bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantum trajectory framework for general time-local master equations
Authors: Donvil Brecht , Muratore-Ginanneschi Paolo
Published: July 2022

Master equations are one of the main avenues to study open quantum systems. When the master equation is of the Lindblad–Gorini–Kossakowski–Sudarshan form, its solution can be “unraveled in quantum trajectories” i.e., represented as an average over the realizations of a Markov process in the Hilbert space of the system. Quantum trajectories of this type are both an element of quantum measurement theory as well as a numerical tool for systems in large Hilbert spaces. We prove that general time-local and trace-preserving master equations also admit an unraveling in terms of a Markov process in the Hilbert space of the system. The crucial ingredient is to weigh averages by a probability pseudo-measure which we call the “influence martingale”. The influence martingale satisfies a 1d stochastic differential equation enslaved to the ones governing the quantum trajectories. We thus extend the existing theory without increasing the computational complexity.
Hidden spin-orbital texture at the $$\overline{{{\Gamma }}}$$-located valence band maximum of a transition metal dichalcogenide semiconductor
Authors: Clark Oliver J. , Dowinton Oliver , Bahramy Mohammad Saeed , Sánchez-Barriga Jaime
Published: July 2022

Finding stimuli capable of driving an imbalance of spin-polarised electrons within a solid is the central challenge in the development of spintronic devices. However, without the aid of magnetism, routes towards this goal are highly constrained with only a few suitable pairings of compounds and driving mechanisms found to date. Here, through spin- and angle-resolved photoemission along with density functional theory, we establish how the p-derived bulk valence bands of semiconducting 1T-HfSe2 possess a local, ground-state spin texture spatially confined within each Se-sublayer due to strong sublayer-localised electric dipoles orientated along the c-axis. This hidden spin-polarisation manifests in a ‘coupled spin-orbital texture’ with in-equivalent contributions from the constituent p-orbitals. While the overall spin-orbital texture for each Se sublayer is in strict adherence to time-reversal symmetry (TRS), spin-orbital mixing terms with net polarisations at time-reversal invariant momenta are locally maintained. These apparent TRS-breaking contributions dominate, and can be selectively tuned between with a choice of linear light polarisation, facilitating the observation of pronounced spin-polarisations at the Brillouin zone centre for all kz. We discuss the implications for the generation of spin-polarised populations from 1T-structured transition metal dichalcogenides using a fixed energy, linearly polarised light source.
Realizing quantum convolutional neural networks on a superconducting quantum processor to recognize quantum phases
Authors: Herrmann Johannes , Llima Sergi Masot , Remm Ants , Zapletal Petr , McMahon Nathan A. , Scarato Colin , Swiadek François , Andersen Christian Kraglund , Hellings Christoph , Krinner Sebastian , Lacroix Nathan , Lazar Stefania , Kerschbaum Michael , Zanuz Dante Colao , Norris Graham J. , Hartmann Michael J. , Wallraff Andreas , Eichler Christopher
Published: July 2022

Quantum computing crucially relies on the ability to efficiently characterize the quantum states output by quantum hardware. Conventional methods which probe these states through direct measurements and classically computed correlations become computationally expensive when increasing the system size. Quantum neural networks tailored to recognize specific features of quantum states by combining unitary operations, measurements and feedforward promise to require fewer measurements and to tolerate errors. Here, we realize a quantum convolutional neural network (QCNN) on a 7-qubit superconducting quantum processor to identify symmetry-protected topological (SPT) phases of a spin model characterized by a non-zero string order parameter. We benchmark the performance of the QCNN based on approximate ground states of a family of cluster-Ising Hamiltonians which we prepare using a hardware-efficient, low-depth state preparation circuit. We find that, despite being composed of finite-fidelity gates itself, the QCNN recognizes the topological phase with higher fidelity than direct measurements of the string order parameter for the prepared states.
Lysosomal protein transmembrane 5 promotes lung-specific metastasis by regulating BMPR1A lysosomal degradation
Authors: Jiang Bo , Zhao Xiaozhi , Chen Wei , Diao Wenli , Ding Meng , Qin Haixiang , Li Binghua , Cao Wenmin , Chen Wei , Fu Yao , He Kuiqiang , Gao Jie , Chen Mengxia , Lin Tingsheng , Deng Yongming , Yan Chao , Guo Hongqian
Published: July 2022

Organotropism during cancer metastasis occurs frequently but the underlying mechanism remains poorly understood. Here, we show that lysosomal protein transmembrane 5 (LAPTM5) promotes lung-specific metastasis in renal cancer. LAPTM5 sustains self-renewal and cancer stem cell-like traits of renal cancer cells by blocking the function of lung-derived bone morphogenetic proteins (BMPs). Mechanistic investigations showed that LAPTM5 recruits WWP2, which binds to the BMP receptor BMPR1A and mediates its lysosomal sorting, ubiquitination and ultimate degradation. BMPR1A expression was restored by the lysosomal inhibitor chloroquine. LAPTM5 expression could also serve as an independent predictor of lung metastasis in renal cancer. Lastly, elevation of LAPTM5 expression in lung metastases is a common phenomenon in multiple cancer types. Our results reveal a molecular mechanism underlying lung-specific metastasis and identify LAPTM5 as a potential therapeutic target for cancers with lung metastasis.
Efficient spatially targeted gene editing using a near-infrared activatable protein-conjugated nanoparticle for brain applications
Authors: Rebelo Catarina , Reis Tiago , Guedes Joana , Saraiva Cláudia , Rodrigues Artur Filipe , Simões Susana , Bernardino Liliana , Peça João , Pinho Sónia L. C. , Ferreira Lino
Published: July 2022

