bluuebunny/crossref_metadata_2025 huggingface dataset:
SMRT and Illumina RNA sequencing reveal novel insights into the heat stress response and crosstalk with leaf senescence in tall fescue
Authors: Qian Yiguang , Cao Liwen , Zhang Qiang , Amee Maurice , Chen Ke , Chen Liang
Published: August 2020

Background

As a cool-season grass species, tall fescue (Festuca arundinacea) is challenged by increasing temperatures. Heat acclimation or activation of leaf senescence, are two main strategies when tall fescue is exposed to heat stress (HS). However, lacking a genome sequence, the complexity of hexaploidy nature, and the short read of second-generation sequencing hinder a comprehensive understanding of the mechanism. This study aims to characterize the molecular mechanism of heat adaptation and heat-induced senescence at transcriptional and post-transcriptional levels.

Results

Transcriptome of heat-treated (1 h and 72 h) and senescent leaves of tall fescue were generated by combining single-molecular real-time and Illumina sequencing. In total, 4076; 6917, and 11,918 differentially expressed genes (DEGs) were induced by short- and long-term heat stress (HS), and senescence, respectively. Venn and bioinformatics analyses of DEGs showed that short-term HS strongly activated heat shock proteins (Hsps) and heat shock factors (Hsfs), as well as specifically activated FK506-binding proteins (FKBPs), calcium signaling genes, glutathione S-transferase genes, photosynthesis-related genes, and phytohormone signaling genes. By contrast, long-term HS shared most of DEGs with senescence, including the up-regulated chlorophyll catabolic genes, phytohormone synthesis/degradation genes, stress-related genes, and NACs, and the down-regulated photosynthesis-related genes, FKBPs, and catalases. Subsequently, transient overexpression in tobacco showed that FaHsfA2a (up-regulated specifically by short-term HS) reduced cell membrane damages caused by HS, but FaNAC029 and FaNAM-B1 (up-regulated by long-term HS and senescence) increased the damages. Besides, alternative splicing was widely observed in HS and senescence responsive genes, including Hsps, Hsfs, and phytohormone signaling/synthesis genes.

Conclusions

The short-term HS can stimulate gene responses and improve thermotolerance, but long-term HS is a damage and may accelerate leaf senescence. These results contribute to our understanding of the molecular mechanism underlying heat adaptation and heat-induced senescence.
Orbital abscess caused by Exophiala dermatitidis following posterior subtenon injection of triamcinolone acetonide: a case report and a review of literature related to Exophiala eye infections
Authors: Iwahashi Chiharu , Eguchi Hiroshi , Hotta Fumika , Uezumi Mayu , Sawa Miki , Kimura Masatomo , Yaguchi Takashi , Kusaka Shunji
Published: August 2020

Background

Subtenon injection of triamcinolone acetonide (STTA) has been widely adopted in the clinical setting of ophthalmology and its infectious complications are rare. However, orbital abscess following STTA has been reported in seven cases. Furthermore, although eye infections due to Exophiala species are uncommon, there have been 19 cases to date. E. jeanselmei, E. phaeomuriformis, E. werneckii, and E. dermatitidis have been reported to cause human eye infections; however, to the best of our knowledge, orbital abscess caused by E. dermatitidis has not yet been reported. We describe the first documented case of fungal orbital abscess caused by E. dermatitidis following STTA. We also review the related literature of orbital abscess following STTA, as well as eye infections caused by the four Exophiala species.

Case presentation

The patient was a 69-year-old Japanese woman with diabetic mellitus. She had a macular oedema in her right eye, which occurred secondary to branch retinal vein occlusion. An orbital abscess caused by E. dermatitidis occurred 4 months after the second STTA for the macular oedema, which was successfully treated by a surgical debridement and systemic administration of voriconazole.

Conclusions

Our findings in the patient and from our literature survey caution ophthalmologists to the fact that STTA can cause fungal orbital infections, especially in diabetic patients. Furthermore, surgical treatment is one of the most important risk factors.
KIF1A-related autosomal dominant spastic paraplegias (SPG30) in Russian families
Authors: Rudenskaya G. E. , Kadnikova V. A. , Ryzhkova O. P. , Bessonova L. A. , Dadali E. L. , Guseva D. S. , Markova T. V. , Khmelkova D. N. , Polyakov A. V.
Published: August 2020

Background

Spastic paraplegia type 30 (SPG30) caused by KIF1A mutations was first reported in 2011 and was initially considered a very rare autosomal recessive (AR) form. In the last years, thanks to the development of massive parallel sequencing, SPG30 proved to be a rather common autosomal dominant (AD) form of familial or sporadic spastic paraplegia (SPG),, with a wide range of phenotypes: pure and complicated. The aim of our study is to detect AD SPG30 cases and to examine their molecular and clinical characteristics for the first time in the Russian population.

Methods

Clinical, genealogical and molecular methods were used. Molecular methods included massive parallel sequencing (MPS) of custom panel ‘spastic paraplegias’ with 62 target genes complemented by familial Sanger sequencing. One case was detected by the whole -exome sequencing.

Results

AD SPG30 was detected in 10 unrelated families, making it the 3rd (8.4%) most common SPG form in the cohort of 118 families. No AR SPG30 cases were detected. In total, 9 heterozygous KIF1A mutations were detected, with 4 novel and 5 known mutations. All the mutations were located within KIF1A motor domain. Six cases had pure phenotypes, of which 5 were familial, where 2 familial cases demonstrated incomplete penetrance, early onset and slow relatively benign SPG course. All 4 complicated cases were caused by novel mutations without familial history. The phenotypes varied from severe in two patients (e.g. lack of walking, pronounced mental retardation) to relatively mild non-disabling symptoms in two others.

