A repeating fast radio burst source localized to a nearby spiral galaxy.

Fast radio bursts (FRBs) are brief, bright, extragalactic radio flashes1,2. Their physical origin remains unknown, but dozens of possible models have been postulated3. Some FRB sources exhibit repeat bursts4-7. Although over a hundred FRB sources have been discovered8, only four have been localized and associated with a host galaxy9-12, and just one of these four is known to emit repeating FRBs9. The properties of the host galaxies, and the local environments of FRBs, could provide important clues about their physical origins. The first known repeating FRB, however, was localized to a low-metallicity, irregular dwarf galaxy, and the apparently non-repeating sources were localized to higher-metallicity, massive elliptical or star-forming galaxies, suggesting that perhaps the repeating and apparently non-repeating sources could have distinct physical origins. Here we report the precise localization of a second repeating FRB source6, FRB 180916.J0158+65, to a star-forming region in a nearby (redshift 0.0337 ± 0.0002) massive spiral galaxy, whose properties and proximity distinguish it from all known hosts. The lack of both a comparably luminous persistent radio counterpart and a high Faraday rotation measure6 further distinguish the local environment of FRB 180916.J0158+65 from that of the single previously localized repeating FRB source, FRB 121102. This suggests that repeating FRBs may have a wide range of luminosities, and originate from diverse host galaxies and local environments.

A nanographene disk rotating a single molecule gear on a Cu(111) surface.

On Cu(111) surface and in interaction with a single hexa-tert-butylphenylbenzene molecule-gear, the rotation of a graphene nanodisk was studied using the large-scale atomic/molecular massively parallel simulator molecular dynamics simulator. To ensure a transmission of rotation to the molecule-gear, the graphene nanodisk is functionalized on its circumference bytert-butylphenyl chemical groups. The rotational motion can be categorized underdriving, driving and overdriving regimes calculating the locking coefficient of this mechanical machinery as a function of external torque applied to the nanodisk. The rotational friction with the surface of both the phononic and electronic contributions is investigated. For small size graphene nanodisks, the phononic friction is the main contribution. Electronic friction dominates for the larger disks putting constrains on the experimental way of achieving the transfer of rotation from a graphene nanodisk to a single molecule-gear.

Copper Centers in the Cryo-EM Structure of Particulate Methane Monooxygenase Reveal the Catalytic Machinery of Methane Oxidation.

The particulate methane monooxygenase (pMMO) is the first enzyme in the C1 metabolic pathway in methanotrophic bacteria. As this enzyme converts methane into methanol efficiently near room temperature, it has become the paradigm for developing an understanding of this difficult C1 chemistry. pMMO is a membrane-bound protein with three subunits (PmoB, PmoA, and PmoC) and 12-14 coppers distributed among different sites. X-ray crystal structures that have revealed only three mononuclear coppers at three sites have neither disclosed the location of the active site nor the catalytic mechanism of the enzyme. Here we report a cyro-EM structure of holo-pMMO from Methylococcus capsulatus (Bath) at 2.5 Å, and develop quantitative electrostatic-potential profiling to scrutinize the nonprotein densities for signatures of the copper cofactors. Our results confirm a mononuclear CuI at the A site, resolve two CuIs at the B site, and uncover additional CuI clusters at the PmoA/PmoC interface within the membrane (D site) and in the water-exposed C-terminal subdomain of the PmoB (E clusters). These findings complete the minimal set of copper factors required for catalytic turnover of pMMO, offering a glimpse of the catalytic machinery for methane oxidation according to the chemical principles underlying the mechanism proposed earlier.

Prevalence of hepatitis B antiviral drug resistance variants in North American patients with chronic hepatitis B not receiving antiviral treatment.

Antiviral drug resistance hepatitis B virus (HBV) variants (HBV-DR) occur spontaneously in chronic hepatitis B (CHB) patients and after exposure to nucleos(t)ide analogues (NUCs). We determined the prevalence of HBV-DR variants among participants of the Hepatitis B Research Network (HBRN) Cohort Study conducted at 21 sites in the United States (US) and Canada. Samples obtained from 1342 CHB participants aged ≥18 years, and who were currently not receiving NUCs, were tested for HBV-DR variants by Sanger sequencing. In addition, next generation sequencing (NGS) was used to characterize HBV-DR variants from 66 participants with and 66 participants with no prior NUC exposure matched for HBV genotype and HBV DNA level. Half the participants were men, 75% Asian, 26% HBeAg positive. Primary HBV-DR variants were detected by Sanger sequencing in 16 (1.2%) participants: 2/142 (1.4%) with and 14/1200 (1.2%) without prior NUC exposure; only 1 of these 16 had a secondary variant. In total, 23 (1.7%) participants had secondary variants, including 1 with prior NUC experience. In the subset of 132 participants, NGS detected HBV-DR variants in a higher proportion of participants: primary variants in 18 (13.6%) (8 [12.1%] with, and 10 [15.2%] without prior NUC therapy) and secondary variants in 10 (7.6%) participants. Based on Sanger sequencing, prevalence of primary HBV-DR variants is low (1.2%) among adults with CHB in US/Canada. The similar low prevalence of HBV-DR variants in participants with and without NUC treatment suggests transmission of these variants is uncommon.

