Aberrant centrosome biogenesis disrupts nephron and collecting duct progenitor growth and fate resulting in fibrocystic kidney disease.

Mutations that disrupt centrosome biogenesis or function cause congenital kidney developmental defects and fibrocystic pathologies. Yet how centrosome dysfunction results in the kidney disease phenotypes remains unknown. Here, we examined the consequences of conditional knockout of the ciliopathy gene Cep120, essential for centrosome duplication, in the nephron and collecting duct progenitor niches of the mouse embryonic kidney. Cep120 loss led to reduced abundance of both cap mesenchyme and ureteric bud populations, due to a combination of delayed mitosis, increased apoptosis and premature differentiation of progenitor cells. These defects resulted in dysplastic kidneys at birth, which rapidly formed cysts, displayed increased interstitial fibrosis and decline in kidney function. RNA sequencing of embryonic and postnatal kidneys from Cep120-null mice identified changes in the pathways essential for development, fibrosis and cystogenesis. Our study defines the cellular and developmental defects caused by centrosome dysfunction during kidney morphogenesis and identifies new therapeutic targets for patients with renal centrosomopathies.

Cep120 is essential for kidney stromal progenitor cell growth and differentiation.

Mutations in genes that disrupt centrosome structure or function can cause congenital kidney developmental defects and lead to fibrocystic pathologies. Yet, it is unclear how defective centrosome biogenesis impacts renal progenitor cell physiology. Here, we examined the consequences of impaired centrosome duplication on kidney stromal progenitor cell growth, differentiation, and fate. Conditional deletion of the ciliopathy gene Cep120, which is essential for centrosome duplication, in the stromal mesenchyme resulted in reduced abundance of interstitial lineages including pericytes, fibroblasts and mesangial cells. These phenotypes were caused by a combination of delayed mitosis, activation of the mitotic surveillance pathway leading to apoptosis, and changes in both Wnt and Hedgehog signaling that are key for differentiation of stromal cells. Cep120 ablation resulted in small hypoplastic kidneys with medullary atrophy and delayed nephron maturation. Finally, Cep120 and centrosome loss in the interstitium sensitized kidneys of adult mice, causing rapid fibrosis after renal injury via enhanced TGF-ß/Smad3-Gli2 signaling. Our study defines the cellular and developmental defects caused by loss of Cep120 and aberrant centrosome biogenesis in the embryonic kidney stroma.

Context-dependent ciliary regulation of hedgehog pathway repression in tissue morphogenesis.

A fundamental problem in tissue morphogenesis is identifying how subcellular signaling regulates mesoscale organization of tissues. The primary cilium is a paradigmatic organelle for compartmentalized subcellular signaling. How signaling emanating from cilia orchestrates tissue organization-especially, the role of cilia-generated effectors in mediating diverse morpho-phenotypic outcomes-is not well understood. In the hedgehog pathway, bifunctional GLI transcription factors generate both GLI-activators (GLI-A) and GLI-repressors (GLI-R). The formation of GLI-A/GLI-R requires cilia. However, how these counterregulatory effectors coordinate cilia-regulated morphogenetic pathways is unclear. Here we determined GLI-A/GLI-R requirements in phenotypes arising from lack of hedgehog pathway repression (derepression) during mouse neural tube and skeletal development. We studied hedgehog pathway repression by the GPCR GPR161, and the ankyrin repeat protein ANKMY2 that direct cAMP/protein kinase-A signaling by cilia in GLI-R generation. We performed genetic epistasis between Gpr161 or Ankmy2 mutants, and Gli2/Gli3 knockouts, Gli3R knock-in and knockout of Smoothened, the hedgehog pathway transducer. We also tested the role of cilia-generated signaling using a Gpr161 ciliary localization knock-in mutant that is cAMP signaling competent. We found that the cilia-dependent derepression phenotypes arose in three modes: lack of GLI-R only, excess GLI-A formation only, or dual regulation of either lack of GLI-R or excess GLI-A formation. These modes were mostly independent of Smoothened. The cAMP signaling-competent non-ciliary Gpr161 knock-in recapitulated Gpr161 loss-of-function tissue phenotypes solely from lack of GLI-R only. Our results show complex tissue-specific GLI-effector requirements in morphogenesis and point to tissue-specific GLI-R thresholds generated by cilia in hedgehog pathway repression. Broadly, our study sets up a conceptual framework for rationalization of different modes of signaling generated by the primary cilium in mediating morphogenesis in diverse tissues.