Conclusion

AD SPG30 is one of the most common forms of SPG in Russia, the disorder has pronounced clinical variability while pure familial cases represent a significant part.
Respectful maternity care during labor and childbirth and associated factors among women who gave birth at health institutions in the West Shewa zone, Oromia region, Central Ethiopia
Authors: Bulto Gizachew Abdissa , Demissie Dereje Bayissa , Tulu Abera Shibru
Published: August 2020

Background

Skilled assistance during pregnancy and childbirth is one of the key interventions in reducing maternal morbidity and mortality. But studies have shown that many women across the globe experience disrespectful and abusive treatment during labor and childbirth in institutions, which forms an important barrier to improving skilled care utilization and improving maternal health outcomes. Although there are few studies done in Ethiopia, information on the status of respectful maternity care (RMC) among women during childbirth at health institutions in the West-Shewa zone is lacking. Therefore, the study aimed to assess RMC during Labor and Childbirth and associated factors among women who gave-birth at health-institutions in the West Shewa zone, Central Ethiopia.

Methods

Cross-sectional study was conducted at Health institutions in the West Shewa zone, Oromia region, Central Ethiopia. A systematic random sampling technique that uses women’s delivery registration number was used to collect data. Data was collected through an exit-interview. Both bivariate and multivariable logistic regressions were used to identify associated factors.

Results

From a total of 567 women who fully responded, only 35.8% received RMC. From categories of RMC, 76.5% of the woman is protected from physical harm/ill-treatment and 89.2% received equitable care free of discrimination. But, only 39.3% of woman’s right to information, informed consent and preferences were protected. Giving birth at health center (AOR:5.44), discussion on the place of delivery (AOR:4.42), daytime delivery (AOR:5.56), longer duration of stay (≥ 13 h) (AOR:2.10), involvement in decision-making (AOR:8.24), asking for consent before the procedure(AOR:3.45), current pregnancy unintended (AOR:5.56), the presence of < 3 health-workers during childbirth (AOR:2.23) and satisfied on waiting-time to be seen (AOR:2.08) were found to be significantly associated with RMC.

Conclusions

The proportion of RMC during labor and childbirth in the study area was low. Type of institution, discussion during ANC, time of delivery, duration of stay, involvement in decision-making, the number of health workers, waiting time and consent were identified factors. Therefore, giving emphasis to creating awareness of care providers on the standards and categories of RMC, improving care provider-client discussion, monitor and reinforcing accountability mechanisms for health workers to avoid mistreatments during labor and childbirth were recommended.
Evaluation of radioactive 125I seed implantation for the treatment of refractory malignant tumours based on a CT-guided 3D template-assisted technique: efficacy and safety
Authors: Zhao Guang Sheng , Liu Song , Yang Liang , Li Chuang , Wang Ruo Yu , Zhou Jun , Zhang Yue Wei
Published: August 2020

Background

To observe the medium- and long-term clinical efficacy and safety of radioactive 125I seed implantation for refractory malignant tumours based on CT-guided 3D template-assisted technique.

Methods

Twenty-five patients with refractory malignant tumours who underwent radioactive 125I seed implantation based on CT-guided 3D template-assisted technique were selected. The post-operative adverse reactions were recorded. The number of puncture needles and particles used in the operation, dosimetric parameters, post-operative physical strength scores, and tumour response were statistically analysed. The overall survival time and survival rate were calculated, and the effect and prognosis were assessed.

Results

125I seed implantation was successful in all patients without serious complications. The average number of implanted puncture needles was 17 (19.12 ± 13.00), and the median number of particles was 52 (55.12 ± 32.97). D90 in the post-operative clinical target volume (CTV) (93.24 ± 15.70 Gy) was slightly lower than that in the pre-operative CTV (93.92 ± 17.60 Gy; P > 0.05). The D90 in the post-operative planning target volume (PTV) (142.16 ± 22.25 Gy) was lower than the pre-operative PTV (145.32 ± 23.48 Gy; P > 0.05). The tumour responses at 6 months post-operatively: complete remission (CR), 20% (5/25); partial remission (PR), 48% (12/25); stable disease (SD), 24% (6/25); progressive disease (PD), 8% (2/25); CR + PR, 68% (17/25); and local control rate, 92% (23/25). The 6-, 12-, and 24-month survival rates were 100, 88, and 52%, respectively. The post-operative physical strength score (Karnofsky performance score, KPS) exhibited a gradual trend towards recovery, which rose to the highest value 12 months after implantation and then decreased slightly, but the average score was still > 90 points. There was one intra-operative pneumothorax, and two patients with superficial malignant tumours developed skin ulcerations. Multivariate analysis of prognosis showed that tumour sites and types were independent risk factors affecting survival. The number of needles and particles and template types were not the factors.

Conclusions

3D template combined with CT-guided radioactive 125I seed implantation can improve the rational distribution of radiation dose in the tumour target area because accurate radioactive 125I particle implantation was achieved. This technique has fewer complications and can further extend the overall survival and improve the quality of life.

