bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting SIRT3 sensitizes glioblastoma to ferroptosis by promoting mitophagy and inhibiting SLC7A11
Authors: Li Xiaohe , Zhang Wenlong , Xing Zhengcao , Hu Shuming , Zhang Geqiang , Wang Tiange , Wang Tianshi , Fan Qiuju , Chen Guoqiang , Cheng Jinke , Jiang Xianguo , Cai Rong
Published: February 2024

Glioblastoma (GBM) cells require large amounts of iron for tumor growth and progression, which makes these cells vulnerable to destruction via ferroptosis induction. Mitochondria are critical for iron metabolism and ferroptosis. Sirtuin-3 (SIRT3) is a deacetylase found in mitochondria that regulates mitochondrial quality and function. This study aimed to characterize SIRT3 expression and activity in GBM and investigate the potential therapeutic effects of targeting SIRT3 while also inducing ferroptosis in these cells. We first found that SIRT3 expression was higher in GBM tissues than in normal brain tissues and that SIRT3 protein expression was upregulated during RAS-selective lethal 3 (RSL3)-induced GBM cell ferroptosis. We then observed that inhibition of SIRT3 expression and activity in GBM cells sensitized GBM cells to RSL3-induced ferroptosis both in vitro and in vivo. Mechanistically, SIRT3 inhibition led to ferrous iron and ROS accumulation in the mitochondria, which triggered mitophagy. RNA-Sequencing analysis revealed that upon SIRT3 knockdown in GBM cells, the mitophagy pathway was upregulated and SLC7A11, a critical antagonist of ferroptosis via cellular import of cystine for glutathione (GSH) synthesis, was downregulated. Forced expression of SLC7A11 in GBM cells with SIRT3 knockdown restored cellular cystine uptake and consequently the cellular GSH level, thereby partially rescuing cell viability upon RSL3 treatment. Furthermore, in GBM cells, SIRT3 regulated SLC7A11 transcription through ATF4. Overall, our study results elucidated novel mechanisms underlying the ability of SIRT3 to protect GBM from ferroptosis and provided insight into a potential combinatorial approach of targeting SIRT3 and inducing ferroptosis for GBM treatment.
Influence of microbiota-associated metabolic reprogramming on clinical outcome in patients with melanoma from the randomized adjuvant dendritic cell-based MIND-DC trial
Authors: Alves Costa Silva Carolina , Piccinno Gianmarco , Suissa Déborah , Bourgin Mélanie , Schreibelt Gerty , Durand Sylvère , Birebent Roxanne , Fidelle Marine , Sow Cissé , Aprahamian Fanny , Manghi Paolo , Punčochář Michal , Asnicar Francesco , Pinto Federica , Armanini Federica , Terrisse Safae , Routy Bertrand , Drubay Damien , Eggermont Alexander M. M. , Kroemer Guido , Segata Nicola , Zitvogel Laurence , Derosa Lisa , Bol Kalijn F. , de Vries I. Jolanda M.
Published: February 2024

Tumor immunosurveillance plays a major role in melanoma, prompting the development of immunotherapy strategies. The gut microbiota composition, influencing peripheral and tumoral immune tonus, earned its credentials among predictors of survival in melanoma. The MIND-DC phase III trial (NCT02993315) randomized (2:1 ratio) 148 patients with stage IIIB/C melanoma to adjuvant treatment with autologous natural dendritic cell (nDC) or placebo (PL). Overall, 144 patients collected serum and stool samples before and after 2 bimonthly injections to perform metabolomics (MB) and metagenomics (MG) as prespecified exploratory analysis. Clinical outcomes are reported separately. Here we show that different microbes were associated with prognosis, with the health-related Faecalibacterium prausnitzii standing out as the main beneficial taxon for no recurrence at 2 years (p = 0.008 at baseline, nDC arm). Therapy coincided with major MB perturbations (acylcarnitines, carboxylic and fatty acids). Despite randomization, nDC arm exhibited MG and MB bias at baseline: relative under-representation of F. prausnitzii, and perturbations of primary biliary acids (BA). F. prausnitzii anticorrelated with BA, medium- and long-chain acylcarnitines. Combined, these MG and MB biomarkers markedly determined prognosis. Altogether, the host-microbial interaction may play a role in localized melanoma. We value systematic MG and MB profiling in randomized trials to avoid baseline differences attributed to host-microbe interactions.
Complex regulatory networks influence pluripotent cell state transitions in human iPSCs
Authors: Arthur Timothy D. , Nguyen Jennifer P. , D’Antonio-Chronowska Agnieszka , Matsui Hiroko , Silva Nayara S. , Joshua Isaac N. ,   iPSCORE Consortium, Aguiar Lana Ribeiro , Arias Angelo D. , Benaglio Paola , Berggren W. Travis , Belmonte Juan Carlos Izpisua , Borja Victor , Cook Megan , DeBoever Christopher , Diffenderfer Kenneth E. , Donovan Margaret K. R. , Farnam KathyJean , Fujita Kyohei , Garcia Melvin , Henson Benjamin A. , Harismendy Olivier , Jakubosky David , Jepsen Kristen , Li He , Nariai Naoki , O’Connor Daniel T. , Okubo Jonathan , Panopoulos Athanasia D. , Rao Fengwen , Reyna Joaquin , Salgado Bianca M. , Smith Erin N. , Sohmer Josh , Yost Shawn , Luchessi André D. , Greenwald William W. Young , D’Antonio Matteo , Pera Martin F. , Frazer Kelly A.
Published: February 2024

