bluuebunny/crossref_metadata_2025 huggingface dataset:
DUSP1 protects against ischemic acute kidney injury through stabilizing mtDNA via interaction with JNK
Authors: Shi Lang , Zha Hongchu , Pan Zhou , Wang Jiayi , Xia Yao , Li Huimin , Huang Hua , Yue Ruchi , Song Zhixia , Zhu Jiefu
Published: November 2023

The mechanism underlying acute kidney injury (AKI) and AKI-to-Chronic kidney disease (CKD) transition remains unclear, but mitochondrial dysfunction may be a key driving factor. Literature reports suggest that dual-specificity phosphatase 1 (DUSP1) plays a critical role in maintaining mitochondrial function and structural integrity. In this study, ischemic Acute Kidney Injury (AKI) and post-ischemic fibrosis models were established by clamping the renal pedicle with different reperfusion times. To investigate the role of DUSP1, constitutional Dusp1 knockout mice and tubular-specific Sting knockout mice were used. Mitochondrial damage was assessed through electron microscopy observation, measurements of mitochondrial membrane potential, mtDNA release, and BAX translocation. We found that Dusp1 expression was significantly upregulated in human transplant kidney tissue and mouse AKI tissue. Dusp1 gene deletion exacerbated acute ischemic injury, post-ischemic renal fibrosis, and tubular mitochondrial dysfunction in mice. Mechanistically, DUSP1 could directly bind to JNK, and DUSP1 deficiency could lead to aberrant phosphorylation of JNK and BAX mitochondria translocation. BAX translocation promoted mitochondrial DNA (mtDNA) leakage and activated the cGAS-STING pathway. Inhibition of JNK or BAX could inhibit mtDNA leakage. Furthermore, STING knockout or JNK inhibition could significantly mitigate the adverse effects of DUSP1 deficiency in ischemic AKI model. Collectively, our findings suggest that DUSP1 is a regulator for the protective response during AKI. DUSP1 protects against AKI by preventing BAX-induced mtDNA leakage and blocking excessive activation of the cGAS-STING signaling axis through JNK dephosphorylation.
Mitochondrial DNA-triggered innate immune response: mechanisms and diseases
Authors: Hu Ming-Ming , Shu Hong-Bing
Published: November 2023

Various cellular stress conditions trigger mitochondrial DNA (mtDNA) release from mitochondria into the cytosol. The released mtDNA is sensed by the cGAS-MITA/STING pathway, resulting in the induced expression of type I interferon and other effector genes. These processes contribute to the innate immune response to viral infection and other stress factors. The deregulation of these processes causes autoimmune diseases, inflammatory metabolic disorders and cancer. Therefore, the cGAS-MITA/STING pathway is a potential target for intervention in infectious, inflammatory and autoimmune diseases as well as cancer. In this review, we focus on the mechanisms underlying the mtDNA-triggered activation of the cGAS-MITA/STING pathway, the effects of the pathway under various physiological and pathological conditions, and advances in the development of drugs that target cGAS and MITA/STING.
Rapid disintegration and weakening of ice shelves in North Greenland
Authors: Millan R. , Jager E. , Mouginot J. , Wood M. H. , Larsen S. H. , Mathiot P. , Jourdain N. C. , Bjørk A.
Published: November 2023

The glaciers of North Greenland are hosting enough ice to raise sea level by 2.1 m, and have long considered to be stable. This part of Greenland is buttressed by the last remaining ice shelves of the ice sheet. Here, we show that since 1978, ice shelves in North Greenland have lost more than 35% of their total volume, three of them collapsing completely. For the floating ice shelves that remain we observe a widespread increase in ice shelf mass losses, that are dominated by enhanced basal melting rates. Between 2000 and 2020, there was a widespread increase in basal melt rates that closely follows a rise in the ocean temperature. These glaciers are showing a direct dynamical response to ice shelf changes with retreating grounding lines and increased ice discharge. These results suggest that, under future projections of ocean thermal forcing, basal melting rates will continue to rise or remain at high level, which may have dramatic consequences for the stability of Greenlandic glaciers.
An artificially-intelligent cornea with tactile sensation enables sensory expansion and interaction
Authors: Qu Shangda , Sun Lin , Zhang Song , Liu Jiaqi , Li Yue , Liu Junchi , Xu Wentao
Published: November 2023

We demonstrate an artificially-intelligent cornea that can assume the functions of the native human cornea such as protection, tactile perception, and light refraction, and possesses sensory expansion and interactive functions. These functions are realized by an artificial corneal reflex arc that is constructed to implement mechanical and light information coding, information processing, and the regulation of transmitted light. Digitally-aligned, long and continuous zinc tin oxide (ZTO) semiconductor fabric patterns were fabricated as the active channels of the artificial synapse, which are non-toxic, heavy-metal-free, low-cost, and ensure superior comprehensive optical properties (transmittance >99.89%, haze <0.36%). Precisely-tuned crystal-phase structures of the ZTO fibers enabled reconfigurable synaptic plasticity, which is applicable to encrypted communication and associative learning. This work suggests new strategies for the tuning of synaptic plasticity and the design of visual neuroprosthetics, and has important implications for the development of neuromorphic electronics and for visual restoration.
Direct detection of atomic oxygen on the dayside and nightside of Venus
Authors: Hübers Heinz-Wilhelm , Richter Heiko , Graf Urs U. , Güsten Rolf , Klein Bernd , Stutzki Jürgen , Wiesemeyer Helmut
Published: November 2023

