Genome and clonal hematopoiesis stability contrasts with immune, cfDNA, mitochondrial, and telomere length changes during short duration spaceflight.

Background: The Inspiration4 (I4) mission, the first all-civilian orbital flight mission, investigated the physiological effects of short-duration spaceflight through a multi-omic approach. Despite advances, there remains much to learn about human adaptation to spaceflight's unique challenges, including microgravity, immune system perturbations, and radiation exposure. Methods: To provide a detailed genetics analysis of the mission, we collected dried blood spots pre-, during, and post-flight for DNA extraction. Telomere length was measured by quantitative PCR, while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations. A robust bioinformatic pipeline was used for data analysis, including variant calling to assess mutational burden. Result: Telomere elongation occurred during spaceflight and shortened after return to Earth. Cell-free DNA analysis revealed increased immune cell signatures post-flight. No significant clonal hematopoiesis of indeterminate potential (CHIP) or whole-genome instability was observed. The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight. Conclusion: Our findings provide valuable insights into the physiological consequences of short-duration spaceflight, with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to Earth. CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts, an understudied phenomenon as previous studies have focused on career astronauts. This study will serve as a reference point for future commercial and non-commercial spaceflight, low Earth orbit (LEO) missions, and deep-space exploration.

ArCH: improving the performance of clonal hematopoiesis variant calling and interpretation.

MOTIVATION: The acquisition of somatic mutations in hematopoietic stem and progenitor stem cells with resultant clonal expansion, termed clonal hematopoiesis (CH), is associated with increased risk of hematologic malignancies and other adverse outcomes. CH is generally present at low allelic fractions, but clonal expansion and acquisition of additional mutations leads to hematologic cancers in a small proportion of individuals. With high depth and high sensitivity sequencing, CH can be detected in most adults and its clonal trajectory mapped over time. However, accurate CH variant calling is challenging due to the difficulty in distinguishing low frequency CH mutations from sequencing artifacts. The lack of well-validated bioinformatic pipelines for CH calling may contribute to lack of reproducibility in studies of CH. RESULTS: Here, we developed ArCH, an Artifact filtering Clonal Hematopoiesis variant calling pipeline for detecting single nucleotide variants and short insertions/deletions by combining the output of four variant calling tools and filtering based on variant characteristics and sequencing error rate estimation. ArCH is an end-to-end cloud-based pipeline optimized to accept a variety of inputs with customizable parameters adaptable to multiple sequencing technologies, research questions, and datasets. Using deep targeted sequencing data generated from six acute myeloid leukemia patient tumor: normal dilutions, 31 blood samples with orthogonal validation, and 26 blood samples with technical replicates, we show that ArCH improves the sensitivity and positive predictive value of CH variant detection at low allele frequencies compared to standard application of commonly used variant calling approaches. AVAILABILITY AND IMPLEMENTATION: The code for this workflow is available at: https://github.com/kbolton-lab/ArCH.

Nanomechanical Analysis of Living Small Extracellular Vesicles to Identify Gastric Cancer Cell Malignancy Based on a Biomimetic Peritoneum.

Gastric cancer is one of the most prevalent digestive malignancies. The lack of effective in vitro peritoneal models has hindered the exploration of the potential mechanisms behind gastric cancer's peritoneal metastasis. An accumulating body of research indicates that small extracellular vesicles (sEVs) play an indispensable role in peritoneal metastasis of gastric cancer cells. In this study, a biomimetic peritoneum was constructed. The biomimetic model is similar to real peritoneum in internal microstructure, composition, and primary function, and it enables the recurrence of peritoneal metastasis process in vitro. Based on this model, the association between the mechanical properties of sEVs and the invasiveness of gastric cancer was identified. By performing nanomechanical analysis on sEVs, we found that the Young's modulus of sEVs can be utilized to differentiate between malignant clinical samples (ascites) and nonmalignant clinical samples (peritoneal lavage). Furthermore, patients' ascites-derived sEVs were verified to stimulate the mesothelial-to-mesenchymal transition, thereby promoting peritoneal metastasis. In summary, nanomechanical analysis of living sEVs could be utilized for the noninvasive diagnosis of malignant degree and peritoneal metastasis of gastric cancer. This finding is expected to contribute future treatments.

