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Abstract Ceramic aerogels are promising materials for thermal insulation and protection under harsh environments. Yet current synthesis methods fail to provide an energy-, time-, and cost-effective route for high-throughput production and large-scale applications, especially for non-oxide ceramic aerogels. Here we reported a way to synthesize SiC aerogels within seconds and over liter scale, with a demonstrated throughput of ~16 L min−1 in a typical lab experiment. The key lies in renovated combustion synthesis and a fast expansion from powder reactants to aerogel products over 1000% in volume. The synthesis process is self-sustainable and requires minimal energy input. The product is very cheap, with an estimated price of ~$0.7 L−1 (~$7 kg−1). The obtained SiC aerogels have excellent thermo-mechanical properties, including low thermal conductivity, high elasticity, and damage tolerance. Our invention not only offers a practical pathway for large-scale applications of ceramic aerogels, but also calls for rethinking of combustion synthesis in one-step conversion from raw chemicals to bulk products ready for practical applications.

Abstract Background Gemmatimonadota bacteria are widely distributed in nature, but their metabolic potential and ecological roles in marine environments are poorly understood. Results Here, we obtained 495 metagenome-assembled genomes (MAGs), and associated viruses, from coastal to deep-sea sediments around the world. We used this expanded genomic catalog to compare the protein composition and update the phylogeny of these bacteria. The marine Gemmatimonadota are phylogenetically different from those previously reported from terrestrial environments. Functional analyses of these genomes revealed these marine genotypes are capable of degradation of complex organic carbon, denitrification, sulfate reduction, and oxidizing sulfide and sulfite. Interestingly, there is widespread genetic potential for secondary metabolite biosynthesis across Gemmatimonadota, which may represent an unexplored source of novel natural products. Furthermore, viruses associated with Gemmatimonadota have the potential to “hijack” and manipulate host metabolism, including the assembly of the lipopolysaccharide in their hosts. Conclusions This expanded genomic diversity advances our understanding of these globally distributed bacteria across a variety of ecosystems and reveals genetic distinctions between those in terrestrial and marine communities. Video Abstract

Abstract The ankyrin (ANK) SOCS box (ASB) family, encompassing ASB1–18, is the largest group of substrate receptors of cullin 5 Ring E3 ubiquitin ligase. Nonetheless, the mechanism of substrate recognition by ASB family proteins has remained largely elusive. Here we present the crystal structure of ASB7-Elongin B-Elongin C ternary complex bound to a conserved helical degron. ASB7 employs its ANK3-6 to form an extended groove, effectively interacting with the internal α-helix-degron through a network of side-chain-mediated electrostatic and hydrophobic interactions. Our structural findings, combined with biochemical and cellular analyses, identify the key residues of the degron motif and ASB7 required for their recognition. This will facilitate the identification of additional physiological substrates of ASB7 by providing a defined degron motif for screening. Furthermore, the structural insights provide a basis for the rational design of compounds that can specifically target ASB7 by disrupting its interaction with its cognate degron.

N6 adenosine methylation (m6A), one of the most prevalent internal modifications on mammalian RNAs, regulates RNA transcription, stabilization, and splicing. Growing evidence has focused on the functional role of m6A regulators on acute myeloid leukemia (AML). However, the global m6A levels after azacytidine (AZA) plus venetoclax (VEN) treatment in AML patients remain unclear. In our present study, bone marrow (BM) sample pairs (including pre-treatment [AML] and post-treatment [complete remission (CR)] samples) were harvested from three AML patients who had achieved CR after AZA plus VEN treatment for Nanopore direct RNA sequencing. Notably, the amount of m6A sites and the m6A levels in CR BMs was significantly lower than those in the AML BMs. Such a significant reduction in the m6A levels was also detected in AZA-treated HL-60 cells. Thirteen genes with decreased m6A and expression levels were identified, among which three genes (HPRT1, SNRPC, and ANP32B) were closely related to the prognosis of AML. Finally, we speculated the mechanism via which m6A modifications affected the mRNA stability of these three genes. In conclusion, we illustrated for the first time the global landscape of m6A levels in AZA plus VEN treated AML (CR) patients and revealed that AZA had a significant demethylation effect at the RNA level in AML patients. In addition, we identified new biomarkers for AZA plus VEN-treated AML via Nanopore sequencing technology in RNA epigenetics.

