a down-regulation of alpha-1D adrenergic receptor in the PVT. Taken together, the present study indicated a previously unknown target region in the brain for neurotoxic effects of BPA on anxiety and implicated a possible molecular mechanism of action.

The antiestrogen-like activity and reproductive toxicity of 2,6-DCBQ on female zebrafish upon sub-chronic exposure.

2,6-Dichloro-1,4-benzoquinone (2,6-DCBQ), an emerging water disinfection by-product, is widely detected in water resources. However, its potential effects on the reproductive system are largely unknown. Here, we investigated the long-term effects of 2,6-DCBQ on gonadal development by exposing zebrafish from 15 to 180 days postfertilization (dpf). Following exposure to 2,6-DCBQ (20 and 100 µg/L), female-specific effects including delayed puberty onset, retarded ovarian growth and breakdown of the zona radiata were observed, resulting in subfertility in adult females. Adverse effects in folliculogenesis disappeared two months after cessation of 2,6-DCBQ administration. In contrast, no adverse impacts were noted in male testes. The effects on females were associated with significant reduction in 17ß-estradiol (E2) level, suggesting a role for 2,6-DCBQ in anti-estrogenic activity. E2 level change in blood was further supported by dysregulated expression of genes (cyp19a1a, fshb, kiss3, esr2b, vtg1, and vtg3) related to the hypothalamic-pituitary-gonad-liver (HPGL) axis. The present study demonstrates for the first time that 2,6-DCBQ induces reproductive impairments in female zebrafish through disrupting 17ß-estradiol level.

Comparative analysis of the main outer membrane proteins of Brucella in the diagnosis of brucellosis.

Brucellosis has placed a heavy economic burden on numerous countries and has consumed considerable medical resources worldwide. To improve the specificity and sensitivity of serological methods for diagnosing brucellosis, it is important to develop new diagnostic antigens. Brucella outer membrane proteins(omps) possess good immunogenicity, but there is a scarcity of comparative studies of these proteins in the clinical diagnosis of brucellosis. In this study, six recombinant Brucella outer membrane proteins, omp10, omp16, omp19, omp25, omp31 and BP26, were expressed in prokaryotic cells and utilized as diagnostic antigens. The clinical sera of humans, bovines and goats with brucellosis were analyzed by indirect ELISA using these proteins, lipopolysaccharide(LPS) and Rose Bengale Ag, served as positive-control antigens. In diagnosing human and goat serum, BP26 exhibited the highest diagnostic accuracy of 96.45% and 95.00%, respectively, while omp31 exhibited the strongest ability to detect Brucella in bovine serum with an accuracy of 84.03%. Cross-reaction experiments also confirmed that the diagnostic specificities of omp31 and BP26 were higher than those of the LPS and Rose Bengale Ag antigens. The results of this study indicate that omp31 and BP26 are candidate antigens with high potential application value in the clinical diagnosis of brucellosis.

Effects of 3 kinds of processing techniques on the fitness of metal clasp. / 3ç§åŠ å·¥å·¥è‰ºå¯¹é‡‘å±žå¡çŽ¯å¯†åˆæ€§çš„å½±å“.

OBJECTIVES: At present, removable partial denture is still one of the main restoration methods for dentition defects. However, the trend for digital partial denture is becoming more and more obvious in the field of oral repair. However, there are relatively few studies on digital removable partial denture. The aim of this study is to investigate the effects of 3 processing technologies (precision casting, digital cutting, and 3D printing) on the fitness for the clasps of cobalt chromium alloy and pure titanium removable partial denture, and to provide a theoretical basis for the clinical application of digital removable partial denture. METHODS: Clasps of Co-Cr alloy and pure titanium were produced by 3 different processing technologies (precision casting, digital cutting, and 3D printing). There are 6 groups, including a casting pure titanium group, a casting cobalt chromium group, a cutting pure titanium group, a cutting cobalt chromium group, a printing pure titanium group, and a printing cobalt chromium group (n=6 per group). The gaps between the initial, middle, and tip of the lingual opposing arm of the clasp and the abutment were measured by fluorescent microscope, and the average value was taken as the index to measure the fitness between the clasp and the abutment. The fitness difference in three-arm clasp made of cobalt chromium alloy and pure titanium materials under 3 different technologies was compared. RESULTS: There was no statistical difference in fitness between the casting pure titanium group and the casting cobalt chromium group (P>0.05); there was no statistical difference in fitness between the cutting pure titanium group and the cutting cobalt chromium group (P>0.05); there was no statistical difference in fitness between the printing pure titanium group and the printing cobalt chromium group (P>0.05). When pure titanium was used, the fitness of the printing pure titanium group was the best (both P<0.05). There was no significant difference between the casting pure titanium group and the cutting pure titanium group (P>0.05). When cobalt chromium alloy was used, there was no significant difference in fitness among the 3 groups (P>0.05). CONCLUSIONS: The cobalt chromium alloy and pure titanium clasps made by precision casting, digital cutting, and 3D printing have good fitness. Under the same process, there is no significant difference between cobalt chromium alloy and pure titanium clasps. The 3D printing pure titanium clasps have better fitness than casting pure titanium and cutting pure titanium clasps, which meet the needs of clinical application.

