Independent Experiments Research Articles

Robust estimation of lithium-ion battery state of health based on electro-thermal features and machine learning

Accurately estimating the State of Health (SOH) of lithium-ion (Li-ion) batteries is crucial for preventing overcharging and over-discharging, thereby extending battery lifespan. This paper presents a novel method for SOH estimation in lithium-ion batteries by leveraging electro-thermal features, a backpropagation neural network (BPNN), and a particle swarm optimization (PSO) algorithm. First, three health-related features—constant current charging time (CCCT), relative constant current charging time (RCCCT), and maximum temperature during discharge (MTT)—are extracted as indicators of SOH. The correlation between these features and the SOH is validated using Grey Relational Analysis (GRA). Next, a BP neural network is utilized to model the nonlinear relationship between the extracted features and SOH. The PSO algorithm is then employed to optimize the parameters of the BP neural network, enhancing the accuracy of the SOH estimation. The proposed method, which combines electro-thermal features with the optimized BP neural network, is validated through three independent lithium-ion battery aging experiments. Experimental results demonstrate that the proposed approach achieves high estimation accuracy and exhibits strong generalization performance for SOH prediction.

Coastal bacteria and protists assimilate viral carbon and nitrogen.

Free viruses are the most abundant type of biological particles in the biosphere, but the lack of quantitative knowledge about their consumption by heterotrophic protists and bacterial degradation has hindered the inclusion of virovory in biogeochemical models. Using isotope-labeled viruses added to three independent microcosm experiments with natural microbial communities followed by isotope measurements with single-cell resolution and flow cytometry, we quantified the flux of viral C and N into virovorous protists and bacteria and compared the loss of viruses due to abiotic vs biotic factors. We found that some protists can obtain most of their C and N requirements from viral particles and that viral C and N get incorporated into bacterial biomass. We found that bacteria and protists were responsible for increasing the daily removal rate of viruses by 33% to 85%, respectively, compared to abiotic processes alone. Our laboratory incubation experiments showed that abiotic processes removed roughly 50% of the viruses within a week, and adding biotic processes led to a removal of 83% to 91%. Our data provide direct evidence for the transfer of viral C and N back into the microbial loop through protist grazing and bacterial breakdown, representing a globally significant flux that needs to be investigated further to better understand and predictably model the C and N cycles of the hydrosphere.

Abstract 4128189: CD44 Knockdown Attenuates the Abnormal Cellular Phenotype of BMPR2-Deficient Primary Human Pulmonary Artery Endothelial Cells

Background: BMPR2 gene silencing in primary human pulmonary artery endothelial cells (PAECs) produces a proliferative, hypermigratory PAH-like cellular phenotype. Genome-wide expression profiling in BMPR2 -silenced cells uncovered CD44 , a cancer stem cell marker associated with tumor progression and metastasis, among the top upregulated transcripts. Therapeutic strategies that block CD44 or reduce its expression are currently in various stages of development for cancer. Thus, mechanistic studies investigating the contribution of CD44 to vascular remodeling in PAH may reveal new therapeutic targets. Hypothesis: Upregulation of CD44 contributes to the abnormal phenotype of BMPR2-deficient PAECs and thus may contribute to vascular remodeling in PAH. Aims: Determine the effect of CD44 -silencing on gene expression and cell proliferation in BMPR2-deficient PAECs. Methods: Commercially available primary, human PAECs were transfected with scrambled control (siCTRL) or gene specific siRNA(s). PAH patient-derived (N=24) and failed donor-derived (N=11) PAECs were obtained from the PHBI. mRNA and protein expression were determined by quantitative RT-PCR and Western blotting, respectively. Cell proliferation was assessed by BrdU incorporation 96h after siRNA transfection. Data was analyzed using t-tests or ANOVA with post hoc pairwise comparisons. Results: Consistent with our previous findings, CD44 protein expression was increased 4-fold in BMPR2 -silenced PAECs 48h following siRNA transfection (P<0.0001 vs siCTRL; N=10 unique donors). Genes involved in endothelial-mesenchymal transition and cell proliferation were also increased in BMPR2 -silenced PAECs including HMGA1 , ID1 , SNAI1, and SNAI2 (P<0.01 for all vs siCTRL; N=5 independent experiments) and co-silencing CD44 attenuated their upregulation (P<0.05 for all vs siBMPR2 alone). Importantly, CD44 knockdown reduced PAEC proliferation in the absence (P=0.01 vs siCTRL) and presence of BMPR2 deficiency (P=0.002 vs siBMPR2 alone). Like BMPR2 -silenced PAECs, CD44 mRNA levels were higher in PAH patient-derived versus failed donor control PAECs (P=0.07). Conclusions: CD44 knockdown corrected aberrant gene expression associated with endothelial-mesenchymal transition and reduced cellular proliferation in BMPR2-deficient PAECs. Thus, endothelial CD44 upregulation may contribute to pathologic vascular remodeling in PAH and represents an unexplored therapeutic target.