Transition from Schottky to Ohmic contacts in 2D Ge/GaAs heterostructures with high tunneling probability.

The metal-semiconductor (M-S) contact is usually an Ohmic contact or a Schottky contact, which greatly affects the electronic properties of devices, and it remains a huge challenge to realize a low-resistance Ohmic contact in a metal-semiconductor junction (MSJ). Herein, we systematically studied the band structures, electrostatic potential, charge transfer, Schottky barrier height of carriers, effective carrier masses, and tunneling probability of carriers of a germanene (Ge)/GaAs MSJ. The transition from the Schottky to the Ohmic contact can be caused by applying certain biaxial strains or electric fields, which weakens the Fermi level pinning (FLP) effect and reduces contact resistance. Meanwhile, the electron injection efficiency of Ge/(GaAs)As MSJ (PTB > 27%) is far superior to that of other two-dimensional (2D) vdW MSJs. This work indicates that Ge/GaAs heterostructures are the most compatible for applying high-effective 2D electronic nanodevices under controllable conditions.

Exergoeconomic Analysis and Optimization of a Biomass Integrated Gasification Combined Cycle Based on Externally Fired Gas Turbine, Steam Rankine Cycle, Organic Rankine Cycle, and Absorption Refrigeration Cycle.

Adopting biomass energy as an alternative to fossil fuels for electricity production presents a viable strategy to address the prevailing energy deficits and environmental concerns, although it faces challenges related to suboptimal energy efficiency levels. This study introduces a novel combined cooling and power (CCP) system, incorporating an externally fired gas turbine (EFGT), steam Rankine cycle (SRC), absorption refrigeration cycle (ARC), and organic Rankine cycle (ORC), aimed at boosting the efficiency of biomass integrated gasification combined cycle systems. Through the development of mathematical models, this research evaluates the system's performance from both thermodynamic and exergoeconomic perspectives. Results show that the system could achieve the thermal efficiency, exergy efficiency, and levelized cost of exergy (LCOE) of 70.67%, 39.13%, and 11.67 USD/GJ, respectively. The analysis identifies the combustion chamber of the EFGT as the component with the highest rate of exergy destruction. Further analysis on parameters indicates that improvements in thermodynamic performance are achievable with increased air compressor pressure ratio and gas turbine inlet temperature, or reduced pinch point temperature difference, while the LCOE can be minimized through adjustments in these parameters. Optimized operation conditions demonstrate a potential 5.7% reduction in LCOE at the expense of a 2.5% decrease in exergy efficiency when compared to the baseline scenario.

Donor selection for fecal bacterial transplantation and its combined effects with inulin on early growth and ileal development in chicks.

AIMS: To select the best donor and investigate its combined effects with inulin on growth performance, and ileal health of chicks. METHODS AND RESULTS: The chicks (Hy-line Brown) were treated with fecal microbiota suspension from different breeder hens to select the best donor. Treatment with fecal microbiota transplantation (FMT) alone or in combination with inulin resulted in improvement in gut microbiome in chicks. The organ indexes were improved on day 7, especially the bursa of fabricius index (P < 0.05). On day 14, immune performance, ileal morphology, and barrier were improved, and simultaneously, the concentration of short-chain fatty acids was also increased. In addition, for the expression of ileal barrier-related genes, Anaerofustis and Clostridium were positively correlated with them (P < 0.05), Blautia, Prevotella, Veillonella, and Weissella showed a negative correlation (P < 0.05), and RFN20 showed a positive correlation with gut morphology (P < 0.05). CONCLUSION: Combination of homologous FMT and inulin promoted early growth and intestinal health of chicks.

Characterization of photochemical losses of volatile organic compounds and their implications for ozone formation potential and source apportionment during summer in suburban Jinan, China.

