High-resolution detection of copy number alterations in single cells with HiScanner.

Improvements in single-cell whole-genome sequencing (scWGS) assays have enabled detailed characterization of somatic copy number alterations (CNAs) at the single-cell level. Yet, current computational methods are mostly designed for detecting chromosome-scale changes in cancer samples with low sequencing coverage. Here, we introduce HiScanner (High-resolution Single-Cell Allelic copy Number callER), which combines read depth, B-allele frequency, and haplotype phasing to identify CNAs with high resolution. In simulated data, HiScanner consistently outperforms state-of-the-art methods across various CNA types and sizes. When applied to high-coverage scWGS data from human brain cells, HiScanner shows a superior ability to detect smaller CNAs, uncovering distinct CNA patterns between neurons and oligodendrocytes. For 179 cells we sequenced from longitudinal meningioma samples, integration of CNAs with point mutations revealed evolutionary trajectories of tumor cells. These findings show that HiScanner enables accurate characterization of frequency, clonality, and distribution of CNAs at the single-cell level in both non-neoplastic and neoplastic cells.

Phenacetin promoted the rapid start-up and stable maintenance of partial nitrification: Responses of nitrifiers and antibiotic resistance genes.

Phenacetin (PNCT) belongs to one of the earliest synthetic antipyretics. However, impact of PNCT on nitrifying microorganisms in wastewater treatment plants and its potential microbial mechanism was still unclear. In this study, PN could be initiated within six days by PNCT anaerobic soaking treatment (8 mg/L). In order to improve the stable performance of PN, 21 times of PNCT aerobic soaking treatment every three days was conducted and PN was stabilized for 191 days. After PN was damaged, ten times of PNCT aerobic soaking treatment every three days was conducted and PN was recovered after once soaking, maintained over 88 days. Ammonia oxidizing bacteria might change the dominant oligotype to gradually adjust to PNCT, and the increase of abundance and activity of Nitrosomonas promoted the initiation of PN. For nitrite-oxidizing bacteria (NOB), the increase of Candidatus Nitrotoga and Nitrospira destroyed PN, but PN could be recovered after once aerobic soaking illustrating NOB was not resistant to PNCT. KEGG and COG analysis suggested PNCT might disrupt rTCA cycle of Nitrospira, resulting in the decrease of relative abundance of Nitrospira. Moreover, PNCT did not lead to the sharp increase of absolute abundances of antibiotic resistance genes (ARGs), and the risk of ARGs transmission was negligible.

Ecosystem-based management approaches for watershed conservation and geosustainability.

When contributors' goals and legislative and political structures vary, as they often do in the case of worldwide fish populations, it becomes more challenging to implement ethical fishing tactics. Canada, the United States, and Mexico all fish from Pacific regions anchovies in the California Modern. Climate-driven numbers and geographic dynamics may pollute the waters of collaborative aquaculture and lead to overloading. This research expands upon prior works using a game theoretic model of Tran's boundary sardine fisheries in different climatic conditions to account for ecological links. More significant economic advantages accrue from cooperation fishing tactics that consider the mackerel's role as feed for other species in the natural system, as opposed to plans that merely take note of the worth of mackerel harvests to a particular fishing nation. The maximum environmental benefit is obtained at a fishery rate for sardines barely less than the sardine Fishery Management Safe Yield. Ecological-based control of fisheries can increase sustainability and profits, but only if investors and policy makers consider the ecology in business-applicable models. Understanding and adapting to the fast alterations in habitat distributions due to climate change and designing ways to achieve viable and lucrative fishery amidst altering environments will necessitate an increased emphasis on ecosystem-based governance.

Separative and Comprehensive Effects of Grain Coarsening and Grain Refinement of Ni-38Cr-3.8Al Alloy during Thermal Deformation Process.