Atomic oxygen is a key species in the mesosphere and thermosphere of Venus. It peaks in the transition region between the two dominant atmospheric circulation patterns, the retrograde super-rotating zonal flow below 70 km and the subsolar to antisolar flow above 120 km altitude. However, past and current detection methods are indirect and based on measurements of other molecules in combination with photochemical models. Here, we show direct detection of atomic oxygen on the dayside as well as on the nightside of Venus by measuring its ground-state transition at 4.74 THz (63.2 µm). The atomic oxygen is concentrated at altitudes around 100 km with a maximum column density on the dayside where it is generated by photolysis of carbon dioxide and carbon monoxide. This method enables detailed investigations of the Venusian atmosphere in the region between the two atmospheric circulation patterns in support of future space missions to Venus.
Unappreciated subcontinental admixture in Europeans and European Americans and implications for genetic epidemiology studies
Authors: Gouveia Mateus H. , Bentley Amy R. , Leal Thiago P. , Tarazona-Santos Eduardo , Bustamante Carlos D. , Adeyemo Adebowale A. , Rotimi Charles N. , Shriner Daniel
Published: November 2023

European-ancestry populations are recognized as stratified but not as admixed, implying that residual confounding by locus-specific ancestry can affect studies of association, polygenic adaptation, and polygenic risk scores. We integrate individual-level genome-wide data from ~19,000 European-ancestry individuals across 79 European populations and five European American cohorts. We generate a new reference panel that captures ancestral diversity missed by both the 1000 Genomes and Human Genome Diversity Projects. Both Europeans and European Americans are admixed at the subcontinental level, with admixture dates differing among subgroups of European Americans. After adjustment for both genome-wide and locus-specific ancestry, associations between a highly differentiated variant in LCT (rs4988235) and height or LDL-cholesterol were confirmed to be false positives whereas the association between LCT and body mass index was genuine. We provide formal evidence of subcontinental admixture in individuals with European ancestry, which, if not properly accounted for, can produce spurious results in genetic epidemiology studies.
Vegetation controls on channel network complexity in coastal wetlands
Authors: van de Vijsel Roeland C. , van Belzen Jim , Bouma Tjeerd J. , van der Wal Daphne , Borsje Bas W. , Temmerman Stijn , Cornacchia Loreta , Gourgue Olivier , van de Koppel Johan
Published: November 2023

Channel networks are key to coastal wetland functioning and resilience under climate change. Vegetation affects sediment and hydrodynamics in many different ways, which calls for a coherent framework to explain how vegetation shapes channel network geometry and functioning. Here, we introduce an idealized model that shows how coastal wetland vegetation creates more complexly branching networks by increasing the ratio of channel incision versus topographic diffusion rates, thereby amplifying the channelization feedback that recursively incises finer-scale side-channels. This complexification trend qualitatively agrees with and provides an explanation for field data presented here as well as in earlier studies. Moreover, our model demonstrates that a stronger biogeomorphic feedback leads to higher and more densely vegetated marsh platforms and more extensive drainage networks. These findings may inspire future field research by raising the hypothesis that vegetation-induced self-organization enhances the storm surge buffering capacity of coastal wetlands and their resilience under sea-level rise.
Forgotten memory storage and retrieval in Drosophila
Authors: Wang Chih-Ming , Wu Chun-Yuan , Lin Chen-En , Hsu Ming-Chi , Lin Jing-Chun , Huang Chuan-Chin , Lien Ting-Yu , Lin Hsin-Kai , Chang Ting-Wei , Chiang Hsueh-Cheng
Published: November 2023

Inaccessibility of stored memory in ensemble cells through the forgetting process causes animals to be unable to respond to natural recalling cues. While accumulating evidence has demonstrated that reactivating memory-stored cells can switch cells from an inaccessible state to an accessible form and lead to recall of previously learned information, the underlying cellular and molecular mechanisms remain elusive. The current study used Drosophila as a model to demonstrate that the memory of one-trial aversive olfactory conditioning, although inaccessible within a few hours after learning, is stored in KCαβ and retrievable after mild retraining. One-trial aversive conditioning triggers protein synthesis to form a long-lasting cellular memory trace, approximately 20 days, via creb in KCαβ, and a transient cellular memory trace, approximately one day, via orb in MBON-α3. PPL1-α3 negatively regulates forgotten one-trial conditioning memory retrieval. The current study demonstrated that KCαβ, PPL1-α3, and MBON-α3 collaboratively regulate the formation of forgotten one-cycle aversive conditioning memory formation and retrieval.
Candidate genes under selection in song sparrows co-vary with climate and body mass in support of Bergmann’s Rule
Authors: Carbeck Katherine , Arcese Peter , Lovette Irby , Pruett Christin , Winker Kevin , Walsh Jennifer
Published: November 2023

Ecogeographic rules denote spatial patterns in phenotype and environment that may reflect local adaptation as well as a species’ capacity to adapt to change. To identify genes underlying Bergmann’s Rule, which posits that spatial correlations of body mass and temperature reflect natural selection and local adaptation in endotherms, we compare 79 genomes from nine song sparrow (Melospiza melodia) subspecies that vary ~300% in body mass (17 − 50 g). Comparing large- and smaller-bodied subspecies revealed 9 candidate genes in three genomic regions associated with body mass. Further comparisons to the five smallest subspecies endemic to California revealed eight SNPs within four of the candidate genes (GARNL3, RALGPS1, ANGPTL2, and COL15A1) associated with body mass and varying as predicted by Bergmann’s Rule. Our results support the hypothesis that co-variation in environment, body mass and genotype reflect the influence of natural selection on local adaptation and a capacity for contemporary evolution in this diverse species.
Structural basis of peptide secretion for Quorum sensing by ComA
Authors: Yu Lin , Xu Xin , Chua Wan-Zhen , Feng Hao , Ser Zheng , Shao Kai , Shi Jian , Wang Yumei , Li Zongli , Sobota Radoslaw M. , Sham Lok-To , Luo Min
Published: November 2023

