bluuebunny/crossref_metadata_2025 huggingface dataset:
Long noncoding RNA LINC00857 promotes pancreatic cancer proliferation and metastasis by regulating the miR-130b/RHOA axis
Authors: Chen Peng , Zeng Zhirui , Wang Jie , Cao Wenpeng , Song Chunzhuo , Lei Shan , Li Yichuan , Ren Zhangxia
Published: April 2022

Dysregulation of long noncoding RNAs (lncRNAs) is involved in the pathogenesis and progression of pancreatic cancer (PC). In the current study, we investigated the role and molecular mechanism of LINC00857 in PC. The expression of LINC00857 in PC was analyzed by bioinformatics analysis and qRT-PCR, and the relationship between LINC00857 expression and clinical characteristics of patients of PC was analyzed by Fisher’s exact test. Gain- and loss-of-function assays were performed to determine the biological function of LINC00857 in PC. The relationship between LINC00857, miR-130b, and RHOA were determined by RNA pull-down assay, luciferase assay, and qRT-PCR. Our results demonstrated that LINC00857 expression was elevated in PC, and high expression of LINC00857 was positively associated with tumor diameter, T stage, and lymph node metastasis. LINC00857 promoted the proliferation and mobility of PC cells in vitro and in vivo. Mechanistically, LINC00857 acts as a sponge for miR-130b and decreases its expression. miR-130b exhibits tumor suppressor functions in PC, and RHOA was identified as the key target gene of miR-130b. The functions induced by LINC00857 in PC cells were dependent on the miR-130b/RHOA axis. In conclusion, the current study indicated that LINC00857 promotes PC tumorigenesis and metastasis by modulating the miR-130b/RHOA axis, implying that LINC00857 might be a new therapeutic target for PC.
Clitoral reconstruction: challenges and new directions
Authors: Villani Michela
Published: April 2022

Clitoral reconstruction (CR) has been the subject of several studies in recent years, mainly in the medical field. Women with female genital mutilation or cutting (FGM/C) seek clitoral reconstructive surgery to improve their sexual well-being, but also because they are affected by poor self- and body image. CR is supposed to help women with FGM/C reconstruct their sense of self, but the benefits and risks of this surgery have not been sufficiently explored. There are currently no recommendations supporting CR from mainstream medical bodies, and there have been very few ethical studies of the procedure. This article critically discusses the principal studies produced in the medical field and available reflections produced in the social sciences. Through the theoretical frameworks of postcolonial and feminist studies, the article discusses sexuality and pleasure, gender and identity, and race and positionality, with the aim of promoting collaborative work on CR between researchers and social and health professionals.
Data-driven learning how oncogenic gene expression locally alters heterocellular networks
Authors: Klinke David J. , Fernandez Audry , Deng Wentao , Razazan Atefeh , Latifizadeh Habibolla , Pirkey Anika C.
Published: April 2022

Developing drugs increasingly relies on mechanistic modeling and simulation. Models that capture causal relations among genetic drivers of oncogenesis, functional plasticity, and host immunity complement wet experiments. Unfortunately, formulating such mechanistic cell-level models currently relies on hand curation, which can bias how data is interpreted or the priority of drug targets. In modeling molecular-level networks, rules and algorithms are employed to limit a priori biases in formulating mechanistic models. Here we combine digital cytometry with Bayesian network inference to generate causal models of cell-level networks linking an increase in gene expression associated with oncogenesis with alterations in stromal and immune cell subsets from bulk transcriptomic datasets. We predict how increased Cell Communication Network factor 4, a secreted matricellular protein, alters the tumor microenvironment using data from patients diagnosed with breast cancer and melanoma. Predictions are then tested using two immunocompetent mouse models for melanoma, which provide consistent experimental results.
Presenilin 2 N141I mutation induces hyperactive immune response through the epigenetic repression of REV-ERBα
Authors: Nam Hyeri , Lee Younghwan , Kim Boil , Lee Ji-Won , Hwang Seohyeon , An Hyun-Kyu , Chung Kyung Min , Park Youngjin , Hong Jihyun , Kim Kyungjin , Kim Eun-Kyoung , Choe Han Kyoung , Yu Seong-Woon
Published: April 2022

Hyperimmunity drives the development of Alzheimer disease (AD). The immune system is under the circadian control, and circadian abnormalities aggravate AD progress. Here, we investigate how an AD-linked mutation deregulates expression of circadian genes and induces cognitive decline using the knock-in (KI) mice heterozygous for presenilin 2 N141I mutation. This mutation causes selective overproduction of clock gene-controlled cytokines through the DNA hypermethylation-mediated repression of REV-ERBα in innate immune cells. The KI/+ mice are vulnerable to otherwise innocuous, mild immune challenges. The antipsychotic chlorpromazine restores the REV-ERBα level by normalizing DNA methylation through the inhibition of PI3K/AKT1 pathway, and prevents the overexcitation of innate immune cells and cognitive decline in KI/+ mice. These results highlight a pathogenic link between this AD mutation and immune cell overactivation through the epigenetic suppression of REV-ERBα.
Construction of a two-dimensional artificial antioxidase for nanocatalytic rheumatoid arthritis treatment
Authors: Yang Bowen , Yao Heliang , Yang Jiacai , Chen Chang , Shi Jianlin
Published: April 2022