During thermal deformation, grain coarsening due to grain growth and grain refinement resulting from dynamic recrystallization (DRX) collectively influence the deformed grain size. To investigate the separative and comprehensive effects of the two mechanisms in the Ni-38Cr-3.8Al alloy, grain growth experiments and isothermal compression tests were conducted. Kinetics models for grain growth and DRX behaviors were established based on the experimental data, which were integrated with finite element (FE) techniques to simulate the evolution of grain size throughout the entire thermal compression process. The effects of grain coarsening and grain refinement during this process were separated and quantified based on the simulation data. The results revealed that grain coarsening predominated during the heating and holding stages, with a longer holding time and higher holding temperatures intensifying this effect. However, during the compression stage, grain coarsening and grain refinement co-existed, and their competition was influenced by deformation parameters. Specifically, grain refinement dominated at strain rates exceeding 0.1 s-1, while grain coarsening dominated at lower strain rates (<0.1 s-1) and higher deformation temperatures (>1373 K). The simulated grain sizes closely matched the experimental observations.

Construction of a novel near-infrared fluorescent Nile blue@MOF nanoprobe for imaging mitochondrial ATP in living cells.

A near-infrared fluorescent nanoprobe consisting of Nile blue-capped ZIF-90 is first proposed for real-time imaging of mitochondrial ATP. Owing to the strong binding of ATP with Zn2+, the structure of the probe is disrupted, leading to the release of fluorescent NB.

Spectral intelligent detection for aflatoxin B1 via contrastive learning based on Siamese network.

Aflatoxins, harmful substances found in peanuts, corn, and their derivatives, pose significant health risks. Addressing this, the presented research introduces an innovative MSGhostDNN model, merging contrastive learning with multi-scale convolutional networks for precise aflatoxin detection. The method significantly enhances feature discrimination, achieving an impressive 97.87% detection accuracy with a pre-trained model. By applying Grad-CAM, it further refines the model to identify key wavelengths, particularly 416 nm, and focuses on 40 key wavelengths for optimal performance with 97.46% accuracy. The study also incorporates a task dimensionality reduction approach for continuous learning, allowing effective ongoing aflatoxin spectrum monitoring in peanuts and corn. This approach not only boosts aflatoxin detection efficiency but also sets a precedent for rapid online detection of similar toxins, offering a promising solution to mitigate the health risks associated with aflatoxin exposure.

Association of per- and polyfluoroalkyl substances with constipation: The National Health and Nutrition Examination Survey (2005-2010).

BACKGROUND: The impact of per- and polyfluoroalkyl substances (PFAS) on constipation, as mediated through gastrointestinal absorption and perturbations to the intestinal microecology, remains poorly understood. OBJECTIVE: This study seeks to explain the relationship between PFAS and constipation. METHODS: A total of 2945 adults from the National Health and Nutrition Examination Survey (NHANES) 2005-2010 were included in this study. Constipation was defined using the Bristol Stool Form Scale (BSFS) based on stool consistency. The relationship between PFAS and constipation was evaluated using weighted logistic regression and restricted cubic spline (RCS) analysis, while adjusting for confounding variables. RESULTS: The weighted median concentration of total PFAS (ΣPFAS) was significantly lower in individuals with constipation (19.01 µg/L) compared to those without constipation (23.30 µg/L) (p < 0.0001). Subgroup analysis revealed that the cumulative effect of PFAS was more pronounced in the elderly, men, individuals with obesity, high school education or equivalent, and high-income individuals (p < 0.05). After adjusting for confounding factors, multivariable analysis demonstrated an inverse association between PFOA [OR (95% CI), 0.666(0.486,0.914)] and PFHxS [OR (95% CI), 0.699(0.482,1.015)], and constipation. None of the personal and lifestyle factors showed a significant correlation with this negative association, as confirmed by subgroup analysis and interaction testing (p for interaction > 0.05). The RCS analysis demonstrated a linear inverse relationship between PFAS levels and constipation. CONCLUSION: The findings of this study provide evidence of a significant inverse correlation between serum concentrations of PFAS, particularly PFOA and PFHxS, and constipation.

Carbon dots as a novel photosensitizer for photodynamic therapy of cancer and bacterial infectious diseases: recent advances.

