Associations of Serum Per- and Polyfluoroalkyl Substances with Hyperuricemia in Adults: A Nationwide Cross-Sectional Study.

There has been widespread concern about the health hazards of per- and polyfluoroalkyl substances (PFAS), which may be the risk factor for hyperuricemia with evidence still insufficient in the general population in China. Here, we conducted a nationwide study involving 9,580 adults aged 18 years or older from 2017 to 2018, measured serum concentrations of uric acid and PFAS (PFOA, PFOS, 6:2 Cl-PFESA, PFNA, PFHxS) in participants, to assess the associations of individual PFAS with hyperuricemia, and estimated a joint effect of PFAS mixtures. We found positive associations of higher serum PFAS with elevated odds of hyperuricemia in Chinese adults, with the greatest contribution from PFOA (69.37%). The nonmonotonic dose-response (NMDR) relationships were observed for 6:2 Cl-PFESA and PFHxS with hyperuricemia. Participants with less marine fish consumption, overweight, and obesity may be the sensitive groups to the effects of PFAS on hyperuricemia. We highlight the potential health hazards of legacy long-chain PFAS (PFOA) once again because of the higher weights of joint effects. This study also provides more evidence about the NMDR relationships in PFAS with hyperuricemia and emphasizes a theoretical basis for public health planning to reduce the health hazards of PFAS in sensitive groups.

Heavy metals and metalloids exposure and liver function in Chinese adults - A nationally representative cross-sectional study.

BACKGROUND: In China, the effects of heavy metals and metalloids (HMMs) on liver health are not consistently documented, despite their prevalent environmental presence. OBJECTIVE: Our research assessed the association between HMMs and liver function biomarkers in a comprehensive sample of Chinese adults. METHODS: We analyzed data from 9445 participants in the China National Human Biomonitoring survey. Blood and urine were evaluated for HMM concentrations, and liver health was gauged using serum albumin (ALB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) metrics. Various statistical methods were employed to understand the relationship between 11 HMMs and liver function, adjusting for multiple factors. We also explored interactions with alcohol intake, gender, and age. RESULTS: Among HMMs, selenium in blood [weighted geometric mean (GM) = 95.56 µg/L] and molybdenum in urine (GM = 46.44 µg/L) showed the highest concentrations, while lead in blood (GM = 21.92 µg/L) and arsenic in urine (GM = 19.80 µg/L) had the highest levels among risk HMMs. Manganese and thallium consistently indicated potential risk factor to liver in both sample types, while selenium displayed potential liver protection. Blood HMM mixtures were negatively associated with ALB (ß = -0.614, 95% CI: -0.809, -0.418) and positively with AST (ß = 0.701, 95% CI: 0.290, 1.111). No significant associations were found in urine HMM mixtures. Manganese, tin, nickel, and selenium were notable in blood mixture associations, with selenium and cobalt being significant in urine. The relationship of certain HMMs varied based on alcohol consumption. CONCLUSION: This research highlights the complex relationship between HMM exposure and liver health in Chinese adults, particularly emphasizing metals like manganese, thallium, and selenium. The results suggest a need for public health attention to low dose HMM exposure and underscore the potential benefits of selenium for liver health. Further studies are essential to establish causality.

Cryopreservation-enhanced differentiation capacity of embryogenic cultures of Castanea mollissima.

A cryopreservation protocol has been developed for embryogenic cultures (ECs) of Castanea mollissima, an important economic species of the Castanea genus in China. We achieved 100 % regrowth when ECs were treated with Plant Vitrification Solution 2 (PVS2) for 30, 60 and 90 min on ice. Optimal PVS2 treatment for cryopreservation was determined to be 30 min on ice based on the highest biomass regrowth after thawing. Fluorescein diacetate (FDA) staining could rapidly and reliably determine post-thaw cell viability and its use facilitated the optimization of the cryopreservation protocols. Although the proliferation rate of the re-established ECs remained largely unchanged compared to non-cryopreserved ECs, the capacity of the re-established ECs to differentiate (on two media) into somatic embryos nearly doubled to approximately 2200-2300 globular somatic embryos per 1 g of re-established ECs. Based on cell cluster size analysis, this enhanced growth is primarily attributed to the presence of significantly greater cell clusters with a diameter of 100-200 µm, which have the highest level of differentiation ability. In order to understand the increased embryogenic potential following cryopreservation, we analyzed the expression of key genes related to somatic embryogenesis. Genes CmWUS and CmABP1 were downregulated while CmLEC1, CmAGL15, CmGRF2, and CmFUS3 were upregulated in re-established ECs when compared to non-cryopreserved ECs.