Thermal Property of Fullerene Fibers: One-Dimensional Material with Exceptional Thermal Performance.

The recent groundbreaking achievement in the synthesis of large-sized single crystal C60 monolayer, which is covalently bonded in a plane using C60 as building blocks. The asymmetric lattice structure endows it with anisotropic phonon modes and conductivity. If these C60 are arranged in form of 1D fiber, the improved manipulation of phonon conduction along the fiber axis could be anticipated. Here, thermal properties of C60 -fiber, including thermal transfer along the C60 -fiber axis and across the interlayer interface are investigated using molecular dynamic simulations. Taking advantage of the distinctively hollow spherical structure of C60 building blocks, the spherical structure deformation and encapsulation induced thermal reduction can be up to 56% and 80%, respectively. By applying external electronic fields in H2 O@C60 model, its thermal conductivity decreases up to 60%, which realizes the contactless thermal regulation. ln particular, the thermal rectification phenomenon is discovered by inserting atoms/molecules in C60 with a rational designed mass-gradient, and its maximum thermal rectification factor is predicted to ≈45%. These investigations aim to achieve effective regulation of the thermal conductivity of C60 -fibers. This work showcases the potential of C60 -fiber in the realms of thermal management and thermal sensing, paving the way to C60 -based functional materials.

Low-pass sequencing plus imputation using avidity sequencing displays comparable imputation accuracy to sequencing by synthesis while reducing duplicates.

Low-pass sequencing with genotype imputation has been adopted as a cost-effective method for genotyping. The most widely used method of short-read sequencing uses sequencing by synthesis (SBS). Here we perform a study of a novel sequencing technology-avidity sequencing. In this short note, we compare the performance of imputation from low-pass libraries sequenced on an Element AVITI system (which utilizes avidity sequencing) to those sequenced on an Illumina NovaSeq 6000 (which utilizes SBS) with an SP flow cell for the same set of biological samples across a range of genetic ancestries. We observed dramatically lower optical duplication rates in the data deriving from the AVITI system compared to the NovaSeq 6000, resulting in higher effective coverage given a fixed number of sequenced bases, and comparable imputation accuracy performance between sequencing chemistries across ancestries. This study demonstrates that avidity sequencing is a viable alternative to the standard SBS chemistries for applications involving low-pass sequencing plus imputation.

Sequencing by avidity enables high accuracy with low reagent consumption.

We present avidity sequencing, a sequencing chemistry that separately optimizes the processes of stepping along a DNA template and that of identifying each nucleotide within the template. Nucleotide identification uses multivalent nucleotide ligands on dye-labeled cores to form polymerase-polymer-nucleotide complexes bound to clonal copies of DNA targets. These polymer-nucleotide substrates, termed avidites, decrease the required concentration of reporting nucleotides from micromolar to nanomolar and yield negligible dissociation rates. Avidity sequencing achieves high accuracy, with 96.2% and 85.4% of base calls having an average of one error per 1,000 and 10,000 base pairs, respectively. We show that the average error rate of avidity sequencing remained stable following a long homopolymer.

Viral activation and ecological restructuring characterize a microbiome axis of spaceflight-associated immune activation.

Maintenance of astronaut health during spaceflight will require monitoring and potentially modulating their microbiomes, which play a role in some space-derived health disorders. However, documenting the response of microbiota to spaceflight has been difficult thus far due to mission constraints that lead to limited sampling. Here, we executed a six-month longitudinal study centered on a three-day flight to quantify the high-resolution microbiome response to spaceflight. Via paired metagenomics and metatranscriptomics alongside single immune profiling, we resolved a microbiome "architecture" of spaceflight characterized by time-dependent and taxonomically divergent microbiome alterations across 750 samples and ten body sites. We observed pan-phyletic viral activation and signs of persistent changes that, in the oral microbiome, yielded plaque-associated pathobionts with strong associations to immune cell gene expression. Further, we found enrichments of microbial genes associated with antibiotic production, toxin-antitoxin systems, and stress response enriched universally across the body sites. We also used strain-level tracking to measure the potential propagation of microbial species from the crew members to each other and the environment, identifying microbes that were prone to seed the capsule surface and move between the crew. Finally, we identified associations between microbiome and host immune cell shifts, proposing both a microbiome axis of immune changes during flight as well as the sources of some of those changes. In summary, these datasets and methods reveal connections between crew immunology, the microbiome, and their likely drivers and lay the groundwork for future microbiome studies of spaceflight.