Quorum sensing (QS) is a crucial regulatory mechanism controlling bacterial signalling and holds promise for novel therapies against antimicrobial resistance. In Gram-positive bacteria, such as Streptococcus pneumoniae, ComA is a conserved efflux pump responsible for the maturation and secretion of peptide signals, including the competence-stimulating peptide (CSP), yet its structure and function remain unclear. Here, we functionally characterize ComA as an ABC transporter with high ATP affinity and determined its cryo-EM structures in the presence or absence of CSP or nucleotides. Our findings reveal a network of strong electrostatic interactions unique to ComA at the intracellular gate, a putative binding pocket for two CSP molecules, and negatively charged residues facilitating CSP translocation. Mutations of these residues affect ComA’s peptidase activity in-vitro and prevent CSP export in-vivo. We demonstrate that ATP-Mg2+ triggers the outward-facing conformation of ComA for CSP release, rather than ATP alone. Our study provides molecular insights into the QS signal peptide secretion, highlighting potential targets for QS-targeting drugs.
Proenkephalin-A secreted by renal proximal tubules functions as a brake in kidney regeneration
Authors: Liu Chi , Liu Xiaoliang , He Zhongwei , Zhang Jiangping , Tan Xiaoqin , Yang Wenmin , Zhang Yunfeng , Yu Ting , Liao Shuyi , Dai Lu , Xu Zhi , Li Furong , Huang Yinghui , Zhao Jinghong
Published: November 2023

Organ regeneration necessitates precise coordination of accelerators and brakes to restore organ function. However, the mechanisms underlying this intricate molecular crosstalk remain elusive. In this study, the level of proenkephalin-A (PENK-A), expressed by renal proximal tubular epithelial cells, decreases significantly with the loss of renal proximal tubules and increased at the termination phase of zebrafish kidney regeneration. Notably, this change contrasts with the role of hydrogen peroxide (H2O2), which acts as an accelerator in kidney regeneration. Through experiments with penka mutants and pharmaceutical treatments, we demonstrate that PENK-A inhibits H2O2 production in a dose-dependent manner, suggesting its involvement in regulating the rate and termination of regeneration. Furthermore, H2O2 influences the expression of tcf21, a vital factor in the formation of renal progenitor cell aggregates, by remodeling H3K4me3 in renal cells. Overall, our findings highlight the regulatory role of PENK-A as a brake in kidney regeneration.
RNA recognition by Npl3p reveals U2 snRNA-binding compatible with a chaperone role during splicing
Authors: Moursy Ahmed , Cléry Antoine , Gerhardy Stefan , Betz Katharina M. , Rao Sanjana , Mazur Jarosław , Campagne Sébastien , Beusch Irene , Duszczyk Malgorzata M. , Robinson Mark D. , Panse Vikram Govind , Allain Frédéric H.-T.
Published: November 2023

The conserved SR-like protein Npl3 promotes splicing of diverse pre-mRNAs. However, the RNA sequence(s) recognized by the RNA Recognition Motifs (RRM1 & RRM2) of Npl3 during the splicing reaction remain elusive. Here, we developed a split-iCRAC approach in yeast to uncover the consensus sequence bound to each RRM. High-resolution NMR structures show that RRM2 recognizes a 5´-GNGG-3´ motif leading to an unusual mille-feuille topology. These structures also reveal how RRM1 preferentially interacts with a CC-dinucleotide upstream of this motif, and how the inter-RRM linker and the region C-terminal to RRM2 contribute to cooperative RNA-binding. Structure-guided functional studies show that Npl3 genetically interacts with U2 snRNP specific factors and we provide evidence that Npl3 melts U2 snRNA stem-loop I, a prerequisite for U2/U6 duplex formation within the catalytic center of the Bact spliceosomal complex. Thus, our findings suggest an unanticipated RNA chaperoning role for Npl3 during spliceosome active site formation.
C-terminal modification and functionalization of proteins via a self-cleavage tag triggered by a small molecule
Authors: Zeng Yue , Shi Wei , Liu Zhi , Xu Hao , Liu Liya , Hang Jiaying , Wang Yongqin , Lu Mengru , Zhou Wei , Huang Wei , Tang Feng
Published: November 2023

The precise modification or functionalization of the protein C-terminus is essential but full of challenges. Herein, a chemical approach to modify the C-terminus is developed by fusing a cysteine protease domain on the C-terminus of the protein of interest, which could achieve the non-enzymatic C-terminal functionalization by InsP6-triggered cysteine protease domain self-cleavage. This method demonstrates a highly efficient way to achieve protein C-terminal functionalization and is compatible with a wide range of amine-containing molecules and proteins. Additionally, a reversible C-terminal de-functionalization is found by incubating the C-terminal modified proteins with cysteine protease domain and InsP6, providing a tool for protein functionalization and de-functionalization. Last, various applications of protein C-terminal functionalization are provided in this work, as demonstrated by the site-specific assembly of nanobody drug conjugates, the construction of a bifunctional antibody, the C-terminal fluorescent labeling, and the C-terminal transpeptidation and glycosylation.
Efficient PFOA removal from drinking water by a dual-functional mixed-matrix-composite nanofiltration membrane
Authors: Chaudhary Mohit , Sela-Adler Michal , Ronen Avner , Nir Oded
Published: November 2023