Scholars have primarily focused on statistical analysis of exploration practices and simple physical simulation experiments when investigating the relationship between stratigraphic dip and hydrocarbon resources during the hydrocarbon accumulation period. However, there is a notable lack of research on the theoretical relationship between stratigraphic dip and hydrocarbon resources during this critical period. This study addresses this gap by exploring the principle of minimum energy dissipation rate governing oil and gas migration. Through this principle, the existence of a stratigraphic dip window for hydrocarbon migration and accumulation system is strictly proved during the hydrocarbon accumulation period. It is established that when the stratigraphic dip window coincides with the hydrocarbon accumulation period, the effective driving power for hydrocarbon migration is at its weakest, resulting in the lowest energy dissipation rate within the hydrocarbon system. Consequently, the hydrocarbon migration and accumulation yields the highest efficiency, leading to the greatest reserves of hydrocarbon resources. This study resolves the puzzle of why the amount of hydrocarbon resources in 44 natural gas-effective zones and 49 oil-effective zones, that have been put into commercial development in China, as reported by Hou et al. (2021), exhibit the statistical characteristic of “downward parabola of opening” in their average stratigraphic dip during the main hydrocarbon accumulation period. Furthermore, it explains the influence of the stratigraphic dip size during the hydrocarbon accumulation period on oil-gas reservoir formation. Moreover, the theory is used to investigate the evolutionary changes in the stratigraphic dip window of tight gas reservoirs in the Upper Paleozoic strata of the Ordos Basin. The study traces the transition of Upper Paleozoic high-pressure tight paleo-gas reservoirs, where the sum of net buoyancy gradient, excess pressure gradient, and discharge pressure gradient serve as the effective driving force of hydrocarbon migration, to modern low-pressure tight gas reservoirs, where the sum of net buoyancy gradient and discharge pressure gradient prevail. Correspondingly, during the hydrocarbon accumulation period, the stratigraphic dip window of the high-pressure tight paleo-gas reservoirs is relatively small (0.2°–0.3°), gradually evolving into the comparatively larger stratigraphic dip window (0.35°–0.45°) characteristic of the current low-pressure tight gas reservoirs.

To solve the problems in restoring sedimentary facies and predicting reservoirs in loose gas-bearing sediment, based on seismic sedimentologic analysis of the first 9-component S-wave 3D seismic dataset of China, a fourth-order isochronous stratigraphic framework was set up and then sedimentary facies and reservoirs in the Pleistocene Qigequan Formation in Taidong area of Qaidam Basin were studied by seismic geomorphology and seismic lithology. The study method and thought are as following. Firstly, techniques of phase rotation, frequency decomposition and fusion, and stratal slicing were applied to the 9-component S-wave seismic data to restore sedimentary facies of major marker beds based on sedimentary models reflected by satellite images. Then, techniques of seismic attribute extraction, principal component analysis, and random fitting were applied to calculate the reservoir thickness and physical parameters of a key sandbody, and the results are satisfactory and confirmed by blind testing wells. Study results reveal that the dominant sedimentary facies in the Qigequan Formation within the study area are delta front and shallow lake. The RGB fused slices indicate that there are two cycles with three sets of underwater distributary channel systems in one period. Among them, sandstones in the distributary channels of middle-low Qigequan Formation are thick and broad with superior physical properties, which are favorable reservoirs. The reservoir permeability is also affected by diagenesis. Distributary channel sandstone reservoirs extend further to the west of Sebei-1 gas field, which provides a basis to expand exploration to the western peripheral area.

Abstract Shale reservoirs have complex mineral compositions and are rich in micro-scale pores. It is of great scientific and engineering significance to explore the mechanism of external fluids on the pore throat structure of shale. In this paper, pure carbonaceous shale is taken as the research object, and the mechanism of the influence of slip water and reflux fluid on the pore throat structure is analyzed by using nuclear magnetic resonance (NMR) technology. Then, the sensitivity of different types of shale to external fluids is comparatively analyzed and summarized. The results show that (1) the oil slick has a certain effect on the total porosity of different types of shale. The rate of change is shown as carbonaceous shale (− 7.1%) > pure shale (− 1.6%). (b) For slickwater, the average reduction of macro- and micro/nanopores in carbonaceous shale is 90.0% and 5.0%, respectively, while the average reduction of macro- and mesopores in pure shale is 17.7% and 6.8%, respectively. (c) Total porosity of different shale types is insensitive to refluxing fluids. The average increase in macro-, meso-, and small pores of carbonaceous shale is 31.8%, 23.6%, and 20.2%, respectively; the average increase in macro- and small pores of pure shale is 17.1%.

Abstract Post-traumatic epilepsy (PTE) stands as one of the numerous debilitating consequences that follow traumatic brain injury (TBI). Despite its impact on many individuals, the current landscape offers only a limited array of reliable treatment options, and our understanding of the underlying mechanisms and susceptibility factors remains incomplete. Among the potential contributors to epileptogenesis, astrocytes, a type of glial cell, have garnered substantial attention as they are believed to promote hyperexcitability and the development of seizures in the brain following TBI. The current study evaluated the transcriptomic changes in cortical astrocytes derived from animals that developed seizures as a result of severe focal TBI. Using RNA-Seq and ingenuity pathway analysis (IPA), we unveil a distinct gene expression profile in astrocytes, including alterations in genes supporting inflammation, early response modifiers, and neuropeptide-amidating enzymes. The findings underscore the complex molecular dynamics in astrocytes during PTE development, offering insights into therapeutic targets and avenues for further exploration.