Carbon dots (CDs) are novel carbon-based nanomaterials that have been used as photosensitizer-mediated photodynamic therapy (PDT) in recent years due to their good photosensitizing activity. Photosensitizers (PSs) are main components of PDT that can produce large amounts of reactive oxygen species (ROS) when stimulated by light source, which have the advantages of low drug resistance and high therapeutic efficiency. CDs can generate ROS efficiently under irradiation and therefore have been extensively studied in disease local phototherapy. In tumor therapy, CDs can be used as PSs or PS carriers to participate in PDT and play an extremely important role. In bacterial infectious diseases, CDs exhibit high bactericidal activity as CDs are effective in disrupting bacterial cell membranes leading to bacterial death upon photoactivation. We focus on recent advances in the therapy of cancer and bacteria with CDs, and also briefly summarize the mechanisms and requirements for PSs in PDT of cancer, bacteria and other diseases. We also discuss the role CDs play in combination therapy and the potential for future applications against other pathogens.

Multifaceted Materials for Enhanced Osteogenesis and Antimicrobial Properties on Bioplastic Polyetheretherketone Surfaces: A Review.

Implant-associated infections and the increasing number of bone implants loosening and falling off after implantation have become urgent global challenges, hence the need for intelligent alternative solutions to combat implant loosening and falling off. The application of polyetheretherketone (PEEK) in biomedical and medical therapy has aroused great interest, especially because its elastic modulus close to bone provides an effective alternative to titanium implants, thereby preventing the possibility of bone implants loosening and falling off due to the mismatch of elastic modulus. In this Review, we provide a comprehensive overview of recent advances in surface modifications to prevent bone binding deficiency and bacterial infection after implantation of bone implants, starting with inorganics for surface modification, followed by organics that can effectively promote bone integration and antimicrobial action. In addition, surface modifications derived from cells and related products of biological activity have been proposed, and there is increasing evidence of clinical potential. Finally, the advantages and future challenges of surface strategies against medical associated poor osseointegration and infection are discussed, with promising prospects for developing novel osseointegration and antimicrobial PEEK materials.

Discovery of a Novel Orally Bioavailable FLT3-PROTAC Degrader for Efficient Treatment of Acute Myeloid Leukemia and Overcoming Resistance of FLT3 Inhibitors.

Fms-like tyrosine receptor kinase 3 (FLT3) proteolysis-targeting chimeras (PROTACs) represent a promising approach to eliminate the resistance of FLT3 inhibitors. However, due to the poor druggability of PROTACs, the development of orally bioavailable FLT3-PROTACs faces great challenges. Herein, a novel orally bioavailable FLT3-ITD degrader A20 with excellent pharmacokinetic properties was discovered through reasonable design. A20 selectively inhibited the proliferation of FLT3-ITD mutant acute myeloid leukemia (AML) cells and potently induced FLT3-ITD degradation through the ubiquitin-proteasome system. Notably, oral administration of A20 resulted in complete tumor regression on subcutaneous AML xenograft models. Furthermore, on systemic AML xenograft models, A20 could completely eliminate the CD45+CD33+ human leukemic cells in murine and significantly prolonged the survival time of mice. Most importantly, A20 exerted significantly improved antiproliferative activity against drug-resistant AML cells compared to existing FLT3 inhibitors. These findings suggested that A20 could serve as a promising drug candidate for relapsed or refractory AML.

The combination of ciprofloxacin and dialkyldimethyl ammonium compound synergistically proliferated intracellular resistance genes in nitrifying system.

Antibiotics and quaternary ammonium compounds (QACs) usually co-exist in wastewater treatment plants. Hence, three sequencing batch reactors were established and named as R1, R2 and R3, to investigate the effects of individual and combined exposure of different concentrations of ciprofloxacin (CIP) (0.2, 1.0 and 2.0 mg/L) and dialkyldimethyl ammonium compound (DADMAC) (0.4, 2.0 and 4.0 mg/L) on the performance, microbial community structures and resistance genes (RGs) in nitrifying system during 150 days. Results showed that CIP had a slight effect on ammonia oxidation activity, while 2.0 and 4.0 mg/L DADAMAC could obviously inhibit it, and the combination of CIP and DADMAC had a synergistic inhibitory effect. Besides, both CIP and DADMAC caused partial nitrification, and the order of nitrite accumulation rate was ranked as R3 > R2 > R1. The combination of CIP and DADMAC had an antagonistic effect on the increase of sludge particle size and α-Helix/(ß-Sheet + Random coil) was lowest in R3 (0.40). The combination of CIP and DADMAC synergistically stimulated most intracellular RGs in sludge, and the relative abundances of target RGs (e.g., qacEdelta1-01, qacH-01 and qnrS) at the end of operation in R3 were increased by 4.61-18.19 folds compared with those in CK, which were 1.34-5.57 folds higher than the R1 and R2. Moreover, the combination of CIP and DADMAC also promoted the transfer of RGs from sludge to water and enriched more potential hosts of RGs, further promoting the spread of RGs in nitrifying system. Thus, the combined pollution of CIP and DADMAC in wastewaters should attract more attentions.