Constructing nanomaterials mimicking the coordination environments of natural enzymes may achieve biomimetic catalysis. Here we construct a two-dimensional (2D) metal-organic framework (MOF) nanosheet catalyst as an artificial antioxidase for nanocatalytic rheumatoid arthritis treatment. The 2D MOF periodically assembles numbers of manganese porphyrin molecules, which has a metal coordination geometry analogous to those of two typical antioxidases, human mitochondrial manganese superoxide dismutase (Mn-SOD) and human erythrocyte catalase. The zinc atoms of the 2D MOF regulate the metal-centered redox potential of coordinated manganese porphyrin ligand, endowing the nanosheet with both SOD- and catalase-like activities. Cellular experiments show unique anti-inflammatory and pro-biomineralization performances of the 2D MOF, while in vivo animal model further demonstrates its desirable antiarthritic efficacy. It is expected that such a nanocatalytic antioxidation concept may provide feasible approaches to future anti-inflammatory treatments.
The impact of reproductive factors on DNA methylation-based telomere length in healthy breast tissue
Authors: Sehl Mary E. , Henry Jill E. , Storniolo Anna Maria , Horvath Steve , Ganz Patricia A.
Published: April 2022

Estrogen promotes breast tissue proliferation and telomerase activation. We investigated the effects of reproductive history on cell cycling and telomere length using a DNA methylation-based estimate of telomere length (DNAmTL) in breast and blood from healthy women donors. We demonstrate that DNAmTL is shorter in breast than in blood, and that nulliparous women have longer age-adjusted DNAmTL in both breast and blood, potentially explaining their higher risk of breast cancer.
LINC00355 regulates p27KIP expression by binding to MENIN to induce proliferation in late-stage relapse breast cancer
Authors: Eteleeb Abdallah M. , Thunuguntla Prasanth K. , Gelev Kyla Z. , Tang Cynthia Y. , Rozycki Emily B. , Miller Alexander , Lei Jonathan T. , Jayasinghe Reyka G. , Dang Ha X. , White Nicole M. , Reis-Filho Jorge S. , Mardis Elaine R. , Ellis Matthew J. , Ding Li , Silva-Fisher Jessica M. , Maher Christopher A.
Published: April 2022

Late-stage relapse (LSR) in patients with breast cancer (BC) occurs more than five years and up to 10 years after initial treatment and has less than 30% 5-year relative survival rate. Long non-coding RNAs (lncRNAs) play important roles in BC yet have not been studied in LSR BC. Here, we identify 1127 lncRNAs differentially expressed in LSR BC via transcriptome sequencing and analysis of 72 early-stage and 24 LSR BC patient tumors. Decreasing expression of the most up-regulated lncRNA, LINC00355, in BC and MCF7 long-term estrogen deprived cell lines decreases cellular invasion and proliferation. Subsequent mechanistic studies show that LINC00355 binds to MENIN and changes occupancy at the CDKN1B promoter to decrease p27Kip. In summary, this is a key study discovering lncRNAs in LSR BC and LINC00355 association with epigenetic regulation and proliferation in BC.
Bone strength and composition in spacefaring rodents: systematic review and meta-analysis
Authors: Goldsmith Matthew , Crooks Sequoia D. , Condon Sean F. , Willie Bettina M. , Komarova Svetlana V.
Published: April 2022

Studying the effects of space travel on bone of experimental animals provides unique advantages, including the ability to perform post-mortem analysis and mechanical testing. To synthesize the available data to assess how much and how consistently bone strength and composition parameters are affected by spaceflight, we systematically identified studies reporting bone health in spacefaring animals from Medline, Embase, Web of Science, BIOSIS, and NASA Technical reports. Previously, we reported the effect of spaceflight on bone architecture and turnover in rodents and primates. For this study, we selected 28 articles reporting bone strength and composition in 60 rats and 60 mice from 17 space missions ranging from 7 to 33 days in duration. Whole bone mechanical indices were significantly decreased in spaceflight rodents, with the percent difference between spaceflight and ground control animals for maximum load of −15.24% [Confidence interval: −22.32, −8.17]. Bone mineral density and calcium content were significantly decreased in spaceflight rodents by −3.13% [−4.96, −1.29] and −1.75% [−2.97, −0.52] respectively. Thus, large deficits in bone architecture (6% loss in cortical area identified in a previous study) as well as changes in bone mass and tissue composition likely lead to bone strength reduction in spaceflight animals.
Nonlinear control of transcription through enhancer–promoter interactions
Authors: Zuin Jessica , Roth Gregory , Zhan Yinxiu , Cramard Julie , Redolfi Josef , Piskadlo Ewa , Mach Pia , Kryzhanovska Mariya , Tihanyi Gergely , Kohler Hubertus , Eder Mathias , Leemans Christ , van Steensel Bas , Meister Peter , Smallwood Sebastien , Giorgetti Luca
Published: April 2022