Lithospheric structure beneath the northeastern Qinghai-Xizang Plateau is of vital significance for studying the geodynamic processes of crustal thickening and expansion of the Qinghai-Xizang Plateau. We conducted a joint inversion of receiver functions and surface wave dispersions with P-wave velocity constraints using data from the ChinArray II temporary stations deployed across the Qinghai-Xizang Plateau. Prior to joint inversion, we applied the H-κ-c method (Li JT et al., 2019) to the receiver function data in order to correct for the back-azimuthal variations in the arrival times of Ps phases and crustal multiples caused by crustal anisotropy and dipping interfaces. High-resolution images of vS, crustal thickness, and vP/vS structures in the Qinghai-Xizang Plateau were simultaneously derived from the joint inversion. The seismic images reveal that crustal thickness decreases outward from the Qinghai-Xizang Plateau. The stable interiors of the Ordos and Alxa blocks exhibited higher velocities and lower crustal vP/vS ratios. While, lower velocities and higher vP/vS ratios were observed beneath the Qilian Orogen and Songpan-Ganzi terrane (SPGZ), which are geologically active and mechanically weak, especially in the mid-lower crust. Delamination or thermal erosion of the lithosphere triggered by hot asthenospheric flow contributes to the observed uppermost mantle low-velocity zones (LVZs) in the SPGZ. The crustal thickness, vS, and vP/vS ratios suggest that whole lithospheric shortening is a plausible mechanism for crustal thickening in the Qinghai-Xizang Plateau, supporting the idea of coupled lithospheric-scale deformation in this region.

Patient-derived organoids (PDOs) have been proposed as a novel in vitro tumor model that can be applied to tumor research and drug screening. However, current tumor organoid models lack components of the tumor microenvironment, particularly tumor-associated macrophages(TAMs).We collected peripheral blood and tumor samples from 6 patients with extrahepatic cholangiocarcinoma(eCCA). Monocytes were induced into TAMs by cytokine and conditioned medium, and then co-cultured with tumor organoids. Our comprehensive analysis and comparison of histopathology and genomics results confirmed that this co-culture model can better capture intra- and inter-tumor heterogeneity retain the specific mutations of the original tumor. Drug sensitivity data in vitro revealed that gemcitabine and cisplatin are effective drugs for cholangiocarcinoma, but TAMs in the tumor microenvironment promote organoids growth and chemotherapy resistance. In conclusion, our organoid model of cholangiocarcinoma co-cultured with TAMs can not only shorten the model construction cycle, but also preserve the heterogeneity of original tumors to improve the accuracy of drug screening, and can also be applied to the researches of TAMs and tumors.

As a special type of seep carbonate, the many details concerning the formation mode and mechanism of tubular seep carbonates are rarely reported. Here, new geochemical and mineralogical data regarding tubular seep carbonate (SQW-65) are reported. Sample SQW-65 had anomalously negative δ13C values and positive δ18O values, which suggested the dissociation of gas hydrate. Additionally, almost all the sub-samples showed no Ce anomaly (Ce/Ce*average = 0.93), with obvious U enrichment (21.3< UEF

ABSTRACT The microbial communities of marine seep sediments contain unexplored physiological and phylogenetic diversity. Here, we examined 30 bacterial metagenome-assembled genomes (MAGs) from cold seeps in the South China Sea, the Indian Ocean, the Scotian Basin, and the Gulf of Mexico, as well as from deep-sea hydrothermal sediments in the Guaymas Basin, Gulf of California. Phylogenetic analyses of these MAGs indicate that they form a distinct phylum-level bacterial lineage, which we propose as a new phylum, Candidatus Effluviviacota, in reference to its preferential occurrence at diverse seep areas. Based on tightly clustered high-quality MAGs, we propose two new genus-level candidatus taxa, Candidatus Effluvivivax and Candidatus Effluvibates. Genomic content analyses indicate that Candidatus Effluviviacota are chemoheterotrophs that harbor the Embden–Meyerhof–Parnas glycolysis pathway. They gain energy by fermenting organic substrates. Additionally, they display potential capabilities for the degradation of cellulose, hemicellulose, starch, xylan, and various peptides. Extracellular anaerobic respiration appears to rely on metals as electron acceptors, with electron transfer primarily mediated by multiheme cytochromes and by a flavin-based extracellular electron transfer (EET) mechanism that involves NADH-quinone oxidoreductase-demethylmenaquinone-synthesizing enzymes, uncharacterized membrane proteins, and flavin-binding proteins, also known as the NUO-DMK-EET-FMN complex. The heterogeneity within the Ca. Effluviviacota phylum suggests varying roles in energy metabolism among different genera. While NUO-DMK-EET-FMN electron transfer has been reported predominantly in Gram-positive bacteria, it is now identified in Ca. Effluviviacota as well. We detected the presence of genes associated with bacterial microcompartments in Ca. Effluviviacota, which can promote specific metabolic processes and protect the cytosol from toxic intermediates.IMPORTANCEThe newly discovered bacterial phylum Candidatus Effluviviacota is widespread across diverse seepage ecosystems, marine environments, and freshwater environments, with a notable preference for cold seeps. While maintaining an average abundance of approximately 1% in the global gene catalog of cold seep habitats, it has not hitherto been characterized. The metabolic versatility of Ca. Effluviviacota in anaerobic carbon, hydrogen, and metal cycling aligns with its prevalence in anoxic niches, with a preference for cold seep environments. Variations in metabolic potential between Ca. Effluvivivax and Ca. Effluvibates may contribute to shaping their respective habitat distributions.