Convolutional Neural Network for Interface Defect Detection in Adhesively Bonded Dissimilar Structures

This study presents an ultrasonic non-destructive method with convolutional neural networks (CNN) used for the detection of interface defects in adhesively bonded dissimilar structures. Adhesive bonding, as the weakest part of such structures, is prone to defects, making their detection challenging due to various factors, including surface curvature, which causes amplitude variations. Conventional non-destructive methods and processing algorithms may be insufficient to enhance detectability, as some influential factors cannot be fully eliminated. Even after aligning signals reflected from the sample surface and interface, in some cases, due to non-parallel interfaces, persistent amplitude variations remain, significantly affecting defect detectability. To address this problem, a proposed method that integrates ultrasonic NDT and CNN, and which is able to recognize complex patterns and non-linear relationships, is developed in this work. Traditional ultrasonic pulse-echo testing was performed on adhesive structures to collect experimental data and generate C-scan images, covering the time gate from the first interface reflection to the time point where the reflections were attenuated. Two classes of datasets, representing defective and defect-free areas, were fed into the neural network. One subset of the dataset was used for model training, while another subset was used for model validation. Additionally, data collected from a different sample during an independent experiment were used to evaluate the generalization and performance of the neural network. The results demonstrated that the integration of a CNN enabled high prediction accuracy and automation of the analysis process, enhancing efficiency and reliability in detecting interface defects.

Involvement of a Microplusin-like Gene (HlonML-1) in the Olfactory Chemosensation of Haemophysalis longicornis: Expression, RNA Silencing, and Behavioral Implications

The study of tick olfaction is relatively new compared to that of insects, and the molecular mechanisms involved remain poorly understood. Despite several potential chemosensory genes identified in multiple tick species, these are yet to be validated through independent functional experiments. In this research, we cloned and analyzed a microplusin-like gene, HlonML-1, and investigated its role in the chemosensory activities of H. longicornis. The results showed that this gene’s amino acid sequences lack histidine residues essential for antimicrobial activity, and it is evolutionarily linked to putative chemosensory microplusins in ticks. Gene expression analyses indicated that HlonML-1 was significantly more abundant in ticks exposed to potential attractants and in the forelegs of H. longicornis than in non-exposed ticks and the hindlegs, respectively. Tick forelegs support the Haller’s organ, which is a sensory structure mostly specialized for chemosensation. Furthermore, Y-tube olfactometer assays indicated that silencing HlonML-1 significantly impaired adult ticks’ ability to detect selected odors, while their gustatory-related behavior remained unaffected compared to the control groups. Given its unique sequences, relative abundance in chemosensory tissues, and impact on odor detection, HlonML-1 is likely involved in the olfactory chemosensation of H. longicornis. Future research validating putative chemosensory microplusins in the genomes of various tick species may enhance our understanding of their olfactory functions in tick and lead to the identification of new molecular targets for developing tick repellents.

Phenotypic characterization of Echinochloa species in California rice

AbstractTwo independent greenhouse experiments were conducted in December 2020 and July 2021 in Davis, CA to characterize Echinochloa crus‐galli (L.) P. Beauv., Echinochloa colona (L.) Link, Echinochloa oryzicola (Vasinger) Vasinger and Echinochloa walteri (Pursh) A. Heller found in California rice systems based on their morphological traits. Phenotypic data was collected on 10 vegetative traits including plant height, number of tillers, flag leaf length, flag leaf width, flag leaf angle, the colour of leaf sheath, leaf blade colour, internode colour, node colour, growth habit and nine reproductive traits including number of days to heading, number of panicles, length of panicle, length of panicle branches, seeds per panicle, panicle weight, seed colour, awn length and awn pattern. High plasticity was observed in all species characterized in both experiments for both vegetative and reproductive traits, indicating potential inter‐specific hybridization. Awn length, days to heading, length of the panicle, length of the panicle branches, plant height, flag leaf angle, and growth habit were significantly higher in the fall experiment for all species indicating photoperiod could play a role in the expression of these traits. Also, high variation was observed for plant height, number of tillers, awn length, panicle weight, seeds/panicle, length of panicle branch, and number of panicles for all species in both experiments. The results from this study indicate morphological diversity currently present in Echinochloa species could contribute to their adaptation to selection pressure imposed by different management tools in California, emphasizing the need for a diversified management approach to effectively control this weed species.