Increased risk of stroke in patients with osteoarthritis: a population-based cohort study.

OBJECTIVES: Osteoarthritis (OA) is related to carotid atherosclerosis. Few studies have investigated the incidence of cerebrovascular diseases in patients with OA. Therefore, we conducted a population-based cohort study to determine the incidence and risk of stroke in patients with OA. METHODS: We used data from Taiwan's Longitudinal Health Insurance Database 2000 (LHID2000) to investigate the incidence of stroke in 43,635 patients with OA newly diagnosed between 2002 and 2003. The non-osteoarthritis (non-OA) cohort comprised 43,635 people from the general population. The follow-up period was from the index date of OA to the date of censoring date or stroke diagnosis, or to the end of 2010. RESULTS: The overall incidence of stroke was 36% higher in the OA cohort than in the non-OA cohort, with an adjusted hazard ratio (aHR) of 1.10 (95% confidence interval [CI] = 1.06-1.14) after adjustment for covariates. Men, age, comorbidity, non-selective nonsteroidal anti-inflammatory drugs (NSAIDs), and Cox-2 selective NSAIDs are independent risk factors of stroke. The OA adults with mild to moderate OA (aHR = 1.97, 95% CI = 1.70-2.28 for young adults; aHR = 1.33, 95% CI = 1.25-1.42 for middle-aged adults; aHR = 1.16, 95% CI = 1.12-1.21 for older adults) and severe OA (aHR = 3.78, 95% CI = 2.50-5.70 for young adults; aHR = 1.34, 95% CI = 1.16-1.56 for middle-aged adults; and aHR = 1.01, 95% CI = 0.92-1.10 for older adults) exhibited increased risks of stroke compared with their counterparts without OA. CONCLUSION: OA may be associated with a slightly increased risk of stroke.

The application of traffic-light food labelling in a worksite canteen intervention in Taiwan.

OBJECTIVE: This study evaluated customer attitudes, perceptions, and utilisation of a traffic-light food labelling (TFL) programme before and after the TFL was implemented in a worksite canteen in Taiwan. STUDY DESIGN: A one-arm intervention was implemented in the canteen and buffet of a research park in Taiwan. Phase 1 consisted of dissemination of information regarding the TFL, targeting the customers (June-July, 2014); phase 2 consisted of implementation of the TFL in the buffet starting in August 2014. The TFL included red, yellow and green labels, indicating 'unhealthy/stop', 'moderately unhealthy/wait' and 'healthy/go', respectively. METHODS: The evaluation was based on two independent anonymous surveys in July 2014 (in phase 1) and April 2015 (in phase 2). Customers were invited to take a survey regarding the TFL programme, the food environment in the canteen, and their lunch choices. Logistic regression models examined the changes in customers' attention and attitudes towards the labelling and their food choices between the two surveys. RESULTS: The customers reported positive attitudes towards the TFL. The proportion of customers who reported choosing foods based on the recommendations increased from 38% to 50% (P < 0.01). The proportion of the buffet customers who chose green-light entrées and red-light entrées changed from 13% and 63% to 36% and 21%, respectively (P < 0.001). The availability of green-light entrées in the buffet increased as well. CONCLUSIONS: This first report of a TFL intervention in an Asian worksite suggests that TFL is acceptable and well understood by this population and may assist customers in choosing healthier items when healthier choices are available.

[Postoperative analgesia effect of different background volumes of ropivacaine in continuous tibial nerve block in patients with calcaneal surgery].