IL-4/IL-13 upregulates Sonic hedgehog expression to induce allergic airway epithelial remodeling.

We have previously demonstrated that upregulation of Sonic hedgehog (SHH) expression in allergic airway epithelia essentially contributes to the goblet cell metaplasia and mucous hypersecretion. However, the mechanism underlying the upregulation of SHH expression remains completely unknown. In cultured human airway epithelial cells, IL-4/IL-13 but not IL-5 robustly induces the mRNA and protein expression of SHH and in turn activates SHH signaling by promoting the JAK/STAT6-controlling transcription of SHH gene. Moreover, intratracheal instillation of IL-4 and/or IL-13 robustly activates STAT6 and concomitantly upregulates SHH expression in mouse airway epithelia, whereas, in Club cell 10-kDa protein (CC10)-positive airway epithelial cells of children with asthma, activated STAT6 closely correlates with the increased expression of SHH and high activity of SHH signaling. Finally, intratracheal inhibition of STAT6 by AS-1517499 significantly diminished the allergen-induced upregulation of SHH expression, goblet cell phenotypes, and airway hyperresponsiveness, in an ovalbumin- or house dust mite-induced mouse model with allergic airway inflammation,. Together, upregulation of SHH expression by IL-4/IL-13-induced JAK/STAT6 signaling contributes to allergic airway epithelial remodeling, and this study thus provides insight into how morphogen signaling is coordinated with Th2 cytokine pathways to regulate tissue remodeling in chronic airway diseases.

Protein tyrosine phosphatase 11 acts through RhoA/ROCK to regulate eosinophil accumulation in the allergic airway.

Src homology domain 2-containing protein tyrosine phosphatase 2 (SHP2) participates in multiple cell functions including cell shape, movement, and differentiation. Therefore, we investigated the potential role of SHP2 in eosinophil recruitment into lungs in allergic airway inflammation and explored the underlying mechanism. Both SHP2 and Ras homolog family member A (RhoA) kinase were robustly activated in the airway eosinophils of children with allergic asthma and of a mouse model with allergic airway inflammation. Moreover, inhibition of SHP2 activity by its specific inhibitors reverses the dephosphorylation of p190-A Rho GTPase-activating protein and in turn attenuates RhoA/Rho-associated protein kinase (ROCK) signaling, resulting in the attenuation of eosinophil migration in response to platelet-activating factor stimulation. Specifically, SHP2 deletion in myeloid cells did not affect the number and classification of circulating leukocytes but significantly attenuated the allergen-induced inflammatory cell, especially eosinophil, infiltration into lungs, and airway hyperreactivity. Notably, genetic interaction between RhoA and SHP2 indicated that RhoA inactivation and SHP2 deletion synergistically attenuated the allergen-induced eosinophil infiltration into lungs and airway hyperreactivity, whereas overexpression of active RhoA robustly restored the SHP2 deletion-resultant attenuation of allergen-induced eosinophil recruitment into lungs and airway hyperreactivity as well. Thus, this study demonstrates that SHP2 via RhoA/ROCK signaling regulates eosinophil recruitment in allergic airway inflammation and possibly in allergic asthma.-Xu, C., Wu, X., Lu, M., Tang, L., Yao, H., Wang, J., Ji, X., Hussain, M., Wu, J., Wu, X. Protein tyrosine phosphatase 11 acts through RhoA/ROCK to regulate eosinophil accumulation in the allergic airway.