Development of a Core-Shell Heterojunction TiO2 /SrTiO3 Electrolyte with Improved Ionic Conductivity.

The front cover artwork is provided by Prof. Faze Wang's group at the Southeast University. The built-in electric field created by the semiconductor heterostructure confines the proton transport on the surface layer of the nanocomposite core-shell heterostructure imparting faster ion transport and lower activation energy. Read the full text of the Research Article at 10.1002/cphc.202200170.

Development of a Core-Shell Heterojunction TiO2 /SrTiO3 Electrolyte with Improved Ionic Conductivity.

Lately, semiconductor-membrane fuel cells (SMFCs) have attained significant interest and great attention due to the deliverance of high performance at low operational temperatures, <550 °C. This work has synthesized the nanocomposite core-shell heterostructure (TiO2 -SrTiO3 ) electrolyte powder by employing the simple hydrothermal method for the SMFC. The SrTiO3 was grown in situ on the surface of TiO2 to form a core-shell structure. A heterojunction mechanism based on the energy band structure is proposed to explain the ion transport pathway and promoted protonic conductivity. The core-shell heterostructure (TiO2 -SrTiO3 ) was utilized as an electrolyte to reach the peak power density of 951 mW cm-2 with an open-circuit voltage of 1.075 V at 550 °C. The formation of core-shell heterostructure among TiO2 and SrTiO3 causes redistribution of charges and establishes a depletion region at the interface, which confined the protons' transport on the surface layer with accelerated ion transport and lower activation energy. The current work reveals novel insights to understand enhanced proton transport and unique methodology to develop low-temperature ceramic fuel cells with high performance.

Potential Risk of Calcified Nanoparticles for Recurrent Urinary Tract Infection after Minimally Invasive Percutaneous Nephrolithotomy for Renal Calculi.

Among urolithiasis, urolithiasis is a more extensive and difficult to treat disease. In recent years, with the development of endoscopic equipment and related surgical methods, a new treatment, namely minimally invasive percutaneous nephrolithotomy, appears and is widely used in the treatment of renal calculi. It has been developed for more than 50 years since its appearance. Its advantages are a high stone clearance rate, small surgical trauma, fewer intraoperative and postoperative complications, and a short recovery time for postoperative patients. It is widely used in clinical treatment. The purpose of this paper is to study the potential risk factors of recurrence and the possibility of urinary tract infection in patients with renal calculi after minimally invasive percutaneous nephrolithotomy (MPCNL) with calcified nanoparticles, so as to obtain correct nursing knowledge and reduce recurrence and infection. In order to explore the renal calculi caused by calcified nanoparticles (CNPs), we established a rat model of renal calculi, injected CNPs into rats, collected experimental samples after a specified time, and determined NGAL, OPN and MCP-1 by enzyme-linked immunosorbent assay (ELISA) and compared them with the formation of crystallization. In the study of the possible influencing factors of septic shock after PCNL, we established a multivariate regression analysis and model, used statistical methods and professional statistical software, and used the method of classified data analysis to find out the influencing factors. After the experiment, we found that positive urine culture (P < 0.05) and preoperative urinary tract infection (P < 0.05) were significant influencing factors, and the total accuracy was 99.2%. At the same time, it is concluded that calcium nanoparticles can promote the retention, adhesion and aggregation of calcium salt crystals in the kidney, and then lead to the formation of stones.

Enhanced Nontarget Screening Algorithm Reveals Highly Abundant Chlorinated Azo Dye Compounds in House Dust.