Stem cells exist in vitro in a spectrum of interconvertible pluripotent states. Analyzing hundreds of hiPSCs derived from different individuals, we show the proportions of these pluripotent states vary considerably across lines. We discover 13 gene network modules (GNMs) and 13 regulatory network modules (RNMs), which are highly correlated with each other suggesting that the coordinated co-accessibility of regulatory elements in the RNMs likely underlie the coordinated expression of genes in the GNMs. Epigenetic analyses reveal that regulatory networks underlying self-renewal and pluripotency are more complex than previously realized. Genetic analyses identify thousands of regulatory variants that overlapped predicted transcription factor binding sites and are associated with chromatin accessibility in the hiPSCs. We show that the master regulator of pluripotency, the NANOG-OCT4 Complex, and its associated network are significantly enriched for regulatory variants with large effects, suggesting that they play a role in the varying cellular proportions of pluripotency states between hiPSCs. Our work bins tens of thousands of regulatory elements in hiPSCs into discrete regulatory networks, shows that pluripotency and self-renewal processes have a surprising level of regulatory complexity, and suggests that genetic factors may contribute to cell state transitions in human iPSC lines.
Autonomous error correction of a single logical qubit using two transmons
Authors: Li Ziqian , Roy Tanay , Rodríguez Pérez David , Lee Kan-Heng , Kapit Eliot , Schuster David I.
Published: February 2024

Large-scale quantum computers will inevitably need quantum error correction to protect information against decoherence. Traditional error correction typically requires many qubits, along with high-efficiency error syndrome measurement and real-time feedback. Autonomous quantum error correction instead uses steady-state bath engineering to perform the correction in a hardware-efficient manner. In this work, we develop a new autonomous quantum error correction scheme that actively corrects single-photon loss and passively suppresses low-frequency dephasing, and we demonstrate an important experimental step towards its full implementation with transmons. Compared to uncorrected encoding, improvements are experimentally witnessed for the logical zero, one, and superposition states. Our results show the potential of implementing hardware-efficient autonomous quantum error correction to enhance the reliability of a transmon-based quantum information processor.
Insights into structural defect formation in individual InP/ZnSe/ZnS quantum dots under UV oxidation
Authors: Baek Hayeon , Kang Sungsu , Heo Junyoung , Choi Soonmi , Kim Ran , Kim Kihyun , Ahn Nari , Yoon Yeo-Geon , Lee Taekjoon , Chang Jae Bok , Lee Kyung Sig , Park Young-Gil , Park Jungwon
Published: February 2024

InP/ZnSe/ZnS quantum dots (QDs) stand as promising candidates for advancing QD-organic light-emitting diodes (QLED), but low emission efficiency due to their susceptibility to oxidation impedes applications. Structural defects play important roles in the emission efficiency degradation of QDs, but the formation mechanism of defects in oxidized QDs has been less investigated. Here, we investigated the impact of diverse structural defects formation on individual QDs and propagation during UV-facilitated oxidation using high-resolution (scanning) transmission electron microscopy. UV-facilitated oxidation of the QDs alters shell morphology by the formation of surface oxides, leaving ZnSe surfaces poorly passivated. Further oxidation leads to the formation of structural defects, such as dislocations, and induces strain at the oxide-QD interfaces, facilitating In diffusion from the QD core. These changes in the QD structures result in emission quenching. This study provides insight into the formation of structural defects through photo-oxidation, and their effects on emission properties of QDs.
Gonococcal OMV-delivered PorB induces epithelial cell mitophagy
Authors: Gao Shuai , Gao Lingyu , Yuan Dailin , Lin Xu’ai , van der Veen Stijn
Published: February 2024

The bacterial pathogen Neisseria gonorrhoeae is able to invade epithelial cells and survive intracellularly. During this process, it secretes outer membrane vesicles (OMVs), however, the mechanistic details for interactions between gonococcal OMVs and epithelial cells and their impact on intracellular survival are currently not established. Here, we show that gonococcal OMVs induce epithelial cell mitophagy to reduce mitochondrial secretion of reactive oxygen species (ROS) and enhance intracellular survival. We demonstrate that OMVs deliver PorB to mitochondria to dissipate the mitochondrial membrane potential, resulting in mitophagy induction through a conventional PINK1 and OPTN/NDP52 mechanism. Furthermore, PorB directly recruits the E3 ubiquitin ligase RNF213, which decorates PorB lysine residue 171 with K63-linked polyubiquitin to induce mitophagy in a p62-dependent manner. These results demonstrate a mechanism in which polyubiquitination of a bacterial virulence factor that targets mitochondria directs mitophagy processes to this organelle to prevent its secretion of deleterious ROS.
G protein-coupled receptor-based thermosensation determines temperature acclimatization of Caenorhabditis elegans
Authors: Ohnishi Kohei , Sokabe Takaaki , Miura Toru , Tominaga Makoto , Ohta Akane , Kuhara Atsushi
Published: February 2024