Spatial control of gene expression is critical to modulate cellular functions and deconstruct the function of individual genes in biological processes. Light-responsive gene-editing formulations have been recently developed; however, they have shown limited applicability in vivo due to poor tissue penetration, limited cellular transfection and the difficulty in evaluating the activity of the edited cells. Here, we report a formulation composed of upconversion nanoparticles conjugated with Cre recombinase enzyme through a photocleavable linker, and a lysosomotropic agent that facilitates endolysosomal escape. This formulation allows in vitro spatial control in gene editing after activation with near-infrared light. We further demonstrate the potential of this formulation in vivo through three different paradigms: (i) gene editing in neurogenic niches, (ii) gene editing in the ventral tegmental area to facilitate monitoring of edited cells by precise optogenetic control of reward and reinforcement, and (iii) gene editing in a localized brain region via a noninvasive administration route (i.e., intranasal).
Loss of immunity-related GTPase GM4951 leads to nonalcoholic fatty liver disease without obesity
Authors: Zhang Zhao , Xun Yu , Rong Shunxing , Yan Lijuan , SoRelle Jeffrey A. , Li Xiaohong , Tang Miao , Keller Katie , Ludwig Sara , Moresco Eva Marie Y. , Beutler Bruce
Published: July 2022

Obesity and diabetes are well known risk factors for nonalcoholic fatty liver disease (NAFLD), but the genetic factors contributing to the development of NAFLD remain poorly understood. Here we describe two semi-dominant allelic missense mutations (OilyandCarboniferous) ofPredicted gene 4951(Gm4951) identified from a forward genetic screen in mice. GM4951 deficient mice developed NAFLD on high fat diet (HFD) with no changes in body weight or glucose metabolism. Moreover, HFD caused a reduction in the level ofGm4951, which in turn promoted the development of NAFLD. Predominantly expressed in hepatocytes, GM4951 was verified as an interferon inducible GTPase. The NAFLD inGm4951knockout mice was associated with decreased lipid oxidation in the liver and no defect in hepatic lipid secretion. After lipid loading, hepatocyte GM4951 translocated to lipid droplets (LDs), bringing with it hydroxysteroid 17β-dehydrogenase 13 (HSD17B13), which in the absence of GM4951 did not undergo this translocation. We identified a rare non-obese mouse model of NAFLD caused by GM4951 deficiency and define a critical role for GTPase-mediated translocation in hepatic lipid metabolism.
Ritter-type amination of C(sp3)-H bonds enabled by electrochemistry with SO42−
Authors: Zhang Ling , Fu Youtian , Shen Yi , Liu Chengyu , Sun Maolin , Cheng Ruihua , Zhu Weiping , Qian Xuhong , Ma Yueyue , Ye Jinxing
Published: July 2022

By merging electricity with sulfate, the Ritter-type amination of C(sp3)-H bonds is developed in an undivided cell under room temperature. This method features broad substrate generality (71 examples, up to 93% yields), high functional-group compatibility, facile scalability, excellent site-selectivity and mild conditions. Common alkanes and electron-deficient alkylbenzenes are viable substrates. It also provides a straightforward protocol for incorporating C-deuterated acetylamino group into C(sp3)-H sites. Application in the synthesis or modification of pharmaceuticals or their derivatives and gram-scale synthesis demonstrate the practicability of this method. Mechanistic experiments show that sulfate radical anion, formed by electrolysis of sulfate, served as hydrogen atom transfer agent to provide alkyl radical intermediate. This method paves a convenient and flexible pathway for realizing various synthetically useful transformations of C(sp3)-H bonds mediated by sulfate radical anion generated via electrochemistry.
NHC-Ni(II)-catalyzed cyclopropene-isocyanide [5 + 1] benzannulation
Authors: Huang Jian–Qiang , Yu Meng , Yong Xuefeng , Ho Chun–Yu
Published: July 2022

Isocyanides are common compounds in fine and bulk chemical syntheses. However, the direct addition of isocyanide to simple unactivated cyclopropene via transition metal catalysis is challenging. Most of the current approaches focus on 1,1-insertion of isocyanide to M-R or nucleophilc insertion. That is often complicated by the competitive homo-oligomerization reactivity occurring at room temperature, such as isocyanide 1,1-insertion by Ni(II). Here we show a (N-heterocyclic carbene)Ni(II) catalyst that enables cyclopropene-isocyanide [5 + 1] benzannulation. As shown in the broad substrate scope and a [trans-(N-heterocyclic carbene)Ni(isocyanide)Br2] crystal structure, the desired cross-reactivity is cooperatively controlled by the high reactivity of the cyclopropene, the sterically bulky N-heterocyclic carbene, and the strong coordination ability of the isocyanide. This direct addition strategy offers aromatic amine derivatives and complements the Dötz benzannulation and Semmelhack/Wulff 1,4-hydroquinone synthesis. Several sterically bulky, fused, and multi-substituted anilines and unsymmetric functionalized spiro-ring structures are prepared from those easily accessible starting materials expediently.
Self-powered and flexible piezo-sensors based on conductivity-controlled GaN nanowire-arrays for mimicking rapid- and slow-adapting mechanoreceptors
Authors: Waseem Aadil , Abdullah Ameer , Bagal Indrajit V. , Ha Jun-Seok , Lee June Key , Ryu Sang-Wan
Published: July 2022

