Improvement and exacerbation of multiple disparities in sexually transmitted infections among children and adolescents aged 6-22 years: An analysis of national surveillance data from 2013 to 2021.

To investigate the progress of disparities in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), gonorrhea, and syphilis among children and adolescents aged 6-22 years in China during 2013-2021. A total of 614 325 cases data were extracted from the Chinese Information System for Infectious Diseases Control and Prevention during 2013-2021. Puberty health education data were drew from the Student Health Surveillance in 2021. Disparity patterns and average annual percentage changes (AAPCs) in sexually transmitted infections (STIs) incidence or new cases in China were examined using descriptive statistics and joinpoint regression. The incidence across 345 cities was stratified by gross domestic product (GDP). Between 2013 and 2021, there were 614 325 reported cases of HIV/AIDS, gonorrhea, and syphilis among children and adolescents aged 6-22, with an annual average incidence of 24.0967 per 100 000. The expansion of HIV/AIDS has halted, yet the surge in gonorrhea and syphilis remains notably pronounced. The ratio of male to female AIDS incidence increased from 2.75 (2.60, 2.90) to 7.13 (6.68, 7.62), but that of syphilis changed from 0.33 (0.32, 0.34) to 0.56 (0.55, 0.57). Students and out-of-school individuals aged 13-15 experienced a notably high increase in STI cases, surpassing other age groups, with an average annual percentage increase of 29.2% and 26.3%, respectively. Nonstudents consistently had a higher incidence rate than students, with an IRR reaching 31.80 (31.24, 32.37) in 2021. A noticeable clustering pattern of new cases emerged in the southeastern region of the Heihe-Tengchong line, extending inland from the coastal areas. Districts and counties with lower rates of puberty sexual health education tended to have higher average STI incidence rates. At the prefecture and city levels, there was a noticeable upward trend on average STI incidence rates in cities with per capita GDPs. Strategies to address those disparities include promoting equitable health education, and widespread sexual health education, particularly in areas with limited access to education and experiencing rapid economic development. The effectiveness of sexual health education intervention needs to be further evaluated in well-designed studies.

Photochemical mechanistic study of hexafluorobenzene involving the low-lying states.

The photochemical isomerization and nonradiative decay processes of hexafluorobenzene (HFB) were investigated theoretically to gain insights into its photochemical mechanism and the perfluoro effect. A complete mechanistic scheme is presented through the characterization of all the possible minima and transition states of the S0, S1, and S2 states at the CASPT2/6-311G**//CAS(6,7)/6-31G* level. On the S0 potential energy surface, HFB could isomerize to three different products [Dewar-HFB (S0-P1), benzvalene-HFB (S0-P2), and fulvene-HFB (S0-P3)]. Following excitation to the S2 state with the perpendicular π → σ* transition, a chair-type minimum with Cs symmetry was found on the S2 potential energy surface. The adjacent S2/S1 conical intersection was immediately accessible from the S2 minimum. The nature of the S1 state was confirmed to have a π → π* character. Both the S2 and S1 photochemistries of HFB yielded Dewar-HFB via the S1/S0 conical intersection. The regeneration of the S0 state from the S1 and T2 states via intersystem crossing or internal conversion was also revealed.

Geneenvironment interaction between phthalate exposure and pubertal genetic polymorphisms on blood pressure variability in children: Exploring the moderating effects of lifestyle behaviours.