Chromosome structure in mammals is thought to regulate transcription by modulating three-dimensional interactions between enhancers and promoters, notably through CTCF-mediated loops and topologically associating domains (TADs)1–4. However, how chromosome interactions are actually translated into transcriptional outputs remains unclear. Here, to address this question, we use an assay to position an enhancer at large numbers of densely spaced chromosomal locations relative to a fixed promoter, and measure promoter output and interactions within a genomic region with minimal regulatory and structural complexity. A quantitative analysis of hundreds of cell lines reveals that the transcriptional effect of an enhancer depends on its contact probabilities with the promoter through a nonlinear relationship. Mathematical modelling suggests that nonlinearity might arise from transient enhancer–promoter interactions being translated into slower promoter bursting dynamics in individual cells, therefore uncoupling the temporal dynamics of interactions from those of transcription. This uncovers a potential mechanism of how distal enhancers act from large genomic distances, and of how topologically associating domain boundaries block distal enhancers. Finally, we show that enhancer strength also determines absolute transcription levels as well as the sensitivity of a promoter to CTCF-mediated transcriptional insulation. Our measurements establish general principles for the context-dependent role of chromosome structure in long-range transcriptional regulation.
Prolonged viral suppression with anti-HIV-1 antibody therapy
Authors: Gaebler Christian , Nogueira Lilian , Stoffel Elina , Oliveira Thiago Y. , Breton Gaëlle , Millard Katrina G. , Turroja Martina , Butler Allison , Ramos Victor , Seaman Michael S. , Reeves Jacqueline D. , Petroupoulos Christos J. , Shimeliovich Irina , Gazumyan Anna , Jiang Caroline S. , Jilg Nikolaus , Scheid Johannes F. , Gandhi Rajesh , Walker Bruce D. , Sneller Michael C. , Fauci Anthony , Chun Tae-Wook , Caskey Marina , Nussenzweig Michel C.
Published: April 2022

HIV-1 infection remains a public health problem with no cure. Anti-retroviral therapy (ART) is effective but requires lifelong drug administration owing to a stable reservoir of latent proviruses integrated into the genome of CD4+ T cells1. Immunotherapy with anti-HIV-1 antibodies has the potential to suppress infection and increase the rate of clearance of infected cells2,3. Here we report on a clinical study in which people living with HIV received seven doses of a combination of two broadly neutralizing antibodies over 20 weeks in the presence or absence of ART. Without pre-screening for antibody sensitivity, 76% (13 out of 17) of the volunteers maintained virologic suppression for at least 20 weeks off ART. Post hoc sensitivity analyses were not predictive of the time to viral rebound. Individuals in whom virus remained suppressed for more than 20 weeks showed rebound viraemia after one of the antibodies reached serum concentrations below 10 µg ml−1. Two of the individuals who received all seven antibody doses maintained suppression after one year. Reservoir analysis performed after six months of antibody therapy revealed changes in the size and composition of the intact proviral reservoir. By contrast, there was no measurable decrease in the defective reservoir in the same individuals. These data suggest that antibody administration affects the HIV-1 reservoir, but additional larger and longer studies will be required to define the precise effect of antibody immunotherapy on the reservoir.
Somatic mutation rates scale with lifespan across mammals
Authors: Cagan Alex , Baez-Ortega Adrian , Brzozowska Natalia , Abascal Federico , Coorens Tim H. H. , Sanders Mathijs A. , Lawson Andrew R. J. , Harvey Luke M. R. , Bhosle Shriram , Jones David , Alcantara Raul E. , Butler Timothy M. , Hooks Yvette , Roberts Kirsty , Anderson Elizabeth , Lunn Sharna , Flach Edmund , Spiro Simon , Januszczak Inez , Wrigglesworth Ethan , Jenkins Hannah , Dallas Tilly , Masters Nic , Perkins Matthew W. , Deaville Robert , Druce Megan , Bogeska Ruzhica , Milsom Michael D. , Neumann Björn , Gorman Frank , Constantino-Casas Fernando , Peachey Laura , Bochynska Diana , Smith Ewan St. John , Gerstung Moritz , Campbell Peter J. , Murchison Elizabeth P. , Stratton Michael R. , Martincorena Iñigo
Published: April 2022

The rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans1–7. Comparative analyses can shed light on the diversity of mutagenesis across species, and on long-standing hypotheses about the evolution of somatic mutation rates and their role in cancer and ageing. Here we performed whole-genome sequencing of 208 intestinal crypts from 56 individuals to study the landscape of somatic mutation across 16 mammalian species. We found that somatic mutagenesis was dominated by seemingly endogenous mutational processes in all species, including 5-methylcytosine deamination and oxidative damage. With some differences, mutational signatures in other species resembled those described in humans8, although the relative contribution of each signature varied across species. Notably, the somatic mutation rate per year varied greatly across species and exhibited a strong inverse relationship with species lifespan, with no other life-history trait studied showing a comparable association. Despite widely different life histories among the species we examined—including variation of around 30-fold in lifespan and around 40,000-fold in body mass—the somatic mutation burden at the end of lifespan varied only by a factor of around 3. These data unveil common mutational processes across mammals, and suggest that somatic mutation rates are evolutionarily constrained and may be a contributing factor in ageing.
Selective feeding of three bivalve species on the phytoplankton community in a marine pond revealed by high-throughput sequencing
Authors: Qiao Ling , Chang Zhiqiang , Li Jian , Li Tiejun
Published: April 2022

The study of the selective feeding of bivalves is necessary in order to improve our understanding of bivalve growth and development, which helps to better define the roles of bivalves in their ecosystems. Little information is currently available on the feeding preferences of bivalves in natural waters, since all diets are provided as single or mixed algae in experiments. In this study, high-throughput sequencing of the 23S rRNA gene was performed to explore differences in the feeding selectivity ofMercenaria mercenaria,Meretrix meretrixandRuditapes philippinarumduring different stages of their culturing to reveal their feeding preferences in natural waters. We found that the three bivalve species had different preferential selection of phytoplankton genera, indicating specific selection and avoidance of particular types of algae during their development in aquaculture.M. mercenariawas the most selective of the bivalves, followed byM. meretrixand thenR. philippinarum. With the growth ofM. mercenariaandM. meretrix, more kinds of phytoplankton could be ingested. In addition, high-throughput sequencing showed that some picophytoplankton includingSynechococcus,Microchloropsis,andChrysochromulinawere dominant in the hepatopancreas samples obtained from these three bivalves. Therefore, the importance of these pico-sized algae in bivalve diets should be reassessed.
Amplification of elliptically polarized sub-femtosecond pulses in neon-like X-ray laser modulated by an IR field
Authors: Khairulin I. R. , Antonov V. A. , Ryabikin M. Yu. , Berrill M. A. , Shlyaptsev V. N. , Rocca J. J. , Kocharovskaya Olga
Published: April 2022