Trial registration

Registration number: ChiCTR2000034566 2020/7/10 0:00:00

Retrospectively registered.
Factors influencing GPs’ perception of specialised palliative homecare (SPHC) importance – results of a cross-sectional study
Authors: Stichling K. , Krause M. , Ditscheid B. , Hach M. , Jansky M. , Kaufmann M. , Lehmann T. , Meißner W. , Nauck F. , Schneider W. , Schulz S. , Vollmar H. C. , Wedding U. , Bleidorn J. , Freytag A. ,   the SAVOIR Study Group, Bauer Anna , Bergmann Lia , Ditscheid Bianka , Eichhorn Cornelia , Freytag Antje , Hach Michaela , Hammer Ulrike , Helbig Aicko , Hennig Beata , Jansky Maximiliane , Kaufmann Michelle , Krause Markus , Krauss Sabine , Lehmann Thomas , L’hoest Helmut , Maddela Srikanth , Marschall Ursula , Mboulla Martial , Meißner Winfried , Melching Heiner , Mühler Florian , Nageler Cornelia , Nauck Friedemann , Rothaug Judith , Saam Joachim , Schneider Werner , Schulz Sven , Stichling Kathleen , Vollmar Horst C. , von Hayek Julia , Wedding Ulrich , Völker Marie-Luise , Kley Vivienne , Feustel Jana , Herklotz Ketura
Published: August 2020

Background

General Practitioners (GPs) are the main providers of primary palliative care (PPC). At the same time they are the main initiators of specialised palliative homecare (SPHC). In Germany, little is known about factors which influence GPs in their involvement of SPHC. Aim of our study is to identify factors that drive GPs to give value to and involve SPHC.

Methods

A cross-sectional survey was performed. In 2018, questionnaires were mailed to 6000 randomly selected GPs from eight German federal states, focusing on the extent of GPs’ palliative care activities and their involvement of SPHC.

Results

With a response rate of 19.4% and exclusion of GPs working in SPHC-teams,n = 1026 questionnaires were appropriate for analysis. GPs valued SPHC support as the most “important/very important” for both “technical/invasive treatment measures” (95%) and availability outside practice opening hours (92%).

The most relevant factor influencing perceived SPHC-importance was GPs’ self-reported extent of engagement in palliative care (β = − 0.283; CI 95% = − 0.384;−0.182), followed by the perceived quality of utilised SPHC (β = 0.119; CI 95% = 0.048;0.190), involvement in treatment of palliative patients after SPHC initiation (β = 0.088; CI 95% = 0.042;0.134), and conviction that palliative care should be a central part of GPs’ work (β = − 0.062; CI 95% = − 0.116;−0.008). Perceived SPHC-importance is also associated with SPHC-referrals (β =0.138;p < 0.001). The lower the engagement of GPs in palliative care, the more they involve SPHC and vice versa.

Conclusions

GPs with low reported activity in palliative care are more likely to initialise SPHC for palliative care activities they do not deliver themselves for various reasons, which might mean that the involvement of SPHC is substitutive instead of complementary to primary palliative care. This finding and its interpretation should be given more attention in the future policy framework for (specialised) palliative homecare.

Trial registration

German Clinical Trials RegisterDRKS00014726, 14.05.2018.
Inequity under equality: research on the benefits equity of Chinese basic medical insurance
Authors: Diao Li , Liu Yiwei
Published: August 2020

Background

The pursuit of equity is one of the basic principles behind the strengthening of health care reform. China’s new rural cooperative medical insurance (NRCMI) and urban residents’ basic medical insurance (URBMI) are both “equalized” in terms of fundraising and reimbursement. This paper studies the benefits equity under this “equalized” system.

Methods

The data analysed in this paper are from the China Family Panel Studies (CFPS) from 2014 to 2016, implemented by the Institute of Social Science Survey at Peking University. A two-part model and a binary choice model are used in the empirical test.

Results

The empirical test revealed that high-income people benefit more from basic medical insurance than low-income people. Mechanism analysis demonstrated that high-income people have higher medical insurance applicability and can utilize better health care. Since low-income people are unhealthier, inequity in benefits exacerbates health inequity. We also found that the benefits equity of URBMI is better than that of NRCMI.

Conclusions

The government needs to pay more attention to the issue of medical insurance inequity. We should consider allowing different income groups to pay different premiums according to their medical expenses or applying different reimbursement policies for different income groups.
Hypomethylation in HBV integration regions aids non-invasive surveillance to hepatocellular carcinoma by low-pass genome-wide bisulfite sequencing
Authors: Zhang Haikun , Dong Peiling , Guo Shicheng , Tao Chengcheng , Chen Wei , Zhao Wenmin , Wang Jiakang , Cheung Ramsey , Villanueva Augusto , Fan Jian , Ding Huiguo , Schrodi Steven J. , Zhang Dake , Zeng Changqing
Published: August 2020

Background

Circulating cell-free DNA (cfDNA) methylation has been demonstrated to be a promising approach for non-invasive cancer diagnosis. However, the high cost of whole genome bisulfite sequencing (WGBS) hinders the clinical implementation of a methylation-based cfDNA early detection biomarker. We proposed a novel strategy in low-pass WGBS (~ 5 million reads) to detect methylation changes in circulating cell-free DNA (cfDNA) from patients with liver diseases and hepatocellular carcinoma (HCC).

Methods

The effective small sequencing depth were determined by 5 pilot cfDNA samples with relative high-depth WGBS. CfDNA of 51 patients with hepatitis, cirrhosis, and HCC were conducted using low-pass WGBS. The strategy was validated in an independent WGBS cohort of 32 healthy individuals and 26 early-stage HCC patients. Fifteen paired tumor tissue and buffy coat samples were used to characterize the methylation of hepatitis B virus (HBV) integration regions and genome distribution of cfDNA.