Aridity-Driven Change in Microbial Carbon Use Efficiency and Its Linkage to Soil Carbon Storage.

Global warming is generally predicted to increase aridity in drylands, while the effects of aridity changes on microbial carbon use efficiency (CUE) and its linkage to soil organic carbon (SOC) storage remain unresolved, limiting the accuracy of soil carbon dynamic predictions under changing climates. Here, by employing large-scale soil sampling from 50 sites along an ~6000 km aridity gradient in northern China, we report a significant decreasing trend in microbial CUE (ranging from approximately 0.07 to 0.59 across the aridity gradient) with increasing aridity. The negative effect of aridity on microbial CUE was further verified by an independent moisture manipulation experiment, which revealed that CUE was lower under lower moisture levels than under higher moisture levels. Aridity-induced increases in physicochemical protection or decreases in microbial diversity primarily mediated the decrease in CUE with increasing aridity. Moreover, we found a highly positive microbial CUE-SOC relationship, and incorporating CUE improved the explanatory power of SOC variations along the aridity gradient. Our findings provide empirical evidence for aridity-induced reductions in microbial CUE over a broad geographic scale and highlight that increasing aridity may be a crucial mechanism underlying SOC loss by suppressing the ability of soil microorganisms to sequester carbon.

A prefrontal thalamocortical readout for conflict-related executive dysfunction in schizophrenia.

Executive dysfunction is a prominent feature of schizophrenia and may drive core symptoms. Dorsolateral prefrontal cortex (dlPFC) deficits have been linked to schizophrenia executive dysfunction, but mechanistic details critical for treatment development remain unclear. Here, capitalizing on recent animal circuit studies, we develop a task predicted to engage human dlPFC and its interactions with the mediodorsal thalamus (MD). We find that individuals with schizophrenia exhibit selective performance deficits when attention is guided by conflicting cues. Task performance correlates with lateralized MD-dlPFC functional connectivity, identifying a neural readout that predicts susceptibility to conflict during working memory in a larger independent schizophrenia cohort. In healthy subjects performing a probabilistic reversal task, this MD-dlPFC network predicts switching behavior. Overall, our three independent experiments introduce putative biomarkers for executive function in schizophrenia and highlight animal circuit studies as inspiration for the development of clinically relevant readouts.

Effective drug design screening in bacterial glycolytic enzymes via targeting alternative allosteric sites

Three glycolytic enzymes phosphofructokinase (PFK), glyceraldehyde-3-phosphate dehydrogenase (GADPH) and pyruvate kinase (PK) that belong to Staphylococcus aureus were used as targets for screening a dataset composed of 7229 compounds of which 1416 were FDA-approved. Instead of catalytic sites, evolutionarily less conserved allosteric sites were targeted to identify compounds that would selectively bind the bacteria's glycolytic enzymes instead of the human host. Seven different allosteric sites provided by three enzymes were used in independent screening experiments via docking. For each of the seven sites, a total of 723 compounds were selected as the top 10 % which displayed the highest binding affinities. All compounds were then united to yield the top 54 drug candidates shared by all seven sites. Next, 17 out of 54 were selected and subjected to in vitro experiments for testing their inhibition capability for antibacterial growth and enzymatic activity. Accordingly, four compounds displaying antibacterial growth inhibition above 40 % were determined as Candesartan cilexetil, Montelukast (sodium), Dronedarone (hydrochloride) and Thonzonium (bromide). In a second round of experiment, Candesartan cilexetil and Thonzonium displayed exceptionally high killing efficiencies on two bacterial strains of S.aureus (methicillin-sensitive and methicillin-resistant) with concentrations as low as 4 μg/mL and 0.5 μg/mL. Yet, their enzymatic assays were not in accordance with their killing effectiveness. Different inhibitory effects was observed for each compound in each enzymatic assay. A more effective target strategy would be to screen for drug compounds that woud inhibit a combination of glycolytic enzymes observed in the glycolytic pathway.