Volatile organic compounds (VOCs) undergo substantial photochemical losses during their transport from emission sources to receptor sites, resulting in serious implications for their source apportionment and ozone (O3) formation. Based on the continuous measurements of VOCs in suburban Jinan in August 2022, the effects of photochemical losses on VOC source contributions and O3 formation were evaluated in this study. The observed and initial concentrations of total VOCs (TVOC) were 12.0 ± 5.1 and 16.0 ± 7.4 ppbv, respectively. Throughout the observation period, alkenes had the most prominent photochemical losses (58.2%), followed by aromatic hydrocarbons (23.1%), accounting for 80.6% and 6.9% of the total losses, respectively. During high O3 episodes, the photochemical loss of VOCs was 6.9 times higher than that during the cleaning period. Alkene losses (exceeding 67.3%), specifically losses of isoprene, propylene, ethylene, and n-butene, dominated the total losses of VOCs during the O3 increase period. Eight sources of VOCs were identified by positive matrix factorization (PMF) based on the observed and initial concentration data (OC-PMF and IC-PMF, respectively). Concentrations of all emission sources in the OC-PMF were underestimated by 2.4%-57.1%. Moreover, the contribution of each emission source was over- or underestimated compared with that in case of the IC-PMF. The contributions of biogenic and motor vehicle exhaust emissions were underestimated by 5.3 and 2.8 percentage points, respectively, which was associated with substantial oxidation of the emitted high-reactive species. The contributions of coal/biomass burning and natural gas were overestimated by 2.4 and 3.9 percentage points, respectively, which were related to the emission of low-reactive species (acetylene, ethane, and propane). Based on our results, the photochemical losses of VOCs grossly affect their source apportionment and O3 formation. Thus, photochemical losses of VOCs must be thoroughly accounted to establish a precise scientific foundation for air-pollution control strategies.

Mediating effects of DNA methylation in the association between sleep quality and infertility among women of childbearing age.

BACKGROUND: This study aims to investigate the association between sleep quality and infertility among women and to explore the mediating effects of DNA methylation in this association. METHODS: This study is a population-based case-control study. The relationship between sleep quality and infertility was investigated in women with anovulatory infertility (n = 43) and healthy controls (n = 43). Genome-wide DNA methylation was profiled from peripheral blood samples using the Illumina Infinium Human Methylation 850k BeadChip. Differentially methylated CpGs between cases and controls were identified using the ChAMP R package. The mediating effect of DNA methylation between sleep quality and infertility among women was investigated using the Bayesian estimation method provided by the R package "mediation". RESULTS: The survey included 86 women of reproductive age, with 43 participants each in the case and control groups. The average age of the women was 27.6 ± 2.8 years (case group: 27.8 ± 3.0 years, control group: 27.4 ± 2.7 years). A total of 262 differentially methylated CpGs corresponding to 185 genes were identified. Difficulty falling asleep was a risk factor for infertility in women (OR = 3.69, 95%CI = 1.14, 11.99), and a causal mediation effect of DNA methylation CpGs was found. The mediating effect coefficient for cg08298632 was 0.10 (95%CI = 0.01-0.22), and the proportion of the total effect mediated by this methylation site increased to 64.3%. CONCLUSION: These results suggest that DNA methylation CpGs (cg08298632) play a significant role in the relationship between difficulty falling asleep and infertility in females. These findings contribute to our understanding of the underlying mechanisms that connect difficulty falling asleep and infertility in women. Further studies are necessary to fully understand the biological significance and potential therapeutic applications of these findings. The identified DNA methylation sites provide new and valuable insights and potential targets for future studies aiming to prevent and treat female infertility.

Effect of fecal microbiota transplantation on early intestinal immune function and histomorphology of immune organs in chicks.

