Stereodivergent Total Synthesis of Tacaman Alkaloids.

This paper describes a concise, asymmetric and stereodivergent total synthesis of tacaman alkaloids. A key step in this synthesis is the biocatalytic Baeyer-Villiger oxidation of cyclohexanone, which was developed to produce seven-membered lactones and establish the required stereochemistry at the C14 position (92% yield, 99% ee, 500 mg scale). Cis- and trans-tetracyclic indoloquinolizidine scaffolds were rapidly synthesized through an acid-triggered, tunable acyl-Pictet-Spengler type cyclization cascade, serving as the pivotal reaction for building the alkaloid skeleton. Computational results revealed that hydrogen bonding was crucial in stabilizing intermediates and inducing different addition reactions during the acyl-Pictet-Spengler cyclization cascade. By strategically using these two reactions and the late-stage diversification of the functionalized indoloquinolizidine core, the asymmetric total syntheses of eight tacaman alkaloids were achieved. This study may potentially advance research related to the medicinal chemistry of tacaman alkaloids.

Long non-coding RNA X-Inactive Specific Transcript (XIST) interacting with USF2 promotes osteogenic differentiation of periodontal ligament stem cells through regulation of WDR72 transcription.

BACKGROUND: Periodontal ligament stem cells (PDLSCs) are the most potential cells in periodontal tissue regeneration and bone tissue regeneration. Our prior work had revealed that WD repeat-containing protein 72 (WDR72) was crucial for osteogenic differentiation of PDLSCs. Here, we further elucidated its underlying mechanism in PDLSC osteogenic differentiation. METHODS: Human PDLSCs, isolated and identified by flow cytometry, were prepared for osteogenic differentiation induction. Levels of WDR72, long non-coding RNA X-Inactive Specific Transcript (XIST), upstream stimulatory factor 2 (USF2), and osteogenic marker genes (Runx2, Osteocalcin, and Collagen I) in human PDLSCs and clinical specimens were detected by RT-qPCR. Protein expressions of WDR72, Runx2, Osteocalcin, and Colla1 were tested by Western blot. The interactions among the molecules were verified by RIP, RNA pull-down, ChIP, and luciferase reporter assays. Osteogenic differentiation was evaluated by alkaline phosphatase (ALP) and alizarin red staining (ARS). RESULTS: WDR72 was decreased in periodontal tissues of periodontitis patients, and overexpression reversed TNF-α-mediated suppressive effects on PDLSC osteogenic differentiation. Mechanically, XIST recruited the enrichment of USF2 to the WDR72 promoter region, thereby positively regulating WDR72. WDR72 silencing overturned XIST-mediated biological effects in PDLSCs. CONCLUSION: WDR72, regulated by the XIST/USF2 axis, enhances osteogenic differentiation of PDLSCs, implying a novel strategy for alleviating periodontitis.

Characteristics of wintertime carbonaceous aerosols in two typical cities in Beijing-Tianjin-Hebei region, China: Insights from multiyear measurements.

In order to investigate the impact of "Blue Sky War" implemented during 2018-2020 on carbonaceous aerosols in Beijing-Tianjin-Hebei (BTH) region, China, fine particulate matter (PM2.5) samples were collected simultaneously in Tianjin and Handan in three consecutive winters from 2018 to 2020. Organic carbon (OC) and elemental carbon (EC) in PM2.5 were measured with the same thermal-optical methods and analysis protocols. Significant reductions in primary organic carbon (POC) and EC concentrations were observed both in Tianjin and Handan, with decreasing rates of 0.65 and 2.95 µg m-3 yr-1 for POC and 0.13 and 0.64 µg m-3 yr-1 for EC, respectively. The measured absorption coefficients of EC (babs, EC) also decreased year by year, with a decreasing rate of 1.82 and 6.16 Mm-1 yr-1 in Tianjin and Handan, respectively. The estimated secondary organic carbon (SOC) concentrations decreased first and then increased in both Tianjin and Handan, accounting for more than half of the total OC in winter of 2020-2021 and with increasing contributions especially in highly polluted days. SOC was recognized as one of key factors influencing EC light absorption. EC in the two cities was relatively more related to coal combustion and industrial sources. The reductions of primary carbonaceous components may be attributed to the air quality regulations targeting coal combustion and industrial sources emissions in BTH area. Potential source contribution function (PSCF) analysis results indicated that the major source areas of OC and EC in Tianjin were the southwest region of the sampling site, while the southeast areas for Handan. These findings demonstrated the effectiveness of air quality regulation in primary emissions in typical polluted cities in BTH region and highlighted the needs for further control and in-depth investigation of SOC formation along with implementation of air pollution control act in the future.