Novel mitochondria-targeted therapy AP39 limits mitochondrial dysregulation and diastolic dysfunction in 2D & 3D human models of diabetic cardiomyopathy

Abstract Introduction Mitochondrial dysregulation has been implicated in many complications of diabetes. Mitochondrial-targeted therapies AP39 and SS31 are renoprotective, but their cardioprotective potential in diabetes has not been fully resolved. Purpose We investigated AP39 and SS31 in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-hCM) and endothelial cells (iPSC-hEC) independently in 2D culture, as well as collectively in a 3D cardiac organoid (iPSC-hCO) model also comprising fibroblasts (iPSC-hFB), under type 2 diabetes (T2D)-like conditions. Methods Cells (iPSC-hCM, iPSC-hEC, iPSC-hFB; foreskin-2 cell line) were exposed to either 5.55mM glucose (control) or T2D conditions (20mM glucose plus fatty acids, endothelin-1 and cortisol) ± AP39 (50nM) or SS31 (1µM) for 48h. Cardiac organoids were subjected to 5.55mM glucose (control) or T2D for 4 days, with AP39 (50nM) or SS31 (1µM) added on day 2. Data are expressed as mean±SEM (fold) with n=4-6 from 2-3 independent experiments. One-way ANOVA with Dunnett`s post hoc analysis was performed with P<0.05 considered significant. Results 2D human cells: After 48h, T2D increased mitochondrial superoxide in iPSC-hCM (2.4±0.1 fold vs control) and iPSC-hEC (3.2±0.29 fold vs control), both P<0.05 (measured by MitoSOX). This was blunted by both AP39 (to 1.1±0.17) and SS31 (to 1.5±0.17) in T2D iPSC-hCM (P<0.05), with similar impact in iPSC-hEC, to 2.9±0.26 and 1.3±0.16 fold, both P<0.05. T2D increased cell death in both iPSC-hCM (1.6±0.09 fold vs control) and iPSC-hEC (1.6±0.12 fold, both P<0.05 measured by propidium iodide staining. Interestingly, AP39 selectively blunted cell death in T2D iPSC-hCM (to 1.1±0.06, P<0.05), mimicked by SS31 in T2D iPSC-hEC only (to 1.0±0.10, P<0.05). Further, T2D-induced mitochondrial hyperpolarisation in iPSC-hCM (1.5±0.09 fold vs control, assessed using TMRM), was only protected by AP39 (1.2±0.06 fold, P<0.05), but not SS31. 3D human cardiac organoids: After 4 days, T2D increased total contraction duration (1.6±0.10 fold control), time to peak (1.7±0.11) and relaxation duration (1.5±0.13, indicative of diastolic dysfunction), assessed by Olympus IX71 with a DP72 camera. All 3 contractile parameters were attenuated with AP39 (to 1.5±0.06, 1.3±0.09 and 1.0±0.04 fold, respectively) or SS31 (to 1.1±0.05, 1.2±0.15 and 1.2±0.12 fold, respectively), all P<0.05. T2D increased mitochondrial superoxide (2.7±0.16 fold control), blunted by AP39 (to 1.8±0.16) and SS31 (to 1.9±0.17), both P<0.05. Cellular injury measured by LDH was evident in T2D iPSC-hCO (2.1±0.23 fold control) was limited by AP39 (to 1.2±0.09) and SS31 (to 1.1±0.07), both P<0.05. Conclusion Our results highlight the cardioprotective potential of AP39 and SS31 to limit mitochondrial dysregulation, cell death and contractile dysfunction in human in vitro models of T2D. These findings may facilitate their clinical progression as therapeutic options for diabetic cardiomyopathy.

A human isolate of bovine H5N1 is transmissible and lethal in animal models.