Notch Signaling: Linking Embryonic Lung Development and Asthmatic Airway Remodeling.

Lung development is mediated by assorted signaling proteins and orchestrated by complex mesenchymal-epithelial interactions. Notch signaling is an evolutionarily conserved cell-cell communication mechanism that exhibits a pivotal role in lung development. Notably, both aberrant expression and loss of regulation of Notch signaling are critically linked to the pathogenesis of various lung diseases, in particular, pulmonary fibrosis, lung cancer, pulmonary arterial hypertension, and asthmatic airway remodeling; implying that precise regulation of intensity and duration of Notch signaling is imperative for appropriate lung development. Moreover, evidence suggests that Notch signaling links embryonic lung development and asthmatic airway remodeling. Herein, we summarized all-recent advances associated with the mechanistic role of Notch signaling in lung development, consequences of aberrant expression or deletion of Notch signaling in linking early-impaired lung development and asthmatic airway remodeling, and all recently investigated potential therapeutic strategies to treat asthmatic airway remodeling.

Wnt/ß-catenin signaling links embryonic lung development and asthmatic airway remodeling.

Embryonic lung development requires reciprocal endodermal-mesodermal interactions; mediated by various signaling proteins. Wnt/ß-catenin is a signaling protein that exhibits the pivotal role in lung development, injury and repair while aberrant expression of Wnt/ß-catenin signaling leads to asthmatic airway remodeling: characterized by hyperplasia and hypertrophy of airway smooth muscle cells, alveolar and vascular damage goblet cells metaplasia, and deposition of extracellular matrix; resulting in decreased lung compliance and increased airway resistance. The substantial evidence suggests that Wnt/ß-catenin signaling links embryonic lung development and asthmatic airway remodeling. Here, we summarized the recent advances related to the mechanistic role of Wnt/ß-catenin signaling in lung development, consequences of aberrant expression or deletion of Wnt/ß-catenin signaling in expansion and progression of asthmatic airway remodeling, and linking early-impaired pulmonary development and airway remodeling later in life. Finally, we emphasized all possible recent potential therapeutic significance and future prospectives, that are adaptable for therapeutic intervention to treat asthmatic airway remodeling.

Low birth weight contributed to increased serum IL-6 levels in infantile respiratory syncytial virus infection.

BACKGROUND: To evaluate the role of serum cytokines in the pathogenesis of respiratory syncytial virus (RSV) infection in infants with low birth weight (LBW). METHODS: A prospective observational study was performed, and hospitalized children with lower respiratory tract infection (LRTI) were recruited. Three hundred fifty-eight patients < 1 year met the inclusion criteria: 116 patients had only RSV infection (RSV group); 242 patients had no RSV or other specific pathogen (non-RSV group). Serum interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were detected through flow cytometry. RESULTS: No significant differences in serum IL-2, 4, 6, 10, and IFN-γ levels were observed between the RSV and non-RSV groups. For RSV infected infants with or without wheezing, delivery mode had no obvious effect on the changes of serum cytokine levels. However, the level of IL-6 in the RSV-infected infants with LBW was significantly higher than that in infants with normal birth weight. CONCLUSIONS: Serum IL-6 level was significantly increased in RSV infected infants with LBW. It is likely that the specific serum cytokine pattern will contribute to our understanding of the pathogenesis of RSV infections, especially in RSV-infected infants with LBW.

hMSH5 Facilitates the Repair of Camptothecin-induced Double-strand Breaks through an Interaction with FANCJ.

Replication stress from stalled or collapsed replication forks is a major challenge to genomic integrity. The anticancer agent camptothecin (CPT) is a DNA topoisomerase I inhibitor that causes fork collapse and double-strand breaks amid DNA replication. Here we report that hMSH5 promotes cell survival in response to CPT-induced DNA damage. Cells deficient in hMSH5 show elevated CPT-induced γ-H2AX and RPA2 foci with concomitant reduction of Rad51 foci, indicative of impaired homologous recombination. In addition, CPT-treated hMSH5-deficient cells exhibit aberrant activation of Chk1 and Chk2 kinases and therefore abnormal cell cycle progression. Furthermore, the hMSH5-FANCJ chromatin recruitment underlies the effects of hMSH5 on homologous recombination and Chk1 activation. Intriguingly, FANCJ depletion desensitizes hMSH5-deficient cells to CPT-elicited cell killing. Collectively, our data point to the existence of a functional interplay between hMSH5 and FANCJ in double-strand break repair induced by replication stress.