Amplification of attosecond pulses produced via high harmonic generation is a formidable problem since none of the amplifiers can support the corresponding PHz bandwidth. Producing the well defined polarization state common for a set of harmonics required for formation of the circularly/elliptically polarized attosecond pulses (which are on demand for dynamical imaging and coherent control of the spin flip processes) is another big challenge. In this work we show how both problems can be tackled simultaneously on the basis of the same platform, namely, the plasma-based X-ray amplifier whose resonant transition frequency is modulated by an infrared field.
Household air pollution from solid fuel use as a dose-dependent risk factor for cognitive impairment in northern China
Authors: Tseng Tzu-Wei Joy , Carter Ellison , Yan Li , Chan Queenie , Elliott Paul , Ezzati Majid , Kelly Frank , Schauer James J. , Wu Yangfeng , Yang Xudong , Zhao Liancheng , Baumgartner Jill
Published: April 2022

The relationship between exposure to household air pollution (HAP) from solid fuel use and cognition remains poorly understood. Among 401 older adults in peri-urban northern China enrolled in the INTERMAP-China Prospective Study, we estimated the associations between exposure to HAP and z-standardized domain-specific and overall cognitive scores from the Montreal Cognitive Assessment. Interquartile range increases in exposures to fine particulate matter (53.2-µg/m3) and black carbon (0.9-µg/m3) were linearly associated with lower overall cognition [− 0.13 (95% confidence interval: − 0.22, − 0.04) and − 0.10 (− 0.19, − 0.01), respectively]. Using solid fuel indoors and greater intensity of its use were also associated with lower overall cognition (range of point estimates: − 0.13 to − 0.03), though confidence intervals included zero. Among individual cognitive domains, attention had the largest associations with most exposure measures. Our findings indicate that exposure to HAP may be a dose-dependent risk factor for cognitive impairment. As exposure to HAP remains pervasive in China and worldwide, reducing exposure through the promotion of less-polluting stoves and fuels may be a population-wide intervention strategy to lessen the burden of cognitive impairment.
Oscillatory calcium release and sustained store-operated oscillatory calcium signaling prevents differentiation of human oligodendrocyte progenitor cells
Authors: Seidman Richard A. , Khattab Heba , Polanco Jessie J. , Broome Jacqueline E. , Sim Fraser J.
Published: April 2022

Endogenous remyelination in demyelinating diseases such as multiple sclerosis is contingent upon the successful differentiation of oligodendrocyte progenitor cells (OPCs). Signaling via the Gαq-coupled muscarinic receptor (M1/3R) inhibits human OPC differentiation and impairs endogenous remyelination in experimental models. We hypothesized that calcium release following Gαq-coupled receptor (GqR) activation directly regulates human OPC (hOPC) cell fate. In this study, we show that specific GqR agonists activating muscarinic and metabotropic glutamate receptors induce characteristic oscillatory calcium release in hOPCs and that these agonists similarly block hOPC maturation in vitro. Both agonists induce calcium release from endoplasmic reticulum (ER) stores and store operated calcium entry (SOCE) likely via STIM/ORAI-based channels. siRNA mediated knockdown (KD) of obligate calcium sensors STIM1 and STIM2 decreased the magnitude of muscarinic agonist induced oscillatory calcium release and attenuated SOCE in hOPCs. In addition, STIM2 expression was necessary to maintain the frequency of calcium oscillations and STIM2 KD reduced spontaneous OPC differentiation. Furthermore, STIM2 siRNA prevented the effects of muscarinic agonist treatment on OPC differentiation suggesting that SOCE is necessary for the anti-differentiative action of muscarinic receptor-dependent signaling. Finally, using a gain-of-function approach with an optogenetic STIM lentivirus, we demonstrate that independent activation of SOCE was sufficient to significantly block hOPC differentiation and this occurred in a frequency dependent manner while increasing hOPC proliferation. These findings suggest that intracellular calcium oscillations directly regulate hOPC fate and that modulation of calcium oscillation frequency may overcome inhibitory Gαq-coupled signaling that impairs myelin repair.
Estradiol inhibits HIV-1BaL infection and induces CFL1 expression in peripheral blood mononuclear cells and endocervical mucosa
Authors: Verma N. , Mukhopadhyay S. , Barnable P. , Plagianos M. G. , Teleshova N.
Published: April 2022