Drinking water contamination by per- and polyfluorinated alkyl substances (PFAS) is a global concern. Nanofiltration is a promising PFAS removal technology due to its scalability and cost-effectiveness. However, nanofiltration cannot typically reduce PFAS concentrations below current drinking water recommendations. To enhance PFAS removal, we developed mixed-matrix-composite nanofiltration (MMCNF) membranes—an active nanofiltration layer on porous adsorptive support that synergetically combines filtration and adsorption. We synthesized MMCNF membranes comprising thin polyelectrolyte multilayer films deposited on thick (~400 µm) polyethersulfone supports incorporating β-cyclodextrin microparticles. These membranes achieved near complete removal (>99.9%) of model PFAS (PFOA: perfluorooctanoic acid) for significantly longer filtration times compared to a control membrane without β-cyclodextrin, but otherwise identical. The spent MMCNF membrane was regenerated using ethanol, and high PFOA removal performance was regained during three filtration cycles. Perfluorooctanoic acid was concentrated 38-fold in the ethanol eluent. Further concentration by evaporation is straightforward and can enable eluent recycling and effective PFAS removal.
Early Eocene low orography and high methane enhance Arctic warming via polar stratospheric clouds
Authors: Dutta Deepashree , Jucker Martin , Sherwood Steven C. , Meissner Katrin J. , Sen Gupta Alex , Zhu Jiang
Published: November 2023

Proxy data suggest that the early Eocene (∼56–47.8 million years ago) was characterized by a much weaker equator-to-pole temperature gradient than today. However, general circulation models consistently underestimate high-latitude temperatures indicated by proxy records, suggesting that they may miss important processes. Previous studies hypothesized that wintertime polar stratospheric clouds may have played an important role in Arctic warming through greenhouse forcing, but these studies did not consider the effects of atmospheric chemistry or the early Eocene topography. Here we examine these factors using a high-top atmospheric model with interactive chemistry. The lower orography in the low- to mid-latitude Northern Hemisphere early Eocene weakens the stratospheric circulation which, in combination with sufficiently high methane concentrations, leads to a substantial increase in polar stratospheric clouds in the Arctic winter. Furthermore, an increase in early Eocene polar stratospheric clouds due to a 16- to 64-fold higher than pre-industrial methane concentration results in a radiative forcing larger than the direct greenhouse effect from the methane itself. This polar stratospheric cloud-induced radiative forcing could cause up to 7.4 K of Arctic surface warming. These results point to the potential for nonlinear interactions between individual forcings.
Improved high-quality reference genome of red drum facilitates the processes of resistance-related gene exploration
Authors: Xiao Yongshuang , Liu Jing , Wei Jiehong , Xiao Zhizhong , Li Jun , Ma Yuting
Published: November 2023

Sciaenops ocellatus is among the most important artificially introduced farmed fish across 11 countries and regions. However, the frequent occurrence of extreme weather events and breeding escapes have placed great pressure on local marine biodiversity and ecosystems. We reported the de novo assembly and annotation with a contig N50 of 28.30 Mb using PacBio HiFi sequencing and Hi-C technologies, which resulted in a 283-fold increase in contig N50 length and improvement in continuity and quality in complex repetitive region for S. ocellatus compared to the previous version. In total, 257.36 Mb of repetitive sequences accounted for 35.48% of the genome, and 22,845 protein-coding genes associated with a BUSCO value of 98.32%, were identified by genome annotation. Moreover, 54 hub genes rapidly responding to hypoosmotic stress were identified by WGCNA. The high-quality chromosome-scale S. ocellatus genome and candidate resistance-related gene sets will not only provide a genomic basis for genetic improvement via molecular breeding, but will also lay an important foundation for investigating the molecular regulation of rapid responses to stress.
Modified early intensive and treat-and-extend regimen of anti-vascular endothelial growth factor for diabetic macular edema in Taiwan
Authors: Chou Jui-Feng , Wu Jian-Sheng , Chen Yi-Ling , Chen San-Ni
Published: November 2023

Given the rising prevalence of patients with diabetes and increasing treatment burden for patients with vision-threatening diabetic macular edema (DME), we aimed to explore the efficacy of modified early intensive and treat-and-extend regimen of anti-vascular endothelial growth factor (VEGF) therapy under the Taiwan National Insurance Bureau reimbursement policy. We obtained data on 69 eyes treated with initial 4-monthly intravitreal injections of aflibercept or ranibizumab, plus individualized treat-and-extend regimen. At 12 months, the mean (SD) change in LogMAR best corrected visual acuity from baseline was − 0.28 (0.31) in all eyes, while that in the aflibercept and ranibizumab groups were − 0.30 (0.34) and − 0.25 (0.28), respectively. Central retinal thickness decreased by 137.2 (122.4) in all eyes, 138.1 (134.2) in the aflibercept group, and 136.2 (110.9) in the ranibizumab group. Additionally, the aflibercept group had a lower mean number of injections than the ranibizumab group (8.5 vs. 8.7). The last extended dosing interval of > 12 weeks was 31.0% and 16.7% of the eyes in the aflibercept and ranibizumab groups, respectively. The modified anti-VEGF regimens effectively managed DME in terms of functional and anatomical outcomes, and efficiently reduced the healthcare burden by reducing the number of injections and extending treatment intervals within 12 months.
Safety comparisons among monoamine oxidase inhibitors against Parkinson’s disease using FDA adverse event reporting system
Authors: Asano Hiroto , Tian Yu-Shi , Hatabu Asuka , Takagi Tatsuya , Ueda Mikiko , Ikeda Kenji
Published: November 2023