EWELD: A Large-Scale Industrial and Commercial Load Dataset in Extreme Weather Events.

Load forecasting is crucial for the economic and secure operation of power systems. Extreme weather events, such as extreme heat and typhoons, can lead to more significant fluctuations in power consumption, making load forecasting more difficult. At present, due to the lack of relevant public data, the research on load forecasting under extreme weather events is still blank, so it is necessary to release a large-scale load dataset containing extreme weather events. The dataset includes electricity consumption data of industrial and commercial users under extreme weather events such as typhoons and extreme heat, which are collected at 15-minute intervals. The data is collected over six years from smart meters installed at the power entry points of users in southern China. The dataset consists of electricity consumption data from 386 industrial and commercial users in 17 industries, with more than 50 million records. During the recording period, extreme weather events such as typhoons and extreme heat are marked to form a total of 5,741 event records.

A novel diagnostic signature of circulating tsRNAs and miRNAs in esophageal squamous cell carcinoma detected with a microfluidic platform.

Small non-coding RNAs (sncRNAs) consisting of tRNA-derived small RNAs (tsRNAs) and miRNAs can be released by cancer cells and detected in blood, offering great potential for diagnosis of malignant tumors such as squamous cell carcinoma of the esophagus (ESCC). One of the major challenges for the clinical application of blood-based sncRNAs biomarkers is the difficulty of detection because of their small sncRNA size and low abundance. The deferentially expressed tsRNAs and miRNAs in plasma were studied with high-throughput sequencing and polymerase chain reaction in ESCC cohorts. A novel signature containing tRF-55:74-chrM.Phe-GAA, tRF-56:75-Ala-CGC-1-M4 and miR-4488 was identified with diagnostic potential. The signature was further confirmed by an attomolar-level ultrasensitive and rapid microfluidic biochip, which can achieve a multiplex, simple and low-cost detection. Our results indicated that a combination of tsRNAs and miRNAs has high diagnostic efficiency and tremendous potential to act as specific biomarkers through a reliable, highly sensitive, fast, and economic microfluidic biochip for ESCC diagnosis.

Separation and single-cell analysis for free gastric cancer cells in ascites and peritoneal lavages based on microfluidic chips.

BACKGROUNDS: Detecting free cancer cells from ascites and peritoneal lavages is crucial for diagnosing gastric cancer (GC). However, traditional methods are limited for early-stage diagnosis due to their low sensitivity. METHODS: A label-free, rapid, and high-throughput technique was developed for separating cancer cells from ascites and peritoneal lavages using an integrated microfluidic device, taking advantage of dean flow fractionation and deterministic lateral displacement. Afterward, separated cells were analyzed using a microfluidic single-cell trapping array chip (SCTA-chip). In situ immunofluorescence for EpCAM, YAP-1, HER-2, CD45 molecular expressions, and Wright-Giemsa staining were performed for cells in SCTA-chips. At last, YAP1 and HER-2 expression in tissues was analyzed by immunohistochemistry. FINDINGS: Through integrated microfluidic device, cancer cells were successfully separated from simulated peritoneal lavages containing 1/10,000 cancer cells with recovery rate of 84.8% and purity of 72.4%. Afterward, cancer cells were isolated from 12 patients' ascites samples. Cytological examinations showed cancer cells were efficiently enriched with background cells excluded. Afterwards, separated cells from ascites were analyzed by SCTA-chips, and recognized as cancer cells through EpCAM+/CD45- expression and Wright-Giemsa staining. Interestingly, 8 out of 12 ascites samples showed HER-2+ cancer cells. At last, the results through a serial expression analysis showed that YAP1 and HER-2 have discordant expression during metastasis. INTERPRETATION: Microfluidic Chips developed in our study could not only rapidly detect label-free free GC cells in ascites and peritoneal lavages with high-throughput, they could also analyze ascites cancer cells at the single-cell level, improving peritoneal metastasis diagnosis and investigation of therapeutic targets. FUNDING: This research was supported by National Natural Science Foundation of China (22134004, U1908207, 91859111); Natural Science Foundation of Shandong Province of China (ZR2019JQ06); Taishan Scholars Program of Shandong Province tsqn (201909077); Local Science and Technology Development Fund Guided by the Central Government (YDZX20203700002568); Applied Basic Research Program of Liaoning Province (2022020284-JH2/1013).