[Relationship between expression of endothelial nitric oxide synthase and NADPH oxidase in lungs of mice exposed to chronic hypoxia].

OBJECTIVE: To explore the relationship between the expression of endothelial nitric oxide synthase (eNOS) and NADPH oxidase (NOX) in the lungs of mice treated by chronic hypoxic exposure. METHODS: Thirty male wild-type (WT) C57Bl/6 mice and thirty male eNOS-knockout (KO) C57BL/6 mice were randomly divided into normoxic groups (exposed to normoxia for 7 days or 21 days), hypoxic groups (exposed to 10% oxygen for 7 days or 21 days), and treatment groups (exposed to 10% oxygen and orally administrated 10 mmol/L 4-hydroxy TEMPO in drinking water for 7 days or 21 days) (n=6 in each group). The remodeling of the small pulmonary arteries was evaluated by the percentage of media wall thickness (MT%). The weight ratio of right ventricle to left ventricle plus septum (RV/[LV+S]) was calculated to evaluate the hypertrophy of right ventricle. Real-time PCR was used to measure the mRNA expression of NOX2, NOX4, and eNOS in mouse lungs. ELISA was used to determine the concentration of reactive oxygen species (ROS) in mouse lungs. RESULTS: In WT mice and KO mice, the hypoxic groups had significantly increased pulmonary vascular remodeling and RV/[LV+S] compared with the normoxic and treatment groups (P<0.05), but there were no significant differences between the normoxic and treatment groups (P>0.05). In WT mice, the hypoxic and treatment groups had significantly lower ROS concentrations than the normoxic group (P<0.05), but there were no significant differences between the hypoxic and treatment groups (P>0.05). In WT mice, the mRNA expression of eNOS, NOX2, and NOX4 was significantly higher in the hypoxic group than in the normoxic group (P<0.05), and 4-hydroxy TEMPO reversed their over-expression. In the normoxic group, the KO mice had significantly higher NOX2 and NOX4 mRNA expression than the WT mice (P<0.05); in KO mice, the hypoxic group showed no significant changes in NOX4 mRNA expression (P>0.05), but had significantly reduced NOX2 mRNA expression (P<0.05), as compared with the normoxic group; the treatment group had reduced expression of NOX2 mRNA expression and increased NOX4 mRNA expression (P<0.05), as compared with the hypoxic group. CONCLUSIONS: eNOS plays a key role in the regulation of expression of NOX2 and NOX4 in the lungs exposed to hypoxia. It suggests that NOX and eNOS may physically interact with one another in pulmonary vascular remodeling induced by chronic hypoxia.

Efficient Charge Transport in Inverted Perovskite Solar Cells via 2D/3D Ferroelectric Heterojunction.

While the 2D/3D heterojunction is an effective method to improve the power conversion efficiency (PCE) of perovskite solar cells (PSCs), carriers are often confined in the quantum wells (QWs) due to the unique structure of 2D perovskite, which makes the charge transport along the out-of-plane direction difficult. Here, a 2D/3D ferroelectric heterojunction formed by 4,4-difluoropiperidine hydrochloride (2FPD) in inverted PSCs is reported. The enriched 2D perovskite (2FPD)2PbI4 layer with n = 1 on the perovskite surface exhibits ferroelectric response and has oriented dipoles along the out-of-plane direction. The ferroelectricity of the oriented dipole layer facilitates the enhancement of the built-in electric field (1.06 V) and the delay of the cooling process of hot carriers, reflected in the high carrier temperature (above 1400 K) and the prolonged photobleach recovery time (139.85 fs, measured at bandgap), improving the out-of-plane conductivity. In addition, the alignment of energy levels is optimized and exciton binding energy (32.8 meV) is reduced by changing the dielectric environment of the surface. Finally, the 2FPD-treated PSCs achieve a PCE of 24.82% (certified: 24.38%) with the synergistic effect of ferroelectricity and defect passivation, while maintaining over 90% of their initial efficiency after 1000 h of maximum power point tracking.