Animals must sense and acclimatize to environmental temperatures for survival, yet their thermosensing mechanisms other than transient receptor potential (TRP) channels remain poorly understood. We identify a trimeric G protein-coupled receptor (GPCR), SRH-40, which confers thermosensitivity in sensory neurons regulating temperature acclimatization in Caenorhabditis elegans. Systematic knockdown of 1000 GPCRs by RNAi reveals GPCRs involved in temperature acclimatization, among which srh-40 is highly expressed in the ADL sensory neuron, a temperature-responsive chemosensory neuron, where TRP channels act as accessorial thermoreceptors. In vivo Ca2+ imaging demonstrates that an srh-40 mutation reduced the temperature sensitivity of ADL, resulting in supranormal temperature acclimatization. Ectopically expressing SRH-40 in a non-warmth-sensing gustatory neuron confers temperature responses. Moreover, temperature-dependent SRH-40 activation is reconstituted in Drosophila S2R+ cells. Overall, SRH-40 may be involved in thermosensory signaling underlying temperature acclimatization. We propose a dual thermosensing machinery through a GPCR and TRP channels in a single sensory neuron.
Substrate binding and catalytic mechanism of the Se-glycosyltransferase SenB in the biosynthesis of selenoneine
Authors: Huang Wei , Song Jun , Sun Tianxue , He Yue , Li Xiang , Deng Zixin , Long Feng
Published: February 2024

Selenium is an essential multifunctional trace element in diverse organisms. The only Se-glycosyltransferase identified that catalyzes the incorporation of selenium in selenoneine biosynthesis is SenB from Variovorax paradoxus. Although the biochemical function of SenB has been investigated, its substrate specificity, structure, and catalytic mechanism have not been elucidated. Here, we reveal that SenB exhibits sugar donor promiscuity and can utilize six UDP-sugars to generate selenosugars. We report crystal structures of SenB complexed with different UDP-sugars. The key elements N20/T23/E231 contribute to the sugar donor selectivity of SenB. A proposed catalytic mechanism is tested by structure-guided mutagenesis, revealing that SenB yields selenosugars by forming C-Se glycosidic bonds via spontaneous deprotonation and disrupting Se-P bonds by nucleophilic water attack, which is initiated by the critical residue K158. Furthermore, we functionally and structurally characterize two other Se-glycosyltransferases, CbSenB from Comamonadaceae bacterium and RsSenB from Ramlibacter sp., which also exhibit sugar donor promiscuity.
Virtual histological staining of unlabeled autopsy tissue
Authors: Li Yuzhu , Pillar Nir , Li Jingxi , Liu Tairan , Wu Di , Sun Songyu , Ma Guangdong , de Haan Kevin , Huang Luzhe , Zhang Yijie , Hamidi Sepehr , Urisman Anatoly , Keidar Haran Tal , Wallace William Dean , Zuckerman Jonathan E. , Ozcan Aydogan
Published: February 2024

Traditional histochemical staining of post-mortem samples often confronts inferior staining quality due to autolysis caused by delayed fixation of cadaver tissue, and such chemical staining procedures covering large tissue areas demand substantial labor, cost and time. Here, we demonstrate virtual staining of autopsy tissue using a trained neural network to rapidly transform autofluorescence images of label-free autopsy tissue sections into brightfield equivalent images, matching hematoxylin and eosin (H&E) stained versions of the same samples. The trained model can effectively accentuate nuclear, cytoplasmic and extracellular features in new autopsy tissue samples that experienced severe autolysis, such as COVID-19 samples never seen before, where the traditional histochemical staining fails to provide consistent staining quality. This virtual autopsy staining technique provides a rapid and resource-efficient solution to generate artifact-free H&E stains despite severe autolysis and cell death, also reducing labor, cost and infrastructure requirements associated with the standard histochemical staining.
Durable cross-protective neutralizing antibody responses elicited by lipid nanoparticle-formulated SARS-CoV-2 mRNA vaccines
Authors: Bae Ki Hyun , Shunmuganathan Bhuvaneshwari , Zhang Li , Lim Andrew , Gupta Rashi , Wang Yanming , Chua Boon Lin , Wang Yang , Gu Yue , Qian Xinlei , Tan Isabelle Siang Ling , Purushotorman Kiren , MacAry Paul A. , White Kevin P. , Yang Yi Yan
Published: February 2024

The advent of SARS-CoV-2 variants with defined mutations that augment pathogenicity and/or increase immune evasiveness continues to stimulate global efforts to improve vaccine formulation and efficacy. The extraordinary advantages of lipid nanoparticles (LNPs), including versatile design, scalability, and reproducibility, make them ideal candidates for developing next-generation mRNA vaccines against circulating SARS-CoV-2 variants. Here, we assess the efficacy of LNP-encapsulated mRNA booster vaccines encoding the spike protein of SARS-CoV-2 for variants of concern (Delta, Omicron) and using a predecessor (YN2016C isolated from bats) strain spike protein to elicit durable cross-protective neutralizing antibody responses. The mRNA-LNP vaccines have desirable physicochemical characteristics, such as small size (~78 nm), low polydispersity index (<0.13), and high encapsulation efficiency (>90%). We employ in vivo bioluminescence imaging to illustrate the capacity of our LNPs to induce robust mRNA expression in secondary lymphoid organs. In a BALB/c mouse model, a three-dose subcutaneous immunization of mRNA-LNPs vaccines achieved remarkably high levels of cross-neutralization against the Omicron B1.1.529 and BA.2 variants for extended periods of time (28 weeks) with good safety profiles for all constructs when used in a booster regime, including the YN2016C bat virus sequences. These findings have important implications for the design of mRNA-LNP vaccines that aim to trigger durable cross-protective immunity against the current and newly emerging variants.
Simultaneous high-definition transcranial direct current stimulation and robot-assisted gait training in stroke patients
Authors: Kim Eunmi , Lee Gihyoun , Lee Jungsoo , Kim Yun-Hee
Published: February 2024