The intestinal microbiota drives the maturation of the immune system, which is essential for maintaining lifetime homeostasis. Whether fecal microbiota transplantation can promote the development of the immune system in chicks? On days 1, 3, and 5, the post-hatch Hy-line Brown chicks were treated with fecal suspension from breeding hens. Intestinal length, blood biochemical indicators, the morphology of immune organs, and intestinal immunity-related indicators were focused on days 7 and 14. Short-chain fatty acids were determined by gas chromatography. We discovered that fecal microbial transplantation significantly increased the area of the follicles and medulla from the bursa of Fabricius, as well as the area of the medulla, cortex, and both ratios from the thymus on 14 d, the concentration of butyric acid in feces, the levels of immunologically active substances (transforming growth factor-ß, interleukin 10, forkhead box protein P3, G-Protein Coupled Receptor 43, immunoglobulin A, etc.) in serum or the intestine, and the number of goblet cells. Correlation analysis indicated that short-chain fatty acids, as metabolites of the gut microbiota, were correlated with intestinal immunity. In short, fecal microbiota transplantation regulated early intestinal immunity, which provided the possibility for the processing and utilization of gut microbiota as germplasm resources. IMPACT STATEMENT: Modern management of eggs causes the normal vertical transmission of microbiota from hens to be significantly reduced. The risk of environmental threats to newborn chicks is raised. The microbial community helps to mature the immune system of chicks and protect them from pathogen invasion. We still have doubts about whether transplanting the microbiota can regulate gut immunity. Using the gut microbiota of hens as an excellent resource to improve the immunity of chicks may provide new ideas for the development of the poultry industry.

Association between antibiotic exposure and the risk of infertility in women of childbearing age: A case-control study.

BACKGROUND: Based on self-report questionnaires, two previous epidemiological studies investigated the association between the exposure of women to antibiotics and their fertility. However, biomonitoring studies on low-dose antibiotic exposure, mainly from food and water, and its relation to the risk of infertility are missing. METHODS: Based on a case-control study design, 302 women with infertility (144 primary infertility, 158 secondary infertility) and 302 women with normal fertility, all aged 20-49 years, were recruited from Anhui Province, China, in 2020 and 2021. A total of 41 common antibiotics and two antibiotic metabolites in urine samples were determined by liquid chromatography-triple quadrupole tandem mass spectrometry (LC-QqQ-MS/MS). RESULTS: Twenty-eight antibiotics with detection rates from 10% to 100% in both cases (median concentration: ∼2.294 ng/mL) and controls (∼1.596 ng/mL) were included in the analysis. Logistic regression analysis revealed that after controlling for confounding factors, high concentrations of eight individual antibiotics (sulfamethoxazole, sulfaclozine, sulfamonomethoxine, penicillin G, chlorotetracycline, ofloxacin, norfloxacin, and cyadox) and four antibiotic classes (sulfonamides, tetracyclines, quinoxalines, and veterinary antibiotics) were related to a high risk of female infertility, with odds ratios (ORs) ranging from 1.30 to 2.86, except for chlorotetracycline (OR = 6.34), while another nine individual antibiotics (sulfamethazine, azithromycin, cefaclor, amoxicillin, oxytetracycline, pefloxacin, sarafloxacin, enrofloxacin, and florfenicol) and classes of chloramphenicol analogs and human antibiotics were related to a reduced risk of infertility, with ORs ranging from 0.70 to 0.20. Based on restricted cubic spline models after controlling for confounding factors, we observed that the relationship between all of the above protective antibiotics and infertility was nonlinear: A certain concentration could reduce the risk of female infertility while exceeding a safe dose could increase the risk of infertility. CONCLUSION: These results provide preliminary evidence that the effects of antibiotics on female fertility vary based on the active ingredient and usage and imply the importance of exposure dose. Future studies are needed to verify these results by controlling for multiple confounding factors.

Preconception exposure to environmental antibiotics among childbearing couples in Anhui and health risk assessment: A multicenter population-based representative study.