Abstract Aim Pathologists are currently supposed to be aware of both domestic and international guidelines for breast cancer diagnosis, but it is unclear how successfully these guidelines have been integrated into routine clinical practice in China. Thus, this national proficiency testing (PT) scheme for breast pathology was set up to conduct a baseline assessment of the diagnostic capability of pathologists in China. Methods This national PT plan is designed and implemented according to the “Conformity assessment—General requirements for proficiency testing” (GB/T27043—2012/ISO/IEC 17043:2010). Five cases of breast cancer with six key items, including histologic type, grade, ER, PR, HER2, and Ki67, were selected for testing among 96 participants. The final PT results were published on the website of the National Quality Control Center for Cancer ( http://117.133.40.88:3927/cn/col22/362 ). Results Our study demonstrated that the median PT score was 89.5 (54–100). Two institutions with scores 86%). However, the histologic grade showed low accuracy (74.0%). The unacceptable results mainly included incorrect evaluation of histologic grade (36.7%), inaccurate evaluation of ER/PR/HER2/Ki67 (28.2%), incorrect identification of C-AD as IBC-NST (15.7%), inappropriate use of 1+/2+/3+ rather than staining percentage for ER/PR (6.1%), misclassification of ER/PR

Abstract Background Breast cancer is the most common malignant tumor in the world. Intraoperative frozen section of sentinel lymph nodes is an important basis for determining whether axillary lymph node dissection is required for breast cancer surgery. We propose an RRCART model based on a deep-learning network to identify metastases in 2362 frozen sections and count the wrongly identified sections and the associated reasons. The purpose is to summarize the factors that affect the accuracy of the artificial intelligence model and propose corresponding solutions. Methods We took the pathological diagnosis of senior pathologists as the gold standard and identified errors. The pathologists and artificial intelligence engineers jointly read the images and heatmaps to determine the locations of the identified errors on sections, and the pathologists found the reasons (false reasons) for the errors. Through NVivo 12 Plus, qualitative analysis of word frequency analysis and nodal analysis was performed on the error reasons, and the top-down error reason framework of “artificial intelligence RRCART model to identify frozen sections of breast cancer lymph nodes” was constructed based on the importance of false reasons. Results There were 101 incorrectly identified sections in 2362 slides, including 42 false negatives and 59 false positives. Through NVivo 12 Plus software, the error causes were node-coded, and finally, 2 parent nodes (high-frequency error, low-frequency error) and 5 child nodes (section quality, normal lymph node structure, secondary reaction of lymph nodes, micrometastasis, and special growth pattern of tumor) were obtained; among them, the error of highest frequency was that caused by normal lymph node structure, with a total of 45 cases (44.55%), followed by micrometastasis, which occurred in 30 cases (29.70%). Conclusions The causes of identification errors in examination of sentinel lymph node frozen sections by artificial intelligence are, in descending order of influence, normal lymph node structure, micrometastases, section quality, special tumor growth patterns and secondary lymph node reactions. In this study, by constructing an artificial intelligence model to identify the error causes of frozen sections of lymph nodes in breast cancer and by analyzing the model in detail, we found that poor quality of slices was the preproblem of many identification errors, which can lead to other errors, such as unclear recognition of lymph node structure by computer. Therefore, we believe that the process of artificial intelligence pathological diagnosis should be optimized, and the quality control of the pathological sections included in the artificial intelligence reading should be carried out first to exclude the influence of poor section quality on the computer model. For cases of micrometastasis, we suggest that by differentiating slices into high- and low-confidence groups, low-confidence micrometastatic slices can be separated for manual identification. The normal lymph node structure can be improved by adding samples and training the model in a targeted manner.