Colchicine delivered by a novel nanoparticle platform alleviates atherosclerosis by targeted inhibition of NF-κB/NLRP3 pathways in inflammatory endothelial cells.

Atherosclerosis, a chronic inflammatory disease characterized by arterial plaque formation, is one of the most prominent causes of cardiovascular diseases. However, the current treatments often do not adequately compromise the chronic inflammation-mediated plaque accumulation and the disease progression. Therefore, a new and effective strategy that blocks atherosclerosis-associated inflammation is urgently needed to further reduce the risk. Colchicine, a potent anti-inflammatory medication, has shown great potential in the treatment of atherosclerosis, but its adverse effects have hampered its clinical application. Herein, we developed a novel delivery nanosystem encapsulated with colchicine (VHPK-PLGA@COL), which exhibited improved biosafety and sustained drug release along with the gradual degradation of PLGA and PEG as confirmed both in vitro and in vivo. Surface modification of the nanoparticles with the VHPK peptide ensured its capability to specifically target inflammatory endothelial cells and alleviate atherosclerotic plaque accumulation. In the ApoE - / - atherosclerotic mouse model, both colchicine and VHPK-PLGA@COL treatment significantly decreased the plaque area and enhanced plaque stability by blocking the NF-κB/NLRP3 pathways, while VHPK-PLGA@COL exhibited enhanced therapeutic effects due to its unique ability to target inflammatory endothelial cells without obvious long-term safety concerns. In summary, VHPK-PLGA@COL has the potential to overcome the key translational barriers of colchicine and open new avenues to repurpose this drug for anti-atherosclerotic therapy.

Perfluoroalkyl substances (PFASs) as risk factors for breast cancer: a case-control study in Chinese population.

BACKGROUND: Perfluoroalkyl substances (PFASs) are a large family of synthetic chemicals, some of which are mammary toxicants and endocrine disruptors. Recent studies have implicated exposure to PFASs as a risk factor for breast cancer in Europe and America. Little is known about the role of PFASs with respect to breast cancer in the Chinese population. METHODS: Participants who were initially diagnosed with breast cancer at Tianjin Medical University Cancer Institute and Hospital between 2012 and 2016 were recruited as cases. The controls were randomly selected from the participants with available blood samples in the Chinese National Breast Cancer Screening Program (CNBCSP) cohort. Ultimately, we enrolled 373 breast cancer patients and 657 controls. Plasma PFASs were measured by an ultra-performance liquid chromatography (UPLC) system coupled to a 5500 Q-Trap triple quadrupole mass spectrometer. A logistic regression model with least absolute shrinkage and selection operator (LASSO) regularization was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the relationships between PFASs and breast cancer. The three most predictive variables in the LASSO model were selected from 17 PFASs, which was based on the optimal penalty coefficient (λ = 0.0218) identified with the minimum criterion. Additionally, Bayesian kernel machine regression (BKMR) and quantile g-computation models were applied to evaluate the associations between separate and mixed exposure to PFASs and breast cancer. RESULTS: Perfluorooctanesulfonic acid (PFOS) exhibited the highest concentration in both the cases and controls. Perfluorooctanoic acid (PFOA) and perfluoro-n-decanoic acid (PFDA) were positively associated with breast cancer, and perfluoro-n-tridecanoic acid (PFTrDA) was negatively associated with breast cancer according to both the continuous-PFASs and the quartile-PFASs logistic regression models. Of note, PFOA was associated with the occurrence of estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-positive breast cancer (ORER+ = 1.47, 95% CI: 1.19, 1.80; ORPR+ = 1.36, 95% CI: 1.09, 1.69; ORHER2 = 1.62, 95% CI: 1.19, 2.21). CONCLUSIONS: Overall, we observed that PFASs were associated with breast cancer in Chinese women. Prospective cohort studies and mechanistic experiments are warranted to elucidate whether these associations are causal.

Transgenerational male reproductive effect of prenatal arsenic exposure: abnormal spermatogenesis with Igf2/H19 epigenetic alteration in CD1 mouse.