Phthalates (PAEs) are synthetic compounds extensively employed in consumer products. Blood pressure (BP) in children can vary, the degree of visit-to-visit BP variability (VVV) is at least partially independent of BP. The interactions between PAEs exposure, pubertal-related genetic susceptibility and lifestyles on childhood VVV are not investigated. This study utilized data from a cohort collected from Oct 2017-2020 in Xiamen, China. Seven urine PAE metabolites were measured. The long-term VVV was characterized employing the standard deviation (SD) and average real variability. We constructed a genetic risk score (GRS) of pubertal-related genes and healthy lifestyle scores. Exposed to high levels of mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) (OR=1.43, 95 %CI=1.07, 1.92) and mono-2-ethyl-5-oxohexyl phthalate (OR=1.36, 95 % CI=1.01, 1.83) was related to increased SBP-SD, and the OR for high SBP-SD related to high GRS was 1.38 (95 % CI=1.02, 1.85). Compared to participants who had low GRS and low MEHHP exposure, participants exhibiting high GRS and MEHHP levels were more likely to experience high SBP-SD (OR=2.00, P<0.05). Individuals exhibiting low GRS, low MEHHP levels, and adhering to healthy lifestyles were associated with the least probability of experiencing high SBP-SD (OR=0.31, P<0.05). Increased PAEs exposure could elevate childhood systolic VVV, and exacerbated the adverse impact of pubertal-related genetic susceptibility on the high VVV of SBP; however, healthy lifestyles might alleviate these adverse effects. Promoting healthy lifestyles and reducing PAEs exposure for preventing elevated BP variability among children is important, especially for individuals with greater genetic susceptibility to early pubertal onset. ENVIRONMENTAL IMPLICATION: Blood pressure (BP) in children can vary, as a noninvasive, inexpensive and applicable method, the extent of visit-to-visit variability (VVV) is at least partially independent of BP. The interactions between phthalates (PAEs) exposure, variants of puberty-related genes and lifestyles on VVV are not investigated. Increased childhood systolic VVV might be associated with PAEs exposure, with the associations more pronounced combined with pubertal genetic susceptibility. Yet, healthy habits could partly eliminate such adverse effects. Our study underscores the importance of advocating for healthy lifestyles and reducing exposure to PAEs, especially among individuals with high genetic susceptibility to early puberty onset.

Variations on the Bergman Cyclization Theme: Electrocyclizations of Ionic Penta-, Hepta-, and Octadiynes.

The Bergman cyclization of (Z)-hexa-3-ene-1,5-diyne to form the aromatic diradical p-benzyne has garnered attention as a potential antitumor agent due to its relatively low cyclization barrier and the stability of the resulting diradical. Here, we present a theoretical investigation of several ionic extensions of the fundamental Bergman cyclization: electrocyclizations of the penta-1,4-diyne anion, hepta-1,6-diyne cation, and octa-1,7-diyne dication, leveraging the spin-flip formulation of the equation-of-motion coupled cluster theory with single and double substitutions (EOM-SF-CCSD). Though the penta-1,4-diyne anion exhibits a large cyclization barrier of +66 kcal mol-1, cyclization of both the hepta-1,6-diyne cation and octa-1,7-diyne dication along a previously unreported triplet pathway requires relatively low energy. We also identified the presence of significant aromaticity in the triplet diradical products of these two cationic cyclizations.

Astragaloside IV suppresses the migration and EMT progression of cervical cancer cells by inhibiting macrophage M2 polarization through TGFß/Smad2/3 signaling.

Cervical cancer (CC) is a gynecological malignant tumor worldwide. Astragaloside IV (AS-IV) has been found to exert antitumor effects on CC. In addition, M2-polarized macrophages, known as tumor-associated macrophages (TAMs), play an important role in promoting cancer cell growth and angiogenesis. Thus, we explored the association between the antitumor effect of AS-IV and macrophage polarization in CC. Flow cytometry, ELISA, and RT‒qPCR assays were applied to detect the levels of CD163, IL-10, TGFß, and CD206 in M2 macrophages with or without AS-IV treatment. In addition, conditioned medium (CM) was collected from these M2 macrophages, and CC cells were then cultured in various CMs. Wound healing and transwell assays were used to assess the migratory ability of CC cells. In this study, we found that AS-IV significantly inhibited M2 polarization of macrophages, as shown by decreased CD163, IL-10, TGFß, and CD206 expression. In addition, compared with CM from M2 macrophages, CM from AS-IV-treated M2 macrophages notably inhibited angiogenesis, migration, and epithelial-mesenchymal transition (EMT) in CC cells. Furthermore, compared with CM from M2 macrophages, CM from AS-IV-treated M2 macrophages markedly reduced p-Smad2 and p-Smad3 protein expression in CC cells, and these changes were reversed by TGF-ß treatment. Collectively, suppression of M2-like polarization of macrophages by AS-IV could prevent the migration and EMT of CC cells by inactivating TGF-ß/Smad2/3 signaling. These findings might provide some theoretical support for exploring novel treatments for CC.