Humans spend 90% of their time indoors, but the majority of indoor pollutants remain unknown. In this study, a nontarget screening algorithm with reduced false discovery rates was developed to screen indoor pollutants using the Toxic Substances Control Act (TSCA) database. First, a putative lock mass algorithm was developed for post-acquisition calibration of Orbitrap mass spectra to sub-ppm mass accuracy. Then, a one-stop screening algorithm was developed by combining MS1 spectra, isotopic peaks, retention time prediction, and in silico MS2 spectra. A sufficient true positive rate (73%) and false discovery rate (5%) were achieved for the screening of halogenated compounds at a score cutoff of 0.28. Above this cutoff, 427 chemicals were detected from 24 house dust samples, including 39 chlorinated compounds. While some identified halogenated compounds (e.g., triclosan) are well known, 18 previously unrecognized chlorinated azo dyes were detected with high abundance as the largest class of chlorinated compounds. Two chlorinated azo dyes were confirmed with authentic standards, but the two most abundant chlorinated azo dyes were missed by the algorithm due to the limited breadth of the TSCA database. These compounds were annotated as chlorinated analogues of Disperse Blue 373 and Disperse Violet 93 using the DIPIC-Frag method. This study revealed the presence of highly abundant chlorinated azo dyes in house dusts, highlighting their potential health risks in the indoor environment.

New MR-based measures for the evaluation of age-related lumbar paraspinal muscle degeneration.

PURPOSE: Although signal intensity on T2W axial images is sensitive in detection of fatty infiltration to assess paraspinal muscle degeneration, it is affected by inhomogeneities of magnetic fields and individual variabilities. The purpose of this study was to propose reference adjusted signal measures on T2W axial images and determine their capacities in reflecting age-related lumbar paraspinal muscle degeneration. METHODS: Lumbar MR images of 421 population-based subjects (177 men and 244 women, mean age 53.1 years, range 19.8-87.9 years) were studied. A custom software Spine Explore (Tulong 2.0) was used to automatically obtain paraspinal measurements of multifidus, erector spinae and psoas major. FCSA/TCSA was defined as functional cross-sectional area relative to total cross-sectional area of paraspinal muscle. Two new signal measures were canal-adjusted and cerebrospinal fluid (CSF)-adjusted signal, defined as the ratio between mean signal measurements and the mean signal of the canal and CSF. RESULTS: The raw signal measurements of the paraspinal muscles were weakly correlated to age (r = 0.28-0.39, P < 0.001). When the signal of canal (r = 0.43-0.59, P < 0.001) or CSF (r = 0.45-0.61, P < 0.001) was used as reference, the correlations substantially increased. Signal measurements of three paraspinal muscles, adjusted or not, were strongly associated with Goutallier score (ρ = 0.60-0.65, P < 0.001) and FCSA/TCSA (r = -0.64 to -0.82, P < 0.001). Greater Goutallier score was associated with greater age (r = 0.38-0.60, P < 0.001), while Lumbar indentation value (LIV) not. CONCLUSION: On routine T2W axial MR images the adjusted signal measurements using an internal reference of CSF or canal can better reflect age-related degenerative changes in the paraspinal muscles.

The Trp183 is essential in lactonohydrolase ZHD detoxifying zearalenone and zearalenols.

Lactonohydrolase ZHD can detoxify oestrogenic mycotoxin zearalenone and zearalenols through hydrolysis and decarboxylation. The detail mechanism, especially the role of Trp183, which interacts with substrate through p-π interaction and one hydrogen bond, is still unknown. The Trp183 mutants abolished activity to ZEN, α-ZOL and ß-ZOL, except that W183F mutant retained about 40% activity against α-ZOL. In two W183F-reactant complex structures the reactants still bind at the active position and it suggested that this p-π interaction takes responsible for the reactants recognization and allocation. Further, the ZHD-productant complex structures showed that the resorcinol ring of hydrolysed α-ZOL and hydrolysed ß-ZOL move a distance of one ring as compare to the resorcinol ring of reactant α-ZOL and ß-ZOL. The same movement also found in comparison of hydrolysed ZEN and ZEN. In the structure of W183F complex with hydrolysed α-ZOL the resorcinol ring of hydrolysed α-ZOL doesn't move as compare to the resorcinol ring of reactant α-ZOL. It suggested the Trp183 coordinated hydrogen bond takes responsible for the movement of the hydrolysed product. These functional and structural results suggested that Trp183 is essential for ZHD detoxifying zearalenone and zearalenols.