Developmental exposure to environmental toxicants can induce transgenerational reproductive disease phenotypes through epigenetic mechanisms. We treated pregnant CD-1 (F0) mice with drinking water containing sodium arsenite (85 ppm) from days 8 to 18 of gestation. Male offspring were bred with untreated female mice until the F3 generation was produced. Our results revealed that F0 transient exposure to arsenic can cause decreased sperm quality and histological abnormalities in the F1 and F3. The overall methylation status of Igf2 DMR2 and H19 DMR was significantly lower in the arsenic-exposed group than that of the control group in both F1 and F3. The relative mRNA expression levels of Igf2 and H19 in arsenic-exposed males were significantly increased in both F1 and F3. This study indicates that ancestral exposure to arsenic may result in transgenerational inheritance of an impaired spermatogenesis phenotyping involving both epigenetic alterations and the abnormal expression of Igf2 and H19.

The Longitudinal Plasma Modes of κ-Deformed Kaniadakis Distributed Plasmas Carrying Orbital Angular Momentum.

Based on plasma kinetic theory, the dispersion and Landau damping of Langmuir and ion-acoustic waves carrying finite orbital angular momentum (OAM) were investigated in the κ-deformed Kaniadakis distributed plasma system. The results showed that the peculiarities of the investigated subjects relied on the deformation parameter κ and OAM parameter η. For both Langmuir and ion-acoustic waves, dispersion was enhanced with increased κ, while the Landau damping was suppressed. Conversely, both the dispersion and Landau damping were depressed by OAM. Moreover, the results coincided with the straight propagating plane waves in a Maxwellian plasma system when κ=0 and η→∞. It was expected that the present results would give more insight into the trapping and transportation of plasma particles and energy.

Ghrelin attenuate cerebral microvascular leakage by regulating inflammation and apoptosis potentially via a p38 MAPK-JNK dependent pathway.

Ghrelin is a peptide hormone with strong anti-inflammatory properties. In fact, Ghrelin was reported to improve endothelial dysfunction caused by excessive fat. However, its role in preserving the integrity of brain microvascular, under conditions of lipid dysregulation and inflammation, is not known. The objective of this study is to characterize the role of Ghrelin in the protection of cerebral microvascular integrity, during atherosclerosis, and uncover its underlying molecular mechanism. Our results demonstrated that an atherosclerotic condition, brought on by a high fat diet (HFD), can produce massive increases in serum inflammatory factors, blood lipids, cerebral microvascular leakage, and activation of the p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) (p38 MAPK-JNK) pathway. It also produced significantly damaged pericytes morphology, resulting in pericyte decrease. Ghrelin treatment, on the other hand, protected against cerebral microvascular leakage and pericytes damage. Ghrelin effectively downregulated the expression of pro-inflammatory cytokines, and it also suppressed the p38 MAPK-JNK signaling pathway. Additionally, in isolated mouse cerebral microvascular pericytes, ox-LDL lead to increased apoptosis and secretion of inflammatory factors, along with an elevation in phosphorylated p38 MAPK-JNK proteins. Alternately, Ghrelin administration markedly lowered expression of inflammatory factors, suppressed the p38 MAPK-JNK signaling path, and halted cell apoptosis. However, pretreatment of Hesperetin, a p38 MAPK-JNK agonist, abrogated the Ghrelin-mediated suppression of inflammation and apoptosis in pericytes. Taken together, these results suggest that Ghrelin restored cerebral microvascular integrity and reduced vascular leakage in atherosclerosis mice, in part, by its regulation of inflammatory and apoptotic signaling pathways in pericytes.

Prolyl isomerization of the CENP-A N-terminus regulates centromeric integrity in fission yeast.

Centromeric identity and chromosome segregation are determined by the precise centromeric targeting of CENP-A, the centromere-specific histone H3 variant. The significance of the amino-terminal domain (NTD) of CENP-A in this process remains unclear. Here, we assessed the functional significance of each residue within the NTD of CENP-A from Schizosaccharomyces pombe (SpCENP-A) and identified a proline-rich 'GRANT' (Genomic stability-Regulating site within CENP-A N-Terminus) motif that is important for CENP-A function. Through sequential mutagenesis, we show that GRANT proline residues are essential for coordinating SpCENP-A centromeric targeting. GRANT proline-15 (P15), in particular, undergoes cis-trans isomerization to regulate chromosome segregation fidelity, which appears to be carried out by two FK506-binding protein (FKBP) family prolyl cis-trans isomerases. Using proteomics analysis, we further identified the SpCENP-A-localizing chaperone Sim3 as a SpCENP-A NTD interacting protein that is dependent on GRANT proline residues. Ectopic expression of sim3+ complemented the chromosome segregation defect arising from the loss of these proline residues. Overall, cis-trans proline isomerization is a post-translational modification of the SpCENP-A NTD that confers precise propagation of centromeric integrity in fission yeast, presumably via targeting SpCENP-A to the centromere.

