Placental inflammatory injury induced by chlorinated polyfluorinated ether sulfonate (F-53B) through NLRP3 inflammasome activation.

Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5-14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1ß, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B.

Associations of prenatal exposure to perfluoroalkyl substances with preterm birth: A family-based birth cohort study.

Studies have investigated associations between maternal exposure to PFAS and preterm birth, but the impact of paternal and overall family exposure to PFAS mixtures on preterm birth remains unknown. To address this knowledge gap, a total of 355 preterm births and 481 controls were selected for a family-based birth cohort study in a coastal area of China, between 2016 and 2018. Seven PFAS, including perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA), were quantified in maternal, paternal and neonatal sera. Preterm birth was defined as live delivery at <37 completed gestational weeks. Bayesian kernel machine regression (BKMR) model was used to inspect the combined effect of family PFAS mixtures. Latent class analysis was used to identify family-level PFAS exposure profiles. Multiple linear regression analysis showed higher odds of preterm birth in association with higher maternal PFBA (OR = 1.16, 95%CI:1.09, 1.25), PFOA (OR = 1.51, 95%CI:1.27, 1.80), PFOS (OR = 2.07, 95%CI:1.70, 2.52) and PFNA (OR = 1.36, 95%CI: 1.01, 1.83), and neonatal PFBA (OR = 1.16, 95%CI:1.05,1.29), PFHxA (OR = 1.46, 95%CI:1.32, 1.62), PFHxS (OR = 1.15, 95%CI:1.05, 1.26) and PFNA (OR = 1.30, 95%CI:1.09,1.56). The associations were reversed between individual paternal PFAS exposures and preterm birth. At the family level, higher PFAS mixture concentration was associated with higher odds of preterm birth. In particular, higher PFNA and PFDA exposure was associated with greater preterm birth risk (OR = 2.55, 95%CI:1.45, 4.50). The PFAS-preterm association was modified by family-level seafood consumption. Our results suggest that higher family-level PFNA and PFDA exposure was associated with greater preterm birth risk, although the results for individual paternal, maternal and neonatal PFAS exposures were contradictory. If replicated in other coastal areas, these findings highlight a need to focus on the family triad and to consider seafood consumption when assessing the reproductive toxicity of PFAS exposure.

Temperature effect on vibrational properties of crystalline Dibenz[a,h]anthracene.

Vibrational properties associated with the intra- and intermolecular bonding of the crystalline Dibenz[a,h]anthracene at low temperatures are investigated by Raman scattering. A complete characterization of phonon spectra is given for this material. In the 120-150 K temperature region, several lattice modes show abrupt changes of splitting and the discontinuities in the temperature shift, but no emergence of new modes. Moreover, the intensity ratio of I68/38 is greater than 1 below 130 K. Meanwhile, the aromatic C-C stretching modes exhibit anomalous behaviors in frequencies, widths, and intensities at about 130 K. These spectroscopic results demonstrate a disorder-order transition occurred at about 130 K. However, the modes, corresponding to C-H out-of-plane bending, C-H in-plane bending, and/or C-H rocking, have no significant change in the whole temperature range. It indicates that the transition mainly results from the change of the tilt angle between the molecules. Our work is of great significance to understand the internal vibrational properties of Dibenz[a,h]anthracene, and it also provides considerable supports for the further study of this material.

Per- and perfluoroalkyl substances alternatives, mixtures and liver function in adults: A community-based population study in China.