Prediction of ventilator weaning failure in postoperative cardiac surgery patients using vasoactive-ventilation-renal score and nomogram analysis.

Objective: This study evaluated the predictive value of the vasoactive-ventilation-renal (VVR) score in identifying the risk of weaning failure after cardiac surgery and developing a nomogram model to help physicians improve the success rate of weaning from mechanical ventilation in adult patients undergoing postoperative cardiac surgery. Methods: Clinical data were retrospectively collected from adult patients who underwent extracorporeal circulation cardiac surgery at the First Affiliated Hospital of Nanjing Medical University between August 2022 and April 2023 and who were subsequently transferred to the Intensive Care Unit (ICU) and treated with vasoactive drugs. Patients were divided into successful and unsuccessful weaning groups based on first-attempt weaning success. Variable selection was regularized using univariate logistic regression and Least absolute shrinkage and selection operator (LASSO) regularization. Multivariate logistic regression was performed to identify predictors and a nomogram was created to predict the risk of weaning failure. Results: A total of 519 patients were included in the study. After selecting multiple stepwise variables, the VVR score before weaning, the modified Sequential Organ Failure Assessment (mSOFA) score on weaning day, and mechanical ventilation duration before weaning were determined as predictive indicators of weaning failure in adult patients after cardiac surgery. The optimal cut-off values for these indicators were 18.46 points, 4.33 points, and 20.50 h, respectively. The predictive model constructed using these three factors demonstrated good predictive performance. Conclusions: The VVR score before weaning accurately predicts the probability of weaning failure in adult patients after cardiac surgery. The weaning risk-predictive nomogram model, established based on the VVR score, mSOFA score, and mechanical ventilation duration before weaning, demonstrated robust predictive ability.

The application of small intestinal submucosa in tissue regeneration.

The distinctive three-dimensional architecture, biological functionality, minimal immunogenicity, and inherent biodegradability of small intestinal submucosa extracellular matrix materials have attracted considerable interest and found wide-ranging applications in the domain of tissue regeneration engineering. This article presents a comprehensive examination of the structure and role of small intestinal submucosa, delving into diverse preparation techniques and classifications. Additionally, it proposes approaches for evaluating and modifying SIS scaffolds. Moreover, the advancements of SIS in the regeneration of skin, bone, heart valves, blood vessels, bladder, uterus, and urethra are thoroughly explored, accompanied by their respective future prospects. Consequently, this review enhances our understanding of the applications of SIS in tissue and organ repair and keeps researchers up-to-date with the latest research advancements in this area.

MOF-mediated dual energy transfer nanoprobe integrated with exonuclease III amplification strategy for highly sensitive detection of DNA.

Accurate quantitative detection of DNA is an advanced strategy in various fields (such as disease diagnosis and environmental monitoring), but the classical DNA detection method usually suffers from low sensitivity, expensive thermal cyclers, or strict annealing conditions. Herein, a MOF-ERA platform for ultrasensitive HBV-DNA detection is constructed by integrating metal-organic framework (MOF)-mediated double energy transfer nanoprobe with exonuclease III (Exo III)-assisted target recycling amplification. The proposed double energy transfer containing a donor and two receptors is simply composed of MOFs (UiO-66-NH2, a well-studied MOF) modified with a signal probe formed by the hybridization of carboxyuorescein (FAM)-labeled DNA (FDNA) and black hole quencher (BHQ1)-terminated DNA (QDNA), resulting in low fluorescence signal. After the addition of HBV-DNA, Exo III degradation to FDNA is activated, leading to the liberation of the numerous FAM molecules, followed by the generation of a significant fluorescence signal owing to the negligible binding of MOFs with free FAM molecules. The results certify that the MOF-ERA platform can be successfully used to assay HBV-DNA in the range of 1.0-25.0 nM with a detection limit of 97.2 pM, which is lower than that without BHQ1 or Exo III. The proposed method with the superiorities of low background signal and high selectivity holds promise for early disease diagnosis and clinical biomedicine applications.