OBJECTIVE: To observe the clinical effect of different background volumes of ropivacaine in continuous tibial nerve block of postoperative analgesia after calcaneal surgery. METHODS: This study was a prospective, randomized, controlled study. Sixty cases of calcaneal visual analogue scale (ASA) I or II undergoing elective surgery were selected and randomly assigned to two groups, thirty cases in each group. The patients received popliteal fossa posterior tibial nerve block using ultrasound guided. The continuous stimulation catheter was inserted after successful position and the 0.2% ropivacaine was injected. The background volumes of the A and B groups were 5 mL/h and 3.2 mL/h. The VAS score, the sensory block and motor block of tibial nerve and common peroneal nerve, and the satisfaction of the patients at h 12, h 24 and h 48 were recorded after catheter insertion. RESULTS: The VAS scores at the three time points (h 12, h 24 and h 48) on the two groups of the patients were compared, and the difference was not statistically significant (P > 0.05). The difference of the sensory block and the motor block of the tibial nerve at the three time points (h 12, h 24 and h 48) on the two groups of the patients were also compared, and the difference was not statistically significant (P> 0.05). The difference of the sensory block and the motor block of common peroneal nerve at h 48 hs was statistically significant, group A was higher than the group B (P< 0.05). The difference of the patient satisfaction at the three time points (h 12, h 24 and h 48) on the two groups was not statistically significant (P> 0.05). CONCLUSION: The use of 0.2% ropivacaine with the background volume of 3.2 mL/h in continuous tibial nerve block can provide good analgesia and reduce the incidence of the sensory block and motor block of the common peroneal nerve.

Increased risk of erectile dysfunction among patients with sleep disorders: a nationwide population-based cohort study.

AIMS: Few studies have investigated the relationship between sleep disorders (SD) and erectile dysfunction (ED). Therefore, this study explored whether patients with SD in an Asian population are at an increased risk of developing ED. METHODS: This longitudinal nationwide population-based cohort study investigated the incidence and risk of developing ED in 34,548 men newly diagnosed with SD between 2002 and 2008 from the National Health Insurance Research Database. A total of 138,192 controls without SD were randomly recruited from the general population and frequency matched according to age and sex. The follow-up period began from the date of entering the study cohort until the date of an ED event, censoring, or 31 December 2010. We conducted Cox proportional hazard regression analyses to estimate the effects of SD on the risk of ED. RESULTS: The SD cohort had a 2.11-fold adjusted hazard ratio (HR) of subsequent ED development compared with the non-SD cohort [95% confidence interval (CI) = 1.89-2.37]. The incidence of ED increased with age for both cohorts and was higher for the patients in the SD cohort. Compared with the participants without SD or comorbidities, the patients without SD with any comorbidity exhibited a 1.79-fold risk of developing ED (95% CI = 1.54-2.09); the highest risk was for those with both SD and any comorbidity (HR = 3.34, 95% CI = 2.82-3.95). Furthermore, SD patients who had a particular number of comorbidities showed the dose-response effect of developing ED. CONCLUSION: This nationwide cohort study determined that ED risk evidently increased in SD patients compared with the general population.

Palliative enteral feeding for patients with malignant esophageal obstruction: a retrospective study.

BACKGROUND: Malignant esophageal obstruction leads to dysphagia, deterioration in quality of life, and malnutrition. Traditional bedside nasogastric (NG) tube placement is very difficult under these circumstances. However, endoscopically assisted NG tube placement under fluoroscopic guidance could be an alternative option for establishing palliative enteral nutrition. This study aimed to compare the clinical outcomes of enteral tube feeding and esophageal stenting for patients with malignant esophageal obstruction and a short life expectancy. METHODS: Thirty-one patients were divided into 3 groups according to their treatment modality: NG tube (n = 12), esophageal stent group (n = 10), and supportive care with nil per os (NPO) (n = 9). Enteral nutrition, clinical outcomes, length of hospital stay, and median survival were evaluated. RESULTS: There were no significant baseline differences among the groups, except in age. The tube and stent groups had significantly higher enteral calorie intake (p = 0.01), higher serum albumin (p < 0.01), shorter hospital stay (p = 0.01), and longer median survival (p < 0.01) than the NPO group. The incidence of dislodgement in the tube group was significantly higher than in the stent group (58% vs. 20%, respectively; p = 0.01). However, stenting costs more than NG tube placement. CONCLUSIONS: Palliative enteral feeding by NG tube is safe, inexpensive, and has a low complication rate. Endoscopically assisted NG tube placement under fluoroscopic guidance could be a feasible palliative option for malignant esophageal obstruction for patients who have a short life expectancy.

HLA-DPB1 and anti-HBs titer kinetics in hepatitis B booster recipients who completed primary hepatitis B vaccination during infancy.