Results

A significant enrichment of cfDNA in intergenic and repeat regions, especially in previously reported HBV integration sites were observed, as a feature of cfDNA and the bias of cfDNA release. Methylation profiles nearby HBV integration sites were a better indicator for hypomethylation of tumor genome comparing to Alu and LINE (long interspersed nuclear element) repeats, and were able to facilitate the cfDNA-based HCC prediction. Hypomethylation nearby HBV integration sites (5 kb flanking) was detected in HCC patients, but not in patients with hepatitis and cirrhosis (MethylHBV5k, median:0.61 vs 0.72, P = 0.0003). Methylation levels of integration sites certain candidate regions exhibited an area under the receiver operation curve (AUC) value > 0.85 to discriminate HCC from non-HCC samples. The validation cohort achieved the prediction performance with an AUC of 0.954.

Conclusions

Hypomethylation around viral integration sites aids low-pass cfDNA WGBS to serve as a non-invasive approach for early HCC detection, and inspire future efforts on tumor surveillance for oncovirus with integration activity.
Antimicrobial resistance and prevalence of tetracycline resistance genes in Escherichia coli isolated from lesions of colibacillosis in broiler chickens in Sistan, Iran
Authors: Jahantigh Mohammad , Samadi Keyvan , Dizaji Reza Esmaeelzadeh , Salari Saeed
Published: August 2020

Background

Antibiotics have long been the first line of defense to prevent Escherichia coli infections, but they have lost their potency since bacteria have grown increasingly resistant to treatment. The present research aimed to study the drug resistance and the prevalence of tetracycline resistance genes in E. coli isolated from broilers with colibacillosis.

Results

The results showed that the most prevalent type of drug resistance was to tetracycline at 95.0%, and the least was to gentamicin at 21.7%. The prevalences of antimicrobial resistance among the tested antibiotics were significantly different (p < 0.001). A statistically significant difference was observed between the prevalence of the tet genes (p < 0.001). The tetD positive isolates and antibiotic sensitivity to tetracycline showed statistical significant differences (p = 0.017).

Conclusions

Considering the results, tetA is the most common tetracycline resistance gene, and the presence of tetD and antibiotic sensitivity to tetracycline had a significant relationship in E. coli isolated from colibacillosis infections.
Dogs as a source of Salmonella spp. in apparently healthy dogs in the Valencia Region. Could it be related with intestinal lactic acid bacteria?
Authors: Bataller E. , García-Romero E. , Llobat L. , Lizana V. , Jiménez-Trigos E.
Published: August 2020

Background

Although salmonellosis is considered one of the most important food-borne zoonotic diseases in Europe, close contact between dogs and their owners can also be a potential source of Salmonella spp. for humans. This study assessed the prevalence and antimicrobial resistance of Salmonella spp. in apparently healthy dogs in the Valencian Region, eastern Spain. Moreover, a macroscopic comparison of lactic acid bacteria in both Salmonella-positive and Salmonella-negative dogs was carried out.

Results

Of a total of 325 dogs sampled, 6 (1.85%) were positive for Salmonella spp. with 3 different serotypes, Havana (3), Mikawasima (2) and monophasic Typhimurium (1). All isolates were susceptible to all antimicrobials tested except monophasic S. Typhimurium, which was resistant to ampicillin. Finally, macroscopic results revealed that lactic acid bacteria had higher heterogeneity in the Salmonella-negative dogs than in the Salmonella-positive dogs. Although the results in our study showed a low prevalence of Salmonella spp., raw food has been suggested as a risk factor for bacteria in dog faeces.

Conclusions

Public awareness campaigns on good hygiene practices, especially after handling canine faeces or raw food, are necessary. Furthermore, to reduce the potential transmission of bacteria, dogs should be fed food that has been properly cooked, as raw or undercooked food can be a source of zoonotic pathogens. Moreover, further studies must be performed to determine the relationship between lactic acid bacteria and Salmonella spp. in dog faeces.
Repair of alveolar cleft bone defects by bone collagen particles combined with human umbilical cord mesenchymal stem cells in rabbit
Authors: Sun Xue-Cheng , Wang Hu , Li Jian-hui , Zhang Dan , Yin Li-Qiang , Yan Yu-Fang , Ma Xu , Xia Hong-Fei
Published: August 2020

Background

Alveolar cleft is a type of cleft lip and palate that seriously affects the physical and mental health of patients. In this study, a model of the alveolar cleft phenotype was established in rabbits to evaluate the effect of bone collagen particles combined with human umbilical cord mesenchymal stem cells (HUC-MSCs) on the repair of alveolar cleft bone defects.

Methods

A model of alveolar clefts in rabbits was established by removing the incisors on the left side of the upper jaw bone collagen particles combined with HUC-MSCs that were then implanted in the defect area. Blood biochemical analysis was performed 3 months after surgery. Skull tissues were harvested for gross observation, and micro-focus computerised tomography (micro-CT) analysis. Tissues were harvested for histological and immunohistochemical staining. The experiments were repeated 6 months after surgery.

Results

Bone collagen particles and HUC-MSCs showed good biocompatibility. Bone collagen particles combined with HUC-MSCs were markedly better at inducing bone repair and regeneration than bone collagen particles alone.