This study investigates whether simultaneous high-definition transcranial direct current stimulation (HD-tDCS) enhances the effects of robot-assisted gait training in stroke patients. Twenty-four participants were randomly allocated to either the robot-assisted gait training with real HD-tDCS group (real HD-tDCS group) or robot-assisted gait training with sham HD-tDCS group (sham HD-tDCS group). Over four weeks, both groups completed 10 sessions. The 10 Meter Walk Test, Timed Up and Go, Functional Ambulation Category, Functional Reach Test, Berg Balance Scale, Dynamic Gait Index, Fugl-Meyer Assessment, and Korean version of the Modified Barthel Index were conducted before, immediately after, and one month after the intervention. The real HD-tDCS group showed significant improvements in the 10 Meter Walk Test, Timed Up and Go, Functional Reach Test, and Berg Balance Scale immediately and one month after the intervention, compared with before the intervention. Significant improvements in the Dynamic Gait Index and Fugl-Meyer Assessment were also observed immediately after the intervention. The sham HD-tDCS group showed no significant improvements in any of the tests. Application of HD-tDCS during robot-assisted gait training has a positive effect on gait and physical function in chronic stroke patients, ensuring long-term training effects. Our results suggest the effectiveness of HD-tDCS as a complementary tool to enhance robotic gait rehabilitation therapy in chronic stroke patients.
The mediating role of loneliness in the relationship between smartphone addiction and subjective well-being
Authors: Su Peng , He Mu
Published: February 2024

As smartphones become increasingly prevalent worldwide, the relationship between smartphone addiction and subjective well-being has become a focal point in academic circles. Prior research predominantly delved into the direct correlation between smartphone addiction and subjective well-being, yet there remains a dearth in exploring its underlying mechanisms. This study investigated the mediating role of loneliness in the relationship between smartphone addiction and subjective well-being among Chinese university students. Conducted across 16 universities in eight provinces and municipalities in China, this study encompassed 1527 university students. Data collection utilized scales measuring smartphone addiction, loneliness, and subjective well-being. The findings revealed that: (1) demographic variables such as place of origin, educational level, and family income influenced university students' subjective well-being; (2) a significant negative correlation existed between smartphone addiction and subjective well-being among university students, coupled with a significant positive correlation between smartphone addiction and loneliness, indicating the significant negative predictive effect of smartphone addiction on subjective well-being; (3) loneliness partially mediated the relationship between smartphone addiction and subjective well-being among university students, suggesting that smartphone addiction could directly impact university students' subjective well-being, or indirectly through its effect on loneliness.
Impact of zinc supplementation on phenotypic antimicrobial resistance of fecal commensal bacteria from pre-weaned dairy calves
Authors: Lee Katie Y. , Atwill Edward R. , Li Xunde , Feldmann Hillary R. , Williams Deniece R. , Weimer Bart C. , Aly Sharif S.
Published: February 2024

The objective of this study was to evaluate the impact of dietary zinc supplementation in pre-weaned dairy calves on the phenotypic antimicrobial resistance (AMR) of fecal commensal bacteria. A repository of fecal specimens from a random sample of calves block-randomized into placebo (n = 39) and zinc sulfate (n = 28) groups collected over a zinc supplementation clinical trial at the onset of calf diarrhea, calf diarrheal cure, and the last day of 14 cumulative days of zinc or placebo treatment were analyzed. Antimicrobial susceptibility testing was conducted for Enterococcus spp. (n = 167) and E. coli (n = 44), with one representative isolate of each commensal bacteria tested per sample. Parametric survival interval regression models were constructed to evaluate the association between zinc treatment and phenotypic AMR, with exponentiated accelerated failure time (AFT) coefficients adapted for MIC instead of time representing the degree of change in AMR (MIC Ratio, MR). Findings from our study indicated that zinc supplementation did not significantly alter the MIC in Enterococcus spp. for 13 drugs: gentamicin, vancomycin, ciprofloxacin, erythromycin, penicillin, nitrofurantoin, linezolid, quinupristin/dalfopristin, tylosin tartrate, streptomycin, daptomycin, chloramphenicol, and tigecycline (MR = 0.96–2.94, p > 0.05). In E. coli, zinc supplementation was not associated with resistance to azithromycin (MR = 0.80, p > 0.05) and ceftriaxone (MR = 0.95, p > 0.05). However, a significant reduction in E. coli MIC values was observed for ciprofloxacin (MR = 0.17, 95% CI 0.03–0.97) and nalidixic acid (MR = 0.28, 95% CI 0.15–0.53) for zinc-treated compared to placebo-treated calves. Alongside predictions of MIC values generated from these 17 AFT models, findings from this study corroborate the influence of age and antimicrobial exposure on phenotypic AMR.
Correlation between soluble klotho and chronic kidney disease–mineral and bone disorder in chronic kidney disease: a meta-analysis
Authors: Fan Zhongyu , Wei Xuejiao , Zhu Xiaoyu , Yang Kun , Tian Ling , Du Yujun , Yang Liming
Published: February 2024