Association of phthalate exposure with pulmonary function in adults: NHANES 2007-2012.

BACKGROUND: Epidemiological evidence for the adverse effect of phthalate exposure on respiratory health is on the rise, but cross-sectional studies regarding its effects on lung function are limited and contradictory, especially in adults. OBJECTIVE: To assess the associations between individual and a mixture of urinary phthalate metabolites and adult pulmonary function in the United States, and to identify which ones were primarily responsible for impaired respiratory function. METHODS: We obtained a cross-sectional data on 3788 adults aged 20 years and older from the National Health and Nutrition Examination Survey (2007-2012). Respiratory function was evaluated using spirometry, and phthalate exposure was assessed by measuring the levels of ten urinary phthalate metabolites. The effects of individual and mixed phthalate metabolites exposure on lung function were assessed using multivariate linear regression models and the repeated holdout weighted quantile sum (WQS) regression models, respectively, after adjusting for potential confounders including age, gender, family poverty income ratio, body mass index, and serum cotinine. RESULTS: When modeled as continuous variables or quantiles, urinary phthalate metabolites, including mono-ethyl phthalate (MEP), mono-n-butyl phthalate, mono-iso-butyl phthalate, mono-benzyl phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-(3-carboxypropyl) phthalate, and mono-carboxyoctyl phthalate, were identified to be negatively associated with forced vital capacity in percent predicted values (ppFVC) and forced expiratory volume in the first second in percent predicted values (ppFEV1). In addition, per each decile increase in the WQS index, ppFVC (ß = -2.87, 95% CI: -3.56, -2.08) and ppFEV1 (ß = -2.53, 95% CI: -3.47, -1.54) declined significantly, primarily due to the contribution of MEP and MECPP. Furthermore, there were no significant interactions between co-exposure to urinary phthalate metabolites and each covariate. CONCLUSION: Our findings reveal that urinary phthalate metabolites are significantly associated with adult respiratory decrements, with diethyl and di-(2-ethylhexyl) phthalate contributing the most to the impaired lung function.

Rydberg state dynamics and fragmentation mechanism of N,N,N',N'-tetramethylmethylenediamine.

The non-adiabatic relaxation processes and the fragmentation dynamics of Rydberg-excited N,N,N',N'-tetramethylmethylenediamine (TMMDA) are investigated using femtosecond time-resolved photoelectron imaging and time-resolved mass spectroscopy. Excitation at 208 nm populates TMMDA in a charge-localized 3p state. Rapid internal conversion (IC) to 3s produces two charge-delocalized conformers with independent time constants and distinct population ratios. As the system explores the 3s potential surface, the structural evolution continues on a 1.55 ps timescale, followed by a slower (12.1 ps) relaxation to the ground state. A thorough comparison of the time-dependent mass and photoelectron spectra suggests that ionization out of the 3p state ends up with the parent ion, the vibrational energy of which is insufficient for the bond cleavage. On the contrary, by virtue of the additional energy acquired by IC from 3p, the internal energy deposited in 3s is available to break the C-N bond, leading to the fragment ion. The fragmentation is found to occur on the ion surface instead of the Rydberg surface.

Persistent high exposure to exogenous phthalates and endogenous sex hormones associated with early pubertal onset among children: A 3.5-year longitudinal cohort study in China.