Previously we reported significant associations of the human leukocyte antigen (HLA)-DPB1 05:01 with memory against hepatitis B (HB) vaccination. However, the effects of HLA-DPB1 on antibodies to hepatitis B surface antigen (anti-HBs) kinetics were not explored. We followed up a cohort of 1974 HB booster recipients and quantified their 1-month and 1-year post-booster anti-HBs titers. A total of 681 subjects were randomly selected and typed for HLA-DPB1. We found that male subjects, undetectable pre-booster titers, and 05:01 homozygotes led to significantly lower post-booster anti-HBs titers. The geometric means (95% confidence interval (CI)) of 1-month post-booster anti-HBs titers were 4.68 (2.69-8.12), 23.01 (14.96-35.40) and 50.06 (27.20-92.13) mIU ml(-1) for subjects carrying two, one and no HLA-DPB1 05:01 allele. The corresponding figures for 1-year post-booster anti-HBs titers were 1.26 (0.73-2.18), 4.72 (3.08-7.25) and 7.32 (3.75-13.56) mIU ml(-1). There were significant associations of post-booster anti-HBs titers with the number of HLA-DPB1 risk and protective alleles. Among booster responders, anti-HBs decay rates were significantly reduced in subjects who had detectable pre-booster anti-HBs titers and the HLA-DPB1 05:01 allele. Our results indicated that HLA-DPB1 influences the kinetics of anti-HBs. The long-term memory against hepatitis B surface antigen (HBsAg) and the residual serum titers of anti-HBs after HB vaccination may be influenced by different mechanisms as evidenced by their inverse trend of associations with the 05:01 allele.

Association between polymorphisms in the csrRS two-component regulatory system and invasive group A streptococcal infection.

The csrRS two-component regulatory system is an important element in the pathogenesis of group A Streptococcus (GAS). The main goal of this study is to understand the association between csrRS polymorphisms and GAS infection. We sequenced the csrRS genes from 172 clinical isolates, including 81 invasive and 91 noninvasive isolates, and then employed phylogenetic analyses to determine the consequences of the csrRS polymorphisms. In total, 13 and 26 polymorphic loci were detected in the csrR and csrS genes, respectively. These polymorphisms constituted 14 csrR and 25 csrS alleles, producing two CsrR and seven CsrS variants, respectively. Three invasive isolates contained an indel in csrS, but no indel was identified in csrR. The frequency and distribution of polymorphisms in csrR and csrS was significantly different between the invasive and noninvasive infection isolates (p < 0.001). For CsrR, only one noninvasive isolate was identified to have a V29I mutation. The amino acid substitutions in CsrS included S32P (0.6 %), E265G (0.6 %), E265K (0.6 %), I332V (1.7 %), and N498K (82.6 %). Isolates with an N498K single mutation were more likely to be associated with invasive infections (p < 0.001). The dN/dS ratio indicated that both csrR and csrS were under purifying selection. The fixation index suggested a moderate evolutionary differentiation of the csrR and csrS alleles between invasive and noninvasive isolates. The identification of these genetic differences within the csrRS loci will provide a better understanding of the pathogenesis of GAS.

First Report of Chilli veinal mottle virus Infecting Tomato (Solanum lycopersicum) in China.

Chilli veinal mottle virus (ChiVMV), a potyvirus, is widespread over the world. In China, it was first reported in chili pepper (Capsicum annuum) in Hainan Province (south China) in 2006 (2). Subsequently, it was reported in tobacco (Nicotiana tabacum) in Yunnan Province (southwest China) in 2011 (1). Sichuan Province is one of the largest vegetable producing areas of China. In May 2012, tomatoes with leaves displaying virus-infected symptoms like mottling, mosaic, narrowing, or curling were observed in several fields of Chengdu, eastern Sichuan Province, southwest China. Of the 20 fields we investigated, four fields with 90% tomato plants were infected. During 2012 and 2013, six samples were collected from symptomatic tomato leaves based on different symptoms and locations. All six samples were assayed by western blotting using polyclonal antisera (Cucumber mosaic virus [CMV], Tobacco mosaic virus [TMV]) obtained from Agdia (Elkhart) and one antiserum to ChiVMV obtained from Yunnan Academy of Agricultural Science (China). Two samples from Pengzhou and one sample from Shuangliu exhibiting mosaic leaves were positive for TMV, one sample from Pixian exhibiting narrowing leaves was positive for CMV, and the other two samples from Shuangliu exhibiting mottle and leaf distortion were positive for ChiVMV. Total RNAs was extracted from all six samples and healthy tomato leaves using Trizol reagent (Invitrogen), First-strand cDNA synthesis primed with oligo(dT) by SuperScript III Reverse Transcriptase (Invitrogen). RT-PCR was performed using primer pairs ChiVMV-CP F (5'-GCAGGAGAGAGTGTTGATGCTG-3') and ChiVMV-CP R (5'-(T)16AACGCCAACTATTG-3'), which were designed to direct the amplification of the entire capsid protein (CP) gene and 3' untranslated region (3'-UTR) of ChiVMV (GenBank Accession No. KC711055). The expected 1,166-bp DNA fragment was amplified from the two tomato samples from Shuangliu that were positive for ChiVMV in the western blot tests, but not from the others. The obtained fragments were purified and cloned into the PMD18-T vector (TaKaRa) and sequenced. The sequencing results showed that the two ChiVMV isolates from tomato in Shuangliu were identical (KF738253). Nucleotide BLAST analysis revealed that this ChiVMV isolate shared ~84 to 99% nucleotide identities with other ChiVMV isolates available in GenBank (KC711055 to KF220408). To fulfill Koch's postulates, we isolated this virus by three cycle single lesion isolation in N. tabacum, and mechanically inoculated it onto tomato leaves. The same mottle and leaf distortion symptoms in systemic leaves were observed. Subsequent RT-PCR, fragment clone, and sequence determination tests were repeated and the results were the same. All the evidence from these tests revealed that the two tomato plants were infected by ChiVMV. To our knowledge, this is the first report of ChiVMV naturally infecting tomato in China. It shows that ChiVMV is spreading in China and is naturally infecting a new solanaceous crop in the southwest area, and the spread of the virus may affect tomato crop yields in China. Thus, it is very important to seek an effective way to control this virus. References: (1) M. Ding et al. Plant Dis. 95:357, 2011. (2) J. Wang et al. Plant Dis. 90:377, 2006.