An inhibitory effect of estradiol (E2) on HIV-1 infection was suggested by several reports. We previously identified increased gene expression of actin-binding protein cofilin 1 (CFL1) in endocervix in the E2-dominated proliferative phase of the menstrual cycle. Actin cytoskeleton has an integral role in establishing and spreading HIV-1 infection. Herein, we studied in vitro effects of E2 on HIV-1 infection and on CFL1 expression to gain insight into the mechanism of HIV-1 inhibition by E2. E2 dose-dependently inhibited HIV-1BaL infection in peripheral blood mononuclear cells (PBMCs) and endocervix. In PBMCs and endocervix, E2 increased protein expression of total CFL1 and phosphorylated CFL1 (pCFL1) and pCFL1/CFL1 ratios. LIMKi3, a LIM kinase 1 and 2 inhibitor, abrogated the phenotype and restored infection in both PBMCs and endocervix; inhibited E2-induced expression of total CFL1, pCFL1; and decreased pCFL1/CFL1 ratios. Knockdown of CFL1 in PBMCs also abrogated the phenotype and partially restored infection. Additional analysis of soluble mediators revealed decreased concentrations of pro-inflammatory chemokines CXCL10 and CCL5 in infected tissues incubated with E2. Our results suggest a link between E2-mediated anti-HIV-1 activity and expression of CFL1 in PBMCs and endocervical mucosa. The data support exploration of cytoskeletal signaling pathway targets for the development of prevention strategies against HIV-1.
Predicting outcomes for locally advanced rectal cancer treated with neoadjuvant chemoradiation with CT-based radiomics
Authors: Wang Fuqiang , Tan Boon Fei , Poh Sharon Shuxian , Siow Tian Rui , Lim Faye Lynette Wei Tching , Yip Connie Siew Poh , Wang Michael Lian Chek , Nei Wenlong , Tan Hong Qi
Published: April 2022

A feasibility study was performed to determine if CT-based radiomics could play an augmentative role in predicting neoadjuvant rectal score (NAR), locoregional failure free survival (LRFFS), distant metastasis free survival (DMFS), disease free survival (DFS) and overall survival (OS) in locally advanced rectal cancer (LARC). The NAR score, which takes into account the pathological tumour and nodal stage as well as clinical tumour stage, is a validated surrogate endpoint used for early determination of treatment response whereby a low NAR score (< 8) has been correlated with better outcomes and high NAR score (> 16) has been correlated with poorer outcomes. CT images of 191 patients with LARC were used in this study. Primary tumour (GTV) and mesorectum (CTV) were contoured separately and radiomics features were extracted from both segments. Two NAR models (NAR > 16 and NAR < 8) models were constructed using Least Absolute Shrinkage and Selection Operator (LASSO) and the survival models were constructed using regularized Cox regressions. Area under curve (AUC) and time-dependent AUC were used to quantify the performance of the LASSO and Cox regression respectively, using ten folds cross validations. The NAR > 16 and NAR < 8 models have an average AUCs of 0.68 ± 0.13 and 0.59 ± 0.14 respectively. There are statistically significant differences between the clinical and combined model for LRFFS (from 0.68 ± 0.04 to 0.72 ± 0.04), DMFS (from 0.68 ± 0.05 to 0.70 ± 0.05) and OS (from 0.64 ± 0.06 to 0.66 ± 0.06). CTV radiomics features were also found to be more important than GTV features in the NAR prediction model. The most important clinical features are age and CEA for NAR > 16 and NAR < 8 models respectively, while the most significant clinical features are age, surgical margin and NAR score across all the four survival models.
Instability motion characteristics of overburden rock and the distribution pattern of fissures in shallow thick seam mining
Authors: Li Jianwei , Liu Changyou , Guo Xinwei , Wu Xiangye
Published: April 2022

This paper analyzes the instability movement characteristics of overburden in shallow thick coal seam mining and its influence on the development and distribution of fault fractures. The similarity simulation experiment and theoretical analysis were combined based on the classification of the occurrence characteristics of the key bearing layer in the overburden rock of shallow thick seam mining. This study investigated the fracture characteristics and the instability motion mode of the key bearing layer in shallow thick seam mining and their effects on the distribution of fissures in the overburden rock. The results indicated that according to the horizon of the key bearing layer, the occurrence of overburden rock could be classified into 2 categories, i.e., the horizon of the key bearing layer within the caving zone and within the fissure zone. The horizon of the key bearing layer has a significant effect on the fracture characteristics and the instability motion mode of the key bearing layer. When the horizon of the key bearing layer is in the overburden caving zone, a "step rock beam" develops after fracture, and the instability motion mode is sliding instability. When the horizon of the key bearing layer is in the overburden fissure zone, a "masonry-like beam" develops after fracture, and the instability motion mode is rotary instability. The fracture instability of the key bearing layer could control the development and distribution of fissures in the overburden rock, and the whole favorable zone for the development of fissures extends along the advancing direction of the working face in a form of "diagonal stripes" with the instability motion of the key bearing layer.
RETRACTED ARTICLE: Functionalized graphene oxide nanosheets with folic acid and silk fibroin as a novel nanobiocomposite for biomedical applications
Authors: Eivazzadeh-Keihan Reza , Alimirzaloo Farkhondeh , Aghamirza Moghim Aliabadi Hooman , Bahojb Noruzi Ehsan , Akbarzadeh Ali Reza , Maleki Ali , Madanchi Hamid , Mahdavi Mohammad
Published: April 2022

In this paper, a novel graphene oxide-folic acid/silk fibroin (GO-FA/SF) nanobiocomposite scaffold was designed and fabricated using affordable and non-toxic materials. The GO was synthesized using the hummer method, covalently functionalized with FA, and then easily conjugated with extracted SF via the freeze-drying process. For characterization of the scaffold, several techniques were employed: Fourier-transform infrared (FT-IR), field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray (EDX), and thermogravimetric analysis (TGA). The cell viability method, hemolysis, and anti-biofilm assays were performed, exploring the biological capability of the nanobiocomposite. The cell viability percentages were 96.67, 96.35 and 97.23% for 24, 48, and 72 h, respectively, and its hemolytic effect was less than 10%. In addition, it was shown that this nanobiocomposite prevents the formation of Pseudomonas aeruginosa biofilm and has antibacterial activity.
Redeployment of odontode gene regulatory network underlies dermal denticle formation and evolution in suckermouth armored catfish
Authors: Mori Shunsuke , Nakamura Tetsuya
Published: April 2022