Monoamine oxidase B (MAO-B) inhibitors are used to control Parkinson’s disease (PD). Selegiline, rasagiline, and safinamide are widely used as MAO-B inhibitors worldwide. Although these drugs inhibit MAO-B, there are pharmacological and chemical differences, such as the inhibitory activity, the non-dopaminergic properties in safinamide, and the amphetamine-like structure in selegiline. MAO-B inhibitors may differ in adverse events (AEs). However, differences in actual practical clinics are not fully investigated. A retrospective study was conducted using FAERS, the largest database of spontaneous adverse events. AE signals for MAO-B inhibitors, including selegiline, rasagiline, and safinamide, were detected using the reporting odds ratio method and compared. Hypocomplementemia, hepatic cyst, hepatic function abnormal, liver disorder and cholangitis were detected for selegiline as drug-specific signals. The amphetamine effect was not confirmed for any of the three MAO-B inhibitors. The tyramine reaction was detected as an AE signal only for rasagiline. Moreover, the REM sleep behavior disorder was not detected as an AE signal for safinamide, suggesting that non-dopaminergic effects might be beneficial. Considering the differences in AEs for MAO-B inhibitors will assist with the appropriate PD medication.
Research on the damage characteristics of rock masses based on double guide-hole blasting under high in-situ stress
Authors: Xu Ruizong , Xie Liangfu , Ma Long , Wang Benfeng
Published: November 2023

In complex high in-situ stress conditions, how to achieve the ideal rock blasting effect through effective methods is often a difficult point of blasting operations. This paper analyzes the influence of guide holes on blasting effect by adding guide holes to the rock pre-treatment method. Based on the particle expansion method to carry out double-hole blasting experiments, the influence of the blasthole spacing and ground stress on the blasting effect is investigated from the levels of macroscopic cracking effect, microscopic particle contact and so on. The study shows that: (i) the setting of empty holes between the gun holes can enhance the crack penetration effect, and the penetration effect is more obvious when the distance between the gun holes and the empty holes is less than 2.5 times the radius of the crushed zone. (ii) At the level of contact force chain, when the distance between blastholes and empty holes is less than 2.5 times the radius of the crushing zone. The compressive stress in the direction perpendicular to the direction of the blasthole line inhibits crack development, and the tensile stress in the direction parallel to the blasthole line promotes crack development. The main stress direction is perpendicular to the direction of the blasthole line. (iii) As the distance between the blastholes increases, the effect of crack suppression by stresses in the vertical direction decreases, and the main force direction is parallel to the direction of the blasthole line.
Six-pack holography for dynamic profiling of thick and extended objects by simultaneous three-wavelength phase unwrapping with doubled field of view
Authors: Mirsky Simcha K. , Shaked Natan T.
Published: November 2023

Dynamic holographic profiling of thick samples is limited due to the reduced field of view (FOV) of off-axis holography. We present an improved six-pack holography system for the simultaneous acquisition of six complex wavefronts in a single camera exposure from two fields of view (FOVs) and three wavelengths, for quantitative phase unwrapping of thick and extended transparent objects. By dynamically generating three synthetic wavelength quantitative phase maps for each of the two FOVs, with the longest wavelength being 6207 nm, hierarchical phase unwrapping can be used to reduce noise while maintaining the improvements in the 2π phase ambiguity due to the longer synthetic wavelength. The system was tested on a 7 μm tall PDMS microchannel and is shown to produce quantitative phase maps with 96% accuracy, while the hierarchical unwrapping reduces noise by 93%. A monolayer of live onion epidermal tissue was also successfully scanned, demonstrating the potential of the system to dynamically decrease scanning time of optically thick and extended samples.
Identification of serum miR-1246 and miR-150-5p as novel diagnostic biomarkers for high-grade serous ovarian cancer
Authors: Niemira Magdalena , Erol Anna , Bielska Agnieszka , Zeller Anna , Skwarska Anna , Chwialkowska Karolina , Kuzmicki Mariusz , Szamatowicz Jacek , Reszec Joanna , Knapp Pawel , Moniuszko Marcin , Kretowski Adam
Published: November 2023

Epithelial ovarian cancer (EOC) is one of the leading cancers in women, with high-grade serous ovarian cancer (HGSOC) being the most common and lethal subtype of this disease. A vast majority of HGSOC are diagnosed at the late stage of the disease when the treatment and total recovery chances are low. Thus, there is an urgent need for novel, more sensitive and specific methods for early and routine HGSOC clinical diagnosis. In this study, we performed miRNA expression profiling using the NanoString miRNA assay in 34 serum samples from patients with HGSOC and 36 healthy women. We identified 13 miRNAs that were differentially expressed (DE). For additional exploration of expression patterns correlated with HGSOC, we performed weighted gene co-expression network analysis (WGCNA). As a result, we showed that the module most correlated with tumour size, nodule and metastasis contained 8 DE miRNAs. The panel including miR-1246 and miR-150-5p was identified as a signature that could discriminate HGSOC patients with AUCs of 0.98 and 1 for the training and test sets, respectively. Furthermore, the above two-miRNA panel had an AUC = 0.946 in the verification cohorts of RT-qPCR data and an AUC = 0.895 using external data from the GEO public database. Thus, the model we developed has the potential to markedly improve the diagnosis of ovarian cancer.
Probabilistic modelling is superior to deterministic approaches in the human health risk assessment: an example from a tribal stretch in central India
Authors: Herojeet Rajkumar , Dewangan Rakesh K. , Naik Pradeep K. , Verma Janak R.
Published: November 2023