First Report of Sweet potato chlorotic fleck virus Infecting Sweet Potato in Sichuan Province, China.

Sweet potato chlorotic fleck virus (SPCFV) is one of several viruses naturally infecting sweet potato (Ipomoea batatas L.), and it has recently been classified as a new member of the genus Carlavirus (family Flexiviridae) (1). However, SPCFV is distantly related to typical carlaviruses, as most of its putative gene products share amino acid sequence identities of <40% with those of typical carlaviruses (1). China is the largest sweet potato producing country in the world. So far, SPCFV has been reported in eastern China, such as Jiangsu, Anhui, Henan (3), and Guangdong (2) provinces, but no reports exist in western China. Sichuan Province, located in southwestern China, is the largest sweet potato producing area in the country. There are big differences between the environment and climate conditions between Sichuan and eastern China. During 2012, a survey was constructed to determine the genetic diversity and distribution of sweet potato viruses in Sichuan. Forty-seven sweet potato samples exhibiting virus-like symptoms were collected from four different geographic areas of the province. Western blotting using the antisera obtained from the International Potato Center showed that two samples were positive for SPCFV, whereas with reverse transcription (RT)-PCR, only one isolate of SPCFV was obtained from a sample exhibiting symptoms of chlorosis, leaf distortion, and vein clearing. Serological detection indicated that the plant was co-infected with SPCFV, Sweet potato feathery mottle virus (SPFMV), and Sweet potato virus G (SPVG). Total RNA was extracted from symptomatic leaves using Trizol reagent (Invitrogen) according to the manufacturer's protocol, and RT-PCR was performed by using primer pairs SPCFV-CP F (5'-ATGGCGGCGAAGGAGGCTGATA-3') and SPCFV-CP R (5'-TCACTTGCACTTCCCATTAC-3') corresponding to the entire coat protein (CP) gene of SPCFV. Expected DNA fragments of 900 bp were obtained from the symptomatic plant but not from control plants. The obtained fragments were purified and cloned into the PMD19-T vector (TaKaRa). Recombinant plasmids were then transformed into competent cells of Escherichia coli strain DH5α. Nucleotide BLAST analysis revealed that the 900-bp fragment (GenBank Accession No. KC414676) shared 87 to 91% nucleotide identities with other SPCFV isolates available in the GenBank database. To our knowledge, this is the first report of the co-infection between SPCFV and other sweet potato viruses including SPFMV and SPVG in China, and this is the first molecular report of SPCFV in Sichuan, western China. It shows that SPCFV is spreading to a new ecological area of China, and the spread of the virus may affect sweet potato crop yields in western China. Some measures must be carried out quickly to control the virus. References: (1) V. Aritua et al. Arch. Virol. 152:813, 2007. (2) V. Aritua et al. Plant Dis. 93:87, 2009. (3) Q. Wang et al. Crop. Prot. 29:110, 2010.

Primary carcinoid tumor of the ovary arising in a mature cystic teratoma: a case report.