Land Resources for Wind Energy Development Requires Regionalized Characterizations.

Estimates of the land area occupied by wind energy differ by orders of magnitude due to data scarcity and inconsistent methodology. We developed a method that combines machine learning-based imagery analysis and geographic information systems and examined the land area of 318 wind farms (15,871 turbines) in the U.S. portion of the Western Interconnection. We found that prior land use and human modification in the project area are critical for land-use efficiency and land transformation of wind projects. Projects developed in areas with little human modification have a land-use efficiency of 63.8 ± 8.9 W/m2 (mean ±95% confidence interval) and a land transformation of 0.24 ± 0.07 m2/MWh, while values for projects in areas with high human modification are 447 ± 49.4 W/m2 and 0.05 ± 0.01 m2/MWh, respectively. We show that land resources for wind can be quantified consistently with our replicable method, a method that obviates >99% of the workload using machine learning. To quantify the peripheral impact of a turbine, buffered geometry can be used as a proxy for measuring land resources and metrics when a large enough impact radius is assumed (e.g., >4 times the rotor diameter). Our analysis provides a necessary first step toward regionalized impact assessment and improved comparisons of energy alternatives.

Multi-centers experience using therapeutic plasma exchange for corticosteroid/tocilizumab-refractory cytokine release syndrome following CAR-T therapy.

The chimeric antigen receptor T (CAR-T) cell therapy significantly enhances the prognosis of various hematologic malignancies; however, the systemic expansion of CAR-T cells also gives rise to severe cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). Despite the successful application of corticosteroids and tocilizumab in alleviating severe CRS in most patients, there are still individuals who experience life-threatening CRS without responding to the aforementioned therapies. In our retrospective cohort, we conducted an analysis of clinical and laboratory parameters, including inflammatory cytokines, in 17 patients from three centers who underwent therapeutic plasma exchange (TPE) for refractory CRS with or without ICANS following CAR-T products treatment. Our findings demonstrate a significant improvement in both clinical symptoms and laboratory parameters subsequent to TPE treatment. The rapid decrease in temperature and levels of inflammatory indexes indicates the remarkable scavenging efficacy of TPE against cytokine storm following CAR-T therapy. In conclusion, TPE may serve as a valuable and safe adjunct to corticosteroids and tocilizumab in the management of severe CRS resulting from CAR-T cell infusion. We eagerly await further prospective studies to validate this finding.

Utility of marking and fusion image-guided technique with cone-beam CT in kidney ruptured haemorrhage without extravascular leakage in angiography: a pilot study.

OBJECTIVE: To explore the feasibility of using marking and fusion image-guided technique with cone-beam CT (CBCT) in cases of kidney ruptured haemorrhage without extravascular leakage in digital subtraction angiography (DSA) images. METHODS: This is a retrospective case-control study that included 43 patients who underwent transcatheter arterial embolization for kidney ruptured haemorrhage and difficult haemostasis. The patients were divided into two groups: the CBCT group (cases without extravascular leakage observed in angiography) and the control group (cases with clearly identifiable target vessels in angiography). The baseline characteristics and clinical outcomes were collected and analysed. RESULTS: The results showed no statistically significant differences in the duration of the procedure and intraoperative blood transfusion between the control and CBCT groups (P > .05). The study clarified that the CBCT group had a significantly higher rate of improvement of gross haematuria compared to the control group (P < .05). The CBCT group showed a greater increase in haemoglobin and a lesser increase in creatinine. The clinical success rates were 87.5% in the control group and 90.9% in the CBCT group (P > .05). CONCLUSIONS: The marking and fusion image-guided technique is useful in cases of kidney ruptured haemorrhage without extravascular leakage of contrast agent. The technique is safe, feasible, and effective, and we believe it is superior to purely DSA-guidance. ADVANCES IN KNOWLEDGE: The use of the marking and fusion image-guided technique is recommended to overcome the challenge of undetectable target vessels during interventional procedures. This technique is considered as non-inferior to purely DSA-guided interventional procedures where the target vessels are clearly identifiable.