The outbreak of clade 2.3.4.4b highly pathogenic avian influenza viruses of the H5N1 subtype (HPAI H5N1) in dairy cows in the US has so far resulted in spillover infections of at least thirteen farm workers1-3, who presented with mild respiratory symptoms or conjunctivitis, and one individual with no known animal exposure who was hospitalized but recovered3,4. Here, we characterized A/Texas/37/2024 (huTX37-H5N1), a virus isolated from the eyes of an infected farm worker who developed conjunctivitis5. huTX37-H5N1 replicated efficiently in primary human alveolar epithelial cells, but less efficiently in corneal epithelial cells. Despite causing mild disease in the infected worker, huTX37-H5N1 was lethal in mice and ferrets and spread systemically with high titres in respiratory and non-respiratory organs. Importantly, in four independent experiments in ferrets, huTX37-H5N1 transmitted via respiratory droplets in 17%-33% of transmission pairs and five of six exposed ferrets that became infected died. PB2-631L (encoded by bovine isolates), promoted influenza polymerase activity in human cells, suggesting a role in mammalian adaptation like that of PB2-627K (encoded by huTX37-H5N1). Additionally, bovine HPAI H5N1 viruses were found to be susceptible to polymerase inhibitors both in vitro and in mice. Thus, HPAI H5N1 virus derived from dairy cattle transmits by respiratory droplets in mammals without prior adaptation and causes lethal disease in animal models.

In Vitro Assessment of Thermo-Responsive Scaffold as a 3D Synthetic Matrix for CAR-T Potency Testing Against Glioblastoma Spheroids.

Chimeric antigen receptor (CAR) T cell immunotherapy has demonstrated exceptional efficacy against hematological malignancies, but notably less against solid tumors. To overcome this limitation, it is critical to investigate antitumor CAR-T cell potency in synthetic 3D microenvironments that can simulate the physical barriers presented by solid tumors. The overall goal of this study was the preliminary assessment of a synthetic thermo-responsive material as a substrate for invitro co-cultures of anti-disialoganglioside (GD2) CAR-T cells and patient-derived glioblastoma (GBM) spheroids. Independent co-culture experiments demonstrated that the encapsulation process did not adversely affect the cell cycle progression of glioma stem cells (GSCs) or CAR-T cells. GSC spheroids grew over time within the terpolymer scaffold, when seeded in the same ratio as the suspension control. Co-cultures of CAR-T cells in suspension with hydrogel-encapsulated GSC spheroids demonstrated that CAR-T cells could migrate through the hydrogel and target the encapsulated GSC spheroids. CAR-T cells killed approximately 80% of encapsulated GSCs, while maintaining effective CD4:CD8 T cell ratios and secreting inflammatory cytokines after interacting with GD2-expressing GSCs. Importantly, the scaffolds also facilitated cell harvesting for downstream cellular analysis. This study demonstrated that a synthetic 3D terpolymer hydrogel can serve as an artificial scaffold to investigate cellular immunotherapeutic potency against solid tumors.

In-Depth Proteomic Analysis of Paraffin-Embedded Tissue Samples from Colorectal Cancer Patients Revealed TXNDC17 and SLC8A1 as Key Proteins Associated with the Disease.

A deeper understanding of colorectal cancer (CRC) biology would help to identify specific early diagnostic markers. Here, we conducted quantitative proteomics on FFPE healthy, adenoma, and adenocarcinoma tissue samples from six stage I sporadic CRC patients to identify dysregulated proteins during early CRC development. Two independent quantitative 10-plex TMT experiments were separately performed. After protein extraction, trypsin digestion, and labeling, proteins were identified and quantified by using a Q Exactive mass spectrometer. A total of 2681 proteins were identified and quantified after data analysis and bioinformatics with MaxQuant and the R program. Among them, 284 and 280 proteins showed significant upregulation and downregulation (expression ratio ≥1.5 or ≤0.67, p-value ≤0.05), respectively, in adenoma and/or adenocarcinoma compared to healthy tissue. Ten dysregulated proteins were selected to study their role in CRC by WB, IHC, TMA, and ELISA using tissue and plasma samples from CRC patients, individuals with premalignant colorectal lesions (adenomas), and healthy individuals. In vitro loss-of-function cell-based assays and in vivo experiments using three CRC cell lines with different metastatic properties assessed the important roles of SLC8A1 and TXNDC17 in CRC and liver metastasis. Additionally, SLC8A1 and TXNDC17 protein levels in plasma possessed the diagnostic ability of early CRC stages.

Potentiation of Motor Adaptation Via Cerebellar tACS: Characterization of the Stimulation Frequency.