BACKGROUND: Early onset of puberty could have significant impacts on childhood health, but the extent to which it was affected by phthalate esters (PAEs) and sex hormone disruption was not understood. The aim of this study is to investigate the associations between exposure to PAEs and sex hormone disruption and early onset of puberty in children. METHODS: A longitudinal cohort study was conducted in China from May 2017 to Oct 2020, involving 740 children during consecutive visits. The onset of puberty was evaluated using Tanner definition, and early puberty was defined as an onset age less than the first 25 %, with cut-offs of 10.33 and 8.97 years for boys and girls, respectively. Serum testosterone (TT), estradiol (E2) and urinary PAE metabolites were measured during three visits. Generalized linear models were used to explore the associations between PAE and sex hormones with the age of puberty onset, while log-binomial regressions were applied to assess the associations of persistent exposure to PAEs and sex hormones with early pubertal onset. RESULTS: Approximately 86.0 % of boys and 90.2 % of girls completed puberty onset from pre-puberty, and more than 95 % of participants had PAE concentrations higher than the limit of detection. Boys showed higher exposure to PAE pollutants and higher TT levels. Persistent exposure to PAEs was positively associated with early pubertal onset in girls (ARR = 1.97, 95 %CI = 1.12, 3.46). Moreover, persistent exposure to PAEs and E2 had synergistic associations with early pubertal onset in both boys (ARR = 4.77, 95 %CI = 1.06, 21.54) and girls (ARR = 7.07, 95 %CI = 1.51, 33.10). However, PAEs and TT had antagonistic associations only in boys (ARR = 0.44, 95 %CI = 0.07, 2.58). CONCLUSION: Long-term exposure to PAEs might increase the risk of early pubertal onset, and it appears to work in synergy with E2, while in antagonism with TT in boys' early pubertal onset. Reducing PAEs exposure might promote pubertal health.

[Active components and mechanism of Jinwugutong Capsules in treatment of osteoporosis: a study based on UPLC-Q-Exactive-MS/MS combined with network pharmacology].

UPLC-Q-Exactive-MS/MS and network pharmacology were employed to preliminarily study the active components and mechanism of Jinwugutong Capsules in the treatment of osteoporosis. Firstly, UPLC-Q-Exactive-MS/MS was employed to characterize the chemical components of Jinwugutong Capsules, and network pharmacology was employed to establish the "drug-component-target-pathway-disease" network. The key targets and main active components were thus obtained. Secondly, AutoDock was used for the molecular docking between the main active components and key targets. Finally, the animal model of osteoporosis was established, and the effect of Jinwugutong Capsules on the expression of key targets including RAC-alpha serine/threonine-protein kinase(AKT1), albumin(ALB), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA). A total of 59 chemical components were identified from Jinwugutong Capsules, among which coryfolin, 8-prenylnaringenin, demethoxycurcumin, isobavachin, and genistein may be the main active components of Jinwugutong Capsules in treating osteoporosis. The topological analysis of the protein-protein interaction(PPI) network revealed 10 core targets such as AKT1, ALB, catenin beta 1(CTNNB1), TNF, and epidermal growth factor receptor(EGFR). The Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment showed that Jinwugutong Capsules mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, neuroactive ligand-receptor interaction, mitogen-activated protein kinase(MAPK) signaling pathway, Rap1 signaling pathway and so on. Molecular docking showed that the main active components of Jinwugutong Capsules well bound to the key targets. ELISA results showed that Jinwugutong Capsules down-regulated the protein levels of AKT1 and TNF-α and up-regulated the protein level of ALB, which preliminarily verified the reliability of network pharmacology. This study indicates that Jinwugutong Capsules may play a role in the treatment of osteoporosis through multiple components, targets, and pathways, which can provide reference for the further research.

Experimental and Theoretical Study of Oxolan-3-one Thermal Decomposition.

The thermal decomposition of oxolan-3-one, a common component of the bio-oil formed during biomass pyrolysis, has been studied using ab initio calculations and experiments employing pulsed gas-phase pyrolysis with matrix-isolation FTIR product detection. Four pathways for unimolecular decomposition were predicted using computational methods. The dominant reaction channel led to carbon monoxide, formaldehyde, and ethylene, all of which were observed experimentally. The other channels led to an assortment of products including ketene, water, propyne, and acetylene, which were all confirmed in the matrix-isolation FTIR spectra. There is also evidence for the production of substituted ketenes in pyrolysis, most likely hydroxyketene and methylketene.

Wavepacket dynamics of the excited (S1) state of 2,5-difluoroaniline by accidental resonance with the Rydberg states.