The microtubule-associated protein HURP recruits the centrosomal protein TACC3 to regulate K-fiber formation and support chromosome congression.

Kinetochore fibers (K-fibers) are microtubule bundles attached to chromosomes. Efficient K-fiber formation is required for chromosome congression, crucial for faithful chromosome segregation in cells. However, the mechanisms underlying K-fiber formation before chromosome biorientation remain unclear. Depletion of hepatoma up-regulated protein (HURP), a RanGTP-dependent microtubule-associated protein localized on K-fibers, has been shown to result in low-efficiency K-fiber formation. Therefore, here we sought to identify critical interaction partners of HURP that may modulate this function. Using co-immunoprecipitation and bimolecular fluorescence complementation assays, we determined that HURP interacts directly with the centrosomal protein transforming acidic coiled coil-containing protein 3 (TACC3), a centrosomal protein, both in vivo and in vitro through the HURP1-625 region. We found that HURP is important for TACC3 function during kinetochore microtubule assembly at the chromosome region in prometaphase. Moreover, HURP regulates stable lateral kinetochore attachment and chromosome congression in early mitosis by modulation of TACC3. These findings provide new insight into the coordinated regulation of K-fiber formation and chromosome congression in prometaphase by microtubule-associated proteins.

Urinary Metabolites of Polycyclic Aromatic Hydrocarbons and the Association with Lipid Peroxidation: A Biomarker-Based Study between Los Angeles and Beijing.

Air pollution is among the top threats to human health in China. As air toxicants, polycyclic aromatic hydrocarbons (PAHs) could bring significant risks to population; however, the exposure to PAHs in China and its health impact are not fully understood. In 2012, a summer exchange program allowed 10 students to travel from Los Angeles to Beijing and stay there for 10 weeks. Based on the program, this study investigated the difference in urinary concentration of 12 hydroxylated-PAHs (Σ12OH-PAHs) and malondialdehyde (MDA) between the two cities. The median concentration of Σ12OH-PAHs in Beijing (14.1 µg g(-1) creatinine) was significantly higher than that in Los Angeles (5.78 µg g(-1) creatinine), indicating a higher exposure in Beijing. The ratios of homogeneous OH-PAHs (e.g., 1-/2-OH-NAP) changed significantly between the two cities (p < 0.01), which might suggest a potential alteration in metabolism subsequent to exposure. A significant association between Σ12OH-PAHs and MDA (p < 0.01) was observed, with the association varying between the two cities. This study suggests that exposure to PAHs might be linked to metabolism alteration and calls for future studies to investigate the role this possible alteration played in the health effects of PAHs exposure.

Association of serum levels of typical organic pollutants with polycystic ovary syndrome (PCOS): a case-control study.