Human skin contains slowly adaptive (SA) and rapidly adaptive (RA) mechanoreceptors, which respond differently to external stimuli. Based on human tactile perception principles, the fabrication of a self-powered electronic skin (e-skin) that simultaneously mimics SA- and RA-mechanoreceptors is a prime need for robots and artificial prosthetics to interact with the surrounding environment. However, the complex process of merging multimode sensors to mimic SA- and RA-mechanoreceptors hinders their utilization in e-skins. We proposed SA- and RA-mechanoreceptors based on n-type and semi-insulating GaN nanowire arrays. The SA- and RA-mechanoreceptors demonstrated distinguished features such as grasping of objects and detection of their surface textures. Based on piezoelectric sensing principles, the proposed e-skin can simultaneously mimic static and dynamic pressure signals. Mechanoreceptors further detected several stimuli of various pressures with low and high frequencies. The response and reset times showed by SA-mechanoreceptors were 11 and 18 ms under 1-Hz frequency, which are rapid enough for practical e-skin applications.
Smart quantum statistical imaging beyond the Abbe-Rayleigh criterion
Authors: Bhusal Narayan , Hong Mingyuan , Miller Ashe , Quiroz-Juárez Mario A. , León-Montiel Roberto de J. , You Chenglong , Magaña-Loaiza Omar S.
Published: July 2022

The wave nature of light imposes limits on the resolution of optical imaging systems. For over a century, the Abbe-Rayleigh criterion has been utilized to assess the spatial resolution limits of imaging instruments. Recently, there has been interest in using spatial projective measurements to enhance the resolution of imaging systems. Unfortunately, these schemes require a priori information regarding the coherence properties of “unknown” light beams and impose stringent alignment conditions. Here, we introduce a smart quantum camera for superresolving imaging that exploits the self-learning features of artificial intelligence to identify the statistical fluctuations of unknown mixtures of light sources at each pixel. This is achieved through a universal quantum model that enables the design of artificial neural networks for the identification of photon fluctuations. Our protocol overcomes limitations of existing superresolution schemes based on spatial mode projections, and consequently provides alternative methods for microscopy, remote sensing, and astronomy.
Dissecting the role of adult hippocampal neurogenesis towards resilience versus susceptibility to stress-related mood disorders
Authors: Jones Katherine L. , Zhou Mei , Jhaveri Dhanisha J.
Published: July 2022

Adult hippocampal neurogenesis in the developmental process of generating and integrating new neurons in the hippocampus during adulthood and is a unique form of structural plasticity with enormous potential to modulate neural circuit function and behaviour. Dysregulation of this process is strongly linked to stress-related neuropsychiatric conditions such as anxiety and depression, and efforts have focused on unravelling the contribution of adult-born neurons in regulating stress response and recovery. Chronic stress has been shown to impair this process, whereas treatment with clinical antidepressants was found to enhance the production of new neurons in the hippocampus. However, the precise role of adult hippocampal neurogenesis in mediating the behavioural response to chronic stress is not clear and whether these adult-born neurons buffer or increase susceptibility to stress-induced mood-related maladaptation remains one of the controversial issues. In this review, we appraise evidence probing the causal role of adult hippocampal neurogenesis in the regulation of emotional behaviour in rodents. We find that the relationship between adult-born hippocampal neurons and stress-related mood disorders is not linear, and that simple subtraction or addition of these neurons alone is not sufficient to lead to anxiety/depression or have antidepressant-like effects. We propose that future studies examining how stress affects unique properties of adult-born neurons, such as the excitability and the pattern of connectivity during their critical period of maturation will provide a deeper understanding of the mechanisms by which these neurons contribute to functional outcomes in stress-related mood disorders.
A three-year data set of gaseous field emissions from crop sequence at three sites in Germany
Authors: Mallast Janine , Stichnothe Heinz , Kreuter Thomas , Thiel Enrico , Pommer Claudia , Döhler Johannes , Eissner Florian , Kühling Insa , Rücknagel Jan , Pamperin Henning , Augustin Jürgen , Hoffmann Mathias , Simon Anja , Hülsbergen Kurt-Jürgen , Maidl Franz-Xaver , Tauchnitz Nadine , Bischoff Joachim , Böttcher Falk
Published: July 2022

The purpose of the StaPlaRes project was to evaluate two innovative techniques of urea fertiliser application and to quantify greenhouse gas (GHG) emissions. All GHG emissions, as well as other gaseous emissions, agronomic and environmental variables were collected for three years (2016/2017–2018/2019) at three experimental field sites in Germany. All management activities were consistently documented. Multi-variable data sets of gas fluxes (N2O and NH3), crop parameters (grain and straw yield, N content, etc.), soil characteristics (NH4-N, NO3-N, etc.), continuously recorded meteorological variables (air and soil temperatures, radiation, precipitation, etc.), management activities (sowing, harvest, soil tillage, fertilization, etc.), were documented and metadata (methods, further information about variables, etc.) described. Additionally, process-related tests were carried out using lab (N2 emissions), pot and lysimeter experiments (nitrate leaching). In total, 2.5 million records have been stored in a Microsoft Access database (StaPlaRes-DB-Thuenen). The database is freely available for (re)use by others (scientists, stakeholders, etc.) on the publication server and data repository OpenAgrar for meta-analyses, process modelling and other environmental studies.
C698R mutation in Lrsam1 gene impairs nerve regeneration in a CMT2P mouse model
Authors: Moiseev Daniel , Wazir Zafar , Liu Donghao , Li Jun , Hu Bo
Published: July 2022