We conducted a systematic search across medical databases, including PubMed, Web of Science, EMBASE, and Cochrane Library, up to March 2023. A total of 1944 subjects or individuals from 17 studies were included in our final analysis. The correlation coefficient (r) between sKlotho and calcium was [0.14, (0.02, 0.26)], and a moderate heterogeneity was observed (I2 = 66%, P < 0.05). The correlation coefficient (r) between Klotho and serum phosphate was [− 0.21, (− 0.37, − 0.04)], with apparent heterogeneity (I2 = 84%, P < 0.05). The correlation coefficient (r) between sKlotho and parathyroid hormone and vascular calcification was [− 0.23,(− 0.29, − 0.17); − 0.15, (− 0.23, − 0.08)], with no significant heterogeneity among the studies. (I2 = 40%, P < 0.05; I2 = 30%, P < 0.05). A significant correlation exists between low sKlotho levels and an increased risk of CKD–MBD in patients with CKD. According to the findings, sKlotho may play a role in alleviating CKD–MBD by lowering phosphorus and parathyroid hormone levels, regulating calcium levels, and suppressing vascular calcification. As analysis showed that sKlotho has an important impact on the pathogenesis and progression of CKD–MBD in CKD patients. Nonetheless, further comprehensive and high-quality studies are needed to validate our conclusions.
New examples of ferroelectric nematic materials showing evidence for the antiferroelectric smectic-Z phase
Authors: Nacke Pierre , Manabe Atsutaka , Klasen-Memmer Melanie , Chen Xi , Martinez Vikina , Freychet Guillaume , Zhernenkov Mikhail , Maclennan Joseph E. , Clark Noel A. , Bremer Matthias , Giesselmann Frank
Published: February 2024

We present a new ferroelectric nematic material, 4-((4′-((trans)-5-ethyloxan-2-yl)-2′,3,5,6′-tetrafluoro-[1,1′-biphenyl]-4-yl)difluoromethoxy)-2,6-difluorobenzonitrile (AUUQU-2-N) and its higher homologues, the molecular structures of which include fluorinated building blocks, an oxane ring, and a terminal cyano group, all contributing to a large molecular dipole moment of about 12.5 D. We observed that AUUQU-2-N has three distinct liquid crystal phases, two of which were found to be polar phases with a spontaneous electric polarization Ps of up to 6 µC cm–2. The highest temperature phase is a common enantiotropic nematic (N) exhibiting only field-induced polarization. The lowest-temperature, monotropic phase proved to be a new example of the ferroelectric nematic phase (NF), evidenced by a single-peak polarization reversal current response, a giant imaginary dielectric permittivity on the order of 103, and the absence of any smectic layer X-ray diffraction peaks. The ordinary nematic phase N and the ferroelectric nematic phase NF are separated by an antiferroelectric liquid crystal phase which has low permittivity and a polarization reversal current exhibiting a characteristic double-peak response. In the polarizing light microscope, this antiferroelectric phase shows characteristic zig-zag defects, evidence of a layered structure. These observations suggest that this is another example of the recently discovered smectic ZA (SmZA) phase, having smectic layers with the molecular director parallel to the layer planes. The diffraction peaks from the smectic layering have not been observed to date but detailed 2D X-ray studies indicate the presence of additional short-range structures including smectic C-type correlations in all three phases—N, SmZA and NF—which may shed new light on the understanding of polar and antipolar order in these phases.
Increased reliance on temporal coding when target sound is softer than the background
Authors: Alamatsaz Nima , Rosen Merri J. , Ihlefeld Antje
Published: February 2024

Everyday environments often contain multiple concurrent sound sources that fluctuate over time. Normally hearing listeners can benefit from high signal-to-noise ratios (SNRs) in energetic dips of temporally fluctuating background sound, a phenomenon called dip-listening. Specialized mechanisms of dip-listening exist across the entire auditory pathway. Both the instantaneous fluctuating and the long-term overall SNR shape dip-listening. An unresolved issue regarding cortical mechanisms of dip-listening is how target perception remains invariant to overall SNR, specifically, across different tone levels with an ongoing fluctuating masker. Equivalent target detection over both positive and negative overall SNRs (SNR invariance) is reliably achieved in highly-trained listeners. Dip-listening is correlated with the ability to resolve temporal fine structure, which involves temporally-varying spike patterns. Thus the current work tests the hypothesis that at negative SNRs, neuronal readout mechanisms need to increasingly rely on decoding strategies based on temporal spike patterns, as opposed to spike count. Recordings from chronically implanted electrode arrays in core auditory cortex of trained and awake Mongolian gerbils that are engaged in a tone detection task in 10 Hz amplitude-modulated background sound reveal that rate-based decoding is not SNR-invariant, whereas temporal coding is informative at both negative and positive SNRs.
Powdered plant beverages obtained by spray-drying without carrier addition-physicochemical and chemometric studies
Authors: Samborska Katarzyna , Budziak-Wieczorek Iwona , Matwijczuk Arkadiusz , Witrowa-Rajchert Dorota , Gagoś Mariusz , Gładyszewska Bożena , Karcz Dariusz , Rybak Katarzyna , Jaskulski Maciej , Barańska Alicja , Jedlińska Aleksandra
Published: February 2024