Primary ovarian carcinoid tumors are rare entities, they may appear with other teratomatous components, and can be often being mistaken as part of mature cystic teratomas. Consistent with their rarity and low incidence, imaging clues that could have led to suspicion of this tumor are not well-documented. Herein, the authors present a rare case of primary ovarian carcinoid tumor in a mature cystic teratoma, who initially presented with complaints of abdominal distension for months. Contrast-enhanced computerized tomography (CT) demonstrated a multilobular mass with different density components including fat, soft tissue, and calcification materials, as well as rich vascular supply from the right ovarian vein. Serum tumor markers were within normal limits. Bilateral salpingo-oophorectomy was performed and the pathological diagnosis was mature cystic teratoma with coexisting primary ovarian carcinoid tumor, insular type. The patient has remained well with no residual disease for over one year of follow-up.

Preceding pain symptoms and Parkinson's disease: a nationwide population-based cohort study.

BACKGROUND AND PURPOSE: Painful sensations are recently reported to be a non-motor feature of Parkinson's disease (PD). The non-steroidal anti-inflammatory drug ibuprofen is a common painkiller and was reported to be associated with a decreased risk of PD. The aim of the present study was to examine the relationship amongst preceding pain symptoms, use of ibuprofen and risk of PD in a nationwide population-based cohort. METHODS: The data of participants who were free of PD at baseline were obtained from two large National Health Interview Surveys (NHIS) in Taiwan, conducted in 2001 and 2005. The information regarding pain status included severity and location of pain. Information regarding pain status, use of ibuprofen, comorbidity of depression and PD-associated risk/protective behaviors was adjusted using proportional hazards models. RESULTS: Amongst 33 388 participants, 32 cases of incident PD were identified after a mean follow-up of 3 years. After adjusting for the use of ibuprofen and other PD risk factors, subjects with preceding pain symptoms had a higher incidence of PD than those without pain at baseline, and the hazard ratio was 1.79 (95% CI: 0.71-4.51, P = 0.21) for mild pain and 2.88 (95% CI: 1.05-7.86, P = 0.04) for moderate or severe pain. The PD risk increased by 34% with each additional increment in pain score [hazard ratio = 1.34 (1.03-1.75), P = 0.03], showing a dose-response relationship. CONCLUSIONS: These findings support the hypothesis that pain is associated with PD in the pre-motor stage of the disease. Further research is needed to clarify the role of sensory system involvement in the pre-motor phase of PD.

Role of monokine induced by interferon-γ in liver injury induced by hepatitis B virus in mice.

The chemokine monokine induced by interferon-γ (Mig) is involved in the recruitment of inflammatory cells and liver injury during hepatitis B virus (HBV) infection. HBV protein X contributes to Mig expression in vitro by activation of nuclear factor (NF)-κB; however, the molecular mechanisms by which HBV induces Mig expression in vivo are unknown. In this paper, we established a mouse model for HBV study by tail vein injection of HBV genome-containing adenovirus vectors. Host immune response to the secreted hepatitis B surface antigen and e antigen was detected and serum alanine aminotransferase (ALT) was elevated at different time points. We also demonstrated that peripheral and intrahepatic Mig expression was increased after Ad-HBV infection. This was followed by inflammatory cell migration and formation of inflammatory foci in the liver. In addition, NF-κB p65 subunit translocated from the cytoplasm to the nucleus, and phosphoinositide 3-kinase/Akt, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were to some extent phosphorylated after HBV injection. Following tail vein injection of Mig siRNA/in vivo-jetPEI-Gal complex, Mig expression was partially suppressed, inflammatory cell migration was inhibited, serum level of ALT were reduced. In conclusion, through NF-κB activation, HBV induced Mig expression in vivo, which recruited peripheral inflammatory cells to the liver and resulted in liver damage. Phosphorylation of phosphoinositide 3-kinase/Akt, ERK and JNK but not p38 might involved in the molecular mechanisms underlying HBV induced Mig expression in vivo.

Differential association of proinflammatory cytokines with left ventricular diastolic dysfunction in subjects with and without continuous ambulatory peritoneal dialysis.