Minimizing Interfacial Energy Loss and Volatilization of Formamidinium via Polymer-Assisted D-A supramolecular Self-Assembly Interface for Inverted Perovskite Solar Cells with 25.78% Efficiency.

2D perovskite passivation strategies effectively reduce defect-assisted carrier nonradiative recombination losses on the perovskite surface. Nonetheless, severe energy losses are causing by carrier thermalization, interfacial nonradiative recombination, and conduction band offset still persist at heterojunction perovskite/PCBM interfaces, which limits further performance enhancement of inverted heterojunction PSCs. Here, 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (5FTPP) is introduced between 3D/2D perovskite heterojunction and PCBM. Compared to tetraphenylporphyrin without electron-withdrawing fluoro-substituents, 5FTPP can self-assemble with PCBM at interface into donor-acceptor (D-A) complex with stronger supramolecular interaction and lower energy transfer losses. This rapid energy transfer from donor (5FTPP) to acceptor (PCBM) within femtosecond scale is demonstrated to enlarge hot carrier extraction rates and ranges, reducing thermalization losses. Furthermore, the incorporation of polystyrene derivative (PD) reinforces D-A interaction by inhibiting self-π-π stacking of 5FTPP, while fine-tuning conduction band offset and suppressing interfacial nonradiative recombination via Schottky barrier, dipole, and n-doping. Notably, the multidentate anchoring of PD-5FTPP with FA+, Pb2+, and I- mitigates the adverse effects of FA+ volatilization during thermal stress. Ultimately, devices with PD-5FTPP achieve a power conversion efficiency of 25.78% (certified: 25.36%), maintaining over 90% of initial efficiency after 1000 h of continuous illumination at the maximum power point (65 °C) under ISOS-L-2 protocol.

Assessment of anti-recombination and double-strand break-induced gene conversion in human cells by a chromosomal reporter.

Gene conversion is one of the frequent end results of homologous recombination, and it often underlies the inactivation of tumor suppressor genes in cancer cells. Here, we have developed an integrated assay system that allows simultaneous examination of double-strand break (DSB)-induced gene conversion events at the site of a DSB (proximal region) and at a surrounding region ~1 kb away from the break (distal region). Utilizing this assay system, we find that gene conversion events at the proximal and distal regions are relatively independent of one another. The results also indicate that synthesis-dependent strand annealing (SDSA) plays a major role in DSB-induced gene conversion. In addition, our current study has demonstrated that hMLH1 plays an essential role in anti-recombination and gene conversion. Specifically, the anti-recombination activity of hMLH1 is partially dependent on its interaction with hMRE11. Our data suggests that the role of hMLH1 and hMRE11 in the process of gene conversion is complex, and these proteins play different roles in DSB-induced proximal and distal gene conversions. In particular, the involvement of hMLH1 and hMRE11 in the distal gene conversion requires both hMSH2 and heteroduplex formation.

MutS homologue hMSH4: interaction with eIF3f and a role in NHEJ-mediated DSB repair.

BACKGROUND: DNA mismatch repair proteins participate in diverse cellular functions including DNA damage response and repair. As a member of this protein family, the molecular mechanisms of hMSH4 in mitotic cells are poorly defined. It is known that hMSH4 is promiscuous, and among various interactions the hMSH4-hMSH5 interaction is involved in recognizing DNA intermediate structures arising from homologous recombination (HR). RESULTS: We identified a new hMSH4 interacting protein eIF3f--a protein that functions not only in translation but also in the regulation of apoptosis and tumorigenesis in humans. Our studies have demonstrated that hMSH4-eIF3f interaction is mediated through the N-terminal regions of both proteins. The interaction with eIF3f fosters hMSH4 protein stabilization, which in turn sustains γ-H2AX foci and compromises cell survival in response to ionizing radiation (IR)-induced DNA damage. These effects can be, at least partially, attributed to the down-regulation of NHEJ activity by hMSH4. Furthermore, the interplay between hMSH4 and eIF3f inhibits IR-induced AKT activation, and hMSH4 promotes eIF3f-mediated bypass of S phase arrest, and ultimately enhancing an early G2/M arrest in response to IR treatment. CONCLUSION: Our current study has revealed a role for hMSH4 in the maintenance of genomic stability by suppressing NHEJ-mediated DSB repair.