Motor adaptation is critical to update motor tasks in new or modified environmental conditions. While the cerebellum supports error-based adaptations, its neural implementation is partially known. By controlling the frequency of cerebellar transcranial alternating current stimulation (c-tACS), we can test the influence of neural oscillation from the cerebellum for motor adaptation. Two independent experiments were conducted. In Experiment 1, 16 participants received four c-tACS protocols (45Hz, 50Hz, 55Hz, and sham) on four different days while they practiced a visuomotor adaptation task (30 degrees CCW) with variable intensity (within-subject design). In Experiment 2, 45 participants separated into three groups received the effect of 45Hz, 55Hz c-tACS, and sham, respectively (between-subject design), performing the same visuomotor task with a fixed intensity (0.9mA). In Experiment 1, 45Hz and 50Hz of c-tACS accelerated motor adaptation when participants performed the task only for the first time, independent of the time interval between sessions or the stimulation intensity. The effect of active c-tACS was ratified in Experiment 2, where 45Hz c-tACS benefits motor adaptation during the complete practice period. Reaction time, velocity, or duration of reaching are not affected by c-tACS. Cerebellar alternating current stimulation is an effective strategy to potentiate visuomotor adaptations. Frequency-dependent effects on the gamma band, especially for 45Hz c-tACS, ratify the oscillatory profile of cerebellar processes behind the motor adaptation. This can be exploited in future interventions to enhance motor learning.

Collateral susceptibility-guided alternation of ceftolozane/tazobactam with imipenem prevents resistance development in XDR Pseudomonas aeruginosa biofilms

ObjectivesNew combinations of β-lactams and β-lactamase inhibitors, such as ceftolozane/tazobactam could be useful to combat biofilm-driven chronic infections by extensively resistant (XDR) Pseudomonas aeruginosa but resistance development by mutations in the Ω-loop of AmpC has been described. However, these mutations confer collateral susceptibility to carbapenems. Thus we aimed to evaluate the therapeutic efficacy and the prevention of resistance development of regimen alternating ceftolozane/tazobactam and imipenem. MethodsA carbapenem-resistant XDR P. aeruginosa clinical strain (ST175, 104-B7) and its isogenic imipenem-susceptible ceftolozane/tazobactam-resistant mutant derivative (AmpC T96I, 104-I9) were used. Experiments of single strains and mixed (104-B7 and 104-I9, 1:0.01 ratio) biofilms were performed. 48h biofilms (flow cell system) were treated for 6 days with either ceftolozane/tazobactam, 4/4 mg/L or the alternation of ceftolozane/tazobactam (2 days)-imipenem 4 mg/L (2 days) - ceftolozane/tazobactam (2 days). After treatment, biofilms were collected and plated on Mueller-Hinton agar± ceftolozane/tazobactam 4/4 mg/L. Structural dynamics were monitored using confocal laser scanning microscopy and images were processed with IMARIS software. At least, three independent triplicate experiments per condition were performed. Emerging resistant mutants were characterized through whole genome sequencing (Illumina). ResultsCeftolozane/tazobactam monotherapy failed to reduce the biofilms of the 104-B7 XDR strain and led to the selection of resistant mutants that showed AmpC Ω-loop mutations (T96I, L244R or aa236Δ7). On the contrary, alternation with imipenem enhanced activity (3 Logs reduction at day 6) and prevented the emergence of ceftolozane/tazobactam-resistant mutants. Likewise, treatment with ceftolozane/tazobactam dramatically amplified the resistant strain 104-I9 in mixed biofilms (>90 % of the population), while the alternation regimen counterselected it. ConclusionsCollateral susceptibility-guided alternation of ceftolozane/tazobactam with imipenem effectively prevented the selection of resistant mutants and thus could be a potential therapeutic strategy for the treatment of P. aeruginosa XDR chronic infections.

Hyperbaric oxygen-induced acute lung injury: A mouse model study on pathogenic characteristics and recovery dynamics.