The detection rate of ground glass nodules (GGNs) has increased in recent years because of their malignant potential but relatively indolent biological behavior; thus, correct GGN recognition and management has become a research focus. Many scholars have explored the underlying mechanism of the indolent progression of GGNs from several perspectives, such as pathological type, genomic mutational characteristics, and immune microenvironment. GGNs have different major mutated genes at different stages of development; EGFR mutation is the most common mutation in GGNs, and p53 mutation is the most abundant mutation in the invasive stage of GGNs. Pure GGNs have fewer genomic alterations and a simpler genomic profile and exhibit a gradually evolving genomic mutation profile as the pathology progresses. Compared to advanced lung adenocarcinoma, GGN lung adenocarcinoma has a higher immune cell percentage, is under immune surveillance, and has less immune escape. However, as the pathological progression and solid component increase, negative immune regulation and immune escape increase gradually, and a suppressive immune environment is established gradually. Currently, regular computer tomography monitoring and surgery are the main treatment strategies for persistent GGNs. Stereotactic body radiotherapy and radiofrequency ablation are two local therapeutic alternatives, and systemic therapy has been progressively studied for lung cancer with GGNs. In the present review, we discuss the characterization of the multidimensional molecular evolution of GGNs that could facilitate more precise differentiation of such highly heterogeneous lesions, laying a foundation for the development of more effective individualized treatment plans.

Background: We developed a novel minimally invasive transapical beating-heart septal myectomy (TA-BSM) procedure for patients with midventricular obstruction (MVO), without the aid of cardiopulmonary bypass. This study aims to describe the TA-BSM procedure for the relief of MVO and to detail the clinical outcomes in these patients. Methods: Sixty-one patients receiving TA-BSM for MVO were included: isolated MVO (n = 12) and combined MVO and subaortic obstruction (n = 49). We reviewed the electronic medical record to collect information on preoperative, intraoperative, and postoperative parameters. Results: The intraventricular pressure gradient after the resection was largely attenuated. On the catheter measurement, the median resting and provoked gradient decreased by 29.0 and 71.0 mm Hg, respectively. Likewise, the resting intraventricular gradient was successfully reduced from 58.0 to 11.0 mm Hg, and the maximal intraventricular gradient was reduced from 88.0 to 20.0 mm Hg at 6 months follow-up. In addition, all patients showed significantly improved MR and 37 of 42 patients with preoperative MR grade ≥2+ showed MR grade ≤1+ after TA-BSM. During the follow-up, no death was observed and no one had HCM-related rehospitalization. All patients reported improvement in symptoms and the mean New York Heart Association class improved from 3.0 (IQR, 3.0–3.0) preoperatively to 1.0 (IQR, 1.0–1.0) at 6 months follow-up. Conclusions: The TA-BSM procedure is a valuable therapy to relieve MVO, improving hemodynamics and providing satisfactory clinical outcomes. The procedure can also preserve favorable outcomes for patients with MVO and concomitant subaortic obstruction.

Background Lipoprotein(a) (Lp(a)) is considered to be a causal risk factor of atherosclerotic cardiovascular disease (ASCVD), but whether there is an independent or joint association of Lp(a) and atherosclerotic plaque with ASCVD risk remains uncertain. This study aims to assess ASCVD risk independently or jointly conferred by Lp(a) and carotid atherosclerotic plaque. Methods and Results A total of 5471 participants with no history of cardiovascular disease at baseline were recruited and followed up for ASCVD events (all fatal and nonfatal acute coronary and ischemic stroke events) over a median of 11.5 years. Independent association of Lp(a), or the joint association of Lp(a) and carotid plaque with ASCVD risk, was explored using Cox proportional hazards models. Overall, 7.6% of the participants (60.0±7.9 years of age; 2649 [48.4%] men) had Lp(a) ≥50 mg/dL, and 539 (8.4/1000 person‐years) incident ASCVD events occurred. Lp(a) concentrations were independently associated with long‐term risk of total ASCVD events, as well as coronary events and ischemic stroke events. Participants with Lp(a) ≥50 mg/dL had a 62% higher risk of ASCVD incidence (95% CI, 1.19–2.21) than those with Lp(a)

Abstract Background Leakages of cold, methane-rich fluids from subsurface reservoirs to the sea floor are termed cold seeps. Recent exploration of the deep sea has shed new light on the microbial communities in cold seeps. However, conventional metagenomic methods largely rely on reference databases and neglect the phylogeny of functional genes. Results In this study, we developed the REMIRGE program to retrieve the full-length functional genes from shotgun metagenomic reads and fully explored the phylogenetic diversity in cold seep sediments. The abundance and diversity of functional genes involved in the methane, sulfur, and nitrogen cycles differed in the non-seep site and five cold seep sites. In one Haima cold seep site, the divergence of functional groups was observed at the centimeter scale of sediment depths, with the surface layer potentially acting as a reservoir of microbial species and functions. Additionally, positive correlations were found between specific gene sequence clusters of relevant genes, indicating coupling occurred within specific functional groups. Conclusion REMIRGE revealed divergent phylogenetic diversity of functional groups and functional pathway preferences in a deep-sea cold seep at finer scales, which could not be detected by conventional methods. Our work highlights that phylogenetic information is conducive to more comprehensive functional profiles, and REMIRGE has the potential to uncover more new insights from shotgun metagenomic data. Video Abstract