Plant-based beverages (PBs) are currently gaining interest among consumers who are seeking alternative sustainable options to traditional dairy drinks. The study aimed to obtain powdered plant beverages without the addition of carriers by spray drying method to implement them in the future as an alternative to the liquid form of dairy drinks. Some of the most well-known commercial beverages sources like soy, almond, rice and oat were analyzed in this work. The effect of different treatments (concentration, addition of oat fiber) and two approaches od spray drying (conventional high temperature spray drying—SD, and dehumidified air spray drying at low temperature—DASD) were presented. Moreover, moisture content, water activity, particle morphology and size of obtained powders were analyzed. It was possible to obtain PBs without the addition of carriers, although the drying yield of four basic beverages was low (16.1–37.4%). The treatments and change in spray drying approach enhanced the drying yield, especially for the concentrated beverage dried using DASD (59.2%). Additionally, Fourier Transform Infrared (FTIR) spectroscopy was applied to evaluate the differences in chemical composition of powdered PBs. FTIR analysis revealed differences in the range of the absorption frequency of amide I, amide II (1700–1500 cm−1) and carbohydrate region (1200–900 cm−1). Principal component analysis (PCA) was carried out to study the relationship between spray dried plant beverages samples based on the fingerprint region of FTIR spectra, as well as the physical characteristics. Additionally, hierarchical cluster analysis (HCA) was employed to explore the clustering of the powders.
A comparative analysis of three distinct fractional derivatives for a second grade fluid with heat generation and chemical reaction
Authors: Sehra  , Sadia Haleema , Haq Sami Ul , Alhazmi Hadil , Khan Ilyas , Niazai Shafiullah
Published: February 2024

This article provides a comparison among the generalized Second Grade fluid flow described by three recently proposed fractional derivatives i.e. Atangana Baleanu fractional derivative in Caputo sense (ABC), Caputo Fabrizio (CF) and Constant Proportional-Caputo hybrid (CPC) fractional derivative. The heat mass transfer is observed during the flow past a vertical porous plate that is accelerated exponentially under the effects of the Magneto hydro dynamics. The effects of the heat generation and exponential heating in the temperature boundary layer and chemical reaction at the concentration boundary layer are also analyzed in this article. The flow model is described by three partial differential equations and the set of non-dimensional PDE’s is transformed into ODE’s by utilization of the integral transform technique (Laplace transform). For the better understanding of the rheological properties of the Second Grade fluid we used the CF, ABC and CPC operators to describe the memory effects. The analytical exact solution of the problem is obtained in the form of G-functions and Mittag Leffler functions. For the physical significance of flow parameters, different parameters are graphed. From this analysis it is concluded that the CPC is the most suitable operator to describe the memory effects.
Exosomes of endothelial progenitor cells repair injured vascular endothelial cells through the Bcl2/Bax/Caspase-3 pathway
Authors: Tan Wei , Li Yanling , Ma Lu , Fu Xinying , Long Qingyin , Yan Fanchen , Li Wanyu , Liu Xiaodan , Ding Huang , Wang Yang , Zhang Wei
Published: February 2024

The main objective of this study is to evaluate the influence of exosomes derived from endothelial progenitor cells (EPC-Exo) on neointimal formation induced by balloon injury in rats. Furthermore, the study aims to investigate the potential of EPC-Exo to promote proliferation, migration, and anti-apoptotic effects of vascular endothelial cells (VECs) in vitro. The underlying mechanisms responsible for these observed effects will also be thoroughly explored and analyzed. Endothelial progenitor cells (EPCs) was isolated aseptically from Sprague–Dawley (SD) rats and cultured in complete medium. The cells were then identified using immunofluorescence and flow cytometry. The EPC-Exo were isolated and confirmed the identities by western-blot, transmission electron microscope, and nanoparticle analysis. The effects of EPC-Exo on the rat carotid artery balloon injury (BI) were detected by hematoxylin and eosin (H&E) staining, ELISA, immunohistochemistry, immunofluorescence, western-blot and qPCR. LPS was used to establish an oxidative damage model of VECs. The mechanism of EPC-Exo repairing injured vascular endothelial cells was detected by measuring the proliferation, migration, and tube function of VECs, actin cytoskeleton staining, TUNEL staining, immunofluorescence, western-blot and qPCR. In vivo, EPC-Exo exhibit inhibitory effects on neointima formation following carotid artery injury and reduce the levels of inflammatory factors, including TNF-α and IL-6. Additionally, EPC-Exo downregulate the expression of adhesion molecules on the injured vascular wall. Notably, EPC-Exo can adhere to the injured vascular area, promoting enhanced endothelial function and inhibiting vascular endothelial hyperplasia Moreover, they regulate the expression of proteins and genes associated with apoptosis, including B-cell lymphoma-2 (Bcl2), Bcl2-associated x (Bax), and Caspase-3. In vitro, experiments further confirmed that EPC-Exo treatment significantly enhances the proliferation, migration, and tube formation of VECs. Furthermore, EPC-Exo effectively attenuate lipopolysaccharides (LPS)-induced apoptosis of VECs and regulate the Bcl2/Bax/Caspase-3 signaling pathway. This study demonstrates that exosomes derived from EPCs have the ability to inhibit excessive carotid intimal hyperplasia after BI, promote the repair of endothelial cells in the area of intimal injury, and enhance endothelial function. The underlying mechanism involves the suppression of inflammation and anti-apoptotic effects. The fundamental mechanism for this anti-apoptotic effect involves the regulation of the Bcl2/Bax/Caspase-3 signaling pathway.
Performance evaluation of a deep learning model for automatic detection and localization of idiopathic osteosclerosis on dental panoramic radiographs
Authors: Tassoker Melek , Öziç Muhammet Üsame , Yuce Fatma
Published: February 2024