Missense mutation C694R in the RING domain of the LRSAM1 gene results in a dominantly inherited polyneuropathy, Charcot-Marie-Tooth disease type 2P (CMT2P). We have generated and characterized a Lrsam1C698R knock-in mouse model produced through CRISPR/Cas9 technology. Both heterozygous (Lrsam1+/C698R) and homozygous (Lrsam1C698/C698R) knock-in mice exhibited normal motor functions on behavioral tests as well as normal on nerve conduction studies. Axonal density and myelin thickness were not significantly different between mutants and wild-type mice by sciatic nerve morphometric analysis up to 17 months of age. In line with these normal findings, protein–protein interactions between mutant LRSAM1 and RNA-binding proteins (such as FUS and G3BP1) were still present in mouse cells, which differs from the disrupted interactions between these proteins in human CMT2P cells. However, after crush nerve injury, Lrsam1+/C698R mice had a mild, but statistically significant, reduced compound nerve action potential and conduction velocity during recovery. Therefore, C698R mutation results in a mild impaired nerve regeneration in mice. We speculate that repetitive nerve injuries may, at least partially, contribute to the slowly progressive axonal loss in CMT2P.
Depression is a main determinant of health-related quality of life in patients with diabetic kidney disease
Authors: Kim Suhyun , Jeon Junseok , Lee Yu-Ji , Jang Hye Ryoun , Joo Eun Yeon , Huh Wooseong , Kim Yoon-Goo , Kim Dae Joong , Lee Jung Eun
Published: July 2022

Low health-related quality of life (HRQOL) is associated with adverse outcomes in diabetic kidney disease (DKD) patients. We examined the modifiable factors associated with low HRQOL in these patients. We enrolled 141 DKD patients. HRQOL was assessed with the Short Form 36 (SF-36) questionnaire. Low HRQOL was defined as a score > one standard deviation below the mean. Depression and anxiety were assessed with the Hospital Anxiety and Depression Scale (HADS-D and HDAS-A, respectively). The patients’ median age was 65 years, and 73% were men. The prevalence rates of anxiety and depression were 8% (n = 11) and 17% (n = 24), respectively. Forty (28%) patients were identified as poor sleepers, and 40 (28%) had low physical activity levels. Anxiety, depression, and poor sleep quality were negatively correlated with SF-36 scores. Higher levels of physical activity and the estimated glomerular filtration rate (eGFR) were correlated with higher SF-36 scores, which indicated better health status. Higher depression scores (HADS-D scores) were associated with low HRQOL, independent of factors including age, sex, smoking status, comorbidities, eGFR, anemia, sleep quality, anxiety levels, and physical activity levels (odds ratio, 1.43; 95% confidence interval, 1.17–1.75). Among the clinical and psycho-physical factors, depression was a main determinant of low HRQOL in DKD patients.
Single-cell transcriptome analysis of embryonic and adult endothelial cells allows to rank the hemogenic potential of post-natal endothelium
Authors: Adamov Artem , Serina Secanechia Yasmin Natalia , Lancrin Christophe
Published: July 2022

Hematopoietic stem cells (HSCs) are crucial for the continuous production of blood cells during life. The transplantation of these cells is one of the most common treatments to cure patient suffering of blood diseases. However, the lack of suitable donors is a major limitation. One option to get HSCs matching perfectly a patient is cellular reprogramming. HSCs emerge from endothelial cells in blood vessels during embryogenesis through the endothelial to hematopoietic transition. Here, we used single-cell transcriptomics analysis to compare embryonic and post-natal endothelial cells to investigate the potential of adult vasculature to be reprogrammed in hematopoietic stem cells. Although transcriptional similarities have been found between embryonic and adult endothelial cells, we found some key differences in term of transcription factors expression. There is a deficit of expression of Runx1, Tal1, Lyl1 and Cbfb in adult endothelial cells compared to their embryonic counterparts. Using a combination of gene expression profiling and gene regulatory network analysis, we found that endothelial cells from the pancreas, brain, kidney and liver appear to be the most suitable targets for cellular reprogramming into HSCs. Overall, our work provides an important resource for the rational design of a reprogramming strategy for the generation of HSCs.
Genotyping and subtyping of Cryptosporidium spp. and Giardia duodenalis isolates from two wild rodent species in Gansu Province, China
Authors: Xu Jie , Liu Hua , Jiang Yanyan , Jing Huaiqi , Cao Jianping , Yin Jianhai , Li Teng , Sun Yeting , Shen Yujuan , Wang Xin
Published: July 2022

Cryptosporidium spp. and Giardia duodenalis are commonly detected intestinal protozoa species in humans and animals, contributing to global gastroenteritis spread. The present study examined the prevalence and zoonotic potential of Cryptosporidium spp. and G. duodenalis in Himalayan marmots and Alashan ground squirrels in China's Qinghai-Tibetan Plateau area (QTPA) for the first time. Four hundred ninety-eight intestinal content samples were collected from five counties of QTPA of Gansu province, China.
All samples were examined for Cryptosporidium spp. and G. duodenalis by PCR amplification. The resultant data were statistically analyzed by chi-square, Fisher's test and Bonferroni correction using SPSS software 25. 0. Cryptosporidium positive samples were further subtyped through analysis of the 60-kDa glycoprotein (gp60) gene sequence. A total of 11 and 8 samples were positive for Cryptosporidium spp. and G. duodenalis, respectively. Prevalence of Cryptosporidium spp. and G. duodenalis were 2.5% (10/399) and 1.5% (6/399) in Himalayan marmots, 1.0% (1/99) and 2.0% (2/99) in Alashan ground squirrels, respectively. Sequence analysis confirmed the presence of C. rubeyi (n = 2), ground squirrel genotype II (n = 7), chipmunk genotype V (n = 1) and horse genotype (n = 1). The horse genotype was further subtyped as novel subtype VIbA10. G. duodenalis zoonotic assemblages A (n = 1), B (n = 6), E (n = 1) were identified in the present study. This is the first study to identify Cryptosporidium spp. and G. duodenalis in Himalayan marmots and Alashan ground squirrels, suggesting the potential zoonotic transmission of the two pathogens in QTPA.
Effects of solar irradiance noise on a complex marine trophic web
Authors: Grimaudo Roberto , Lazzari Paolo , Solidoro Cosimo , Valenti Davide
Published: July 2022