Coherent nuclear wavepacket behavior obtained by time-resolved spectroscopy is a good choice to capture the real-time evolution of molecular configuration. Using femtosecond time-resolved photoelectron imaging, we investigate the real-time evolution of the vibrational wavepacket of 2,5-difluoroaniline following the coherent excitation of an out-of-plane vibrational mode in the S1 state at 289.8 nm. Probed by an accidental resonance with the Rydberg states, the periodic oscillations with the frequency of 99 cm-1 are observed from the photoelectron kinetic energy (PKE) distributions, corresponding to the energy difference between the out-of-plane mode X1 0 of C-F bond and the band origin. Moreover, phase reversal of π rad between 0.66-0.75 and 1.00-1.08 eV is also observed in the PKE region. Combined with the scan of the potential energy surface in the ground cationic D0 state, the observed two ionization channels corresponding to different phases are attributed to the periodic geometry changes between the planar and the non-planar structures when the coherent wavepacket evolves from the initial vertical Franck-Condon region toward the global minimum of the S1 potential energy surface.

Association of MTHFD1 gene polymorphisms and maternal smoking with risk of congenital heart disease: a hospital-based case-control study.

BACKGROUND: MTHFD1 gene may affect the embryonic development by elevated homocysteine levels, DNA synthesis and DNA methylation, but limited number of genetic variants of MTHFD1 gene was focused on the association with congenital heart disease (CHD). This study examined the role of MTHFD1 gene and maternal smoking on infant CHD risk, and investigated their interaction effects in Chinese populations. METHODS: A case-control study of 464 mothers of CHD infants and 504 mothers of health controls was performed. The exposures of interest were maternal tobacco exposure, single nucleotide polymorphisms (SNPs) of maternal MTHFD1 gene. The logistic regression model was used for accessing the strength of association. RESULTS: Mothers exposed to secondhand smoke during 3 months before pregnancy (adjusted odds ratio [aOR] = 1.56; 95% confidence interval [CI]: 1.13-2.15) and in the first trimester of pregnancy (aOR = 2.24; 95%CI: 1.57-3.20) were observed an increased risk of CHD. Our study also found that polymorphisms of maternal MTHFD1 gene at rs1950902 (AA vs. GG: aOR = 1.73, 95% CI: 1.01-2.97), rs2236222 (GG vs. AA: aOR = 2.38, 95% CI: 1.38-4.12), rs1256142 (GA vs.GG: aOR = 1.57, 95% CI: 1.01-2.45) and rs11849530 (GG vs. AA: aOR = 1.68, 95% CI: 1.02-2.77) were significantly associated with higher risk of CHD. However, we did not observe a significant association between maternal MTHFD1 rs2236225 and offspring CHD risk. Furthermore, we found the different degrees of interaction effects between polymorphisms of the MTHFD1 gene including rs1950902, rs2236222, rs1256142, rs11849530 and rs2236225, and maternal tobacco exposure. CONCLUSIONS: Maternal polymorphisms of MTHFD1 gene, maternal tobacco exposure and their interactions are significantly associated with the risk of CHD in offspring in Han Chinese populations. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings. TRIAL REGISTRATION: Registration number: ChiCTR1800016635 .

Association of periconceptional folate supplements and FOLR1 and FOLR2 gene polymorphisms with risk of congenital heart disease in offspring: A hospital-based case-control study. / æ¯äº²å›´å­•æœŸæœç”¨å¶é ¸åŠFOLR1和FOLR2åŸºå› å¤šæ€æ€§ä¸Žå­ä»£å ˆå¤©æ€§å¿ƒè„ç— å ³è”çš„ç— ä¾‹å¯¹ç §ç ”ç©¶.