Idiopathic osteosclerosis (IO) are focal radiopacities of unknown etiology observed in the jaws. These radiopacities are incidentally detected on dental panoramic radiographs taken for other reasons. In this study, we investigated the performance of a deep learning model in detecting IO using a small dataset of dental panoramic radiographs with varying contrasts and features. Two radiologists collected 175 IO-diagnosed dental panoramic radiographs from the dental school database. The dataset size is limited due to the rarity of IO, with its incidence in the Turkish population reported as 2.7% in studies. To overcome this limitation, data augmentation was performed by horizontally flipping the images, resulting in an augmented dataset of 350 panoramic radiographs. The images were annotated by two radiologists and divided into approximately 70% for training (245 radiographs), 15% for validation (53 radiographs), and 15% for testing (52 radiographs). The study employing the YOLOv5 deep learning model evaluated the results using precision, recall, F1-score, mAP (mean Average Precision), and average inference time score metrics. The training and testing processes were conducted on the Google Colab Pro virtual machine. The test process's performance criteria were obtained with a precision value of 0.981, a recall value of 0.929, an F1-score value of 0.954, and an average inference time of 25.4 ms. Although radiographs diagnosed with IO have a small dataset and exhibit different contrasts and features, it has been observed that the deep learning model provides high detection speed, accuracy, and localization results. The automatic identification of IO lesions using artificial intelligence algorithms, with high success rates, can contribute to the clinical workflow of dentists by preventing unnecessary biopsy procedure.
Applicability analysis of flame height estimation based on Byram’s fireline intensity model under flat and windless conditions
Authors: Zhang Yunlin , Luo Aixia
Published: February 2024

Forest fire have a serious impact on forest ecosystems, the safety of people’s lives and property, and social stability. The height of surface flames, as the main indicator of forest fire behavior, which is an important parameter for forest fire management. The relationship between fireline intensity and flame height proposed by Byram has been widely used in estimating flame height; however, its applicability to the surface fuel of typical forest stands in the Yunnan–Guizhou Plateau of China has not yet been analyzed. In this study, the surface fuel in the area was taken as the research object, and the flame height of different fuel bed characteristics was measured through an indoor burning experiment. The applicability of three methods—the directly used Byram’s model, corrected model, and re-established prediction model—was analyzed to estimate the flame height in the Yunnan–Guizhou Plateau. We found that the flame height of the typical forest stands in the Yunnan–Guizhou Plateau ranged from 0.05 to 1.2 m and was significantly affected by the moisture content, load, and height of the fuel bed. Although the fireline intensity exhibited a significant linear relationship with the flame height, directly using Byram’s method to predict the flame height of surface fires was impractical, as its mean prediction error exceeded 150%. The mean relative errors of the prediction model obtained by modifying Byram’s method and that based on the characteristics of the fuel bed were both within 15%, which is significantly lower than that of the original Byram’s method. Based on the results of this study, we propose two methods that are suitable for predicting the flame height of surface fires in the typical forests of the Yunnan–Guizhou Plateau in China, which is of great significance for further understanding the relationship between flame height, fireline intensity, and scientific forest fire management.
Effect of multidrug therapy on the prognosis of Mycobacterium avium complex pulmonary disease
Authors: Ushiki Atsuhito , Tanaka Shunnosuke , Yamanaka Miwa , Akahane Jumpei , Ikuyama Yuichi , Komatsu Masamichi , Sonehara Kei , Ichiyama Takashi , Wada Yosuke , Tateishi Kazunari , Kitaguchi Yoshiaki , Hanaoka Masayuki
Published: February 2024

Multidrug therapy for Mycobacterium avium complex pulmonary disease (MAC-PD) results in negative sputum cultures. However, the prognostic value of this treatment approach remains unclear. This study aimed to clarify whether multidrug therapy reduces the incidence of events related to MAC-PD and improves the mortality rate. Patients who met the diagnostic criteria for MAC-PD at our hospital between 2003 and 2019 were retrospectively evaluated using medical records. Events related to MAC-PD were defined as hospitalisation for haemoptysis or respiratory infection and the development of chronic respiratory failure. There were 90 and 108 patients in the multidrug and observation groups, respectively. The median observation period was 86 months. Intergroup differences in body mass index, proportion of patients with cavities, and erythrocyte sedimentation rate were not significant. However, the observation group was older with a higher mean age (multidrug group: 62 years, observation group: 69 years; P < 0.001) and had a higher proportion of male patients (multidrug group: 13/90 [14.4%], observation group: 35/108 [32.4%]; P < 0.01). Furthermore, intergroup differences in the incidence of events related to MAC-PD (multidrug group: 26.69/1000 person-years, observation group: 25.49/1000 person-years), MAC-PD-associated mortality rate (multidrug group: 12.13/1000 person-years, observation group: 12.74/1000 person-years), and total mortality (multidrug group: 24.26/1000 person-years, observation group: 29.50/1000 person-years) were not significant. Many patients relapse even after multidrug therapy, and our findings suggest that multidrug therapy has no effect in preventing the onset of respiratory events or prolonging life expectancy.
Leveraging a meta-learning approach to advance the accuracy of Nav blocking peptides prediction
Authors: Shoombuatong Watshara , Homdee Nutta , Schaduangrat Nalini , Chumnanpuen Pramote
Published: February 2024