The analysis of experimental data of the solar irradiance, collected on the marine surface, clearly highlights the intrinsic stochasticity of such an environmental parameter. Given this result, effects of randomly fluctuating irradiance on the population dynamics of a marine ecosystem are studied on the basis of the stochastic 0-dimensional biogeochemical flux model. The noisy fluctuations of the irradiance are formally described as a multiplicative Ornstein-Uhlenbeck process, that is a self-correlated Gaussian noise. Nonmonotonic behaviours of the variance of the marine populations’ biomass are found with respect to the intensity and the autocorrelation time of the noise source, manifesting a noise-induced transition of the ecosystem to an out-of-equilibrium steady state. Moreover, evidence of noise-induced effects on the organic carbon cycling processes underlying the food web dynamics are highlighted. The reported results clearly show the profound impact the stochastic environmental variables can have on both the populations and the biogeochemistry at the basis of a marine trophic network.
A novel hardmask-to-substrate pattern transfer method for creating 3D, multi-level, hierarchical, high aspect-ratio structures for applications in microfluidics and cooling technologies
Authors: Hazra Sougata , Zhang Chi , Wu Qianying , Asheghi Mehdi , Goodson Kenneth , Dede Ercan M. , Palko James , Narumanchi Sreekant
Published: July 2022

This letter solves a major hurdle that mars photolithography-based fabrication of micro-mesoscale structures in silicon. Conventional photolithography is usually performed on smooth, flat wafer surfaces to lay a 2D design and subsequently etch it to create single-level features. It is, however, unable to process non-flat surfaces or already etched wafers and create more than one level in the structure. In this study, we have described a novel cleanroom-based process flow that allows for easy creation of such multi-level, hierarchical 3D structures in a substrate. This is achieved by introducing an ultra-thin sacrificial silicon dioxide hardmask layer on the substrate which is first 3D patterned via multiple rounds of lithography. This 3D pattern is then scaled vertically by a factor of 200–300 and transferred to the substrate underneath via a single shot deep etching step. The proposed method is also easily characterizable—using features of different topographies and dimensions, the etch rates and selectivities were quantified; this characterization information was later used while fabricating specific target structures. Furthermore, this study comprehensively compares the novel pattern transfer technique to already existing methods of creating multi-level structures, like grayscale lithography and chip stacking. The proposed process was found to be cheaper, faster, and easier to standardize compared to other methods—this made the overall process more reliable and repeatable. We hope it will encourage more research into hybrid structures that hold the key to dramatic performance improvements in several micro-mesoscale devices.
Systemic gene therapy with thymosin β4 alleviates glomerular injury in mice
Authors: Mason William J. , Jafree Daniyal J. , Pomeranz Gideon , Kolatsi-Joannou Maria , Rottner Antje K. , Pacheco Sabrina , Moulding Dale A. , Wolf Anja , Kupatt Christian , Peppiatt-Wildman Claire , Papakrivopoulou Eugenia , Riley Paul R. , Long David A. , Vasilopoulou Elisavet
Published: July 2022

Plasma ultrafiltration in the kidney occurs across glomerular capillaries, which are surrounded by epithelial cells called podocytes. Podocytes have a unique shape maintained by a complex cytoskeleton, which becomes disrupted in glomerular disease resulting in defective filtration and albuminuria. Lack of endogenous thymosin β4 (TB4), an actin sequestering peptide, exacerbates glomerular injury and disrupts the organisation of the podocyte actin cytoskeleton, however, the potential of exogenous TB4 therapy to improve podocyte injury is unknown. Here, we have used Adriamycin (ADR), a toxin which injures podocytes and damages the glomerular filtration barrier leading to albuminuria in mice. Through interrogating single-cell RNA-sequencing data of isolated glomeruli we demonstrate that ADR injury results in reduced levels of podocyte TB4. Administration of an adeno-associated viral vector encoding TB4 increased the circulating level of TB4 and prevented ADR-induced podocyte loss and albuminuria. ADR injury was associated with disorganisation of the podocyte actin cytoskeleton in vitro, which was ameliorated by treatment with exogenous TB4. Collectively, we propose that systemic gene therapy with TB4 prevents podocyte injury and maintains glomerular filtration via protection of the podocyte cytoskeleton thus presenting a novel treatment strategy for glomerular disease.
DNA-aptamer-nanographene oxide as a targeted bio-theragnostic system in antimicrobial photodynamic therapy against Porphyromonas gingivalis
Authors: Pourhajibagher Maryam , Etemad-Moghadam Shahroo , Alaeddini Mojgan , Miri Mousavi Rezvaneh sadat , Bahador Abbas
Published: July 2022