Abstract Modern Fe‐Si oxyhydroxide deposits occur in global marine hydrothermal vent sites. Despite their role as biogenic substrates and potential ore resources, much remains unknown about their formation processes. Here, we apply analyses of major and trace elements as well as Sr‐Nd‐Pb‐Fe isotopes combined with 238U‐230Th dating to Fe‐Si oxyhydroxides obtained from several hydrothermal fields along the Southwest Indian Ridge. These mineralized oxyhydroxides primarily consist of poorly crystalline two‐line ferrihydrite and amorphous opal‐A, with lesser amounts of nontronite and birnessite. The ubiquitous and characteristic Fe‐rich ultrastructures in the oxyhydroxides directly indicate microbial activity. The 238U‐230Th dating constrains their crystallization ages from ca. 11,873 to 384 years old. The seawater‐like 87Sr/86Sr and varying 143Nd/144Nd ratios underline a high proportion of seawater mixed with hydrothermal fluids. The radiogenic Pb isotopic patterns suggest a primary derivation of Pb leached from substrate basalts and to a lesser extent Pb from seawater. Stable iron isotopic compositions for different oxyhydroxides display a remarkable range between −1.47 and 0.82‰, which were interpreted as reflecting the fractionation processes during the formation of the deposits under evolving depositional redox conditions. The partial oxidation of Fe(II) and the subsurface removal of isotopically heavy Fe oxyhydroxides are suggested to play a vital role in shifting the Fe isotopic signature toward more negative values. Given that these Fe‐Si oxyhydroxide deposits exhibit features similar to certain ancient iron formations (IFs), Fe isotope systematics of these deposits may hold significant potential for fingerprinting the biological Fe oxidation processes that drove IF deposition on early Earth.

Abstract Geriatric assessment can aid in optimizing treatment strategies and supportive interventions for older patients with diffuse large B‐cell lymphoma (DLBCL). Fondazione Italiana Linformi has recently introduced novel geriatric assessment tools, simplified Geriatric Assessment (sGA) and Elderly Prognostic Index (EPI), aimed at tailoring the treatment and predicting the outcomes for older patients with DLBCL. The objectives of this study are the validation and possible modification of the sGA and EPI in China. In the study, both sGA and EPI demonstrated the predictive capabilities for overall survival (OS) and early mortality (both p

Abstract Maternal nutrition and the uterine environment can influence placental development in mammals, leading to the birth of abnormal infants who often experience difficulties in independent standing. This article documents an adolescent female African elephant (Loxodonta africana) giving birth to an African elephant calf with a shoulder height below the mean, and its inability to stand for the first 10 h after birth, a time span that significantly exceeds the average duration for independent standing. Through the implementation of assisted feeding and assisted standing measures, the calf eventually achieved independent standing and nursing from its mother after 27 h and subsequent catch‐up growth at 5 months of age. This study presents the first case report on the growth parameters during pregnancy of an adolescent African elephant, the birth and care (feeding, assisted standing) of a small African elephant calf with the inability to stand alone and nurse independently for several hours, highlighting pregnancy may influence the growth of cows during their ongoing growth and development phase, the calf's survival and subsequent catch‐up growth at 5 months of age. These findings offer valuable insights into the care of abnormal African elephant calves.

Quantitatively assessing the porewater dissolved inorganic carbon (DIC) cycling in methane-enriched marine sediments is crucial to understanding the contributions of different carbon sources to the global marine carbon pool. In this study, Makran accretionary wedge was divided into Zone 1 (high methane flux area) and Zone 2 (background area). Porewater geochemical compositions (Cl–, SO42–, NH4+, Mg2+, Ca2+, Ba2+, DIC and δ13C-DIC) and a reaction-transport model were used to determine the DIC source and calculate the DIC flux through carbonate precipitation and releasing into overlying seawater in sediments. Zone 1 is characterized by the shallower depth of sulfate-methane transition (SMT), where most of porewater sulfate was consumed by anaerobic oxidation of methane (AOM). In contrast, a relatively low flux of methane diffusion in Zone 2 results in a deeper SMT depth and shallow sulfate is predominantly consumed by organoclastic sulfate reduction (OSR). Based on the porewater geochemical profiles and δ13C mass balance, the proportions of porewater DIC originating from methane were calculated as 51% in Zone 1 and nearly 0% in Zone 2. An increase of porewater DIC concentration leads to authigenic carbonate precipitation. Solid total inorganic carbon (TIC), X-ray diffractometry (XRD) and scanning electron microscopy (SEM) analysis display that carbonate content increases with depth and aragonite appears at or below the depths of SMT. Meanwhile, the flux of DIC released from sediments calculated by the reaction-transport model is 51.3 ~ 90.4 mmol/m2·yr in Zone 1, which is significantly higher than that in Zone 2 (22.4 mmol/m2·yr). This study demonstrates that AOM serves as the dominant biogeochemical process regulating the porewater DIC cycle, which has an important impact on the authigenic carbonate burial and the seawater carbonate chemistry.