Only few studies have assessed the health effects due to preconception exposure to antibiotics among childbearing couples. This study investigated the status of preconception exposure to antibiotics among childbearing couples in Anhui, associated with health risks, and influencing factors. Overall, 1500 childbearing couples were randomly selected from the Reproductive Health of Childbearing Couples - Anhui Cohort (RHCC-AC). The urinary levels of 40 antibiotics and 2 metabolites were determined, and specific gravity (SG) adjusted concentrations of antibiotics were measured to assess health risks. Generalized linear models were used to assess the associations of urinary SG-adjusted concentration of antibiotics with demographic parameters and diet frequency. The total detection rates of all antibiotics were 98.9 % and 99.3 % in wives and husbands, respectively. The detection rates of veterinary antibiotics (VAs) and preferred as VAs (PVAs) were above 90 %. Among eight antibiotics, sulfonamides (95.1 %) and fluoroquinolones (87.6 %) had the highest detection rates in couples. Approximately four-fifths of couples were simultaneously exposed to at least three different antibiotics, and more than half of them were exposed to low concentrations of antibiotics. 8.9 % and 9.2 % of wives and husbands had hazard index value of antibiotics exposure greater than 1. Antibiotic concentrations were associated with residence, sampling season, and diet frequency. In Anhui, nearly 98 % of childbearing couples have environmental exposure to antibiotics, and VAs and PVAs are the primary antibiotics. More than 8 % of couples had health risks due to antibiotic exposure. Several potential determinants of urinary antibiotics deserve more attention in future research.

Neutralizing Immunity Induced Against the Omicron BA.1 and BA.2 Variants in Vaccine Breakthrough Infections.

BACKGROUND: As of early 2022, the Omicron variants are the predominant circulating lineages globally. Understanding neutralizing antibody responses against Omicron BA.1 and BA.2 after vaccine breakthrough infections will provide insights into BA.2 infectivity and susceptibility to subsequent reinfection. METHODS: Live virus neutralization assays were used to study immunity against Delta and Omicron BA.1 and BA.2 variants in samples from 86 individuals, 24 unvaccinated (27.9%) and 62 vaccinated (72.1%), who were infected with Delta (n = 42, 48.8%) or BA.1 (n = 44, 51.2%). Among the 62 vaccinated individuals, 39 were unboosted (62.9%), whereas 23 were boosted (37.1%). RESULTS: In unvaccinated infections, neutralizing antibodies (nAbs) against the three variants were weak or undetectable, except against Delta for Delta-infected individuals. Both Delta and BA.1 breakthrough infections resulted in strong nAb responses against ancestral wild-type and Delta lineages, but moderate nAb responses against BA.1 and BA.2, with similar titers between unboosted and boosted individuals. Antibody titers against BA.2 were generally higher than those against BA.1 in breakthrough infections. CONCLUSIONS: These results underscore the decreased immunogenicity of BA.1 compared to BA.2, insufficient neutralizing immunity against BA.2 in unvaccinated individuals, and moderate to strong neutralizing immunity induced against BA.2 in Delta and BA.1 breakthrough infections.

Matrine induces hepatocellular carcinoma apoptosis and represses EMT and stemness through microRNA-299-3p/PGAM1 axis.

This study explored the impacts of matrine on hepatocellular carcinoma (HCC) cell growth, metastasis, epithelial-mesenchymal transition (EMT), and stemness through regulating the microRNA (miR)-299-3p/phosphoglycerate mutase 1 (PGAM1) axis. The association between miR-299-3p expression with the prognosis of HCC patients was studied. miR-299-3p and PGAM1 sequences were transfected into matrine-treated HCC cells, and cell proliferation, invasion, apoptosis, and stemness were detected, as well as protein expression of EMT- and stemness-related makers. The targeting relationship between miR-299-3p and PGAM1 was identified. Matrine elevated miR-299-3p expression, repressed proliferation, invasion, and anti-apoptosis of HCC cells, and constrained EMT and stemness in vitro. PGAM1 was a target of miR-299-3p. Repression of PGAM1 rescued the effects of miR-299-3p downregulation on HCC cells. Matrine stimulates HCC cell apoptosis and represses the process of EMT and stemness through the miR-299-3p/PGAM1 axis.

COVID-19 Variant Detection with a High-Fidelity CRISPR-Cas12 Enzyme.