Oxygen is an essential substance for the maintenance of human life. It is also widely used in clinical and diving medicine. Although oxygen is crucial for survival, too much oxygen can be harmful. Excessive oxygen inhalation in a short period of time can lead to injury, and the lung is one of the main target organs. Acute lung injury (ALI) induced by hyperbaric oxygen (HBO) is notably more severe than that caused by normobaric oxygen, yet systematic research on such injury and its regression is scarce. In this study, two independent experiments were designed. In the first experiment, mice were exposed to 2 atmospheres absolute (ATA), ≥95% oxygen for 2, 4, 6, and 8 h. Changes in lung histopathology, inflammation and expression of chemokines, alveolar-capillary barrier, and 8-OHdG were detected before and after the exposure. In the second experiment, these parameters were measured at 0 h, 12 h, and 24 h following 6 h of exposure to 2 ATA of ≥95% oxygen. Research indicates that ALI induced by HBO is characterized histologically by alveolar expansion, atelectasis, inflammatory cell infiltration, and hemorrhage. At 2 ATA, significant changes in the alveolar-capillary barrier were observed after more than 95% oxygen exposure for 4 h, as evidenced by increased Evans blue (EB) extravasation (p = 0.0200). After 6 h of HBO exposure, lung tissue pathology scores, 8-OHdG levels, and inflammatory and chemotactic factors (such as Il6, CCL2, CCL3, CXCL5, and CXCL10), intercellular adhesion molecule 1 (ICAM1), and vascular cell adhesion molecule 1 (VCAM1) were significantly elevated. Compared to lung injury caused by normobaric oxygen, the onset time of injury was significantly shortened. Additionally, it was observed that these markers continued to increase after leaving the HBO environment, peaking at 12 h and starting to recover at 24 h, indicating that the peak of inflammatory lung injury occurs within 12 h post-exposure, with recovery beginning at 24 h. This contradicts the common belief that lung injury is alleviated upon removal from a high-oxygen environment. However, EB levels, which reflect damage to the alveolar-capillary barrier, and VE-Cadherin (VE-Cad), tight junction protein 1 (ZO-1), ICAM1, and VCAM1 remained significantly altered 24 h after leaving the HBO environment. This suggests that the alveolar-capillary barrier is the most sensitive and slowest recovering part of the lung injury induced by HBO. These findings can provide insights into the pathogenesis and progression of lung injury caused by HBO and offer references for identifying corresponding intervention targets.

New measurement of the Hoyle state radiative transition width

The radiative decay of the Hoyle state serves as the gateway to the production of heavier elements in a stellar environment. Here, we present an exclusive measurement of electric quadruple (E2) transitions of the Hoyle state to the ground state of 12C through the 12C(p, p′γγ)12C reaction. A triple coincidence measurement yields the radiative branching ratio Γrad/Γ = 4.01 (30) × 10−4. This result was corroborated by an independent experiment based on the complete kinematical measurement via12C(p, p′)12C reaction, yielding a consistent result of Γrad/Γ = 4.04 (30) × 10−4. Combining our results with the currently adopted values of Γπ(E0)/Γ and Γπ(E0), the radiative width of the Hoyle state is determined to be 3.75 (40) × 10−3 eV. It is important to note that our finding do not align with a recently reported 34% increase in the radiative decay width of the Hoyle state but is consistent with the currently accepted value.

A proportional fusion adaptation algorithm to reduce noise in sEMG signals of the lower limb

Abstract To address issues related to unknown noise pollution and the inadequate performance of single adaptive noise reduction algorithms in measuring lower limb surface electromyography (sEMG) signals, this paper proposes an algorithm that combines the fast convergence speed and strong noise reduction capability of recursive least-squares (RLS) with the low computational complexity of the normalized least-mean-square (NLMS) and improved proportionate NLMS (IPNLMS). Through the proportional fusion of RLS with NLMS and RLS with IPNLMS, the proposed algorithm greatly improves convergence speed, stability, and noise reduction performance while effectively reducing computational complexity. Moreover, considering the influence of the initial value of weights on the noise reduction performance during the updating process of the adaptive noise reduction algorithm, a weight initial value setting (WIS) module is proposed to optimize the initial value of the weights by the known amount of data. Based on 50 independent experiments, an adaptive noise reduction algorithm and WIS module were used to reduce the unknown noise in the lower limb sEMG signals, which was generated by white Gaussian noise, power line interference, or hybrid noise interfered by an unknown environment. The noise reduction performance was evaluated by using the average value of the signal-to-noise ratio (SNR), the root-mean-square error, and R-square. Compared with the RLS, NLMS, and IPNLMS algorithms for noise reduction of vastus lateralis, rectus femoris, and biceps femoris signals containing unknown noise, the SNR of RLS-NLMS, RLS-IPNLMS, WIS-RLS-NLMS, and WIS-RLS-IPNLMS is improved by an average of [7.92%, 55.54%, 55.63%], [7.45%, 54.90%, 54.99%], [19.70%, 72.38%, 72.71%], [19.32%, 71.84%, 72.19%]. The simulation results verify that the proportional fusion adaptive noise reduction algorithm and the WIS module effectively accelerate the convergence speed, enhance the noise reduction capability, and reduce the computational complexity.