RNA-Seq analysis revealed the molecular mechanisms of photobiomodulation effect on human fibroblasts.

BACKGROUND: The photobiomodulation (PBM) effect has been applied to various clinical therapy for a long time. However, the mechanism related to the PBM effect in terms of wavelengths has been lack of in-depth study, except that ultraviolet radiation has attracted much attention due to its strong cell-killing effect. PURPOSE: To clarify the principle behind PBM and the main mechanism of improvement. METHODS: To carry on this study, we created light equipment using three LED chips, which emit 390 nm ultraviolet radiation, 415 nm blue light and 660 nm red light, respectively. We choose human fibroblasts (HF) to be irradiated by three different wavelengths for PBM test. In this study, we used cell counting kit (CCK-8) test to show the cell proliferation roughly and reported on a systematic RNA sequencing (RNA-seq) analysis at transcriptional expression levels from HF, which accepted PBM of different wavelengths of light. RESULTS: We found that 415 nm blue light inhibited cell proliferation and 660 nm red light stimulated cell proliferation while 390 nm ultraviolet radiation has little influence on cell proliferation. Furthermore, RNA-seq results showed that CSF1R, PPP3CC, ITGAL, ITGAM, IL2RB, and several other differentially expressed genes (DEGs) are involved in the cell proliferation. Relative DEGs values for matrix metalloproteinases (MMPs) gene family have shown a great difference in blue and red light radiation especially on MMP25, MMP9, MMP21, and MMP13. CONCLUSION: Taken together, the results provide a valuable resource to describe the variation of HFs under PBM of different light at gene level.

Structural insights into the complex of trigger factor chaperone and ribosomal protein S7 from Mycobacterium tuberculosis.

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), has threaten human health for thousands years. The chaperone trigger factor (TF) of Mtb (mtbTF), a ribosome-associated molecule, plays important roles in co-translational nascent chain folding and post-translational protein assembly. However, due to lack of structural information, the dynamic regulatory mechanism of mtbTF remains barely investigated. Herein we report the structural basis of the complex of TF and ribosomal protein S7 (mtbS7) from Mtb. The mtbTF-mtbS7 complex was obtained with high purity and homogeneity in vitro. MtbTF bound with mtbS7 in a Kd value of 1.433 µM, and formed a complex with mtbS7 at 1:2 M ratios as shown by isothermal titration calorimetry. In addition, the crystal structure of mtbS7 was solved to a resolution at 1.8 Å, which was composed of six α-helices and two ß-strands. Moreover, the molecular envelopes of mtbTF and mtbTF-mtbS7 complex were built and consisted with these homologous structures by small-angle X-ray scattering method. Our current findings might provide structural basis for understanding the molecular mechanism of TF in protein folding and the regulation of ribosomal assembly in Mtb.

A novel SGNH family hydrolase Ali5 with thioesterase activity and a GNSL motif but without a classic GDSL motif from Altererythrobacter ishigakiensis.

OBJECTIVE: We aimed to characterize a novel SGNH (Ser-Gly-Asn-His) family hydrolase from the annotated genome of marine bacteria with new features. RESULTS: A novel esterase Ali5 from Altererythrobacter ishigakiensis has been identified and classified into SGNH family. Ali5 presented a novel GNSL (Gly-Asn-Ser-Leu(X)) motif that differs from the classic GDSL (Gly-Asp-Ser-Leu(X)) motif of SGNH family. The enzyme has esterase and thioesterase activity and exhibited apparent temperature and pH optima of 40 °C and pH 7.5 (in phosphate buffer), respectively. Ali5 was found to be halotolerant and thermostable, and exhibited strong resistance to several organic solvents and metal ions. The residue Tyr196 has a great influence on the catalytic activity, which was proved by site-directed mutagenesis and subsequent kinetic characterization. CONCLUSION: The esterase Ali5 with esterase and thioesterase activities, salt and metal ions resistance and unique structural features was identified, which holds promise for research on the SGNH family of hydrolases.

A rare case of concomitant cervical disc herniation and intradural meningioma treated with one-stage posterior surgery.