Conclusions

Combining HUC-MSCs with bone collagen particles provides a simple, rapid and suitable method to fill a bone defect site and treat of alveolar cleft bone defects.
Near-infrared photoresponsive drug delivery nanosystems for cancer photo-chemotherapy
Authors: Wang Xiaoying , Xuan Zeliang , Zhu Xiaofeng , Sun Haitao , Li Jingchao , Xie Zongyu
Published: August 2020

Drug delivery systems (DDSs) based on nanomaterials have shown a promise for cancer chemotherapy; however, it remains a great challenge to localize on-demand release of anticancer drugs in tumor tissues to improve therapeutic effects and minimize the side effects. In this regard, photoresponsive DDSs that employ light as an external stimulus can offer a precise spatiotemporal control of drug release at desired sites of interest. Most photoresponsive DDSs are only responsive to ultraviolet-visible light that shows phototoxicity and/or shallow tissue penetration depth, and thereby their applications are greatly restricted. To address these issues, near-infrared (NIR) photoresponsive DDSs have been developed. In this review, the development of NIR photoresponsive DDSs in last several years for cancer photo-chemotherapy are summarized. They can achieve on-demand release of drugs into tumors of living animals through photothermal, photodynamic, and photoconversion mechanisms, affording obviously amplified therapeutic effects in synergy with phototherapy. Finally, the existing challenges and further perspectives on the development of NIR photoresponsive DDSs and their clinical translation are discussed.
Identifying the pattern of immune related cells and genes in the peripheral blood of ischemic stroke
Authors: Li Zijian , Cui Yueran , Feng Juan , Guo Yanxia
Published: August 2020

Background

Ischemic stroke (IS) is the second leading cause of death worldwide which is a serious hazard to human health. Evidence suggests that the immune system plays a key role in the pathophysiology of IS. However, the precisely immune related mechanisms were still not been systematically understood.

Methods

In this study, we aim to identify the immune related modules and genes that might play vital role in the occurrence and development of IS by using the weighted gene co-expression network analysis (WGCNA). Meanwhile, we applied a kind of deconvolution algorithm to reveal the proportions of 22 subsets of immune cells in the blood samples.

Results

There were total 128 IS patients and 67 healthy control samples in the three Gene Expression Omnibus (GEO) datasets. Under the screening criteria, 1082 DEGs (894 up-regulated and 188 down-regulated) were chosen for further analysis. A total of 11 clinically significant modules were identified, from which immune-related hub modules and hub genes were further explored. Finally, 16 genes were selected as real hub genes for further validation analysis. Furthermore, these CIBERSORT results suggest that detailed analysis of the immune subtype distribution pattern has the potential to enhance clinical prediction and to identify candidates for immunotherapy. More specifically, we identified that neutrophil emerge as a promising target for IS therapies.

Conclusions

In the present study, we investigated the immune related gene expression modules, in which the SLAMF1, IL7R and NCF4 may be novel therapeutic targets to promote functional and histological recovery after ischemic stroke. Furthermore, these hub genes and neutrophils may become important biological targets in the drug screening and drug designing.
C6-ceramide treatment inhibits the proangiogenic activity of multiple myeloma exosomes via the miR-29b/Akt pathway
Authors: Liu Liping , Ye Qinmao , Liu Langni , Bihl Ji Chen , Chen Yanfang , Liu Jing , Cheng Qian
Published: August 2020

Background

The increased bone marrow angiogenesis is involved in the progression of multiple myeloma (MM) with the underlying mechanism poorly understood. Cancer-released exosomes could play an important role in the pathological angiogenesis through exosomal microRNAs (miRs) delivery. It is reported that miR-29b played an important role in regulating the tumor angiogenesis.

Methods

In this study, we explored the role of C6-ceramide (C6-cer, a Ceramide pathway activator) in the angiogenic effect of MM exosomes and its potential mechanism. MM cells (OPM2 and RPMI-8226) treated with C6-cer were studied for its effects on the endothelial cell (EC) functions.

Results

Our results showed that exosomes released from MM cells treated by C6-cer (ExoC6-cer) significantly inhibited the proliferation, migration and tube formation of ECs. For mechanism studies, we found that the level of miR-29b was increased in ECs treated by ExoC6-cer, while mRNA and protein expressions of Akt3, PI3K and VEGFA were decreased in ECs, indicating the involvement of Akt pathway. Furthermore, downregulation of miR-29b by inhibitor administration could prevent the ExoC6-cer-induced cell proliferation, migration and angiogenesis of ECs, accompanied with the increased expressions of Akt3, PI3K and VEGFA.

Conclusions

Collectively, our data suggest that ExoC6-cer-mediated miR-29b expression participates in the progression of MM through suppressing the proliferation, migration and angiogenesis of ECs by targeting Akt signal pathway.
Association of human cytomegalovirus (HCMV) neutralizing antibodies with antibodies to the HCMV glycoprotein complexes
Authors: Shibamura Miho , Yoshikawa Tomoki , Yamada Souichi , Inagaki Takuya , Nguyen Phu Hoang Anh , Fujii Hikaru , Harada Shizuko , Fukushi Shuetsu , Oka Akira , Mizuguchi Masashi , Saijo Masayuki
Published: August 2020

Background

Human cytomegalovirus (HCMV) causes asymptomatic infections, but also causes congenital infections when women were infected with HCMV during pregnancy, and life-threatening diseases in immunocompromised patients. To better understand the mechanism of the neutralization activity against HCMV, the association of HCMV NT antibody titers was assessed with the antibody titers against each glycoprotein complex (gc) of HCMV.

Methods

Sera collected from 78 healthy adult volunteers were used. HCMV Merlin strain and HCMV clinical isolate strain 1612 were used in the NT assay with the plaque reduction assay, in which both the MRC-5 fibroblasts cells and the RPE-1 epithelial cells were used. Glycoprotein complex of gB, gH/gL complexes (gH/gL/gO and gH/gL/UL128–131A [PC]) and gM/gN were selected as target glycoproteins. 293FT cells expressed with gB, gM/gN, gH/gL/gO, or PC, were prepared and used for the measurement of the antibody titers against each gc in an indirect immunofluorescence assay (IIFA). The correlation between the IIFA titers to each gc and the HCMV-NT titers was evaluated.