Odontodes, i.e., teeth and tooth-like structures, consist of a pulp cavity and dentin covered by a mineralized cap. These structures first appeared on the outer surface of vertebrate ancestors and were repeatedly lost and gained across vertebrate clades; yet, the underlying genetic mechanisms and trajectories of this recurrent evolution remain long-standing mysteries. Here, we established suckermouth armored catfish (Ancistrus sp.; Loricariidae), which have reacquired dermal odontodes (dermal denticles) all over most of their body surface, as an experimental model animal amenable to genetic manipulation for studying odontode development. Our histological analysis showed that suckermouth armored catfish develop dermal denticles through the previously defined odontode developmental stages. De novo transcriptomic profiling identified the conserved odontode genetic regulatory network (oGRN) as well as expression ofpaired like homeodomain 2(pitx2), previously known as an early regulator of oGRN in teeth but not in other dermal odontodes, in developing dermal denticles. The early onset ofpitx2expression in cranial dermal denticle placodes implies its function as one of the inducing factors of the cranial dermal denticles. By comprehensively identifying the genetic program for dermal odontode development in suckermouth armored catfish, this work illuminates how dermal odontodes might have evolved and diverged in distinct teleost lineages via redeployment of oGRN.
The assessment of microencapsulated Lactobacillus plantarum survivability in rose petal jam and the changes in physicochemical, textural and sensorial characteristics of the product during storage
Authors: Shoaei Fateme , Heshmati Ali , Mahjub Reza , Garmakhany Amir Daraei , Taheri Mehdi
Published: April 2022

The present study aimed to develop a probiotic rose petal jam containing microencapsulated L. plantarum. The attributes of L. plantarum microcapsules and bacteria viability in simulated gastrointestinal conditions and jam were assessed. In addition, L. plantarum effects on physicochemical, textural and sensorial properties of jam were studied. The microencapsulation yield, diameter, and zeta potential value of the microcapsules ranged from 90.23 to 92.75%, 14.80–35.02 µm, and − 16.83 to − 14.71 mV, respectively. The microencapsulation process significantly increases the survival of L. plantarum in simulated gastrointestinal tract and jam. In jam samples containing L. plantarum microencapsulated with 2% sodium alginate and 3.5% or 5% Arabic gum and stored for 90 days, the bacterial count was higher than the acceptable level (106 CFU/g). While there was no significant difference (P > 0.05) between physicochemical characteristics of non-probiotic and probiotic jams, taste and overall acceptance scores of microencapsulated probiotic jams were higher. The microencapsulation of L. plantarum in sodium alginate (2%) and Arabic gum (5%) and its inoculation into rose petal jam could yield a new probiotic product with increased health benefits.
Hydrogen-generating Si-based agent protects against skin flap ischemia–reperfusion injury in rats
Authors: Otani Naoya , Tomita Koichi , Kobayashi Yuki , Kuroda Kazuya , Koyama Yoshihisa , Kobayashi Hikaru , Kubo Tateki
Published: April 2022

Hydrogen is effective against ischemia–reperfusion (I/R) injury in skin flaps. However, the difficulty of continuously administering a sufficient amount of hydrogen using conventional methods has been an issue in the clinical application of hydrogen-based therapy. An Si-based agent administered orally was previously shown to continuously generate a large amount of hydrogen in the intestinal environment. In this study, we assessed the effect of the Si-based agent on the inhibition of I/R injury in skin flaps using a rat model. In the I/R groups, the vascular pedicle of the abdominal skin flap was occluded for three hours followed by reperfusion. In the I/R + Si group, the Si-based agent was administered perioperatively. After reperfusion, flap survival rate, blood flow, oxidative stress markers, inflammatory markers/findings, and degree of apoptosis were evaluated. Flap survival rate was significantly higher, and histological inflammation, apoptotic cells, oxidative stress markers, and levels of inflammatory cytokine mRNA and protein expression were significantly lower, in the I/R + Si group compared to the I/R group. The Si-based agent suppressed oxidative stress, apoptosis, and inflammatory reactions resulting from I/R injury, thereby contributing to improvements in skin flap survival.
Visual estimation of the force applied by another person
Authors: Ujitoko Yusuke , Kawabe Takahiro
Published: April 2022

As observers, we believe that we can visually estimate the force that another person is applying to a material. However, it is unclear what kind of cues we use to do this. We focused on two types of visual change that occur when actors push an elastic material from above with their fingers: visual shaking and visual indentation depth. The first one relates to a finger/hand shaking, known as an “induced tremor”, and the second one relates to material deformation due to the application of force. We found that human observers mainly used visual shaking to estimate the force being applied by another person in a video clip. Overall, the apparent applied force was perceived to be stronger when the level of visual shaking was greater. We also found that observers mainly used visual indentation depth and visual shaking to estimate the softness rating of materials. Overall, the apparent softness was perceived to be greater when the visual indentation depth was larger and the level of visual shaking was lower, which indicates that observers use visual shaking to estimate the force being applied, and that estimated force is then used for an estimation of softness.
Impaired surface marker expression in stimulated Epstein-Barr virus transformed lymphoblasts from Barth Syndrome patients
Authors: Zegallai Hana M. , Hatch Grant M.
Published: April 2022