Nitrogen input strategies impact fertilizer nitrogen saving by intercropping: A global meta-analysis

ContextSeveral meta-analyses have demonstrated that intercropping increases land use efficiency and fertilizer use efficiency of grain-producing crop species, but no overarching synthesis has been made on the effects of fertilizer management on fertilizer use efficiency. Research questionsHere we assess the relative N use efficiency of species mixtures compared to sole crops under different N input strategies using global data. MethodsWe built a global database of yield and fertilizer N input with 600 data records representing the results of 136 independent experiments from 80 publications with four main types of species functional combinations (SFCs), based on key traits that were found relevant in previous intercropping studies: C3-cereal/legume, maize/legume, C4-non-maize/legume and maize/C3-cereal. ResultsWe found that the literature reports results for four main N input strategies in the intercrop and sole crops: (1) zero fertilizer N input (Nic=N1=N2=0), (2) equal fertilizer N input (Nic=N1=N2>0), (3) intermediate fertilizer N input (N1≥Nic≥N2 and N1>N2), and (4) transgressive fertilizer N input (Nic>N1≥N2), where N1, N2 and Nic represent the N input in sole crop 1, sole crop 2 and the intercrop. With zero N input, high land equivalent ratio was found in cereal/legume intercrops but not in maize/C3-cereal intercrops. Intermediate N input (strategy 3) resulted in high LER (land equivalent ratio) and FNER (fertilizer N equivalent ratio) because of the high intercropping advantage of cereals in C3-cereal/legume, maize/legume, and C4-non-maize/legume intercrops and maize in maize/C3-cereal intercrops. Equal N input in the sole crops and the intercrops resulted in LER and FNER being equal and N saving was entirely due to land saving, regardless of SFCs. Transgressive N input resulted in high LER but low FNER. ConclusionsThe study confirms that cereal/legume intercropping increases LER at zero N input. Strategies that tailor N input in intercropping to species demand (strategy 3) pair high productivity and LER to high fertilizer N use efficiency. The transgressive N input strategy maximizes LER at the expense of FNER, thus potentially generating high N losses.

Effects of the auxin-dependent degradation of the cohesin and condensin complexes on the repair of distant DNA double-strand breaks in mouse embryonic stem cells.

The SMC protein family, including cohesin and condensin I/II, plays a pivotal role in maintaining the topological structure of chromosomes and influences many cellular processes, notably the repair of double-stranded DNA breaks (DSBs). The cohesin complex impacts DSB repair by spreading γH2AX signal and containing DNA ends in close proximity by loop extrusion. Cohesin supports DNA stability by sister chromatid cohesion during the S/G2 phase, which limits DNA end mobility. Cohesin knockdown was recently shown to stimulate frequencies of genomic deletions produced by distant paired DSBs, but does not affect DNA repair of a single or close DSBs. We examined how auxin-inducible protein degradation of Rad21 (cohesin) or Smc2 (condensins I+II) changes the frequencies of rearrangements between paired distant DSBs in mouse embryonic stem cells (mESCs). We used Cas9 RNP nucleofection to generate deletions and inversions with high efficiency without additional selection. We determined optimal Neon settings and deletion appearance timings. Two strategies for auxin addition were tested (4 independent experiments in total). We examined deletion/inversion frequencies for two regions spanning 3.5 and 3.9 kbp in size. Contrary to expectations, in our setting, Rad21 depletion did not increase deletion/inversion frequencies, not even for the region with an active Ctcf boundary. We actually observed a 12 % decrease in deletions (but not inversions). At the same time, double condensin depletion (Smc2 degron line) demonstrated high biological variability between experiments, complicating the analysis, and requires additional examination in the future. TIDE analysis revealed that editing frequency was consistent (30-50 %) for most experiments with a minor decrease after auxin addition. In the end, we discuss the Neon/ddPCR method for deletion generation and detection in mESCs.