STUDY QUESTION: Is polycystic ovary syndrome (PCOS) associated with increased serum levels of typical organic pollutants? SUMMARY ANSWER: PCOS in Han females from Northern China was significantly associated with elevated serum levels of pollutants, including polychlorinated biphenyls (PCBs), organochlorine pesticides and polycyclic aromatic hydrocarbons (PAHs). WHAT IS KNOWN ALREADY: PCOS is arguably the most common endocrinopathy in females of reproductive age. The etiology of PCOS is thought to be multifactorial. STUDY DESIGN, SIZE, DURATION: This was a preliminary case-control study undertaken at the Division of Reproductive Center, Peking University Third Hospital. Fifty participants affected by PCOS and 30 normal controls were recruited between August and October 2012 from Northern China. All participants were Han women. PARTICIPANTS/MATERIALS, SETTING, METHODS: PCOS participants were diagnosed according to the 2003 Rotterdam criteria. The control participants were non-pregnant females unable to conceive solely due to male azoospermia. Serum levels of a wide range of organic pollutants, including PCBs, organochlorine pesticides, PAHs and more than 20 phenolic pollutants, were analyzed using gas chromatographic mass spectrometry. MAIN RESULTS AND THE ROLE OF CHANCE: Serum levels of PCBs, pesticides and PAHs were significantly higher in the PCOS group than the control group. Concentrations of PCBs, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) and PAHs in serum above median levels were associated with PCOS with odds ratios of 3.81 [95% confidence interval (CI), 1.45-10.0], 4.89 (95% CI, 1.81-13.2) and 2.39 (95% CI, 0.94-6.05), respectively. Partial least-squares-discriminant analysis (PLS-DA) confirmed that serum levels of organic pollutants were associated with PCOS, especially for p,p'-DDE and PCBs. LIMITATIONS, REASONS FOR CAUTION: Some other possible covariates (e.g. dietary and income) were missed in this study, although education and occupation have been considered as an indicator of personal income. The PLS-DA model allowed a quasi-exposome analysis with over 60 kinds of typical organic pollutants; however, the possibility of other pollutants involved in the PCOS still could not be excluded. WIDER IMPLICATIONS OF THE FINDINGS: Our study identified that bodily retention of environmental organic pollutants-including PCBs, pesticides (especially p,p'-DDE) and PAHs-was associated with PCOS. STUDY FUNDING/COMPETING INTERESTS: This research was supported by the Ministry of Science and Technology of China Grants (973 program; 2014CB943203 and 2015CB553401), National Natural Science Foundation of China (21322705, 21190051, 41121004 and 81170538), National Key Technology R&D Program in the Twelve Five-Year Plan (2012BAI32B01) and the Collaborative Innovation Center for Regional Environmental Quality. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: None. This is not a clinical trial.

Significant accumulation of persistent organic pollutants and dysregulation in multiple DNA damage repair pathways in the electronic-waste-exposed populations.

Electronic waste (e-waste) has created a worldwide environmental and health problem, by generating a diverse group of hazardous compounds such as persistent organic pollutants (POPs). Our previous studies demonstrated that populations from e-waste exposed region have a significantly higher level of chromosomal aberrancy and incidence of DNA damage. In this study, we further demonstrated that various POPs persisted at a significantly higher concentration in the exposed group than those in the unexposed group. The level of reactive oxygen species and micronucleus rate were also significantly elevated in the exposed group. RNA sequencing analysis revealed 31 genes in DNA damage responses and repair pathways that were differentially expressed between the two groups (Log2 ratio >1 or <-1). Our data demonstrated that both females and males of the exposed group have activated a series of DNA damage response genes; however many important DNA repair pathways have been dysregulated. Expressions of NEIL1/3 and RPA3, which are critical in initiating base pair and nucleotide excision repairs respectively, have been downregulated in both females and males of the exposed group. In contrast, expression of RNF8, an E3 ligase involved in an error prone non-homologous end joining repair for DNA double strand break, was upregulated in both genders of the exposed group. The other genes appeared to be differentially expressed only when the males or females of the two groups were compared respectively. Importantly, the expression of cell cycle regulatory gene CDC25A that has been implicated in multiple kinds of malignant transformation was significantly upregulated among the exposed males while downregulated among the exposed females. In conclusion, our studies have demonstrated significant correlations between e-waste disposing and POPs accumulation, DNA lesions and dysregulation of multiple DNA damage repair mechanisms in the residents of the e-waste exposed region.

Genotoxic effects and serum abnormalities in residents of regions proximal to e-waste disposal facilities in Jinghai, China.

Electronic waste (e-waste) disposal is a growing problem in China, and its effects on human health are a concern. To determine the concentrations of pollutants in peripheral blood and genetic aberrations near an e-waste disposal area in Jinghai, China, blood samples were collected from 30 (age: 41±11.01 years) and 28 (age: 33±2.14 years) individuals residing within 5 and 40km of e-waste disposal facilities in Jinghai (China), respectively, during the week of October 21-28, 2011. Levels of inorganic pollutants (calcium, copper, iron, lead, magnesium, selenium, and zinc) and malondialdehyde (MDA), identities of persistent organic pollutants (POPs), micronucleus rates, and lymphocyte subsets were analyzed in individuals. Total RNA expression profiles were analyzed by group and gender. The population group living in proximity to the e-waste site displayed significantly higher mean levels of copper, zinc, lead, MDAs, POPs (B4-6DE, B7-9DE, total polychlorinated biphenyls, and BB-153). In addition, micronucleus rates of close-proximity group were higher compared with the remote group (18.27% vs. 7.32%). RNA expression of genes involved in metal ion binding and transport, oxidation/reduction, immune defense, and tumorigenesis varied between groups, with men most detrimentally affected (p<0.05). CD4(+)/CD8(+)T cell ratios, CD4(+)CD25(nt/hi)CD127(lo)regulatory T cell percentages, and CD95 expression were greater in the e-waste group (p<0.05). Residing in close proximity to e-waste disposal facilities (≤5km) may be associated with the accumulation of potentially harmful inorganic/organic compounds and gender-preferential genetic aberrations.