This case drew national attention in 2018. About 100 people died and more than 300 hospitalized in a span of few years in a village of 1200 people in a tribal stretch in central India. Medical teams visiting the area reported severe renal failure and blamed the local eating and drinking habits as causative factors. This human health assessment based on geochemical investigations finds nitrate (NO3−) and fluoride (F−) pollution as well in village’s groundwater. Both deterministic and probabilistic techniques are employed to decipher the contamination pathways and extent of contamination. Source apportionments of NO3− and F− and their relationship with other ions in groundwater are carried out through chemometric modelling. Latent factors controlling the hydrogeochemistry of groundwater too are explored. While hazard quotients ($$HQ$$

HQ

) of the chemical parameters ($$HQ_{{{\text{NO}}_{3}^{ - } }}$$

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and $$HQ_{{{\text{F}}^{ - } }}$$

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) identify ingestion as the prominent pathway, the calculated risk certainty levels (RCL) of the hazard index (HI) values above unity are compared between the deterministic and probabilistic approaches. Deterministic model overestimates the HI values and magnify the contamination problems. Probabilistic model gives realistic results that stand at infants ($$HI_{{{\text{NO}}_{3}^{ - } }}$$

H

I

NO

3

-

 = 34.03%, $$HI_{{{\text{F}}^{ - } }}$$

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I

F

-

 = 24.17%) > children ($$HI_{{{\text{NO}}_{3}^{ - } }}$$

H

I

NO

3

-

 = 23.01%, $$HI_{{{\text{F}}^{ - } }}$$

H

I

F

-

 = 10.56%) > teens ($$HI_{{{\text{NO}}_{3}^{ - } }}$$

H

I

NO

3

-

 = 13.17%, $$HI_{{{\text{F}}^{ - } }}$$

H

I

F

-

 = 2.00%) > adults ($$HI_{{{\text{NO}}_{3}^{ - } }}$$

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 = 11.62%, $$HI_{{{\text{F}}^{ - } }}$$

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F

-

 = 1.25%). Geochemically, about 90% of the samples are controlled by rock-water interaction with Ca2+–Mg2+–HCO3− (~ 56%) as the dominant hydrochemical facies. Chemometric modelling confirms Ca2+, Mg2+, HCO3−, F−, and SO42− to originate from geogenic sources, Cl− and NO3− from anthropogenic inputs and Na+ and K+ from mixed factors. The area needs treated groundwater for human consumption.
Serum Angiopoietin-2 level increase differs between polytraumatized patients with and without central nervous system injuries
Authors: Negrin Lukas L. , Hajdu Stefan
Published: November 2023

Since endothelial cells rapidly release Angiopoietin-2 (Ang-2) in response to vascular injury and inflammatory stimuli, we aimed to investigate if its serum levels increase in polytraumatized patients. Our cohort study evaluated 28 blunt polytrauma survivors (mean age, 38.4 years; median ISS, 34) who were directly admitted to our level I trauma center in 2018. We assessed the serum Ang-2 level at admission and on days 1, 3, 5, 7, and 10 during hospitalization. Ang-2 was released into the circulation immediately after polytrauma. At admission (day 0), it amounted to 8286 ± 5068 pg/mL, three-and-a-half times the reference value of 2337 ± 650 pg/mL assessed in a healthy control group. Subgroup analysis provided a higher mean Ang-2 level in the CNSI group combining all patients suffering a brain or spinal cord injury compared to the non-CNSI group solely on day 0 [11083 ± 5408 pg/mL versus 3963 ± 2062 pg/mL; p < 0.001]. Whereas the mean Ang-2 level increased only in the non-CNSI group from day 0 to day 3 (p = 0.009), the respective curves showed similar continuous decreases starting with day 3. Multivariate logistic regression analysis revealed an association between the Ang-2 day 0 level and the presence of a CNSI (OR = 1.885; p = 0.048). ROC analysis provided a cutoff level of 5352 pg/mL. In our study group, serum Ang-2 levels assessed at admission differed between polytraumatized patients with and without brain or spinal cord injuries. Based on our findings, we consider serum Ang-2 levels an effective biomarker candidate for indicating CNSI in these patients at admission, worthy of further evaluation in large multicenter studies.
Your smartphone could act as a pulse-oximeter and as a single-lead ECG
Authors: Mehmood Ahsan , Sarouji Asma , Rahman M. Mahboob Ur , Al-Naffouri Tareq Y.
Published: November 2023

In the post-covid19 era, every new wave of the pandemic causes an increased concern/interest among the masses to learn more about their state of well-being. Therefore, it is the need of the hour to come up with ubiquitous, low-cost, non-invasive tools for rapid and continuous monitoring of body vitals that reflect the status of one’s overall health. In this backdrop, this work proposes a deep learning approach to turn a smartphone—the popular hand-held personal gadget—into a diagnostic tool to measure/monitor the three most important body vitals, i.e., pulse rate (PR), blood oxygen saturation level (aka SpO2), and respiratory rate (RR). Furthermore, we propose another method that could extract a single-lead electrocardiograph (ECG) of the subject. The proposed methods include the following core steps: subject records a small video of his/her fingertip by placing his/her finger on the rear camera of the smartphone, and the recorded video is pre-processed to extract the filtered and/or detrended video-photoplethysmography (vPPG) signal, which is then fed to custom-built convolutional neural networks (CNN), which eventually spit-out the vitals (PR, SpO2, and RR) as well as a single-lead ECG of the subject. To be precise, the contribution of this paper is twofold: (1) estimation of the three body vitals (PR, SpO2, RR) from the vPPG data using custom-built CNNs, vision transformer, and most importantly by CLIP model (a popular image-caption-generator model); (2) a novel discrete cosine transform+feedforward neural network-based method that translates the recorded video-PPG signal to a single-lead ECG signal. The significance of this work is twofold: (i) it allows rapid self-testing of body vitals (e.g., self-monitoring for covid19 symptoms), (ii) it enables rapid self-acquisition of a single-lead ECG, and thus allows early detection of atrial fibrillation (abormal heart beat or arrhythmia), which in turn could enable early intervention in response to a range of cardiovascular diseases, and could help save many precious lives. Our work could help reduce the burden on healthcare facilities and could lead to reduction in health insurance costs.
Retinal venular vessel diameters are smaller during ten days of bed rest
Authors: Saloň Adam , Çiftci Göktuğ Mert , Zubac Damir , Šimunič Boštjan , Pišot Rado , Narici Marco , Fredriksen Per Morten , Nkeh-Chungag Benedicta Ngwenchi , Sourij Harald , Šerý Omar , Schmid-Zalaudek Karin , Steuber Bianca , De Boever Patrick , Goswami Nandu
Published: November 2023