Laboratory tests for the accurate and rapid identification of SARS-CoV-2 variants can potentially guide the treatment of COVID-19 patients and inform infection control and public health surveillance efforts. Here, we present the development and validation of a rapid COVID-19 variant DETECTR assay incorporating loop-mediated isothermal amplification (LAMP) followed by CRISPR-Cas12 based identification of single nucleotide polymorphism (SNP) mutations in the SARS-CoV-2 spike (S) gene. This assay targets the L452R, E484K/Q/A, and N501Y mutations, at least one of which is found in nearly all major variants. In a comparison of three different Cas12 enzymes, only the newly identified enzyme CasDx1 was able to accurately identify all targeted SNP mutations. An analysis pipeline for CRISPR-based SNP identification from 261 clinical samples yielded a SNP concordance of 97.3% and agreement of 98.9% (258 of 261) for SARS-CoV-2 lineage classification, using SARS-CoV-2 whole-genome sequencing and/or real-time RT-PCR as test comparators. We also showed that detection of the single E484A mutation was necessary and sufficient to accurately identify Omicron from other major circulating variants in patient samples. These findings demonstrate the utility of CRISPR-based DETECTR as a faster and simpler diagnostic method compared with sequencing for SARS-CoV-2 variant identification in clinical and public health laboratories.

Recycled Bifunctional Heterostructure Material: g-GaN/SnS for Photocatalytic Decomposition of Water and Efficient Detection of NO2.

Recently, the energy crisis and environmental pollution problems have become increasingly severe. There is an urgent need to develop a class of multifunctional materials that can both produce clean energy and detect harmful gases. Herein, we propose a g-GaN/SnS heterostructure and explored its dual-optimal performance in photocatalytic hydrogen production and gas detection. Our results demonstrated that the g-GaN/SnS heterostructure has a suitable type II band alignment and excellent absorption in the visible range, which both indicate its potential application in photocatalysis. Furthermore, when the g-GaN/SnS heterostructure acted as a gas detection material, it was consistently susceptible to NO2 gas molecules, according to charge transfer. Additionally, it has a very suitable material recovery time (∼0.5 h) when used for NO2 detection, illustrating the recyclability of the material. Interestingly, the applied electric field of -0.4 V/Šcan greatly increase the absorption coefficient in the visible range to 150% of the original. Also, the applied electric field of 0.6 V/Šcan substantially enhance the gas detection sensitivity by 27% compared to the case without the electric field. Thus, the g-GaN/SnS heterostructure we proposed not only has the advantage of being bifunctional but also has the potential to be recycled.

Evaluation of amentoflavone metabolites on PARP-1 inhibition and the potentiation on anti-proliferative effects of carboplatin in A549 cells.

The present study aims to determine the major metabolites of amentoflavone (AMF) and further evaluate their inhibitory effects on PARP-1. First, different fractions (Frs. 1-9), which were collected according to retention time of AMF metabolites based on UHPLC-QTOF-MS/MS qualitative analysis, were evaluated on their inhibitory effects against PARP-1. Then, two mono-sulfate metabolites in the fractions with potent PARP-1 inhibitory effect were targetedly semi-synthesized. Moreover, three mono-sulfate conjugates (compound 8, 9 and 10), including one disulfate conjugate (compound 10), were isolated and their structures were fully elucidated by UHPLC-QTOF-MS/MS and NMR. Finally, the binding mode of compound 8 (amentoflavone-4‴-O-sulfate) toward PARP-1 and its potentiation on carboplatin (CBP) in A549 cells were investigated. This study was the first report on bioactivity evaluation of AMF metabolites in rat bile on PARP-1 and the potentiation of compound 8 on carboplatin (CBP) in A549 cells in vitro. This paper also provided scientific basis for the AMF metabolites on PARP-1 inhibition and chemosensitization.

T-lymphoma invasion and metastasis 1 promotes invadopodia formation and is regulated by the PI3K/Akt signaling pathway in hepatocellular carcinoma.