Gridded field observations of polybrominated diphenyl ethers in soils of North China.

Polybrominated diphenyl ethers (PBDEs) were measured in 87 soil samples collected from North China. Eleven PBDE congeners (BDE28, 47, 49, 66, 99, 100, 119, 183, 196, 203, and 209) were identified with a high frequency of detection (84-100 %) in soil samples, and their frequencies were used for statistical analysis in the present study. PBDE concentrations ranged from 0.08 to 8260 ng/g with a mean of 202 ng/g, thus indicating severe pollution at these sample sites. BDE209 was the predominant congener with concentrations of 0.08-8140 ng/g (mean 188). Analysis of the spatial distribution of PBDEs in North China soils indicated that relatively high concentrations of both lower- and higher-brominated BDEs were present in Shandong Province, and a decreasing trend in PBDE concentrations from the east toward the west of North China was observed. Source identification analysis suggested that Jinghai County in Tianjin and the coastal area of Laizhou Bay, Shandong province, were the major sources in North China. The sources in Jinghai County were connected with the dismantling of electronic waste, whereas the sources in the coastal area of Laizhou Bay were connected with the production of PBDEs. Modeling results showed that the distance between the sampling sites and these point sources had a large influence on the transfer of PBDEs.

Polybromobenzene pollutants in the atmosphere of North China: levels, distribution, and sources.

Brominated flame retardants (BFRs) are important persistent organic pollutants. Analysis of BFRs in atmospheric samples in a previous study led us to suspect the presence of unidentified organic bromides, other than polybrominated diphenyl ethers (PBDEs), in the atmosphere. In this study, we identified and quantified polybromobenzenes, a group of organic bromides, in air samples collected through passive sampling in gridded observations in North China. We investigated their concentrations and spatial distribution, and estimated the proportion due to different sources. We detected seven species of polybromobenzenes, including hexabromobenzene (HBB), pentabromotoluene (PBT), pentabromoethylbenzene (PBEB), pentabromobenzene (PeBB), tetrabromobenzenes (TeBBs), and tribromotoluene (TrBT), in all or most of the field samples, indicating widespread occurrence of this class of pollutants. The median concentrations of each pollutant ranged from 20.0 to 144 pg/sample (or from 0.07 to 1.16 pg/m(3)), with relatively high concentrations found near e-waste recycling sites, BFR manufacturing sites, and areas of high population density. Positive matrix factorization (PMF) analysis revealed that ∼70% of HBB, PBT, PBEB, and PeBB was from commercial products, while ∼80% of 1,2,3,5-TeBB, 1,2,4,5-TeBB, and 2,4,5-TrBT was linked with BFR manufacturing. This study provides essential information on widespread polybromobenzene pollutants in the atmosphere, particularly TeBBs and TrBT, for which this is the first report of their presence as atmospheric pollutants.

Gridded field observations of polybrominated diphenyl ethers and decabromodiphenyl ethane in the atmosphere of north China.

Brominated flame retardants (BFRs) such as polybrominated diphenyl ethers (PBDEs) are important pollutants, yet few data on ambient BFRs levels have been available for North China, one of the most developed regions of the country. In this study, we investigated levels and spatial distributions of BFRs based on gridded field observations coupled with passive air sampling in the aforementioned region. A model incorporating both point and nonpoint sources was developed to simulate the spatial distribution and to achieve source apportionment. Although high concentration was observed at an electronic-waste (e-waste) recycling site, the median level of the sum of tri-, tetra-, hepta-, hexa-, and hepta-PBDEs (∑10PBDEs) was 0.56 ng/sample, which was lower than those observed previously in mainland China. Source apportionment revealed that nonpoint emissions contributed nearly 78% of ∑10PBDEs observed in this study. In contrast, high levels of BDE-209 and DBDPE were observed, with median concentrations of 4.0 and 10.2 ng/sample, respectively. Point sources located in the region around Laizhou Bay, Shandong Province were the major sources, which contributed 31% of BDE-209 and 70% of DBDPE observed in this study, indicating that this manufacturing base was the most important source region for atmospheric deca-BFRs in North China. To our knowledge, this is the first study to report source apportionment of atmospheric BFRs based on gridded field observations.