Primary B lymphocytes rapidly respond to lipopolysaccharide (LPS) and cytosine linked to a guanine by a phosphate bond deoxyribonucleic acid (CpG DNA) stimulation to promote adaptive immune function through increased surface marker expression. Here we examined expression of surface markers in LPS and CpG DNA stimulated Epstein-Barr virus transformed B lymphoblasts from control and BTHS patients with different mutations. The percentage of cluster of differentiation (CD) positive cells including CD38 + , CD138 + , CD80 + surface expression and programmed cell death protein 1 (PD1 +) surface expression was similar between control and BTHS lymphoblasts incubated plus or minus LPS. The percentage of CD24 + , CD38 + and CD138 + cells was similar between control and BTHS lymphoblasts incubated plus or minus CpG DNA. CD27 + surface marker expression was reduced in both BTHS lymphoblasts and controls incubated with CpG DNA and PD1 + surface marker expression was higher in BTHS cells compared to controls but was unaltered by CpG DNA treatment. Thus, Epstein-Barr virus transformed control and BTHS lymphoblasts fail to increase selected surface markers upon stimulation with LPS and exhibit variable surface marker expression upon stimulation with CpG DNA. Since B lymphocyte surface marker expression upon activation is involved in B cell proliferation and differentiation, cell–cell interaction and the adaptive immune response, we suggest that caution should be exercised when interpreting immunological data obtained from Epstein-Barr virus transformed BTHS cells. Based upon our observations in control cells, our conclusions may be more broadly applicable to other diseases which utilize transformed B lymphocytes for the study of immune biology.
Enhanced photoluminescence and shortened lifetime of DCJTB by photoinduced metal deposition on a ferroelectric lithography substrate
Authors: Chau Yuan-Fong Chou , Chang Hao-En , Huang Po-Sheng , Wu Pin Chieh , Lim Chee Ming , Chiang Li-Ming , Wang Tzyy-Jiann , Chao Chung-Ting Chou , Kao Tsung Sheng , Shih Min-Hsiung , Chiang Hai-Pang
Published: April 2022

The photodeposition of metallic nanostructures onto ferroelectric surfaces could enable new applications based on the assembly of molecules and patterning local surface reactivity by enhancing surface field intensity. DCJTB (4-(dicyanomethylene)-2-t-butyl-6-(1,1,7,7-tetramethyljulolidyl-9-enyl)-4H-pyran) is an excellent fluorescent dye and dopant material with a high quantum efficiency used for OLED displays on the market. However, how to raise the photoluminescence (PL) and reduce the lifetime of DCJTB in a substrate remain extraordinary challenges for its application. Here, we demonstrate a tunable ferroelectric lithography plasmon-enhanced substrate to generate photo-reduced silver nanoparticles (AgNPs) and achieve enhanced PL with a shortened lifetime depending on the substrate’s annealing time. The enhanced PL with shortened lifetimes can attribute to the localized electromagnetic (EM) wave produced by the nanotextured AgNPs layers' surface and gap plasmon resonances. The simulation is based on the three-dimensional finite element method to explain the mechanism of experimental results. Since the absorption increases, the remarkable enhanced PL of DCJTB can attain in the fabricated periodically proton exchanged (PPE) lithium niobate (LiNbO3) substrate. Furthermore, the proposed fabrication method demonstrates to help tune the surface EM wave distribution in the substrate, which can simultaneously achieve the significantly shortened lifetime and high PL intensity of DCJTB in the substrate. Compared with the un-annealed substrate, the PL intensity of DCJTB in the assembly metallic nanostructures is enhanced 13.70 times, and the PL’s lifetime is reduced by 12.50%, respectively. Thus, the fabricated substrate can be a promising candidate, verifying chemically patterned ferroelectrics' satisfaction as a PL-active substrate.
Association between lipid ratio and depression: a cross-sectional study
Authors: Han A Lum
Published: April 2022

Depression is associated with total cholesterol, low-density lipoprotein cholesterol, triglycerides, and high-density lipoprotein cholesterol levels in the blood. However, evidence is limited on the relationship between depression and lipid ratios. Therefore, this study aimed to investigate the correlation between depression and different lipid ratios. This study was conducted using data from the Korea National Health and Nutrition Examination Survey. A total of 11,648 adult men and women aged ≥ 19 years, without missing data, were included in this study. Depression was diagnosed using the Patient Health Questionnaire-9. The associations between depression and total cholesterol/high-density lipoprotein cholesterol, low-density cholesterol/high-density lipoprotein cholesterol, and triglyceride/high-density lipoprotein cholesterol ratio were analyzed. A complex sample logistic regression test was used for the analysis of the odds ratios of depression. Among men, the total cholesterol/high-density lipoprotein cholesterol and low-density cholesterol/high-density lipoprotein cholesterol ratios were not associated with depression. Additionally, an increase in triglyceride/high-density lipoprotein cholesterol ratio by 1 was associated with a 1.041-fold higher probability of depression in men. Among women, the three lipid ratios were not associated with depression. Triglyceride/high-density lipoprotein cholesterol ratio is associated with depression among men. Future studies should cross-validate, explore the biological mechanism, and identify the clinical implication of this correlation.
Estimating the expected planting area of double- and single-season rice in the Hunan-Jiangxi region of China by 2030
Authors: Huang Min , Chen Jiana , Cao Fangbo
Published: April 2022