At present, there are still many poorly understood aspects of the mechanisms underlying hepatocellular carcinoma (HCC) invasion and metastasis. Invadopodia are important structures for cancer cell invasion and metastasis. We determined that high T-lymphoma invasion and metastasis 1 (Tiam1) expression is associated with HCC invasion and metastasis and poor patient prognosis after surgery. Gain- and loss-of-function studies confirmed that Tiam1 promotes invadopodia formation in HCC by activating Rac1. A series of biochemical experiments confirmed that this effect is regulated by the PI3K/Akt signaling pathway. We also confirmed that PIP2 facilitates this effect. In summary, these findings reveal that Tiam1 plays an important role in invadopodia formation in HCC.

Impacts of Mercury Exposure Levels and Sources on the Demethylation of Methylmercury Through Human Gut Microbiota.

This study aims to investigate methylmercury (MeHg) demethylation processes in human gut. Here, we determined the compositions and MeHg demethylation rates of gut microbiota in residents from different Hg exposure levels (Wanshan (WS) town and Yangtou (YT) town) and different Hg exposure sources (Zhuchang (ZC) town and YT town) regions. MeHg and inorganic Hg exposure levels in residents of WS town were significantly higher than those of YT and ZC town. Desulfovibrio and Methanogens, which related to Hg methylation/demethylation, showed significantly higher abundance in WS and ZC, comparing with YT. In vitro experiments demonstrated that human intestinal microbiota could degrade MeHg directly. Besides, gut microbiota in WS and ZC exhibited significantly higher demethylation rates than YT, suggesting Desulfovibrio and Methanogens may play important roles in intestinal MeHg demethylation. This study highlights Hg exposure levels and sources may affect demethylation efficiency of gut microbiota, which provides new insights for MeHg demethylation processes in human body.

Centrosomal protein Dzip1l binds Cby, promotes ciliary bud formation, and acts redundantly with Bromi to regulate ciliogenesis in the mouse.

The primary cilium is a microtubule-based organelle required for Hedgehog (Hh) signaling and consists of a basal body, a ciliary axoneme and a compartment between the first two structures, called the transition zone (TZ). The TZ serves as a gatekeeper to control protein composition in cilia, but less is known about its role in ciliary bud formation. Here, we show that centrosomal protein Dzip1l is required for Hh signaling between Smoothened and Sufu. Dzip1l colocalizes with basal body appendage proteins and Rpgrip1l, a TZ protein. Loss of Dzip1l results in reduced ciliogenesis and dysmorphic cilia in vivo Dzip1l interacts with, and acts upstream of, Cby, an appendage protein, in ciliogenesis. Dzip1l also has overlapping functions with Bromi (Tbc1d32) in ciliogenesis, cilia morphogenesis and neural tube patterning. Loss of Dzip1l arrests ciliogenesis at the stage of ciliary bud formation from the TZ. Consistent with this, Dzip1l mutant cells fail to remove the capping protein Cp110 (Ccp110) from the distal end of mother centrioles and to recruit Rpgrip1l to the TZ. Therefore, Dzip1l promotes ciliary bud formation and is required for the integrity of the TZ.

Origin of Magnetic Relaxation Barriers in a Family of Cobalt(II)-Radical Single-Chain Magnets: Density Functional Theory and Ab Initio Calculations.

Density functional theory (DFT) and ab initio calculations were performed to probe the origin of the magnetic relaxation barriers for two finite single-chain magnets (SCMs) featuring a one-dimension chain, Co(hfac)2(R-NapNIT) (R-NapNIT = 2-(2'-(R-)naphthyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, R = MeO (1) or EtO (2)). Our calculations show that the strong intrachain CoII-CoII exchange coupling interactions transmitted by radicals can contribute much more than ionic anisotropy to the height of the reversal barrier of magnetization for the single-chain magnets (SCMs) with |2E| < |4J/3|. In addition, the anisotropic energy barrier ΔA decreases with the decrease of |2E/J| ratio and finally vanishes in the limit of broad domain walls (|2E| < < |4 J/3|). Therefore, the total magnetic relaxation energy barriers of two SCMs mostly originate from the correlation energy barrier Δξ deriving from the indirect ferromagnetic interaction between CoII-CoII transmitted by the strong CoII-radical antiferromagnetic interactions.