The aim of this study was to design and evaluate the specificity of a targeted bio-theragnostic system based on DNA-aptamer-nanographene oxide (NGO) against Porphyromonas gingivalis during antimicrobial photodynamic therapy (aPDT). Following synthesis and confirmation of NGO, the binding of selected labeled DNA-aptamer to NGO was performed and its hemolytic activity, cytotoxic effect, and release times were evaluated. The specificity of DNA-aptamer-NGO to P. gingivalis was determined. The antimicrobial effect, anti-biofilm potency, and anti-metabolic activity of aPDT were then assessed after the determination of the bacteriostatic and bactericidal concentrations of DNA-aptamer-NGO against P. gingivalis. Eventually, the apoptotic effect and anti-virulence capacity of aPDT based on DNA-aptamer-NGO were investigated. The results showed that NGO with a flaky, scale-like, and layered structure in non-cytotoxic DNA-aptamer-NGO has a continuous release in the weak-acid environment within a period of 240 h. The binding specificity of DNA-aptamer-NGO to P. gingivalis was confirmed by flow cytometry. When irradiated, non-hemolytic DNA-aptamer-NGO were photoactivated, generated ROS, and led to a significant decrease in the cell viability of P. gingivalis (P < 0.05). Also, the data indicated that DNA-aptamer-NGO-mediated aPDT led to a remarkable reduction of biofilms and metabolic activity of P. gingivalis compared to the control group (P < 0.05). In addition, the number of apoptotic cells increased slightly (P > 0.05) and the expression level of genes involved in bacterial biofilm formation and response to oxidative stress changed significantly after exposure to aPDT. It is concluded that aPDT using DNA-aptamer-NGO as a targeted bio-theragnostic system is a promising approach to detect and eliminate P. gingivalis as one of the main bacteria involved in periodontitis in periopathogenic complex in real-time and in situ.
East–west contrasting changes in Southern Indian Ocean Antarctic Bottom Water salinity over three decades
Authors: Choi Yeon , Nam SungHyun
Published: July 2022

Antarctic Bottom Water (AABW) characteristics, derived from multiple water sources with various properties, are significantly affected by and contribute to climate change. However, the underlying causes of changes in AABW characteristics are not well-understood. In this study, we aimed to analyse the east–west contrasting pattern of AABW characteristics in the Southern Indian Ocean (SIO) over the last three decades. We show that AABW has become warmer and more saline in the western SIO (WSIO) but warmer and fresher in the eastern SIO (ESIO) in 2010s than in 1990s. The warming and salinification of WSIO AABW are primarily explained by changes in source water mixing ratios, although the source water properties also significantly contribute to the observed changes. In contrast, the warming and freshening of ESIO AABW cannot be explained without considering changes in the source water properties as the direction of AABW salinity change due to source water mixing ratios is opposite (salinification) to that of observations (freshening). The east–west contrasting pattern of AABW salinity changes and more rapid warming in the ESIO have important consequences for poleward AABW transport and sea-level rise within and beyond the SIO.
Impact of mild COVID-19 on balance function in young adults, a prospective observational study
Authors: Guzik Agnieszka , Wolan-Nieroda Andżelina , Kochman Maciej , Perenc Lidia , Drużbicki Mariusz
Published: July 2022

Balance is of essential importance in human life. The aim of the study is to examine the incidence of balance impairments in young adults who have recovered from mild COVID-19. The study involved 100 subjects, divided into two groups: the study group (50 individuals) comprised subjects who had recovered from mild COVID-19, and the control group (50 individuals) consisted of healthy subjects matched for gender and age. Balance was assessed using a force platform and clinical tests such as: timed up and go test, 15-s step test, sit-to-stand test and 6-min walk test. The assessment on the platform showed greater balance impairments in the trials with eyes closed; more specifically, compared to the controls, in trials with double-leg support the subjects from the study group acquired significantly higher scores in X average (lateral coordinates) (p < 0.05), Path length, V average (average Centre of Foot Pressure Velocity) (p < 0.05) and Area circular (p < 0.01), with even more significant results in trials with single-leg support in X average (p < 0.001), Y average (anterior–posterior coordinates) (p < 0.001) and Path length (p = 0.004). Higher scores in the timed up and go test were found in the study group (p = 0.013). The control group had higher scores in the remaining tests. The current findings show that mild COVID-19 may lead to balance impairments in young adults. Statistically significant differences in balance were found between the subjects in the study group and the healthy controls. Further studies in this area should take into account more age groups, and patients recovered from severe COVID-19, and should investigate long-term consequences of COVID-19 reflected by balance problems.
High expression of secretory leukocyte protease inhibitor (SLPI) in stage III micro-satellite stable colorectal cancer is associated with reduced disease recurrence
Authors: Nugteren Sandrine , den Uil Sjoerd H. , Delis-van Diemen Pien M. , Simons-Oosterhuis Ytje , Lindenbergh-Kortleve Dicky J. , van Haaften Daniëlle H. , Stockmann Hein B. A. C. , Sanders Joyce , Meijer Gerrit A. , Fijneman Remond J. A. , Samsom Janneke N.
Published: July 2022

Secretory leukocyte protease inhibitor (SLPI) is a pleiotropic protein produced by healthy intestinal epithelial cells. SLPI regulates NF-κB activation, inhibits neutrophil proteases and has broad antimicrobial activity. Recently, increased SLPI expression was found in various types of carcinomas and was suggested to increase their metastatic potential. Indeed, we demonstrated that SLPI protein expression in colorectal cancer (CRC) liver metastases and matched primary tumors is associated with worse outcome, suggesting that SLPI promotes metastasis in human CRC. However, whether SLPI plays a role in CRC before distant metastases have formed is unclear. Therefore, we examined whether SLPI expression is associated with prognosis in CRC patients with localized disease. Using a cohort of 226 stage II and 160 stage III CRC patients we demonstrate that high SLPI protein expression is associated with reduced disease recurrence in patients with stage III micro-satellite stable tumors treated with adjuvant chemotherapy, independently of established clinical risk factors (hazard rate ratio 0.54, P-value 0.03). SLPI protein expression was not associated with disease-free survival in stage II CRC patients. Our data suggest that the role of SLPI in CRC may be different depending on the stage of disease. In stage III CRC, SLPI expression may be unfavorable for tumors, whereas SLPI expression may be beneficial for tumors once distant metastases have established.
Low alanine aminotransferase levels are independently associated with mortality risk in patients with atrial fibrillation
Authors: Saito Yuki , Okumura Yasuo , Nagashima Koichi , Fukamachi Daisuke , Yokoyama Katsuaki , Matsumoto Naoya , Tachibana Eizo , Kuronuma Keiichiro , Oiwa Koji , Matsumoto Michiaki , Nishida Toshihiko , Kojima Toshiaki , Hanada Shoji , Nomoto Kazumiki , Sonoda Kazumasa , Arima Ken , Takahashi Fumiyuki , Kotani Tomobumi , Ohkubo Kimie , Fukushima Seiji , Itou Satoru , Kondo Kunio , Ando Hideyuki , Ohno Yasumi , Onikura Motoyuki , Hirayama Atsushi
Published: July 2022