Older individuals experience cardiovascular dysfunction during extended bedridden hospital or care home stays. Bed rest is also used as a model to simulate accelerated vascular deconditioning occurring during spaceflight. This study investigates changes in retinal microcirculation during a ten-day bed rest protocol. Ten healthy young males (22.9 ± 4.7 years; body mass index: 23.6 ± 2.5 kg·m–2) participated in a strictly controlled repeated-measures bed rest study lasting ten days. High-resolution images were obtained using a hand-held fundus camera at baseline, daily during the 10 days of bed rest, and 1 day after re-ambulation. Retinal vessel analysis was performed using a semi-automated software system to obtain metrics for retinal arteriolar and venular diameters, central retinal artery equivalent and central retinal vein equivalent, respectively. Data analysis employed a mixed linear model. At the end of the bed rest period, a significant decrease in retinal venular diameter was observed, indicated by a significantly lower central retinal vein equivalent (from 226.1 µm, CI 8.90, to 211.4 µm, CI 8.28, p = .026), while no significant changes in central retinal artery equivalent were noted. Prolonged bed rest confinement resulted in a significant (up to 6.5%) reduction in retinal venular diameter. These findings suggest that the changes in retinal venular diameter during bedrest may be attributed to plasma volume losses and reflect overall (cardio)-vascular deconditioning.
Surface-exposed chaperonin 60 derived from Propionibacterium freudenreichii MJ2 inhibits adipogenesis by decreasing the expression of C/EBPα/PPARγ
Authors: An Mirae , Lim Young-Hee
Published: November 2023

Recent studies have shown that the health benefits of probiotics are not limited to those offered by living bacteria. It was reported that both live and killed cells of Propionibacterium freudenreichii MJ2 (MJ2) isolated from raw milk showed antiobesity activity in 3T3-L1 cells and high-fat diet-induced obese mice. This study was aimed at identifying the active component(s) responsible for the antiadipogenic activity of MJ2. Cell wall, surface protein, and cytoplasmic fractions of MJ2 were investigated for their inhibitory effects on adipogenesis in 3T3-L1 cells. Adipocytes treated with the surface protein fraction showed significantly lower lipid accumulation. Using the MASCOT algorithm following LC-MS/MS analysis, 131 surface proteins were identified and they were principally classified into three categories (network clusters related to ribosomes, carbon metabolism, and chaperones). Among them, chaperonin 60 (Cpn60) was selected as a potential candidate protein. Cpn60 inhibited lipid accumulation and adipogenesis during the early period of differentiation (days 0–2) and decreased expression of genes related to adipogenesis (Pparg and Cebpa) and lipogenesis (Fas and Scd1). The expression of Gata2/3, which suppresses adipogenesis, significantly increased in Cpn60-treated cells. Moreover, the nuclear translocation of C/EBPβ was inhibited by Cpn60 treatment. In conclusion, Cpn60, a surface protein in MJ2, shows antiadipogenic activity by reducing the expression of C/EBPβ through the upregulation of Gata2/3 expression followed by downregulation of Pparg and Cebpa expression.
A link between energy metabolism and plant host adaptation states in the two-spotted spider mite, Tetranychus urticae (Koch)
Authors: Maglov Jorden , Feng Min Yi , Lin Dorothy , Barkhouse Kennedy , Alexander Anton , Grbic Miodrag , Zhurov Vladimir , Grbic Vojislava , Tudzarova Slavica
Published: November 2023

Energy metabolism is a highly conserved process that balances generation of cellular energy and maintenance of redox homeostasis. It consists of five interconnected pathways: glycolysis, tricarboxylic acid cycle, pentose phosphate, trans-sulfuration, and NAD+ biosynthesis pathways. Environmental stress rewires cellular energy metabolism. Type-2 diabetes is a well-studied energy metabolism rewiring state in human pancreatic β-cells where glucose metabolism is uncoupled from insulin secretion. The two-spotted spider mite, Tetranychus urticae (Koch), exhibits a remarkable ability to adapt to environmental stress. Upon transfer to unfavourable plant hosts, mites experience extreme xenobiotic stress that dramatically affects their survivorship and fecundity. However, within 25 generations, mites adapt to the xenobiotic stress and restore their fitness. Mites’ ability to withstand long-term xenobiotic stress raises a question of their energy metabolism states during host adaptation. Here, we compared the transcriptional responses of five energy metabolism pathways between host-adapted and non-adapted mites while using responses in human pancreatic islet donors to model these pathways under stress. We found that non-adapted mites and human pancreatic β-cells responded in a similar manner to host plant transfer and diabetogenic stress respectively, where redox homeostasis maintenance was favoured over energy generation. Remarkably, we found that upon host-adaptation, mite energy metabolic states were restored to normal. These findings suggest that genes involved in energy metabolism can serve as molecular markers for mite host-adaptation.
Real-time monitoring of the reaction of KRAS G12C mutant specific covalent inhibitor by in vitro and in-cell NMR spectroscopy
Authors: Zhao Qingci , Haga Ryoka , Tamura Satoko , Shimada Ichio , Nishida Noritaka
Published: November 2023