Experimental evidence has shown that per- and polyfluoroalkyl substances (PFAS) alternatives and mixtures may exert hepatotoxic effects in animals. However, epidemiological evidence is limited. This research aimed to explore associations of PFAS and the alternatives with liver function in a general adult population. The study participants consisted of 1,303 adults from a community-based cross-sectional investigation in Guangzhou, China, from November 2018 to August 2019. We selected 13 PFAS with detection rates > 85% in serum samples and focused on perfluorooctane-sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and their alternatives [6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 Cl-PFESA, and perfluorohexanoic acid (PFHxA)] as predictors of outcome. Six liver function biomarkers (ALB, ALT, AST, GGT, ALP, and DBIL) were chosen as outcomes. We applied regression models with restricted cubic spline function to explore correlations between single PFAS and liver function and inspected the combined effect of PFAS mixtures on liver by applying Bayesian kernel machine regression (BKMR). We discovered positive associations among PFAS and liver function biomarkers except for ALP. For example, compared with the 25th percentile of PFAS concentration, the level of ALT increased by 12.36% (95% CI: 7.91%, 16.98%) for ln-6:2 Cl-PFESA, 5.59% (95% CI: 2.35%, 8.92%) for ln-8:2 Cl-PFESA, 3.56% (95% CI: -0.39%, 7.68%) for ln-PFHxA, 13.91% (95% CI: 8.93%, 19.13%) for ln-PFOA, and 14.25% (95% CI: 9.91%, 18.77%) for ln-PFOS at their 75th percentile. In addition, higher exposed serum PFAS was found to be correlated with greater odds of abnormal liver function. Analysis from BKMR models also showed an adverse association between PFAS mixtures and liver function. The combined effect of the PFAS mixture appeared to be non-interactive, in which PFOS was the main contributor to the overall effect. Our findings provide evidence of associations between PFAS alternatives, PFAS mixtures, and liver function in the general adult population.

Clcn3 deficiency ameliorates high-fat diet-induced obesity and adipose tissue macrophage inflammation in mice.

Obesity induces accumulation of adipose tissue macrophages (ATMs) and ATM-driven inflammatory responses that promote the development of glucose and lipid metabolism disorders. ClC-3 chloride channel/antiporter, encoded by the Clcn3, is critical for some basic cellular functions. Our previous work has shown significant alleviation of type 2 diabetes in Clcn3 knockout (Clcn3-/-) mice. In the present study we investigated the role of Clcn3 in high-fat diet (HFD)-induced obesity and ATM inflammation. To establish the mouse obesity model, both Clcn3-/- mice and wild-type mice were fed a HFD for 4 or 16 weeks. The metabolic parameters were assessed and the abdominal total adipose tissue was scanned using computed tomography. Their epididymal fat pad tissue and adipose tissue stromal vascular fraction (SVF) cells were isolated for analyses. We found that the HFD-fed Clcn3-/- mice displayed a significant decrease in obesity-induced body weight gain and abdominal visceral fat accumulation as well as an improvement of glucose and lipid metabolism as compared with HFD-fed wild-type mice. Furthermore, the Clcn3 deficiency significantly attenuated HFD-induced ATM accumulation, HFD-increased F4/80+ CD11c+ CD206- SVF cells as well as HFD-activated TLR-4/NF-κB signaling in epididymal fat tissue. In cultured human THP-1 macrophages, adenovirus-mediated transfer of Clcn3 specific shRNA inhibited, whereas adenovirus-mediated cDNA overexpression of Clcn3 enhanced lipopolysaccharide-induced activation of NF-κB and TLR-4. These results demonstrate a novel role for Clcn3 in HFD-induced obesity and ATM inflammation.

Detoxification of aflatoxins on prospective approach: effect on structural, mechanical, and optical properties under pressures.

Aflatoxins are sequential of derivatives of coumarin and dihydrofuran with similar chemical structures and well-known carcinogenic agent. Many studies performed to detoxify aflatoxins, but the result is not ideal. Therefore, we studied structural, infrared spectrum, mechanical, and optical properties of these compounds in the aim of perspective physics. Mulliken charge distributions and infrared spectral analysis performed to understand the structural difference between the basic types of aflatoxins. In addition, the effect of pressure, different polarized, and incident directions on their structural changes was determined. It is found that AFB1 is most stable structure among four basic types aflatoxins (AFB1, AFB2, AFG1, and AFG2), and IR spectra are analyzed to exhibit the difference on structures of them. The mechanical properties of AFB1 indicate that the structure of this toxin can be easily changed by pressure. The real [Formula: see text] and imaginary [Formula: see text] parts of the dielectric function, and the absorption coefficient [Formula: see text] and energy loss spectrum [Formula: see text] were also obtained under different polarized and incident directions. Furthermore, biological experiments needed to support the toxic level of AFB1 using optical technologies.