Extremely low alanine aminotransferase (ALT) may reflect aging, frailty, sarcopenia, and malnutrition in several cardiovascular diseases, but the association between low ALT and patient characteristics, cardiovascular and all-cause mortality is not well investigated in the population with atrial fibrillation. We conducted a post hoc analysis of a prospective, observational multicenter study. Patients with nonvalvular AF in the SAKURA AF Registry (n = 3156) were classified into 3 tertiles according to baseline ALT: first (ALT ≤ 15 U/L, n = 1098), second (15 < ALT < 23 U/L, n = 1055), and third (ALT ≥ 23 U/L, n = 1003). The first tertile had an older age; lower body mass index (BMI); higher prevalence of heart failure; and lower hemoglobin, total cholesterol, and triglycerides (all P < 0.05). During median 39.2 months follow-up, the first tertile had significantly higher incidences of cardiovascular and all-cause mortality (log-rank P < 0.001). Lower ALT was significantly associated with the incidence of cardiovascular and all-cause mortality, even after adjusting for clinically relevant factors (P < 0.05). Low ALT may reflect aging, sarcopenia, and malnutrition and be independently associated with a high risk of all-cause mortality in patients with AF.
Severe and long-lasting alteration of albumin redox state by plasmapheresis
Authors: Boss Kristina , Stettner Mark , Szepanowski Fabian , Mausberg Anne K. , Paar Margret , Pul Refik , Kleinschnitz Christoph , Oettl Karl , Kribben Andreas
Published: July 2022

Plasmapheresis (PE) is an established form of therapeutic apheresis (TA). Purpose of this longitudinal prospective single center study was to investigate the effect of PE on albumin redox state (ARS), as infusion of commercial albumin during PE may alter albumin oxidation which has an impact on its functional properties and oxidative stress level. 43 subjects with autoimmune-mediated neurological disorders were included. 20 subjects in the experimental group received five treatments of PE. 13 subjects received five treatments of immunoadsorption and 10 subjects received no TA as controls. ARS was determined before and after TA and 12 days after the last TA by fractionating it into human mercaptalbumin (HMA), human non-mercaptalbumin 1 (HNA-1), and human non-mercaptalbumin 2 (HNA-2) by high-performance liquid chromatography. Irreversibly oxidised HNA-2 increased over the course of five PE treatments from 2.8% (IQR 1.3–3.7%) to 13.6% (IQR 10.9–15.9) (P < 0.01) and remained elevated 12 days after the last PE procedure (7.7% IQR 7.1–10.5, P < 0.05). The study showed for the first time that PE exerts a severe and long-lasting alteration on ARS indicating a new adverse effect of PE, that may influence oxidative stress level.
Acetyl-cholinesterase-inhibitors slow cognitive decline and decrease overall mortality in older patients with dementia
Authors: Zuin Marco , Cherubini Antonio , Volpato Stefano , Ferrucci Luigi , Zuliani Giovanni
Published: July 2022

We evaluated the effect of Acetyl-cholinesterase-inhibitors (AChEIs) on cognitive decline and overall survival in a large sample of older patients with late onset Alzheimer’s disease (LOAD), vascular dementia (VD) or Lewy body disease (LBD) from a real world setting. Patients with dementia enrolled between 2005 and 2020 by the "Alzheimer's Disease Research Centers" were analysed; the mean follow-up period was 7.9 years. A 1:1 propensity score matching was performed generating a cohort of 1.572 patients (786 treated [AChEIs +] and 786 not treated [AChEIs-] with AChEIs. The MMSE score was almost stable during the first 6 years of follow up in AChEIs + and then declined, while in AChEIs− it progressively declined so that at the end of follow-up (13.6 years) the average decrease in MMSE was 10.8 points in AChEIs- compared with 5.4 points in AChEIs + (p < 0.001). This trend was driven by LOAD (Δ-MMSE:−10.8 vs. −5.7 points; p < 0.001), although a similar effect was observed in VD (Δ-MMSE:−11.6 vs. −8.8; p < 0.001). No effect on cognitive status was found in LBD. At multivariate Cox regression analysis (adjusted for age, gender, dependency level and depression) a strong association between AChEIs therapy and lower all-cause mortality was observed (H.R.:0.59; 95%CI: 0.53–0.66); this was confirmed also in analyses separately conducted in LOAD, VD and LBD. Among older people with dementia, treatment with AChEIs was associated with a slower cognitive decline and with reduced mortality, after a mean follow-up of almost eight years. Our data support the effectiveness of AChEIs in older patients affected by these types of dementia.
Effect of tempol and straw size on rooster sperm quality and fertility after post-thawing
Authors: Najafi Abouzar , Mehdipour Mahdieh , Mohammadi Hossein , Mehdipour Zohreh , Khorrami Behzad , Nazari Mahdi
Published: July 2022