KRAS mutations are major drivers of various cancers. Recently, allele-specific inhibitors of the KRAS G12C mutant were developed that covalently modify the thiol of Cys12, thereby trapping KRAS in an inactive GDP-bound state. To study the mechanism of action of the covalent inhibitors in both in vitro and intracellular environments, we used real-time NMR to simultaneously observe GTP hydrolysis and inhibitor binding. In vitro NMR experiments showed that the rate constant of ARS-853 modification is identical to that of GTP hydrolysis, indicating that GTP hydrolysis is the rate-limiting step for ARS-853 modification. In-cell NMR analysis revealed that the ARS-853 reaction proceeds significantly faster than that in vitro, reflecting acceleration of GTP hydrolysis by endogenous GTPase proteins. This study demonstrated that the KRAS covalent inhibitor is as effective in the cell as in vitro and that in-cell NMR is a valuable validation tool for assessing the pharmacological properties of the drug in the intracellular context.
Magnetic silica/graphene oxide nanocomposite supported ionic liquid–manganese complex as a powerful catalyst for the synthesis of tetrahydrobenzopyrans
Authors: Dadvar Farkhondeh , Elhamifar Dawood
Published: November 2023

A novel magnetic silica/graphene oxide nanocomposite supported ionic liquid/manganese complex (Fe3O4@SiO2-NH2/GO/IL-Mn) is prepared, characterized and its catalytic application is investigated. The Fe3O4@SiO2-NH2/GO/IL-Mn catalyst was synthesized via chemical immobilization of graphene oxide on Fe3O4@SiO2 nanoparticles followed by modification with ionic liquid/Mn complex. This nanocomposite was characterized by using SEM, TGA, FT-IR, PXRD, EDX, TEM, nitrogen adsorption–desorption, and VSM analyses. The catalytic application of Fe3O4@SiO2-NH2/GO/IL-Mn was studied in the synthesis of tetrahydrobenzo[b]pyrans (THBPs) in water solvent at RT. This nanocatalyst was successfully recovered and reused at least eight times without a significant decrease in its activity.
A runoff prediction method based on hyperparameter optimisation of a kernel extreme learning machine with multi-step decomposition
Authors: Zhang Xianqi , Liu Fang , Yin Qiuwen , Qi Yu , Sun Shifeng
Published: November 2023

To improve the accuracy of runoff forecasting, a combined forecasting model is established by using the kernel extreme learning machine (KELM) algorithm optimised by the butterfly optimisation algorithm (BOA), combined with the variational modal decomposition method (VMD) and the complementary ensemble empirical modal decomposition method (CEEMD), for the measured daily runoff sequences at Jiehetan and Huayuankou stations and Gaochun and Lijin stations. The results show that the combined model VMD-CEEMD-BOA-KELM predicts the best. The average absolute errors are 30.02, 23.72, 25.75, 29.37, and the root mean square errors are 20.53 m3/s, 18.79 m3/s, 18.66 m3/s, and 21.87 m3/s, the decision coefficients are all above 90 percent, respectively, and the Nash efficiency coefficients are all more than 90%, from the above it can be seen that the method has better results in runoff time series prediction.
Diversity and evolution of the MHC class II DRB gene in the Capra sibirica experienced a demographic fluctuation in China
Authors: Dong Pei-Pei , Wang Rui-Rui , Abduriyim Shamshidin
Published: November 2023

The major histocompatibility complex (MHC) genes are the most polymorphic genes in vertebrates, and their proteins play a critical role in adaptive immunity for defense against a variety of pathogens. MHC diversity was lost in many species after experiencing a decline in size. To understand the variation and evolution of MHC genes in the Siberian ibex, Capra sibirica, which has undergone a population decline, we analyzed the variation of the second exon of MHC class II DRB genes in samples collected from five geographic localities in Xinjiang, China, that belong to three diverged mitochondrial clades. Consequently, we identified a total of 26 putative functional alleles (PFAs) with 260 bp in length from 43 individuals, and found one (for 27 individuals) to three (for 5 individuals) PFAs per individual, indicating the presence of one or two DRB loci per haploid genome. The Casi-DRB1*16 was the most frequently occurring PFA, Casi-DRB1*22 was found in only seven individuals, 14 PFAs occurred once, 7 PFAs twice, implying high frequency of rare PFAs. Interestingly, more than half (15) of the PFAs were specific to clade I, only two and three PFAs were specific to clades II and III, respectively. So, we assume that the polygamy and sexual segregation nature of this species likely contributed to the allelic diversity of DRB genes. Genetic diversity indices showed that PFAs of clade II were lower in nucleotide, amino acid, and supertype diversity compared to those of the other two clades. The pattern of allele sharing and FST values between the three clades was to some extent in agreement with the pattern observed in mitochondrial DNA divergence. In addition, recombination analyses revealed no evidence for significant signatures of recombination events. Alleles shared by clades III and the other two clades diverged 6 million years ago, and systematic neighbor grids showed Trans-species polymorphism. Together with the PAML and MEME analyses, the results indicated that the DRB gene in C. sibirica evolved under balancing and positive selection. However, by comparison, it can be clearly seen that different populations were under different selective pressures. Our results are valuable in understanding the diversity and evolution of the DRB gene in a mountain living C. sibirica and in making decisions on future long-term protection strategies.