STUDY DESIGN: Case report. PURPOSE: To present a rare case of cervical disc herniation concomitant with intradural meningioma which was successfully treated using a single one-stage posterior surgery of tumor resection and transdural discectomy. Coexistence of symptomatic disc herniation and intra-spinal tumor in the same cervical segment is extremely rare. Usually, two-stage anterior and posterior surgeries are needed to treat two conditions, respectively. One-stage posterior surgery to treat two pathologies simultaneously has not been reported in the literature. METHODS AND RESULTS: A 76-year-old man presented with leg weakness and numbness for 6 months and left arm pain for 2 months. Contrast MR imaging revealed C3/4 intervertebral disc herniation and a hyperintense intradural lesion at the right portion of C3 canal. A one-stage posterior surgery, including C3/4 laminectomy, intradural tumor resection, transdural C3/4 discectomy, and C3/4 lateral mass instrumentation and fusion, was performed to treat two distinct pathologies together. The patient's arm pain and numbness disappeared right after the surgery and symptoms of myelopathy fully recovered at 6-month follow-up. Histological studies confirmed a herniated disc and a meningioma. CONCLUSION: In rare case, intradural tumor coexists with cervical disc herniation. When suspicious findings were noticed, or clinical symptoms cannot be fully explained, contrast MR imaging is helpful in differential diagnosis. Microscopic transdural discectomy is safe, and could be used as an optional procedure for cervical disc herniation in some cases.

Is it appropriate to measure age-related lumbar disc degeneration on the mid-sagittal MR image? A quantitative image study.

PURPOSE: Even though phenotypes of disc degeneration vary on different sagittal magnetic resonance images (MRI), measurements typically are acquired on the mid-sagittal MRI. This study investigated the appropriateness of using the mid-sagittal MRI to measure various phenotypes of age-related disc degeneration. METHODS: Lumbar spine MRIs of 66 subjects (mean age 50.3 years, standard deviation 16.5 years, range 22-84 years) were studied. An image analysis program Spine Explorer was used to obtain quantitative measurements for disc height, bulging, and signal on para- and mid-sagittal T2-weighted MRIs. Measurements on para- and mid-sagittal MRIs and their associations with age were compared. RESULTS: Measurements of disc height, signal, and posterior disc bulging acquired on the mid-sagittal MRI were greater than those on the para-sagittal MRIs. Disc height measurements were not linearly associated with age. Greater age was correlated with greater anterior (r = 0.45, P < 0.001) and posterior (r = 0.33, P < 0.01) bulging on para-sagittal MRIs, but not posterior disc bulging on the mid-sagittal MRI (r = - 0.10, P > 0.05). Disc signal intensity measurements on the mid-sagittal MRI had stronger correlations with age than those on para-sagittal MRIs. Mean and standard deviation of disc signal intensity acquired on the mid-sagittal MRI had the strongest correlations with age among all measures of disc degeneration studied (r = - 0.50, - 0.67, respectively, P < 0.001 for both). CONCLUSIONS: Disc signal measurements acquired on the mid-sagittal MRI were reliable and had strong correlations with age and thus can be used as an appropriate measure of disc degeneration. Disc bulging had better be measured on para-sagittal MRIs. Although severe disc narrowing clearly is a sign of severe disc degeneration, disc height was not linearly associated with age.

[Analysis of creatinine in human urine by isotope dilution high performance liquid chromatography/tandem mass spectrometry].

OBJECTIVE: To develop a method for determination of creatinine in human urine by isotope dilution high performance liquid chromatography/tandem mass spectrometry. METHODS: The urine samples were directly diluted 800 fold by mixed solution of methanol and water( 7 ∶ 3, V/V), and filtered with 0. 45 µm filter. The chromatographic separation was carried on an Atlantis Hilic Silica column( 2. 1 mm × 150 mm, 3 µm). Methanol and water mixture solution( 7 ∶ 3, V/V) were used as the mobile phases in an isocratic gradient. Mass detection was then conducted by electrospray ionization in positive ion( ESI+) mode and multiple reaction monitoring( MRM) mode. The concentration of creatinine was quantified by stable isotope labelled d3-creatinine internal standard. Standard reference material of urine creatinine was used to evaluate the accuracy of method, and then the uncertainty of this detection method was also evaluated. RESULTS: The calibration curve of creatinine showed a good linear relationship in the range of 0. 31 µg/mL to 5. 00 µg/mL, and the related coefficient was 0. 999 9. The limit of detection( LOD) and limit of quantitation( LOQ) were 0. 003 mg/mL and 0. 011 mg/mL respectively, in real urine. Recoveries rates at two levels were 93. 9%-104. 0% and 90. 6%-93. 8%, with the relative standard deviation of 4. 4%-7. 6% and 4. 6%-7. 8%( n = 6), respectively. The creatinine concentration of standard reference material was in accordance with the reference value. The measurement uncertainty was mainly due to standard curves, recoveries rates and permissible error of instrument. CONCLUSION: The determination method is successfully applied to measure the concentration of creatinine in human urine with efficiency, accuracy and high sensitivity.