Results

There were no significant correlations between gB-specific IIFA titers and the HCMV-NT titers in epithelial cells or between gM/gN complex-specific IIFA titers and the HCMV-NT titers. On the other hand, there was a statistically significant positive correlation between the IIFA titers to gH/gL complexes and HCMV-NT titers.

Conclusions

The data suggest that the gH/gL complexes might be the major target to induce NT activity against HCMV.
The impact of ATP-binding cassette transporters on metabolic diseases
Authors: Ye Zixiang , Lu Yifei , Wu Tao
Published: August 2020

Currently, many people worldwide suffer from metabolic diseases caused by heredity and external factors, such as diet. One of the symptoms of metabolic diseases is abnormal lipid metabolism. ATP binding cassette (ABC) transporters are one of the largest transport protein superfamilies that exist in nearly all living organisms and are mainly located on lipid-processing cells. ABC transporters have been confirmed to be closely related to the pathogenesis of diseases such as metabolic diseases, cancer and Alzheimer’s disease based on their transport abilities. Notably, the capability to transport lipids makes ABC transporters critical in metabolic diseases. In addition, gene polymorphism in ABC transporters has been reported to be a risk factor for metabolic diseases, and it has been reported that relevant miRNAs have significant roles in regulating ABC transporters. In this review, we integrate recent studies to examine the roles of ABC transporters in metabolic diseases and aim to build a network with ABC transporters as the core, linking their transport abilities with metabolic and other diseases.
Variable phenotypes and outcomes associated with the MMACHC c.609G>A homologous mutation: long term follow-up in a large cohort of cases
Authors: He Ruxuan , Mo Ruo , Shen Ming , Kang Lulu , Song Jinqing , Liu Yi , Chen Zhehui , Zhang Hongwu , Yao Hongxin , Liu Yupeng , Zhang Yao , Dong Hui , Jin Ying , Li Mengqiu , Qin Jiong , Zheng Hong , Chen Yongxing , Li Dongxiao , Wei Haiyan , Li Xiyuan , Zhang Huifeng , Huang Min , Zhang Chunyan , Jiang Yuwu , Liang Desheng , Tian Yaping , Yang Yanling
Published: August 2020

Background

Cobalamin C deficiency (cblC) caused by theMMACHCmutations is the most common type of the disorders of intracellular cobalamin metabolism. While the c.609G > A mutation is most frequent in ChinesecblCpatients, its correlation with phenotype has not been delineated. Here we aim to investigate the factors affecting variable phenotypes and outcomes associated with theMMACHCc.609G > A homologous mutation in 149 Chinese cases to have implications for treatment and prevention.

Methods

We assessed 149cblCpatients caused byMMACHCc.609G > A homozygous mutation. The clinical manifestations, complications, treatment, and outcomes were evaluated; 120 patients were followed-up till December 2019.

Results

Two patients (1.3%) were prenatally diagnosed, treated after birth and consequently showed normal development. In 15 patients (10.1%) detected by newborn screening, 10 were treated at the age of 2 weeks and showed normal development, while the other 5 were treated after onset and showed neurologic disorders. All 132 clinically diagnosed patients (88.6%) developed symptoms at age from few minutes after birth to 72 months. Among them, 101 (76.5%) had early-onset (before the age of 12 months) and 31 (23.5%) had late-onset (after the age of 12 months). Totally 5 patients died and 24 were lost to follow-up. Of the 132 clinical diagnosed patients, 92 (69.7%) presented with developmental delay, 65 (49.2%) had seizures, 37 (28.0%) had anemia, 24 (18.2%) had feeding difficulty, 23 (17.4%) had ocular problems, and 22 (16.7%) had hydrocephalus. Compared with the non-developmental delay group, the onset age, the age at treatment initiation and the time from onset to treatment initiation were later in the developmental delay group. Seizure group showed significantly higher urinary methylmalonic acid concentration. During long-term follow-up, plasma total homocysteine (tHcy) levels were significantly higher in patients in the uncontrolled group than those in the seizure-free group.

Conclusions

MostcblCpatients caused byMMACHCc.609G > A homozygous mutation showed early-onset. The clinically diagnosed patients usually showed the presence of irreversible brain disorders. Patients treated from the pre-symptomatic stage showed favorable outcomes. Therefore, newborn screening, prenatal diagnosis and early treatment are crucial and the c.609G > A mutant allele should be listed in the pre-pregnancy carrier screening panel in China.
Predictors of surgical management of high grade blunt splenic injuries in adult trauma patients: a 5-year retrospective cohort study from an academic level I trauma center
Authors: Nijdam Thomas M. P. , Spijkerman Roy , Hesselink Lilian , Leenen Luke P. H. , Hietbrink Falco
Published: August 2020

Backgrounds

Splenic injury accounts for 40% of all injuries after blunt abdominal trauma. Blunt splenic injury in hemodynamically unstable patients is preferably treated by splenectomy. Nowadays hemodynamically stable patients with low grade splenic injuries are mostly treated by non-operative management (NOM). However no consensus exists about the management of high grade splenic injuries in hemodynamically stable patients. Therefore the aim of this study was to analyze patients with high grade splenic injuries in our institution.

Methods

We retrospectively included all patients with a splenic injury presented to our level I trauma center during the 5-year period from January 1, 2012, until December 31, 2017. Baseline characteristics, data regarding complications and mortality were collected from the electronic patient registry. Patients were grouped based on splenic injury and the treatment they received.