The aim of the present study was to investigate the effects of tempol and straw size on rooster sperm post-thaw quality and fertility. Rooster semen was cryopreserved in Lake extender containing 0 (control), 5, 10, 15 and 20 μM tempol (in two different straw size, 0.25 and 0.5). The percentage of total and progressive sperm motility, VAP and VSL increased in the 10 µM tempol group. Moreover, 10 µM tempol led to lower ROS compared to other groups. The lowest percentage of apoptotic-like changes was detected when the extender was treated with 10 µM of tempol. The minimum ROS was observed in the group treated with 0.5 straw size. Straw size did not have any significantly effect on GPx and SOD activities and TAC of frozen-thawed sperm. The highest significant percentage of fertility and hatching rate were observed in 10 µM of tempol. The results of the present study showed that supplementation of the Lake cryopreservation medium with 10 µM tempol improved cryo-survival. Also, the results of the present study suggested that Lake cryopreservation medium with 0.5-ml straw may perhaps be an appropriate method to improve the quality and fertility post-thawed rooster sperm.
A PCR-lateral flow immunochromatographic assay (PCR-LFA) for detecting Aristolochia species, the plants responsible for aristolochic acid nephropathy
Authors: Thongkhao Kannika , Tungphatthong Chayapol , Sukrong Suchada
Published: July 2022

Aristolochic acids (AAs), which are strong carcinogens, have caused dietary supplements with Aristolochia plants to be discontinued worldwide. Therefore, the development of a method to identify these herbs is critical for customer safety. To support the regulation of Aristolochia-free products, a PCR coupled with lateral flow immunochromatographic assay (PCR-LFA) that is specific to the nucleotide signature in plastid rbcL gene region of Aristolochia species was developed to detect Aristolochia plants and related herbal products. Triplex primers (A397F, C357F and R502) were designed based on specific nucleotides observed exclusively in the rbcL sequences of Aristolochia. Positive results for Aristolochia occur when the three pink lines are clearly developed on the developed lateral flow strip and can be seen by the naked eye. In this study, the lateral flow strip has sensitivity for detecting amplicons amplified from genomic DNA at the concentrations as low as 0.01 ng. Various kinds of samples, including purchased crude drugs and polyherbal samples, have been investigated, and the results showed that Aristolochia crude drugs and Aristolochia-containing products are still present in dispensaries. In conclusion, with the goal of protecting consumers from the health risks associated with Aristolochia contamination, PCR-LFA was developed and demonstrated to be efficient for detecting plants belonging to Aristolochia in various kinds of samples.
Automated identification of hip arthroplasty implants using artificial intelligence
Authors: Gong Zibo , Fu Yonghui , He Ming , Fu Xinzhe
Published: July 2022

The purpose of this study was to develop and evaluate the performance of deep learning methods based on convolutional neural networks (CNN) to detect and identify specific hip arthroplasty models. In this study, we propose a novel deep learning-based approach to identify hip arthroplasty implants’ design using anterior–posterior images of both the stem and the cup. We harness the pre-trained ResNet50 CNN model and employ transfer learning methods to adapt the model for the implants identification task using a total of 714 radiographs of 4 different hip arthroplasty implant designs. Performance was compared with the operative notes and crosschecked with implant sheets. We also evaluate the difference in performance of models trained with the images of the stem, the cup or both. The training and validation data sets were comprised of 357 stem images and 357 cup radiographs across 313 patients and included 4 hip arthroplasty implants from 4 leading implant manufacturers. After 1000 training epochs the model classified 4 implant models with very high accuracy. Our results showed that jointly using stem images and cup images did not improve the classification accuracy of the CNN model. CNN can accurately distinguish between specific hip arthroplasty designs. This technology could offer a useful adjunct to the surgeon in preoperative identification of the prior implant. Using stem images or cup images to train the CNN can both achieve effective identification accuracy, with the accuracy of the stem images being higher. Using stem images and cup images together is not more effective than using images from only one perspective.
Prediction of adult post-hemorrhagic hydrocephalus: a risk score based on clinical data
Authors: Wang Zhiwen , Xi Bin , Yu Bingxiao , Zhou Junhui , Wang Min , Wang Changfeng , Liu Ruen
Published: July 2022

There is lacking research on risk factors and prediction models associated with Post-hemorrhagic hydrocephalus (PHH). Thus, this present study aimed to analyze the risk factors of PHH and establish a risk-scoring system through a large-scale study. A retrospective study of 382 patients with intracranial hemorrhage assessed age, history and diagnosis, Glasgow coma score (GCS), and fever time. After univariate and logistic regression analysis, a risk scoring system was established according to independent risk factors and evaluated using the area under the curve (AUC). Of the 382 patients, 133 (34.8%) had PHH, 43 (11.3%) received surgical treatment. Factor classification showed that age > 60 years old [odds ratio (OR): 0.347, II = 5 points], GCS < 5 (OR: 0.09, IV = 10 points), GCS 6‒8 (OR = 0.232, III = 6 points), fever time > 9 (OR: 0.202, III = 7 points), fever time 5–9 (OR: 0.341, II = 5 points), CSF-TP x time > 14,4000 group (OR: 0.267, IV = 6 points), and CSF-TP x time 9,601‒14,400 group (OR: 0.502, III = 3 points) were independent risk factors. The result of the receiver operating characteristic (ROC) prediction showed that AUC = 0.790 (0.744‒0.836). Low-risk (IV-VII), moderate (VIII-X), and high-risk group (XI-XIII) incidence of PHH were 11.76%, 50.55%, and 70.00% (p < 0.001), respectively. The coincidence rates in the validation cohort were 26.00%, 74.07%, and 100.0% (p < 0.001), respectively. AUC value was 0.860 (0.780‒0.941). The predictive model was conducive to determining the occurrence of PHH and facilitating early intervention.