The voltage-gated sodium (Nav) channel is a crucial molecular component responsible for initiating and propagating action potentials. While the α subunit, forming the channel pore, plays a central role in this function, the complete physiological function of Nav channels relies on crucial interactions between the α subunit and auxiliary proteins, known as protein–protein interactions (PPI). Nav blocking peptides (NaBPs) have been recognized as a promising and alternative therapeutic agent for pain and itch. Although traditional experimental methods can precisely determine the effect and activity of NaBPs, they remain time-consuming and costly. Hence, machine learning (ML)-based methods that are capable of accurately contributing in silico prediction of NaBPs are highly desirable. In this study, we develop an innovative meta-learning-based NaBP prediction method (MetaNaBP). MetaNaBP generates new feature representations by employing a wide range of sequence-based feature descriptors that cover multiple perspectives, in combination with powerful ML algorithms. Then, these feature representations were optimized to identify informative features using a two-step feature selection method. Finally, the selected informative features were applied to develop the final meta-predictor. To the best of our knowledge, MetaNaBP is the first meta-predictor for NaBP prediction. Experimental results demonstrated that MetaNaBP achieved an accuracy of 0.948 and a Matthews correlation coefficient of 0.898 over the independent test dataset, which were 5.79% and 11.76% higher than the existing method. In addition, the discriminative power of our feature representations surpassed that of conventional feature descriptors over both the training and independent test datasets. We anticipate that MetaNaBP will be exploited for the large-scale prediction and analysis of NaBPs to narrow down the potential NaBPs.
Human-induced intensification of terrestrial water cycle in dry regions of the globe
Authors: Guan Yansong , Gu Xihui , Slater Louise J. , Li Xueying , Li Jianfeng , Wang Lunche , Tang Xiongpeng , Kong Dongdong , Zhang Xiang
Published: February 2024

Anthropogenic climate change (ACC) strengthens the global terrestrial water cycle (TWC) through increases in annual total precipitation (PRCPTOT) over global land. While the increase in the average global terrestrial PRCPTOT has been attributed to ACC, it is unclear whether this is equally true in dry and wet regions, given the difference in PRCPTOT changes between the two climatic regions. Here, we show the increase in PRCPTOT in dry regions is twice as fast as in wet regions of the globe during 1961–2018 in both observations and simulations. This faster increase is projected to grow with future warming, with an intensified human-induced TWC in the driest regions of the globe. We show this phenomenon can be explained by the faster warming and precipitation response rates as well as the stronger moisture transport in dry regions under ACC. Quantitative detection and attribution results show that the global increase in PRCPTOT can no longer be attributed to ACC if dry regions are excluded. From 1961–2018, the observed PRCPTOT increased by 5.63%~7.39% (2.44%~2.80%) over dry (wet) regions, and as much as 89% (as little as 5%) can be attributed to ACC. The faster ACC-induced TWC in dry regions is likely to have both beneficial and detrimental effects on dry regions of the globe, simultaneously alleviating water scarcity while increasing the risk of major flooding.
Clonal gene signatures predict prognosis in mesothelioma and lung adenocarcinoma
Authors: Lin Yupei , Burt Bryan M. , Lee Hyun-Sung , Nguyen Thinh T. , Jang Hee-Jin , Lee Claire , Hong Wei , Ripley Robert Taylor , Amos Christopher I. , Cheng Chao
Published: February 2024

Malignant pleural mesothelioma (MPM) is a rare but lethal pleural cancer with high intratumor heterogeneity (ITH). A recent study in lung adenocarcinoma has developed a clonal gene signature (ORACLE) from multiregional transcriptomic data and demonstrated high prognostic values and reproducibility. However, such a strategy has not been tested in other types of cancer with high ITH. We aimed to identify biomarkers from multi-regional data to prognostically stratify MPM patients. We generated a multiregional RNA-seq dataset for 78 tumor samples obtained from 26 MPM patients, each with one sample collected from a superior, lateral, and inferior region of the tumor. By integrating this dataset with the Cancer Genome Atlas MPM RNA-seq data, we selected 29 prognostic genes displaying high variability across different tumors but low ITH, which named PRACME (Prognostic Risk Associated Clonal Mesothelioma Expression). We evaluated PRACME in two independent MPM datasets and demonstrated its prognostic values. Patients with high signature scores are associated with poor prognosis after adjusting established clinical factors. Interestingly, the PRACME and the ORACLE signatures defined respectively from MPM and lung adenocarcinoma cross-predict prognosis between the two cancer types. Further investigation indicated that the cross-prediction ability might be explained by the high similarity between the two cancer types in their genomic regions with copy number variation, which host many clonal genes. Overall, our clonal signature PRACME provided prognostic stratification in MPM and this study emphasized the importance of multi-regional transcriptomic data for prognostic stratification based on clonal genes.
Nonequilibrium thermodynamics of quantum coherence beyond linear response
Authors: Rodrigues Franklin L. S. , Lutz Eric
Published: February 2024

Quantum thermodynamics allows for the interconversion of quantum coherence and mechanical work. Quantum coherence is thus a potential physical resource for quantum machines. However, formulating a general nonequilibrium thermodynamics of quantum coherence has turned out to be challenging. In particular, precise conditions under which coherence is beneficial to or, on the contrary, detrimental for work extraction from a system have remained elusive. We here develop a generic dynamic-Bayesian-network approach to the far-from-equilibrium thermodynamics of coherence. We concretely derive generalized fluctuation relations and a maximum-work theorem that fully account for quantum coherence at all times, for both closed and open dynamics. We obtain criteria for successful coherence-to-work conversion, and identify a nonequilibrium regime where maximum work extraction is increased by quantum coherence for fast processes beyond linear response.