Near-real-time daily estimates of fossil fuel CO2 emissions from major high-emission cities in China.

Cities in China are on the frontline of low-carbon transition which requires monitoring city-level emissions with low-latency to support timely climate actions. Most existing CO2 emission inventories lag reality by more than one year and only provide annual totals. To improve the timeliness and temporal resolution of city-level emission inventories, we present Carbon Monitor Cities-China (CMCC), a near-real-time dataset of daily CO2 emissions from fossil fuel and cement production for 48 major high-emission cities in China. This dataset provides territory-based emission estimates from 2020-01-01 to 2021-12-31 for five sectors: power generation, residential (buildings and services), industry, ground transportation, and aviation. CMCC is developed based on an innovative framework that integrates bottom-up inventory construction and daily emission estimates from sectoral activities and models. Annual emissions show reasonable agreement with other datasets, and uncertainty ranges are estimated for each city and sector. CMCC provides valuable daily emission estimates that enable low-latency mitigation monitoring for cities in China.

Micromechanisms and Characterization of Low-Velocity Impact Damage in 3D Woven Composites.

Low-velocity impact (LVI) damage of 3D woven composites were experimentally and numerically investigated, considering different off-axis angles and impact energies. The impact responses were examined by LVI tests, and the damage morphology inside the composites was observed by X-ray micro-computed tomography (µ-CT). Yarn-level damage evolution was revealed by developing a hybrid finite element analysis model. The results show that the impact damage has significant directionality determined by the weft/warp orientation of the composites. The damage originates at the bottom of the impacted area and then expands outwards and upwards simultaneously, accompanied by in-plane and out-of-plane stress transfers. The straight-line distributed weft/warp yarns play an important role in bearing loads at the beginning of loading, while the w-shape distributed binder warp yarns gradually absorb impact deformation and toughen the whole structure as the loading proceeds. The effect of directional impact damage on post-impact performance was explored by performing compressing-after-impact (CAI) tests. It is revealed that the CAI properties along principal directions are more sensitive to the low-velocity impact, and the damage mode is significantly affected by the loading direction.

The Efficacy and Safety of Celecoxib in Addition to Standard Cancer Therapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The purpose of this meta-analysis was to evaluate the efficacy and safety of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, in addition to standard anticancer therapy. Randomized controlled trials (RCTs) that evaluated the efficacy and safety of celecoxib-combined cancer therapy were systematically searched in PubMed and Embase databases. The endpoints were overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), objective response rate (ORR), disease control rate (DCR), pathological complete response (pCR), and adverse events (AEs). The results of 30 RCTs containing 9655 patients showed limited benefits in celecoxib-combined cancer therapy. However, celecoxib-combined palliative therapy prolonged PFS in epidermal growth factor receptor (EGFR) wild-type patients (HR = 0.57, 95%CI = 0.35-0.94). Moreover, despite a slight increase in thrombocytopenia (RR = 1.35, 95%CI = 1.08-1.69), there was no increase in other toxicities. Celecoxib combined with adjuvant therapy indicated a better OS (HR = 0.850, 95%CI = 0.725-0.996). Furthermore, celecoxib plus neoadjuvant therapy improved the ORR in standard cancer therapy, especially neoadjuvant therapy (overall: RR = 1.13, 95%CI = 1.03-1.23; neoadjuvant therapy: RR = 1.25, 95%CI = 1.09-1.44), but not pCR. Our study indicated that adding celecoxib to palliative therapy prolongs the PFS of EGFR wild-type patients, with good safety profiles. Celecoxib combined with adjuvant therapy prolongs OS, and celecoxib plus neoadjuvant therapy improves the ORR. Thus, celecoxib-combined cancer therapy may be a promising therapy strategy.