Results

A total of 123 patients were included, of which 93 (75.6%) were male with a median age of 31 (24–52) and a median injury severity score of 27 (17–34). High grade injuries (n = 28) consisted of 20 Grade IV injuries and 8 grade V injuries. Splenectomy was required in 15/28 (53.6%) patients, of whom all remained hemodynamically unstable after resuscitation, including all grade V injuries. A total of 13 patients with high grade injuries were treated with spleen preserving therapy. Seven of these patients received angio-embolization. One patient went for laparotomy and the spleen was treated with a hemostatic agent. Secondary hemorrhage was present in 3 of these patients (initial treatment: 1 embolization/ 2 observational), resulting in a success rate of 76.9%. There is no mortality seen in patient with high grade splenic injuries.

Conclusion

Non-operative treatment in high grade splenic injuries is a safe treatment modality in hemodynamically stable patients. Hemodynamic status and peroperative bleeding, not injury severity or splenic injury grade were the drivers for surgical management by splenectomy. This selected cohort of patients must be closely monitored to prevent adverse outcomes from secondary delayed bleeding in case of non-operative management.
Long-read-based human genomic structural variation detection with cuteSV
Authors: Jiang Tao , Liu Yongzhuang , Jiang Yue , Li Junyi , Gao Yan , Cui Zhe , Liu Yadong , Liu Bo , Wang Yadong
Published: August 2020

Long-read sequencing is promising for the comprehensive discovery of structural variations (SVs). However, it is still non-trivial to achieve high yields and performance simultaneously due to the complex SV signatures implied by noisy long reads. We propose cuteSV, a sensitive, fast, and scalable long-read-based SV detection approach. cuteSV uses tailored methods to collect the signatures of various types of SVs and employs a clustering-and-refinement method to implement sensitive SV detection. Benchmarks on simulated and real long-read sequencing datasets demonstrate that cuteSV has higher yields and scaling performance than state-of-the-art tools. cuteSV is available athttps://github.com/tjiangHIT/cuteSV.
Genetic relatedness of Leptospira interrogans serogroup Autumnalis isolated from humans, dogs, and mice in Japan
Authors: Koizumi Nobuo , Izumiya Hidemasa , Ohnishi Makoto
Published: August 2020

Objective

Leptospirosis is a zoonotic disease caused by pathogenic spirochetes ofLeptospiraspp., and peridomiciliary rodents are the most important reservoir animals for human infection. Dogs are known to be the reservoir animal ofL. interrogansserovar Canicola, but the importance of dogs in zoonotic transmission of otherLeptospiraserotypes/genotypes remains unclear. This study reports the isolation ofL. interrogansserogroup Autumnalis from two human patients in Japan and describes the genetic comparison between canine and mouse isolates using multiple-locus variable-number tandem repeat analysis (MLVA).

Results

MLVA revealed that 8 out of the 11 loci compared were identical between the two human isolates. The human isolates clustered with the dog but not the mouse isolates. Moreover, the profile of one of the human isolates was identical to that of one of the dog isolates.
Expression of smooth muscle-like effectors and core cardiomyocyte regulators in the contractile papillae of Ciona
Authors: Johnson Christopher J. , Razy-Krajka Florian , Stolfi Alberto
Published: August 2020

Background

The evolution of vertebrate smooth muscles is obscured by lack of identifiable smooth muscle-like cells in tunicates, the invertebrates most closely related to vertebrates. A recent evolutionary model was proposed in which smooth muscles arose before the last bilaterian common ancestor, and were later diversified, secondarily lost or modified in the branches leading to extant animal taxa. However, there is currently no data from tunicates to support this scenario.

Methods and results

Here, we show that the axial columnar cells, a unique cell type in the adhesive larval papillae of the tunicate Ciona, are enriched for orthologs of vertebrate smooth/non-muscle-specific effectors of contractility, in addition to developing from progenitors that express conserved cardiomyocyte regulatory factors. We show that these cells contract during the retraction of the Ciona papillae during larval settlement and metamorphosis.

Conclusions

We propose that the axial columnar cells of Ciona are a myoepithelial cell type required for transducing external stimuli into mechanical forces that aid in the attachment of the motile larva to its final substrate. Furthermore, they share developmental and functional features with vertebrate myoepithelial cells, vascular smooth muscle cells, and cardiomyocytes. We discuss these findings in the context of the proposed models of vertebrate smooth muscle and cardiomyocyte evolution.
The co-culture of ASCs and EPCs promotes vascularized bone regeneration in critical-sized bone defects of cranial bone in rats
Authors: He Yuanjia , Lin Shuang , Ao Qiang , He Xiaoning
Published: August 2020

Background

The repair of critical-sized bone defect represents a challenging problem in bone tissue engineering. To address the most important problem in bone defect repair, namely insufficient blood supply, this study aimed to find a method that can promote the formation of vascularized bone tissue.

Method

The phenotypes of ASCs and EPCs were identified respectively, and ASCs/EPCs were co-cultured in vitro to detect the expression of osteogenic and angiogenic genes. Furthermore, the co-culture system combined with scaffold material was used to repair the critical-sized bone defects of the cranial bone in rats.

Results

The co-culture of ASCs/EPCs could increase osteogenesis and angiogenesis-related gene expression in vitro. The results of in vivo animal experiments demonstrated that the ASC/EPC group could promote bone regeneration and vascularization in the meantime and then significantly accelerate the repair of critical-sized bone defects.