Electrically Controlled Anomalous Hall Effect and Orbital Magnetization in Topological Magnet MnBi_{2}Te_{4}.

We propose an intrinsic mechanism to understand the even-odd effect, namely, opposite signs of anomalous Hall resistance and different shapes of hysteresis loops for even and odd septuple layers (SLs), of MBE-grown MnBi_{2}Te_{4} thin films with electron doping. The nonzero hysteresis loops in the anomalous Hall effect and magnetic circular dichroism for even-SLs MnBi_{2}Te_{4} films originate from two different antiferromagnetic (AFM) configurations with different zeroth Landau level energies of surface states. The complex form of the anomalous Hall hysteresis loop can be understood from two magnetic transitions, a transition between two AFM states followed by a second transition to the ferromagnetic state. Our model also clarifies the relationship and distinction between axion parameter and magnetoelectric coefficient, and shows an even-odd oscillation behavior of magnetoelectric coefficients in MnBi_{2}Te_{4} films.

Flexible pressure sensors with ultrahigh stress tolerance enabled by periodic microslits.

Stress tolerance plays a vital role in ensuring the effectiveness of piezoresistive sensing films used in flexible pressure sensors. However, existing methods for enhancing stress tolerance employ dome-shaped, wrinkle-shaped, and pyramidal-shaped microstructures in intricate molding and demolding processes, which introduce significant fabrication challenges and limit the sensing performance. To address these shortcomings, this paper presents periodic microslits in a sensing film made of multiwalled carbon nanotubes and polydimethylsiloxane to realize ultrahigh stress tolerance with a theoretical maximum of 2.477 MPa and a sensitivity of 18.092 kPa-1. The periodic microslits permit extensive deformation under high pressure (e.g., 400 kPa) to widen the detection range. Moreover, the periodic microslits also enhance the sensitivity based on simultaneously exhibiting multiple synapses within the sensing interface and between the periodic sensing cells. The proposed solution is verified by experiments using sensors based on the microslit strategy for wind direction detection, robot movement sensing, and human health monitoring. In these experiments, vehicle load detection is achieved for ultrahigh pressure sensing under an ultrahigh pressure of over 400 kPa and a ratio of the contact area to the total area of 32.74%. The results indicate that the proposed microslit strategy can achieve ultrahigh stress tolerance while simplifying the fabrication complexity of preparing microstructure sensing films.

A Gas Therapy Strategy for Intestinal Flora Regulation and Colitis Treatment by Nanogel-Based Multistage NO Delivery Microcapsules.

Current approaches to treating inflammatory bowel disease focus on the suppression of overactive immune responses, the removal of reactive intestinal oxygen species, and regulation of the intestinal flora. However, owing to the complex structure of the gastrointestinal tract and the influence of mucus, current small-molecule and biologic-based drugs for treating colitis cannot effectively act at the site of colon inflammation, and as a result, they tend to exhibit low efficacies and toxic side effects. In this study, nanogel-based multistage NO delivery microcapsules are developed to achieve NO release at the inflammation site by targeting the inflammatory tissues using the nanogel. Surprisingly, oral administration of the microcapsules suppresses the growth of pathogenic bacteria and increases the abundance of probiotic bacteria. Metabolomics further show that an increased abundance of intestinal probiotics promotes the production of metabolites, including short-chain fatty acids and indole derivatives, which modulate the intestinal immunity and restore the intestinal barrier via the interleukin-17 and PI3K-Akt signaling pathways. This work reveals that the developed gas therapy strategy based on multistage NO delivery microcapsules modulates the intestinal microbial balance, thereby reducing inflammation and promoting intestinal barrier repair, ultimately providing a new therapeutic approach for the clinical management of colitis.