Pollutants produced by engines are a significant source of environmental pollution, so the study of engine emissions is very important. In this study, with CONVERGE software, a diesel engine model of the engine was produced. To better obtain the characteristic results of the engine, this was coupled with an improved chemical kinetics mechanism. Then, the results of this model were verified experimentally. Additionally, the effects of four different EGR rates on the combustion, performance, and emissions of a dual-fuel diesel engine were investigated by the verified model under different (50 %, 75 %, and 100 %) load conditions. Lastly, the brake specific fuel consumption, NOx emission, and HC emission were optimized by the response surface methodology (RSM). The results show that the pressure, temperature, and NOx emission in the engine's cylinder can all be reduced by raising the EGR at three different loads. Besides, the optimization results show that the engine achieves the best operating conditions at 100 % load, hydrogen fraction of 6.92 %, and EGR rate of 7.68 %.

Summary: Background: The most recent updated hypertension guidelines recommend individuals with systolic blood pressure (SBP)/diastolic blood pressure (DBP) of 130–139/80–89 mmHg and high cardiovascular risk should receive antihypertensive drug treatment. This study aimed to assess the benefits and cost-effectiveness of medication for people aged ≥35 years with this blood pressure stratum and high cardiovascular risk in China. Methods: The benefits of drug treatment in adults aged ≥35 years with SBP/DBP of 130–139/80–89 mmHg and high cardiovascular risk were evaluated in decision-analytic simulation models. Decreasing numbers of cardiovascular disease (CVD) events and premature deaths from all causes and increasing quality-adjusted life-years (QALYs) from drug treatment were estimated in 10-year and lifetime horizons. The incremental cost-effectiveness ratios (ICER) for drug treatment were calculated. Findings: Among approximately 106.60 million Chinese adults aged ≥35 years with this blood pressure stratum and high cardiovascular risk, drug treatment was estimated to prevent 2,060,000 strokes and 660,000 myocardial infarctions over a 10-year time horizon. Adults prescribed antihypertensive drugs could gain 0.034 incremental QALYs. Over a lifetime horizon, adults who start treatment earlier could benefit more in preventing CVD and gaining incremental QALYs. The medication treatment is cost-effective either over a 10-year time horizon with an ICER of Int$13321.29 per QALY gained or over the remaining lifetime. Interpretation: Antihypertensive treatment of adults with SBP/DBP of 130–139/80–89 mmHg and high cardiovascular risk would gain substantial benefits with cost-effectiveness. The young and middle-aged population would derive the most benefit. Funding: National Natural Science Foundation of China, and Beijing Natural Science Foundation.

Abstract Lactic acidosis is a feature of solid tumors and plays fundamental role(s) rendering cancer cells to adapt to diverse metabolic stresses, but the mechanism underlying its roles in redox homeostasis remains elusive. Here we show that G6PD is phosphorylated at tyrosine 249/322 by the SRC through the formation of a GSTP1-G6PD-SRC complex. Lactic acid attenuates this formation and the phosphorylation of G6PD by non-covalently binding with GSTP1. Furthermore, lactic acid increases the activity of G6PD and facilitates the PPP (NADPH production) through its sensor GSTP1, thereby exhibiting resistance to reactive oxygen species when glucose is scarce. Abrogating a GSTP1-mediated lactic acid signaling showed attenuated tumor growth and reduced resistance to ROS in breast cancer cells. Importantly, positive correlations between immuno-enriched SRC protein and G6PD Y249/322 phosphorylation specifically manifest in ER/PR positive or HER negative types of breast cancer. Taken together, these results suggest that GSTP1 plays a key role in tumor development by functioning as a novel lactate sensor.