Conclusion

It is feasible to replace traditional single seed cells with ASC/EPC co-culture system for vascularized bone regeneration. This system could ultimately enable clinicians to better repair the defect of craniofacial bone and avoid donor site morbidity.
Comprehensive transcriptomic and proteomic analyses of antroquinonol biosynthetic genes and enzymes in Antrodia camphorata
Authors: Liu Xiaofeng , Xia Yongjun , Zhang Yao , Yang Caiyun , Xiong Zhiqiang , Song Xin , Ai Lianzhong
Published: August 2020

Antroquinonol (AQ) has several remarkable bioactivities in acute myeloid leukaemia and pancreatic cancer, but difficulties in the mass production of AQ hamper its applications. Currently, molecular biotechnology methods, such as gene overexpression, have been widely used to increase the production of metabolites. However, AQ biosynthetic genes and enzymes are poorly understood. In this study, an integrated study coupling RNA-Seq and isobaric tags for relative and absolute quantitation (iTRAQ) were used to identify AQ synthesis-related genes and enzymes in Antrodia camphorata during coenzyme Q0-induced fermentation (FM). The upregulated genes related to acetyl-CoA synthesis indicated that acetyl-CoA enters the mevalonate pathway to form the farnesyl tail precursor of AQ. The metE gene for an enzyme with methyl transfer activity provided sufficient methyl groups for AQ structure formation. The CoQ2 and ubiA genes encode p-hydroxybenzoate polyprenyl transferase, linking coenzyme Q0 and the polyisoprene side chain to form coenzyme Q3. NADH is transformed into NAD+ and releases two electrons, which may be beneficial for the conversion of coenzyme Q3 to AQ. Understanding the biosynthetic genes and enzymes of AQ is important for improving its production by genetic means in the future.
Cognitive and psychosocial outcomes of mechanically ventilated intensive care patients with and without delirium
Authors: Bulic Daniella , Bennett Michael , Georgousopoulou Ekavi N. , Shehabi Yahya , Pham Tai , Looi Jeffrey C. L. , van Haren Frank M. P.
Published: August 2020

Objective

Delirium is common in intensive care patients and is associated with short- and long-term adverse outcomes. We investigated the long-term risk of cognitive impairment and post-traumatic stress disorder (PTSD) in intensive care patients with and without delirium.

Methods

This is a prospective cohort study in ICUs in two Australian university-affiliated hospitals. Patients were eligible if they were older than 18 years, mechanically ventilated for more than 24 h and did not meet exclusion criteria. Delirium was assessed using the Confusion Assessment Method for Intensive Care Unit. Variables assessing cognitive function and PTSD symptoms were collected at ICU discharge, after 6 and 12 months: Mini-Mental State Examination, Telephone Interview for Cognitive Status, Impact of Events Scale-Revised and Informant Questionnaire for Cognitive Decline (caregiver).

Results

103 participants were included of which 36% developed delirium in ICU. Patients with delirium were sicker and had longer duration of mechanical ventilation and ICU length of stay. After 12 months, 41/60 (68.3%) evaluable patients were cognitively impaired, with 11.6% representing the presence of symptoms consistent with dementia. When evaluated by the patient’s caregiver, the patient’s cognitive function was found to be severely impaired in a larger proportion of patients (14/60, 23.3%). Delirium was associated with worse cognitive function at ICU discharge, but not with long-term cognitive function. IES-R scores, measuring PTSD symptoms, were significantly higher in patients who had delirium compared to patients without delirium. In regression analysis, delirium was independently associated with cognitive function at ICU discharge and PTSD symptoms at 12 months.

Conclusions

Intensive care survivors have significant rates of long-term cognitive decline and PTSD symptoms. Delirium in ICU was independently associated with short-term but not long-term cognitive function, and with long-term PTSD symptoms.

Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12616001116415, 15/8/2016 retrospectively registered, https://www.anzctr.org.au
Lactobacillus salivarius alleviates inflammation via NF-κB signaling in ETEC K88-induced IPEC-J2 cells
Authors: Qiao Jiayun , Sun Zeyang , Liang Dongmei , Li Haihua
Published: August 2020

Background

Enterotoxigenic Escherichia coli (ETEC) K88 commonly colonize in the small intestine and keep releasing enterotoxins to impair the intestinal barrier function and trigger inflammatory reaction. Although Lactobacillus salivarius (L. salivarius) has been reported to enhance intestinal health, it remains to be seen whether there is a functional role of L. salivarius in intestinal inflammatory response in intestinal porcine epithelial cell line (IPEC-J2) when stimulated with ETEC K88. In the present study, IPEC-J2 cells were first treated with L. salivarius followed by the stimulation of ETEC K88 for distinct time period. ETEC K88 adherent status, pattern recognition receptors (PRRs) mRNA, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) activation, the release of pro-inflammation cytokines and cell integrity were examined.

Results

Aside from an inhibited adhesion of ETEC K88 to IPEC-J2 cells, L. salivarius was capable of remarkably attenuating the expression levels of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), IL-8, Toll-like receptor (TLR) 4, nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein (NLRP) 3 and NLRP6. This alternation was accompanied by a significantly decreased phosphorylation of p38 MAPK and p65 NF-κB during ETEC K88 infection with L. salivarius pretreatment. Western blot analysis revealed that L. salivarius increased the expression levels of zona occludens 1 (ZO-1) and occludin (P < 0.05) in ETEC K88-infected IPEC-J2 cells. Compared with ETEC K88-infected groups, the addition of L. salivarius as well as extra inhibitors for MAPKs and NF-κB to ETEC K88-infected IPEC-J2 cells had the capability to reduce pro-inflammatory cytokines.

Conclusions

Collectively, our results suggest that L. salivarius might reduce inflammation-related cytokines through attenuating phosphorylation of p38 MAPK and blocking the NF-κB signaling pathways. Besides, L. salivarius displayed a potency in the enhancement of IPEC-J2 cell integrity.