LNK deficiency aggravates palmitate-induced preadipocyte apoptosis.

LNK (SH2B3) is an intracellular adaptor protein that negatively regulates cellular proliferation or self-renewal of hematopoietic stem cells and some other progenitor cells. LNK is also recognized as a key regulator of insulin resistance and inflammatory responses in several tissues and organs. The function of LNK in adipose tissue is unknown. We previously demonstrated that type 2 diabetes mellitus (T2DM) mouse model had elevated serum free fatty acids (FFAs) levels and increased preadipocyte apoptosis in visceral fat tissue, showing the occurrence of lipotoxicity. Herein, when compared to control mice, the protein expression of LNK decreased in epididymal fat tissue from the high-sucrose/fat diet, low-dose streptozotocin induced T2DM mouse model. We thus investigated whether LNK could regulate palmitate-induced preadipocyte apoptosis in an in vitro apoptotic model in 3T3-L1 preadipocytes. LNK specific siRNA exacerbated palmitate-induced apoptosis and increased pro-apoptotic protein levels of cleaved caspase-3, Bax and cytochrome C; while overexpression of LNK cDNA exhibited significant anti-apoptotic effects. Consistently, LNK specific siRNA further decreased the Akt Ser-473 phosphorylation reduced by palmitate and located on upstream of Bax and cytochrome C. The siRNA-mediated LNK knockdown exacerbated mitochondrial membrane depolarization and mitochondrial-derived reactive oxygen species production induced by palmitate, whereas overexpression of LNK attenuated that. These results indicated that LNK plays a regulatory role in the palmitate-related preadipocyte apoptosis and might be involved in adipose tissue dysfunction.

Combined experimental and computational study of high-pressure behavior of triphenylene.

We have performed measurements of Raman scattering, synchrotron x-ray diffraction, and visible transmission spectroscopy combined with density functional theory calculations to study the pressure effect on solid triphenylene. The spectroscopic results demonstrate substantial change of the molecular configuration at 1.4 GPa from the abrupt change of splitting, disappearance, and appearance of some modes. The structure of triphenylene is found be to stable at high pressures without any evidence of structural transition from the x-ray diffraction patterns. The obtained lattice parameters show a good agreement between experiments and calculations. The obtained band gap systematically decreases with increasing pressure. With the application of pressure, the molecular planes become more and more parallel relative to each other. The theoretical calculations indicate that this organic compound becomes metallic at 180 GPa, fueling the hope for the possible realization of superconductivity at high pressure.

Comparison of the antiviral effects of different nucleos(t)ide analogues in chinese patients with chronic hepatitis B: a head-to-head study.

BACKGROUND/AIMS: To assess the antiviral efficacy of lamivudine (LAM), entecavir (ETV), telbivudine (LDT), and lamivudine and adefovir dipivoxil (CLA) combination in previously untreated hepatitis B patients at different time points during a 52-week treatment period. PATIENTS AND METHODS: A total of 164 patients were included in this prospective, open-label, head-to-head study. Serum levels of alanine transaminase (ALT), hepatitis B virus (HBV) DNA, and hepatitis B e antigen (HBeAg) were measured at baseline, and at 12, 24, and 52 weeks of treatment. RESULTS: Median reductions in serum HBV DNA levels at 52 weeks (log 10 copies/mL) were as follows: LAM, 3.98; ETV, 3.89; LDT, 4.11; and CLA, 3.36. The corresponding HBV DNA undetectability rates were 83%, 96%, 91%, and 89%, respectively. These two measures showed no significant intergroup differences. Clinical efficacy appeared related to HBV DNA level reduction after 24 weeks of therapy. Patients were divided into three groups based on HBV DNA levels at week 24: Undetectable (<10(3) copies/mL), detectable but <10(4) copies/mL, and >10(4) copies/mL. Patients with levels below quantitation limit (QL) were analyzed at 52 weeks for HBV DNA undetectability rate (94%), ALT normalization rate (83%), and viral breakthrough rate (0%). The corresponding values in the QL-10(4) copies/mL group were 50%, 75%, and 13%, whereas those in the above 10(4) copies/mL group were 53%, 65%, and 18%. There were significant differences at week 52 for HBV DNA levels and viral breakthrough rate between the three groups. CONCLUSIONS: Different nucleos(t)ide (NUC) analogues tested exhibited no significant differences in effectiveness for Chinese NUC-naive HBV patients during 1-year treatment period.