The development of double-season rice cropping systems has made a considerable contribution toward achieving rice self-sufficiency in China. However, the planting area for double-season rice has sharply decreased in the Hunan-Jiangxi region (the most important producing region of double-season rice in China) as a result of the conversion from double- to single-season rice cropping systems (referred as the rice “double-to-single” phenomenon). Due to concerns about the negative effect of the “double-to-single” phenomenon on rice self-sufficiency in China, we have estimated the planting area of double- and single-season rice in the Hunan-Jiangxi region that will be needed by 2030 to maintain the contribution to China’s rice production, based on the most recent 10 years (2011–2020) of historical data available. The results of our analysis can provide guidance for the government’s decision-making when planning the planting area of double- and single-season rice in the Hunan-Jiangxi region.
The underappreciated role of anthropogenic sources in atmospheric soluble iron flux to the Southern Ocean
Authors: Liu Mingxu , Matsui Hitoshi , Hamilton Douglas S. , Lamb Kara D. , Rathod Sagar D. , Schwarz Joshua P. , Mahowald Natalie M.
Published: April 2022

The atmospheric deposition of soluble (bioaccessible) iron enhances ocean primary productivity and subsequent atmospheric CO2sequestration in iron-limited ocean basins, especially the Southern Ocean. While anthropogenic sources have been recently suggested to be important in some northern hemisphere oceans, the role in the Southern Ocean remains ambiguous. By comparing multiple model simulations with the new aircraft observations for anthropogenic iron, we show that anthropogenic soluble iron deposition flux to the Southern Ocean could be underestimated by more than a factor of ten in previous modeling estimates. Our improved estimate for the anthropogenic iron budget enhances its contribution on the soluble iron deposition in the Southern Ocean from about 10% to 60%, implying a dominant role of anthropogenic sources. We predict that anthropogenic soluble iron deposition in the Southern Ocean is reduced substantially (30‒90%) by the year 2100, and plays a major role in the future evolution of atmospheric soluble iron inputs to the Southern Ocean.
A subpopulation of cortical VIP-expressing interneurons with highly dynamic spines
Authors: Georgiou Christina , Kehayas Vassilis , Lee Kok Sin , Brandalise Federico , Sahlender Daniela A. , Blanc Jerome , Knott Graham , Holtmaat Anthony
Published: April 2022

Structural synaptic plasticity may underlie experience and learning-dependent changes in cortical circuits. In contrast to excitatory pyramidal neurons, insight into the structural plasticity of inhibitory neurons remains limited. Interneurons are divided into various subclasses, each with specialized functions in cortical circuits. Further knowledge of subclass-specific structural plasticity of interneurons is crucial to gaining a complete mechanistic understanding of their contribution to cortical plasticity overall. Here, we describe a subpopulation of superficial cortical multipolar interneurons expressing vasoactive intestinal peptide (VIP) with high spine densities on their dendrites located in layer (L) 1, and with the electrophysiological characteristics of bursting cells. Using longitudinal imaging in vivo, we found that the majority of the spines are highly dynamic, displaying lifetimes considerably shorter than that of spines on pyramidal neurons. Using correlative light and electron microscopy, we confirmed that these VIP spines are sites of excitatory synaptic contacts, and are morphologically distinct from other spines in L1.
Spatial covariance analysis reveals the residue-by-residue thermodynamic contribution of variation to the CFTR fold
Authors: Anglès Frédéric , Wang Chao , Balch William E.
Published: April 2022

Although the impact of genome variation on the thermodynamic properties of function on the protein fold has been studied in vitro, it remains a challenge to assign these relationships across the entire polypeptide sequence in vivo. Using the Gaussian process regression based principle of Spatial CoVariance, we globally assign on a residue-by-residue basis the biological thermodynamic properties that contribute to the functional fold of CFTR in the cell. We demonstrate the existence of a thermodynamically sensitive region of the CFTR fold involving the interface between NBD1 and ICL4 that contributes to its export from endoplasmic reticulum. At the cell surface a new set of residues contribute uniquely to the management of channel function. These results support a general ‘quality assurance’ view of global protein fold management as an SCV principle describing the differential pre- and post-ER residue interactions contributing to compartmentalization of the energetics of the protein fold for function. Our results set the stage for future analyses of the quality systems managing protein sequence-to-function-to-structure broadly encompassing genome design leading to protein function in complex cellular relationships responsible for diversity and fitness in biology in response to the environment.
Failure of DNA double-strand break repair by tau mediates Alzheimer’s disease pathology in vitro
Authors: Asada-Utsugi Megumi , Uemura Kengo , Ayaki Takashi , T. Uemura Maiko , Minamiyama Sumio , Hikiami Ryota , Morimura Toshifumi , Shodai Akemi , Ueki Takatoshi , Takahashi Ryosuke , Kinoshita Ayae , Urushitani Makoto
Published: April 2022

DNA double-strand break (DSB) is the most severe form of DNA damage and accumulates with age, in which cytoskeletal proteins are polymerized to repair DSB in dividing cells. Since tau is a microtubule-associated protein, we investigate whether DSB is involved in tau pathologies in Alzheimer’s disease (AD). First, immunohistochemistry reveals the frequent coexistence of DSB and phosphorylated tau in the cortex of AD patients. In vitro studies using primary mouse cortical neurons show that non-p-tau accumulates perinuclearly together with the tubulin after DSB induction with etoposide, followed by the accumulation of phosphorylated tau. Moreover, the knockdown of endogenous tau exacerbates DSB in neurons, suggesting the protective role of tau on DNA repair. Interestingly, synergistic exposure of neurons to microtubule disassembly and the DSB strikingly augments aberrant p-tau aggregation and apoptosis. These data suggest that DSB plays a pivotal role in AD-tau pathology and that the failure of DSB repair leads to tauopathy.