OBJECTIVES: Maternal periconceptional folic acid supplement is by far the most effective primary prevention strategy to reduce the incidence of congenital heart disease (CHD) in offspring. It was revealed that the underlying mechanisms are complex, including a combination of genetic and environmental factors. The purpose of this study is to investigate the association between periconceptional folic acid supplement, the genetic polymorphisms of maternal folic acid receptor 1 gene (FOLR1) and folic acid receptor 2 gene (FOLR2) and the impact of their interaction on the risk of CHD in offspring, and to provide epidemiological evidence for individualized folic acid dosing in hygienic counseling. METHODS: A case-control study on 569 mothers of CHD infants and 652 mothers of health controls was performed. The interesting points were periconceptional folate supplements, single nucleotide polymorphisms (SNPs) of maternal FOLR1 gene and FOLR2 gene. RESULTS: Mothers who took folate in the periconceptional period were observed a decreased risk of CHD [adjusted odds ratio (aOR)=0.58, 95% CI 0.35 to 0.95]. Our study also found that polymorphisms of maternal FOLR1 gene at rs2071010 (G/A vs G/G: aOR=0.67, 95% CI 0.47 to 0.96) and FOLR2 gene at rs514933 (T/C vs T/T: aOR=0.60, 95% CI 0.43 to 0.84; C/C vs T/T: aOR=0.55, 95% CI 0.33 to 0.90; the dominant model: T/C+ C/C vs T/T: aOR=0.59, 95% CI 0.43 to 0.81; and the addictive model: C/C vs T/C vs T/T: aOR=0.70, 95% CI 0.56 to 0.88) were significantly associated with lower risk of CHD [all P<0.05, false discovery rate P value (FDR_P)<0.1]. Besides, significant interaction between periconceptional folate supplements and rs2071010 G→A (aOR=0.59, 95% CI 0.41-0.86) and rs514933 T→C (aOR=0.52, 95% CI 0.37 to 0.74) on CHD risk were observed (all P<0.05, FDR_P<0.1). CONCLUSIONS: Periconceptional folate supplements, polymorphisms of FOLR1 gene and FOLR2 gene and their interactions are significantly associated with risk of CHD. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings.

[Association of maternal MTHFD1 and MTHFD2 gene polymorphisms with congenital heart disease in offspring]. / 母亲MTHFD1及MTHFD2åŸºå› å¤šæ€æ€§ä¸Žå­ä»£å ˆå¤©æ€§å¿ƒè„ç— çš„å ³è”.

OBJECTIVES: To study the association of maternal methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) gene polymorphisms with congenital heart disease (CHD) in offspring. METHODS: A hospital-based case-control study was conducted. The mothers of 683 children with CHD alone who attended Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group, and the mothers of 740 healthy children who attended the same hospital during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect related exposure data, and then venous blood samples (5 mL) were collected from the mothers to detect MTHFD1 and MTHFD2 gene polymorphisms. A multivariate logistic regression analysis was used to evaluate the association of MTHFD1 and MTHFD2 gene polymorphisms with CHD. The four-gamete test in Haploview 4.2 software was used to construct haplotypes and evaluate the association between haplotypes and CHD. The generalized multifactor dimensionality reduction method and logistic regression analysis were used to examine gene-gene interaction and its association with CHD. RESULTS: The multivariate logistic regression analysis showed that maternal MTHFD1 gene polymorphisms at rs11849530 (GA vs AA: OR=1.49; GG vs AA: OR=2.04) andat rs1256142 (GA vs GG: OR=2.34; AA vs GG: OR=3.25) significantly increased the risk of CHD in offspring (P<0.05), while maternal MTHFD1 gene polymorphisms at rs1950902 (AA vs GG: OR=0.57) and MTHFD2 gene polymorphisms at rs1095966 (CA vs CC: OR=0.68) significantly reduced the risk of CHD in offspring (P<0.05). The haplotypes of G-G-G (OR=1.86) and G-A-G (OR=1.35) in mothers significantly increased the risk of CHD in offspring (P<0.05). The gene-gene interaction analyses showed that the first-order interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and the second-order interaction involving MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966 might be associated with risk of CHD (P<0.05). CONCLUSIONS: Maternal MTHFD1 and MTHFD2 gene polymorphisms and their haplotypes, as well as the interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and between MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966, are associated with the risk of CHD in offspring.

Spatial learning and memory impaired after infection of non-neurotropic influenza virus in BALB/c male mice.