Human 3α-hydroxysteroid dehydrogenase type 3: structural clues of 5α-DHT reverse binding and enzyme down-regulation decreasing MCF7 cell growth.

Human 3α-HSD3 (3α-hydroxysteroid dehydrogenase type 3) plays an essential role in the inactivation of the most potent androgen 5α-DHT (5α-dihydrotestosterone). The present study attempts to obtain the important structure of 3α-HSD3 in complex with 5α-DHT and to investigate the role of 3α-HSD3 in breast cancer cells. We report the crystal structure of human 3α-HSD3·NADP(+)·A-dione (5α-androstane-3,17-dione)/epi-ADT (epiandrosterone) complex, which was obtained by co-crystallization with 5α-DHT in the presence of NADP(+) Although 5α-DHT was introduced during the crystallization, oxidoreduction of 5α-DHT occurred. The locations of A-dione and epi-ADT were identified in the steroid-binding sites of two 3α-HSD3 molecules per crystal asymmetric unit. An overlay showed that A-dione and epi-ADT were oriented upside-down and flipped relative to each other, providing structural clues for 5α-DHT reverse binding in the enzyme with the generation of different products. Moreover, we report the crystal structure of the 3α-HSD3·NADP(+)·4-dione (4-androstene-3,17-dione) complex. When a specific siRNA (100 nM) was used to suppress 3α-HSD3 expression without interfering with 3α-HSD4, which shares a highly homologous active site, the 5α-DHT concentration increased, whereas MCF7 cell growth was suppressed. The present study provides structural clues for 5α-DHT reverse binding within 3α-HSD3, and demonstrates for the first time that down-regulation of 3α-HSD3 decreases MCF7 breast cancer cell growth.

The crystal structure of red fluorescent protein TagRFP-T reveals the mechanism of its superior photostability.

The red fluorescent protein variant TagRFP-T has greatly improved photostability over its parent molecule, TagRFP, but the underlying mechanism leading to this improvement is to date unknown. The 1.95 Å resolution crystallographic structure of TagRFP-T showed that its chromophore exists as a mixture of cis and trans coplanar isomers in roughly equal proportions. Interestingly, both isomers are able to fluoresce, a property that has never been observed in any other fluorescent protein. We propose a "circular restoration model" for TagRFP-T to explain its superior photostability: There are four co-existing chromophore states (cis/trans protonated/ionized state) that can be driven by light to transform from one state into another. This model also explains how TagRPF-T essentially eliminates the temporary dark state (reversible photobleaching).

[Determination of four bisphenolic compounds in drinking water by liquid chromatography-tandem mass spectrometry].

OBJECTIVE: To simultaneously determine the four bisphenolic compounds (bisphenol F, bisphenol A, tetrachlorobisphenol A and tetrabromobisphenol A) in drinking water by liquid chromatography tandem mass spectrometry. METHODS: 200 ml water sample was extracted by solid-phase extraction, eluted with methanol and analyzed by liquid chromatography tandem mass spectrometry under the MRM mode. The separation was carried out on a T3 column (2.1 mm x 150 mm, 3 µm). RESULTS: The limits of detection for the four bisphenolic compounds were in the range of 0.20 - 5.5 ng/L. The mean recoveries at the two spiked levels were 87.1% - 109.0% with the intra-day precision between 6.3% - 12.4% and inter-day precision between 4.5% - 15.4%. The method was applied for determination of 15 water samples. CONCLUSION: The method was sensitive, precise and accurate.