Oblique Low-Velocity Impact Response and Damage Behavior of Carbon-Epoxy Composite Laminates.

The low-velocity impact behavior of carbon-epoxy cross-ply composites was numerically investigated, examining the effect of impact angle. A plastic continuum damage model, introducing the cohesive interface to describe delamination damage, was established and was validated by available experimental data. Impact histories, progressive deformation, stress transfer, and impact damage are respectively discussed. The results show that an increase in impact angle intensifies the action of tangential force, and gradually transfers energy absorption from normal plastic deformation to tangential deformation and friction, which dissipates more energy through relatively longer contact duration and larger impactor displacement. The delamination damage to upper layers is more affected by tangential loads, intensifying with the increase of the impact angle, and the damage area to the top interface is increased by 132.1% from 0° impact to 60° impact. Meanwhile, the delamination damage to lower layers is mainly determined by normal loads, weakening with the increasing impact angle overall, and the damage area of the lowest interface decreases by 36.6% from 0° impact to 60° impact.

AI-enabled image fraud in scientific publications.

Destroying image integrity in scientific papers may result in serious consequences. Inappropriate duplication and fabrication of images are two common misconducts in this aspect. The rapid development of artificial-intelligence technology has brought to us promising image-generation models that can produce realistic fake images. Here, we show that such advanced generative models threaten the publishing system in academia as they may be used to generate fake scientific images that cannot be effectively identified. We demonstrate the disturbing potential of these generative models in synthesizing fake images, plagiarizing existing images, and deliberately modifying images. It is very difficult to identify images generated by these models by visual inspection, image-forensic tools, and detection tools due to the unique paradigm of the generative models for processing images. This perspective reveals vast risks and arouses the vigilance of the scientific community on fake scientific images generated by artificial intelligence (AI) models.

Quercetin protects against palmitate-induced pancreatic ß-cell apoptosis by restoring lysosomal function and autophagic flux.

Quercetin, a natural flavonoid, has been reported to prevent pancreatic ß-cell apoptosis in animal models of diabetes. However, the underlying mechanism remains unclear. We investigated the mechanisms through which quercetin protects ß cells from palmitate-induced apoptosis and determined whether autophagy is involved in this process. We found that quercetin treatment partially reduced palmitate-induced ß-cell apoptosis. This protective effect was abolished by pharmacologic inhibition of autophagy and by silencing a key autophagy gene. Further analysis revealed that palmitate treatment promoted the expression of LC3 II, a marker of autophagosomes, but resulted in the blockade of autophagic flux due to lysosome dysfunction. Defective lysosome accumulation can cause lysosomal membrane permeabilization and the release of cathepsins from lysosome into the cytosol that triggers apoptosis. Treatment with quercetin reversed lysosomal dysfunction and promoted autophagosome-lysosome fusion, which restored defective autophagic flux and provoked autophagy. Overall, our results indicate that lysosomal dysfunction is a major factor that contributes to ß-cell apoptosis and demonstrates that quercetin improves cell survival by restoring lysosomal function and autophagic flux. This study provides new evidence regarding the anti-apoptotic mechanism of quercetin in the treatment of type 2 diabetes.

Revealing Density Thresholds of Carbon Nanotube Cross-Links for Load Transfer: A Graph Theory Strategy.

We report that the load transfer in carbon nanotube (CNT) networks is determined by the cross-link density via three critical thresholds, namely, percolation, connection, and saturation, which divide the transfer into four different modes. Reminiscent of the connectivity problem in the graph theory, an individual path for the successive load transfer through the network is formed at the first threshold, then all CNTs are connected together by cross-links at the second one, and finally, the connections are gradually converted into tetrahedrons toward a rigidized connectivity until the third saturation threshold. The power-law distribution of the number of cross-links per CNT shows a preferential linking mechanism, i.e., that the CNTs with high cross-links are more attractive to form new cross-links than the CNTs with low cross-links, while repetitive cross-links could hardly improve the strength of CNT networks.

Bubble-based microrobots enable digital assembly of heterogeneous microtissue modules.