During the influenza pandemic or seasonal influenza outbreak, influenza infection can cause acute influenza-associated encephalopathy/encephalitis (IAE), even death. Patients with severe IAE will also have severe neurological sequelae. Neurologic disorders have been demonstrated in the mice treated with peripheral influenza viruses infection, whether neurotropic or non-neurotropic viruses. However, previous studies focused on the acute phase of infection, and rarely paid attention to a longer range of observations. Therefore, the long-term effect of non-neurotropic virus infection on the host is not very clear. In this study, adult mice were infected with influenza virus H1N1/PR8. Then, spontaneous behavior, body weight, expression of cytokines in brain, spatial learning ability and spatial memory ability were observed, until the complete recovery period. The results showed that cytokines in the brain were highly expressed in the convalescent phase (14 day post inoculation, dpi), especially BDNF, IBA1, CX3CL1 and CD200 were still highly expressed in the recovery phase (28 dpi). Otherwise the emotional and spatial memory ability of mice were impacted in the convalescent phase (14 dpi) and the recovery phase (28 dpi). In brief, BALB/c mice infected with non-neurotropic influenza virus H1N1, the weight and motor ability decreased in acute stage. During the recovery period, the body weight and activity ability were completely restored, whereas the emotion disordered, and the ability of spatial learning and memory were impacted in the infected mice. This long-term behavior impact may be the lag injury caused by non-neurotropic influenza infection.

Association analysis of maternal MTHFR gene polymorphisms and the occurrence of congenital heart disease in offspring.

BACKGROUND: Although many studies showed that the risk of congenital heart disease (CHD) was closely related to genetic factors, the exact pathogenesis is still unknown. Our study aimed to comprehensively assess the association of single nucleotide polymorphisms (SNPs) of maternal MTHFR gene with risk of CHD and its three subtypes in offspring. METHODS: A case-control study involving 569 mothers of CHD cases and 652 health controls was conducted. Thirteen SNPs were detected and analyzed. RESULTS: Our study showed that genetic polymorphisms of maternal MTHFR gene at rs4846052 and rs1801131 were significantly associated with risk of CHD in the homozygote comparisons (TT vs. CC at rs4846052: OR = 7.62 [95%CI 2.95-19.65]; GG vs. TT at rs1801131: OR = 5.18 [95%CI 2.77-9.71]). And six haplotypes of G-C (involving rs4846048 and rs2274976), A-C (involving rs1801133 and rs4846052), G-T (involving rs1801133 and rs4846052), G-T-G (involving rs2066470, rs3737964 and rs535107), A-C-G (involving rs2066470, rs3737964 and rs535107) and G-C-G (involving rs2066470, rs3737964 and rs535107) were identified to be significantly associated with risk of CHD. Additionally, we observed that a two-locus model involving rs2066470 and rs1801131 as well as a three-locus model involving rs227497, rs1801133 and rs1801131 were significantly associated with risk of CHD in the gene-gene interaction analyses. For three subtypes including atrial septal defect, ventricular septal defect and patent ductus arteriosus, similar results were observed. CONCLUSIONS: Our study indicated genetic polymorphisms of maternal MTHFR gene were significantly associated with risk of fetal CHD in the Chinese population. Additionally, there were significantly interactions among different SNPs on risk of CHD. However, how these SNPs affect the development of fetal heart remains unknown, and more studies in different ethnic populations and with a larger sample are required to confirm these findings.

[Preparation of triptolide-loaded dissolving microneedles and its transdermal penetration].

Triptolide(TP), the main active and toxic component of Tripterygium wilfordii, has the limitations of low bioavailability, poor absorption, low concentration in plasma, and small lethal dose. Microneedle(MN), the hybrid of hypodermic needle and transdermal patch, is a physical penetration-enhancing system. Dissolving microneedles(DMNs) can be tailored to specific needs of degradation rate. In this study, the TP-loaded DMNs(DMNs-TP) were prepared with the two-step centrifugation method. The optimal ratio of PVA to PVP K30, water content in matrix solution, demoulding method, and plasticizer for preparing DMNs were investigated with the indexes of formability and mechanical strength. The drug loading capacity was determined by HPLC and morphological characteristics were observed under an optical microscope. The mechanical properties were investigated by H&E staining and Franz diffusion cell was used to detect the in vitro skin permeation characteristics. Through the experiment, we confirmed that the optimal backing material should be PVA and PVP K30(3∶1) and the optimal ratio of matrix material to water should be 3∶4. The prepared DMNs-TP were pyramidal with smooth surface and length of approximately 550 µm. Each patch(2.75 cm~2) had the drug loading capacity of(153.41±2.29) µg, and TP was located in the upper part of the needle. The results of in vitro skin permeation assay demonstrated that the cumulative penetration of TP in DMNs-TP reached 80% in 24 h, while little TP solution penetrated the skin, which proved that DMNs promoted the transdermal delivery of TP.