BACKGROUND AND AIMS: The association between inflammation and left ventricular (LV) diastolic dysfunction in continuous ambulatory peritoneal dialysis (CAPD) and non-CAPD patients is not established. The objective of this study was to test the above association and whether inflammation interacts with CAPD to increase LV diastolic dysfunction risks. METHODS AND RESULTS: 120 subjects with normal creatinine levels and 101 CAPD patients were recruited. Echocardiographic parameters were assessed in all patients. The participants were classified as having LV diastolic dysfunction by echocardiographic findings including mitral inflow E/A ratio < 1, deceleration time > 220 cm/s, or decreased peak annular early diastolic velocity in tissue Doppler imaging. Blood was sampled at the baseline for measurement of inflammation markers, including tissue necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Subjects with LV diastolic dysfunction had higher proinflammation cytokines levels in both groups. Inflamed markers correlated significantly with echocardiography parameters for LV diastolic dysfunction in patients receiving CAPD. In a multivariate regression analysis adjusting for all the factors associated with LV diastolic dysfunction, inflammation is still significantly associated with left ventricular diastolic dysfunction (TNF-alpha, OR: 2.6, 95% CI: 2.0-3.35, p < 0.001; IL-6, OR: 1.26, 95% CI: 1.25-1.26, p = 0.01). In addition, the interaction of CAPD and inflammation significantly contributed to the development of LV diastolic dysfunction (CAPD∗ TNF-α: OR: 1.45, 95% CI: 1.13-1.79, P = 0.004). CONCLUSION: We found inflammation plays a vital role for LV diastolic dysfunction especially in CAPD patients. A synergistic effect between CAPD and inflammation, especially TNF-α, would further aggravate LV diastolic dysfunction.

[Effects of methacrylic anhydride gelatin hydrogel loaded with silver and recombinant human basic fibroblast growth factor on deep partial-thickness burn wounds in rabbits].