The specific spatial distribution of tissue generates a heterogeneous micromechanical environment that provides ideal conditions for diverse functions such as regeneration and angiogenesis. However, to manufacture microscale multicellular heterogeneous tissue modulesin vitroand then assemble them into specific functional units is still a challenging task. In this study, a novel method for the digital assembly of heterogeneous microtissue modules is proposed. This technique utilizes the flexibility of digital micromirror device-based optical projection lithography and the manipulability of bubble-based microrobots in a liquid environment. The results indicate that multicellular microstructures can be fabricated by increasing the inlets of the microfluidic chip. Upon altering the exposure time, the Young's modulus of the entire module and different regions of each module can be fine-tuned to mimic normal tissue. The surface morphology, mechanical properties, and internal structure of the constructed bionic peritoneum were similar to those of the real peritoneum. Overall, this work demonstrates the potential of this system to produce and control the posture of modules and simulate peritoneal metastasis using reconfigurable manipulation.

Early detection of gastric cancer via high-resolution terahertz imaging system.

Terahertz (THz) wave has demonstrated a good prospect in recent years, but the resolution is still one of the problems that restrict the application of THz technology in medical imaging. Paraffin-embedded samples are mostly used in THz medical imaging studies, which are thicker and significantly different from the current gold standard slice pathological examination in sample preparation. In addition, THz absorption in different layers of normal and cancerous tissues also remains to be further explored. In this study, we constructed a high-resolution THz imaging system to scan non-tumorous adjacent tissue slices and gastric cancer (GC) tissue slices. In this system, a THz quantum cascade laser emitted a pulsed 3 THz signal and the transmitted THz wave was received by a THz detector implemented in a 65 nm CMOS process. The slice thickness was only 20 µm, which was close to that of the medical pathology examination. We successfully found THz transmittance differences between different layers of normal gastric tissues based on THz images, and the resolution could reach 60 µm for the first time. The results indicated that submucosa had a lower THz transmittance than that of mucosa and muscular layer in non-tumorous adjacent tissue. However, in GC tissue, THz transmittance of mucosa and submucosa was similar, caused by the decreased transmittance of mucosa, where the cancer occurs. Therefore, we suppose that the similar terahertz transmittance between gastric mucosa and submucosa may indicate the appearance of cancerization. The images obtained from our THz imaging system were clearer than those observed with naked eyes, and can be directly compared with microscopic images. This is the first application of THz imaging technology to identify non-tumorous adjacent tissue and GC tissue based on the difference in THz wave absorption between different layers in the tissue. Our present work not only demonstrated the potential of THz imaging to promote early diagnosis of GC, but also suggested a new direction for the identification of normal and cancerous tissues by analyzing differences in THz transmittance between different layers of tissue.

Electricity-consumption data reveals the economic impact and industry recovery during the pandemic.

Coping with the outbreak of Coronavirus disease 2019 (COVID-19), many countries have implemented public-health measures and movement restrictions to prevent the spread of the virus. However, the strict mobility control also brought about production stagnation and market disruption, resulting in a severe worldwide economic crisis. Quantifying the economic stagnation and predicting post-pandemic recovery are imperative issues. Besides, it is significant to examine how the impact of COVID-19 on economic activities varied with industries. As a reflection of enterprises' production output, high-frequency electricity-consumption data is an intuitive and effective tool for evaluating the economic impact of COVID-19 on different industries. In this paper, we quantify and compare economic impacts on the electricity consumption of different industries in eastern China. In order to address this problem, we conduct causal analysis using a difference-in-difference (DID) estimation model to analyze the effects of multi-phase public-health measures. Our model employs the electricity-consumption data ranging from 2019 to 2020 of 96 counties in the Eastern China region, which covers three main economic sectors and their 53 sub-sectors. The results indicate that electricity demand of all industries (other than information transfer industry) rebounded after the initial shock, and is back to pre-pandemic trends after easing the control measures at the end of May 2020. Emergency response, the combination of all countermeasures to COVID-19 in a certain period, affected all industries, and the higher level of emergency response with stricter movement control resulted in a greater decrease in electricity consumption and production. The pandemic outbreak has a negative-lag effect on industries, and there is greater resilience in industries that are less dependent on human mobility for economic production and activities.