Intranasal administration of pullulan-based nanoparticles for enhanced delivery of adriamycin into the brain: in vitro and in vivo evaluation.

Intranasal (i.n.) administration is an efficient route for enhancing drug delivery to the brain, bypassing the blood-brain barrier (BBB) and eliminating systemic side effects. The purpose of this study was to investigate the nose-to-brain delivery efficiency of adriamycin (ADM) loaded in cholesterol-modified pullulan self-assembled nanoparticles (CHSP-SAN) via i.n. administration. The prepared nanodrugs (ADM-CHSP-SAN) were characterized as uniform size (112.8±1.02 nm), high drug loading capacity (7.65±0.58 %), and sustained release. CHSP-SAN showed good biocompatibility and low toxicity on HBMEC and C6 cells. The enhanced delivery of ADM across the BBB with CHSP-SAN was demonstrated by the reduced half maximal inhibitory concentration (IC50) value and the increased apoptosis proportion of C6 cells. The pharmacokinetics of ADM-CHSP-SAN was accessed by cerebral microdialysis technique. The pharmacokinetic results showed higher peak concentration (Cmax), area under the curve (AUC0-12h) and shorter peak time (Tmax) after i.n. administration that after intravenous (i.v.) administration. The i.n. administration of CHSP-SAN greatly increased ADM availability in cerebral tissue compared to that of ADM solution. Collectively, CHSP-SAN strikingly increased ADM transport across the BBB and improved its availability in brain via i.n. administration.

Real-time visualization of the vibrational wavepacket dynamics in electronically excited pyrimidine via femtosecond time-resolved photoelectron imaging.

The vibrational wavepacket dynamics at the very early stages of the S1-T1 intersystem crossing in photoexcited pyrimidine is visualized in real time by femtosecond time-resolved photoelectron imaging and time-resolved mass spectroscopy. A coherent superposition of the vibrational states is prepared by the femtosecond pump pulse at 315.3 nm, resulting in a vibrational wavepacket. The composition of the prepared wavepacket is directly identified by a sustained quantum beat superimposed on the parent-ion transient, possessing a frequency in accord with the energy separation between the 6a1 and 6b2 states. The dephasing time of the vibrational wavepacket is determined to be 82 ps. More importantly, the variable Franck-Condon factors between the wavepacket components and the dispersed cation vibrational levels are experimentally illustrated to identify the dark state and follow the energy-flow dynamics on the femtosecond time scale. The time-dependent intensities of the photoelectron peaks originated from the 6a1 vibrational state exhibit a clear quantum beating pattern with similar periodicity but a phase shift of π rad with respect to those from the 6b2 state, offering an unambiguous picture of the restricted intramolecular vibrational energy redistribution dynamics in the 6a1/6b2 Fermi resonance.

Ultrafast Photodissociation Dynamics of Highly Excited Iodobenzene on the C Band.

The photodissociation dynamics of highly excited iodobenzene from the C band absorption has been studied by femtosecond time-resolved ion yields techniques. Detailed photodissociation routes are discussed with the aid of high-level, spin-orbit resolved ab initio calculations of 1D potential energy curves. Upon 200 nm excitation within the C band, iodobenzene molecules on 7B2 and 7B1 states decay to 7A1 and 8B2 states through internal conversion in 75 fs, with electronic energy converted into high vibrational energy of 7A1 and 8B2 states. Subsequently, 7A1 and 8B2 states decay through internal vibrational energy redistribution in 540 fs, accompanied by the excited C-I mode and the resulting cleavage of the C-I bond. The overall time for the reaction starting from the phenyl-type modes and ending in final C-I fragmentation for I(2P3/2) production is 1.2 ps.