MutS Homologues hMSH4 and hMSH5: Genetic Variations, Functions, and Implications in Human Diseases.

The prominence of the human mismatch repair (MMR) pathway is clearly reflected by the causal link between MMR gene mutations and the occurrence of Lynch syndrome (or HNPCC). The MMR family of proteins also carries out a plethora of diverse cellular functions beyond its primary role in MMR and homologous recombination. In fact, members of the MMR family of proteins are being increasingly recognized as critical mediators between DNA damage repair and cell survival. Thus, a better functional understanding of MMR proteins will undoubtedly aid the development of strategies to effectively enhance apoptotic signaling in response to DNA damage induced by anti-cancer therapeutics. Among the five known human MutS homologs, hMSH4 and hMSH5 form a unique heterocomplex. However, the expression profiles of the two genes are not correlated in a number of cell types, suggesting that they may function independently as well. Consistent with this, these two proteins are promiscuous and thought to play distinct roles through interacting with different binding partners. Here, we describe the gene and protein structures of eukaryotic MSH4 and MSH5 with a particular emphasis on their human homologues, and we discuss recent findings of the roles of these two genes in DNA damage response and repair. Finally, we delineate the potential links of single nucleotide polymorphism (SNP) loci of these two genes with several human diseases.

DNA damage induced MutS homologue hMSH4 acetylation.

Acetylation of non-histone proteins is increasingly recognized as an important post-translational modification for controlling the actions of various cellular processes including DNA repair and damage response. Here, we report that the human MutS homologue hMSH4 undergoes acetylation following DNA damage induced by ionizing radiation (IR). To determine which acetyltransferases are responsible for hMSH4 acetylation in response to DNA damage, potential interactions of hMSH4 with hTip60, hGCN5, and hMof were analyzed. The results of these experiments indicate that only hMof interacts with hMSH4 in a DNA damage-dependent manner. Intriguingly, the interplay between hMSH4 and hMof manipulates the outcomes of nonhomologous end joining (NHEJ)-mediated DNA double strand break (DSB) repair and thereby controls cell survival in response to IR. This study also shows that hMSH4 interacts with HDAC3, by which HDAC3 negatively regulates the levels of hMSH4 acetylation. Interestingly, elevated levels of HDAC3 correlate with increased NHEJ-mediated DSB repair, suggesting that hMSH4 acetylation per se may not directly affect the role of hMSH4 in DSB repair.

Correction: Paper-based ELISA diagnosis technology for human brucellosis based on a multiepitope fusion protein.

[This corrects the article DOI: 10.1371/journal.pntd.0009695.].

Exposure to tris(2,6-dimethylphenyl) phosphate interferes with sexual differentiation via estrogen receptors 2a and 2b in zebrafish.

Tris(2,6-dimethylphenyl) phosphate (TDMPP), an emerging organophosphate flame retardant, is frequently detected in multiple environmental media. Although TDMPP has been proven as a compound with estrogenic activity, its feminizing effects on reproductive system remain unclear. This study investigated the adverse effects of TDMPP on gonadal development by exposing zebrafish for 105 days from 15 days post-fertilization. Exposure to TDMPP (0.5 and 5 µM, corresponding to about 200 and 2000 µg/L) induced ovarian formation in aromatase mutant (cyp19a1a-/-) line which normally presents all-male phenotype for deficiency of endogenous estrogen (E2), suggesting its feminizing effect on sexual differentiation. In addition, TDMPP also interfered with other aspects of reproduction by delaying puberty onset, retarding sexual maturation, impairing gametogenesis and subfertility. Molecular docking and reporter gene assay indicated that all three nuclear estrogen receptors (nERs) can be binded to and activated by TDMPP. Using a series of nERs mutant lines, we confirmed the indispensable role of esr2a and esr2b in mediating the feminizing effects of TDMPP. Further analysis revealed that the prominent effects of TDMPP on sexual differentiation correlated to upregulation of female-promoting genes and downregulation of male-promoting genes. Taken together, the present study provided unequivocal genetic evidence for estrogenic effects of TDMPP on reproductive system and its molecular mechanisms of action.