Objective: To investigate the effects of methacrylic anhydride gelatin (GelMA) hydrogel loaded with silver and recombinant human basic fibroblast growth factor (rh-bFGF) on deep partial-thickness burn wounds in rabbits. Methods: The experimental research method was adopted. Low-concentration GelMA materials, medium-concentration GelMA materials and high-concentration GelMA materials containing different concentrations of methacrylic anhydride (MA) were prepared, after adding photoinitiator, low-concentration GelMA hydrogels, medium-concentration GelMA hydrogels, and high-concentration GelMA hydrogels were obtained, respectively. The nuclear magnetic resonance spectroscopy was performed to detect the hydrogen nuclear magnetic resonance spectra of the above-mentioned three concentrations of GelMA materials, and to calculate the degree of substitution according to the spectrum diagram. The three-dimensional microstructure and pore size of 3 types of above-mentioned GelMA hydrogels were detected by field emission scanning electron microscopy (FESEM), with 9 samples measured. According to the selected concentration of MA, ten kinds of solutions of GelMA with different concentration of silver (silver-containing GelMA) were synthesized, and the silver-containing GelMA solution of each concentration was divided into three parts, and then exposed to ultraviolet light lasting for 20, 25, and 35 s, respectively. After adding photoinitiator,the corresponding silver-containing GelMA hydrogels were obtained. The residual degradation rate of silver-containing GelMA hydrogel with different photocrosslinking times was detected by collagenase degradation method at degradation of 12, 24, 36, and 48 h; and the time required for complete degradation was detected, and the sample number was 5. The inhibition zone diameter of GelMA hydrogel under above screened photocrosslinking times containing 10 concentrations of silver against Staphylococcus aureus was measured to reflect its antibacterial ability, and the sample numbers were all 5. The silver-containing GelMA hydrogel with statistical significance compared with the antibacterial circle diameter of the silver-containing GelMA hydrogel containing the lowest concentration (no silver) was considered as having antibacterial activity. The three-dimensional microstructure and pore size of the silver-containing GelMA hydrogels with antibacterial activity and the lowest drug concentration selected were detected by FESEM, and the sample numbers were all 9. The freeze-dried alone GelMA hydrogel and the freeze-dried silver-containing GelMA hydrogel were soaked in phosphate buffer solution for 24 h, respectively, then the swelling rate of the two GelMA hydrogel were calculated and compared by weighing method, and the sample number was 5. GelMA hydrogel containing silver and rh-bFGF, namely compound hydrogel for short, was prepared according to the preliminary experiment and the above experimental results. The appearance of the composite hydrogel was observed in general, and its three-dimensional microstructure and pore size were detected by FESEM. The deep partial-thickness burn wound was made on the back of 30 rabbits (aged 4-6 months, female half and half). Meanwhile, with the rabbit head as the benchmark, the wounds on the left side of the spine were treated as composite hydrogel treatment group, and the wounds on the right side were treated as gauze control group, and which were treated accordingly. On post injury day (PID) 3, 7, 14, 21, and 28, the healing of wounds in the two groups was observed. On PID 7, 14, 21, and 28, the wound healing area was recorded and the healing rate was calculated, with a sample number of 30. Data were statistically analyzed with analysis of variance for repeated measurement, one-way analysis of variance, and independent sample t test. Results: The substitution degree among low-concentration GelMA materials, medium-concentration GelMA materials, and high-concentration GelMA materials was significantly different (F=1 628.00, P<0.01). The low-concentration GelMA hydrogel had a loose and irregular three-dimensional spatial network structure with a pore size of (60±17) µm; the medium-concentration GelMA hydrogel had a relatively uniform three-dimensional spatial network and pore size with a pore size of (45±13) µm; the high-concentration GelMA hydrogel had the dense and disordered three-dimensional spatial network with a pore size of (25±15) µm, the pore sizes of 3 types of GelMA hydrogels were significantly differences (F=12.20, P<0.01), and medium concentration of MA was selected for the concentration of subsequent materials. The degradability of silver-containing GelMA hydrogels with different concentrations of the same photocrosslinking time was basically same. The degradation residual rates of silver-containing GelMA hydrogels with 20, 25, and 35 s crosslinking time at 12 h were (74.2±1.7)%, (85.3±0.9)%, and (93.2±1.2)%, respectively; the residual rates of degradation at 24 h were (58.3±2.1)%, (65.2±1.8)%, and (81.4±2.6)%, respectively; the residual rates of degradation at 36 h were (22.4±1.9)%, (45.2±1.7)%, and (68.1±1.4)%, respectively; the residual rates of degradation at 48 h were (8.2±1.7)%, (32.4±1.3)%, and (54.3±2.2)%, respectively, and 20, 25, and 30 s photocrosslinking time required for complete degradation of silver-containing GelMA hydrogels were (50.2±2.4), (62.4±1.4), and (72.2±3.2) h, and the difference was statistically significant (F=182.40, P<0.01), 25 s were selected as the subsequent photocrosslinking time. The antibacterial diameters of 10 types of silver-containing GelMA hydrogels against Staphylococcus aureus from low to high concentrations were (2.6±0.4), (2.5±0.4), (3.2±0.4), (12.1±0.7), (14.8±0.7), (15.1±0.5), (16.2±0.6), (16.7±0.5), (16.7±0.4), and (16.7±0.6) mm, respectively, and which basically showed a concentration-dependent increasing trend, and the overall difference was statistically significant (F=428.70, P<0.01). Compared with the silver-containing GelMA hydrogel with the lowest concentration, the antibacterial circle diameters of other silver-containing GelMA hydrogels with antibacterial ability from low to high concentration were significantly increased (with t values of 26.35, 33.84, 43.65, 42.17, 49.24, 55.74, and 43.72, respectively, P<0.01). The silver-containing GelMA hydrogel with the antibacterial diameter of (12.1±0.7) mm had the lowest antibacterial activity against Staphylococcus aureus and the lowest drug loading concentration, and the concentration of silver was selected for the concentration of subsequent materials. The microscopic morphology of the silver-containing GelMA hydrogel containing silver element with a pore size of (45±13) µm had a regular and linear strip-like structure. After soaking for 24 h, the swelling ratio of silver-containing GelMA hydrogel was similar to that of alone GelMA hydrogel. The composite hydrogel was colorless, clear and transparent, and its three-dimensional microstructure was a regular and uniform grid, with a filament network structure inside, and the pore size of (40±21) µm. On PID 3, a large amount of necrotic tissue and exudate of rabbit wound in composite hydrogel group were observed, and scattered scabs, a small amount of necrotic tissue and exudate of rabbit wound in gauze control group were observed. On PID 7, the area of rabbit wound in composite hydrogel group was significantly reduced, and adhesion of rabbit wound and gauze in gauze control group was observed. On PID 14, In composite hydrogel group, the rabbit wound surface was ruddy, and the growth of granulation tissue was observed, and in gauze control group, the rabbit wound base was pale, and the blood supply was poor. On PID 21, the rabbit wounds in composite hydrogel group healed completely, and rabbit wound in gauze control group had healing trend. On PID 28, new hair could be seen on rabbit wound surface in composite hydrogel group; oval wound of rabbit in gauze control group still remained. On PID 7, 14, 21, and 28, the wound healing areas of rabbit in composite hydrogel group were significantly larger than those in gauze control group (with t values of 2.24, 4.43, 7.67, and 7.69, respectively, P<0.05 or P<0.01). Conclusions: The medium-concentration GelMA hydrogel has good physical and chemical properties in terms of swelling and degradability. The screened silver-containing GelMA hydrogels had the lowest antibacterial activity and the lowest drug loading concentration. Composite hydrogel can significantly shorten the healing time of deep partial-thickness burn wounds in rabbits.