Pressure-induced metallization of molybdenum disulfide.

X-ray diffraction, Raman spectroscopy, and electrical conductivity measurements of molybdenum disulfide MoS(2) are performed at pressures up to 81 GPa in diamond anvil cells. Above 20 GPa, we find discontinuous changes in Raman spectra and x-ray diffraction patterns which provide evidence for isostructural phase transition from 2H(c) to 2H(a) modification through layer sliding previously predicted theoretically. This first-order transition, which is completed around 40 GPa, is characterized by a collapse in the c-lattice parameter and volume and also by changes in interlayer bonding. After the phase transition completion, MoS(2) becomes metallic. The reversibility of the phase transition is identified from all these techniques.

High-pressure study of isoviolanthrone by Raman spectroscopy.

Vibrational properties of isoviolanthrone are investigated by Raman scattering at pressures up to 30.5 GPa and room temperature. A complete characterization of phonon spectra under pressure is given for this material. The onset of a phase transition at 11.0 GPa and the formation of a new phase above 13.8 GPa are identified from both the frequency shifts and the changes in the full width half maxima of the intra- and internal modes. The transition is proposed to result from the changes of intra- and intermolecular bonding. The tendencies of the intensity ratios with pressure are in good agreement with the pressure dependence of the resistance at room temperature, indicating that the phase transition may be an electronic origin. The absence of the changes in the lattice modes indicates that the observed phase transition is probably a result of the structural distortions or reorganizations. The reversible character of the transition upon compression and decompression is determined in the entire pressure region studied.

Constraint on the potassium content for the superconductivity of potassium-intercalated phenanthrene.

Raman-scattering measurements were performed on K(x)phenanthrene (0 ⩽ x ⩽ 6.0) at room temperature. Three phases (x = 3.0, 3.5, and 4.0) are identified based on the obtained Raman spectra. Only the K3phenanthrene phase is found to exhibit the superconducting transition at 5 K. The C-C stretching modes are observed to broaden and become disordered in K(x)phenanthrene with x = 2.0, 2.5, 6.0, indicating some molecular disorder in the metal intercalation process. This disorder is expected to influence the nonmetallic nature of these materials. The absence of metallic character in these nonsuperconducting phases is found from the calculated electronic structures based on the local density approximation.

Relationship between interleukin-6 polymorphism and susceptibility to chronic hepatitis B virus infection.