Reactive oxygen species alteration of immune cells in local residents at an electronic waste recycling site in northern China.

The health effects of exposure to pollutants from electronic waste (e-waste) pose an important issue. In this study, we explored the association between oxidative stress and blood levels of e-waste-related pollutants. Blood samples were collected from individuals living in the proximity of an e-waste recycling site located in northern China, and pollutants, as well as reactive oxygen species (ROS), were measured in comparison to a reference population. The geometric mean concentrations of PCBs, dechlorane plus, and 2,2',4,4',5,5'-hexabromobiphenyl in plasma from the exposure group were 60.4, 9.0, and 0.55 ng g(-1) lipid, respectively, which were 2.2, 3.2, and 2.2 times higher than the corresponding measurement in the reference group. Correspondingly, ROS levels in white blood cells, including in neutrophil granulocytes, from the exposure group were significantly higher than in those from the reference group, suggesting potential ROS related health effects for residents at the e-waste site. In contrast, fewer ROS were generated in the respiratory burst of neutrophil granulocytes for the exposure group, indicating a depressed innate immune function for the individuals living at the e-waste site. These findings suggest a potential linkage between exposure to pollutants from e-waste recycling and both elevated oxidative stress and altered immune function.

Efficacy of Continuous Renal Replacement Therapy and Intermittent Hemodialysis in Patients with Renal Failure in Intensive Care Unit: A Systemic Review and Meta-analysis.

Objective: This study aimed to compare the clinical efficacy of continuous renal replacement therapy (CRRT) and intermittent hemodialysis (IHD) in patients with renal failure in intensive care unit (ICU). Methods: Relevant studies were searched in the databases including EMBASE, Cochrane Library, and MEDLINE (PubMed) from inception to January 04, 2021. The inclusion of available studies and the collection of data were independently conducted by two authors after reviewing the full text. Pooled analyses of relative risk (RR) and weighted mean difference (WMD) were performed to compare the outcomes of renal recovery, short-term mortality, length of ICU stays, and length of in-hospital stays between the two different treatment groups. Publication bias was assessed by the funnel plot. Results: A total of 11 RCT studies including 1740 patients with renal failure were eligible for final analysis. Among them, 894 patients (51.4%) underwent CRRT and 846 patients (48.6%) received IHD. Pooled analysis did not find significant differences in renal recovery and short-term mortality between the two groups. Interestingly, patients underwent CRRT showed significantly shorter length of ICU stay and in-hospital stay than those who underwent IHD (ICU stay: RR: -0.61, 95%CI: -1.10--0.11, P < 0.05; I2 = 93.6%; in-hospital stay: RR: -0.56, 95%CI: -1.41-0.28, P < 0.05; I2 = 97.7%). No significant publication biases were observed on the funnel plots. Conclusion: Compared with IHD, CRRT had similar effects on renal recovery and short-term mortality in patients with renal failure in ICU. As a promising technique in clinical practice, CRRT could significantly reduce the length of ICU stay and in-hospital stay of patients, which was of great significance for the reduction of medical costs and the long-term benefits of patients, thereby reducing the burden on society and individuals.

The prolyl isomerase Pin1 stabilizes NeuroD during differentiation of mechanoreceptors.

The peptidyl prolyl cis-trans isomerase Pin1 plays vital roles in diverse cellular processes and pathological conditions. NeuroD is a differentiation and survival factor for a subset of neurons and pancreatic endocrine cells. Although multiple phosphorylation events are known to be crucial for NeuroD function, their mechanisms remain elusive. In this study, we demonstrate that zebrafish embryos deficient in Pin1 displayed phenotypes resembling those associated with NeuroD depletion, characterized by defects in formation of mechanosensory hair cells. Furthermore, zebrafish Pin1 interacts with NeuroD in a phosphorylation-dependent manner. In Pin1-deficient cell lines, NeuroD is rapidly degraded. However, the protein stability of NeuroD is restored upon overexpression of Pin1. These findings suggest that Pin1 functionally regulates NeuroD protein levels by post-phosphorylation cis-trans isomerization during neuronal specification.