AIM: To identify the relationship between tag single nucleotide polymorphisms (tag SNPs) of interleukin-6 (IL-6) gene and susceptibility to chronic hepatitis B virus (HBV) infection in a Han Chinese population. METHODS: We performed a case-control study of 501 Chinese patients with chronic HBV infection and 301 self-limiting HBV-infected individuals as controls. Genomic DNA was isolated from the whole blood of all subjects using phenol/chloroform with MaXtract high-density tubes. Tag SNPs were identified using genotype data from the panel (Han Chinese in Beijing) of the phase II HapMap Project. Four tag SNPs in IL-6 (rs17147230A/T, rs2066992G/T, rs2069837A/G and rs2069852A/G) were genotyped by the Multiplex Snapshot technique. The genotype and allele frequencies were calculated and analyzed. RESULTS: Five haplotypes were involved in the analysis, with frequencies higher than 0.03. One of the haplotypes, TTAA, was significantly different between the two groups. Overall haplotype P values were: ATAA, P = 0.605, OR (95%CI) = 1.056 (0.860-1.297); TGAG, P = 0.385, OR (95%CI) = 1.179 (0.813-1.709); TGGG, P = 0.549, OR (95%CI) = 1.087 (0.827-1.429); TTAA, P = 0.004, OR (95%CI) = 0.655 (0.491-0.873); TTAG, P = 0.266, OR (95%CI) = 1.272 (0.832-1.944). However, the four SNPs showed no significant genotype/allele associations with susceptibility to chronic HBV infection. Overall allele P values were: rs17147230, P = 0.696, OR (95%CI) = 1.041 (0.850-1.276); rs2066992, P = 0.460, OR (95%CI) = 1.090 (0.868-1.369); rs2069837, P = 0.898, OR (95%CI) = 0.983 (0.759-1.274); rs2069852, P = 0.165, OR (95%CI) = 0.859 (0.693-1.064). Overall genotype P values were: rs17147230, P = 0.625; rs2066992, P = 0.500; rs2069837, P = 0.853; and rs2069852, P = 0.380. CONCLUSION: The four tag SNPs of IL-6 gene may be associated with susceptibility to chronic HBV infection in the Han Chinese population.

Phase transformations and vibrational properties of coronene under pressure.

Both the vibrational and structural properties of coronene have been investigated upon compression up to 30.5 GPa at room temperature by a combination of Raman scattering and synchrotron x-ray diffraction measurements. The spectroscopic and crystallographic results demonstrate that two pressure-induced structural phase transitions take place at 1.5 GPa and 12.2 GPa where the high-pressure phases are identified as monoclinic and orthorhombic crystal structures with space groups of P2/m and Pmmm, respectively. A kink in the slope of the cell parameters as a function of pressure is associated with the disappearance of several internal Raman modes, which suggests the existence of structural distortions or reorganizations at approximately 6.0 GPa. Above 17.1 GPa, almost no evidence of crystallinity can be observed, indicating a possible transformation of coronene into an amorphous phase.

[Study on the facial and body terminal hair growth in women in Guangdong by using modified Ferriman-Gallwey scoring system].

OBJECTIVE: To study growth of facial and body terminal hair of women in Guangdong province and its relationship with age, menstrual irregularities and polycystic ovary, and determine normative cut-off score of modified Ferriman and Gallwey (mFG). METHODS: A cross-sectional study was conducted on 2988 women at age of 20-45 years from 16 communities of two urban and two rural regions in Guangdong province from June 2008 to July 2009. Terminal body hair growth was assessed by using the modified Ferriman and Gallwey (mFG) scoring system. The normative cut-off value of mFG were calculated by using the K-means cluster analysis (K=2). Those women were classified into following groups, including 982 women at group of ages of 20- years, 765 women at group of 26- years, 597 women at group of 31- years, 384 women at group of 36- years, 260 women at group of 41-45 years. Due to absence or errors of medical records, some cases were excluded from this study. Based on menses irregularities (MI), polycystic ovaries (PCO), there were 488 cases in MI group, 2413 cases in normal menses group, 568 cases in PCO group, and 2207 cases in non-PCO group finally. The incidences of acne, MI, acanthosis nigricans, and polycystic ovaries were also analyzed in all the hirsute groups. RESULTS: (1) among 2988 women, it was observed 149 women (5%) with mFG≥7,314 women (10.5%) with ≥5,747 women with mFG≥2. (2) Cluster analysis identified an mFG score of 5 as the cut-off value that define abnormal hirsute in the total population and all the sub-groups with/without MI or PCO; (3) Based on age classification, it was found that increased age was associated with decreased trends of the percentile and cut-off value of hirsutism. The value of hirsutism of mFG were 6 in group of 20- years, 5 in group of 26- years, 4 in groups of 31- years, 36- years and 41-45 years. (4) The prevalence of acne, menstrual irregularities and POC were 45.5% (143/314), 73.6% (231/314), 25.8% (81/314) in total population, 25.1% (671/2674), 16.1% (431/2674), 19.8% (529/2674) in normal hair women, which reached statistical difference (P<0.05). The prevalence of acne, menstrual irregularities and acanthosis nigricans were 44.4% (130/293), 23.2% (68/293), 4.1% (12/293) in those age hirsute groups, 25.3% (681/2695), 16.2% (437/2695), 1.9% (51/2695) in normal hair women, which reached statistical difference (P<0.05). CONCLUSIONS: (1) among women in Guangdong province, mFG scoring showed decreased trends in women with increasing age. (2) An mFG score≥5 was cut-off value in diagnosis of hirsutism. (3) The hirsute women exhibited higher incidence of acne, menses irregularity, and acanthosis nigricans than those of women with normal hair growth.

Structural and vibrational properties of phenanthrene under pressure.

The structural and vibrational properties of phenanthrene are measured at high pressures up to 30.2 GPa by Raman spectroscopy and synchrotron X-ray diffraction techniques. Two phase transitions are observed in the Raman spectra at pressures of 2.3 GPa and 5.4 GPa which correspond to significant changes of intermolecular and intramolecular vibrational modes. Above 10.2 GPa, all the Raman peaks are lost within the fluorescence background; however, upon further compression above 20.0 GPa, three broad peaks are observed at 1600, 2993, and 3181 cm(-1), indicating that phenanthrene has transformed into amorphous phase. Using X-ray diffraction, the structures of corresponding phases observed from Raman spectra are indexed with space groups of P2(1) for phase I (0-2.2 GPa), P2/m for phase II (2.2-5.6 GPa), P2/m+Pmmm for phase III (5.6-11.4 GPa) which has a coexistence of structures, and above 11.4 GPa the structure is indexed with space group of Pmmm. Although phenanthrene has transformed to a hydrogenated amorphous carbon structure above 20.0 GPa, these amorphous clusters still show characteristic crystalline behavior based on our X-ray diffraction patterns. Our results suggest that the long-range periodicity and the local disorder state coexist in phenanthrene at high pressures.

[Polymorphism of catechol-O-methyltransferase gene in relation to the risk of endometrial cancer].

OBJECTIVE: The 4- and 16-hydroxylated metabolites of estrogens have been implicated in carcinogenesis, whereas its 2-hydroxylated metabolites have been shown to have antiangiogenic effects. We aimed to examine whether the polymorphisms of catechol-O-methyltransferase (COMT) involved in the estrogen metabolism are associated with endometrial cancer risk. METHODS: Polymerase chain reaction-restrictive fragment length polymorphism (PCR-RFLP) analysis was used to study the variant allele frequency distributions of COMT Val158Met genetic polymorphism in a population based case-control study with 132 endometrial cancer cases and 110 controls. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by unconditional logistic regression after adjustment for known or suspected risk factors for endometrial cancer. RESULTS: The most frequent genotype was COMT(Val/Val) (47.2%, 52/110) in control group and COMT(Val/Met) (58.3%, 77/132) in endometrial cancer group. The difference between the two groups was of statistical significance (P < 0.05). Compared with COMT(Met/Met) genotype, the COMT(Val/Val) genotype was inversely correlated with endometrial cancer risk, and the adjusted OR value was 0.262 (95% CI: 0.080 - 0.862, P = 0.027). CONCLUSIONS: Among the genotypes in women in South China, genotype COMT(Val/Val) is mostly seen, followed by COMT(Val/Met), and COMT(Met/Met) is the least in control group. The endometrial cancer susceptivity of genotype COMT(Val/Val) carriers may be lower than COMT(Met/Met) carriers.