Physical fatigue (peripheral fatigue), which affects a considerable portion of the world population, is a decline in the ability of muscle fibers to contract effectively due to alterations in the regulatory processes of muscle action potentials. However, it lacks an efficacious therapeutic intervention. The present study explored bioactive compounds and the mechanism of action of Citrus reticulata peel (CR-P) in treating physical fatigue by utilizing network pharmacology (NP), molecular docking, and simulation-based molecular dynamics (MD). The bioactive ingredients of CR-P and prospective targets of CR-P and physical fatigue were obtained from various databases. A PPI network was generated by the STRING database, while the key overlapping targets were analyzed for enrichment by adopting KEGG and GO. The binding affinities of bioactive ingredients to the hub targets were determined by molecular docking. The results were further validated by MD simulation. Five bioactive compounds were screened, and 56 key overlapping targets were identified for CR-P and physical fatigue, whereas the hub targets with a greater degree in the PPI network were AKT1, TP53, STAT3, MTOR, KRAS, HRAS, JAK2, IL6, EGFR, and ESR1. The findings of the enrichment analysis indicated significant enrichment of the targets in three key signaling pathways, namely PI3K-AKT, MAPK, and JAK-STAT. The molecular docking and MD simulation results revealed that the bioactive compounds of CR-P exhibit a stronger affinity for interacting with the hub targets. The present work suggests that bioactive compounds of CR-P, specifically Hesperetin and Sitosterol, may ameliorate physical fatigue via the PI3K-AKT signaling pathway by targeting AKT1, KRAS, and MTOR proteins.

Edge computing provides higher computational power and lower transmission latency by offloading tasks to nearby edge nodes with available computational resources to meet the requirements of time-sensitive tasks and computationally complex tasks. Resource allocation schemes are essential to this process. To allocate resources effectively, it is necessary to attach metadata to a task to indicate what kind of resources are needed and how many computation resources are required. However, these metadata are sensitive and can be exposed to eavesdroppers, which can lead to privacy breaches. In addition, edge nodes are vulnerable to corruption because of their limited cybersecurity defenses. Attackers can easily obtain end-device privacy through unprotected metadata or corrupted edge nodes. To address this problem, we propose a metadata privacy resource allocation scheme that uses searchable encryption to protect metadata privacy and zero-knowledge proofs to resist semi-malicious edge nodes. We have formally proven that our proposed scheme satisfies the required security concepts and experimentally demonstrated the effectiveness of the scheme.

The Applications of silica aerogel are limited due to its brittleness and low strength. As a result, it is essential to strengthen and toughen it. Organic nanofibers are one of the preferred reinforcement materials. In this work, we designed and fabricated flexible and compressible nanostructure-assembled aramid nanofiber/silica composites aerogel (ANF/SiO2 aerogel) to improve the mechanical strength and flexibility of silica aerogel without compromising thermal insulation properties. The aramid nanofiber/silica composite aerogels were prepared by immersing the aramid nanofiber wet gel into the silica sol for a certain period of time followed by freeze drying without solvent replacement. The surface modifier 3-aminopropyltriethoxysilane (APTES) was used as a coupling agent to form chemical linkage between the ANF fiber and silica gel. It was observed that APTES can effectively drive the silica sol to infuse into ANF hydrogel, promoting the assembly of silica gel onto the fiber surface and a uniform distribution in the network of ANF. The compressive resilience, thermal stability, and thermal insulation properties of the composite aerogels were evaluated by inducing the silica aerogel into the ANF network to form a protective layer on the fiber and change the pore structure in the ANF network.

Abstract Aims Heart failure (HF) is one of the leading causes of the global burden of disability and mortality. However, the comprehensive epidemic status of HF in China is unclear. Notably, the gender‐specific survey for HF prevalence is lacking. The present study aimed to analyse the gender‐specific prevalence and temporal trend of HF in China and explore the attributable aetiology and risk factors. Methods and results The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 was used to evaluate the age‐standardized prevalence and years lived with disability of HF in China by gender. The temporal trend of HF and attributable risk factors were analysed by Joinpoint regression models from 1990 to 2019. The total age‐standardized prevalence rate of HF steadily decreased over the past two decades from 1079.4 to 1032.8 per 100 000 individuals. Since 2017, the prevalence trend of HF has significantly increased [annual percentage change (APC) of 2.72 for females and 0.61 for males, P

Abstract The crustal thickness and average Vp/Vs ratio are basic parameters to understand the current state and the tectonic processes in the Tibetan Plateau (TP). We gather receiver functions in the central‐southern TP and extract spatial variation of crustal thickness and Vp/Vs ratio using the H‐κ‐c method with careful quality control and stability analysis. Our results highlight the regions with high Vp/Vs ratios in the central‐southern Qiangtang block and two isolated patches around the Yarlung‐Zangbo suture, suggesting crustal partial melting. The disconnected high‐Vp/Vs patches imply a restrained pattern for present‐day crustal flow in the southern TP. Further correlation with mantle observations suggests that the high Vp/Vs region in the north can be attributed to mantle upwelling after lithospheric delamination, and the two isolated patches in the south may be related to the tearing of the Indian mantle lithosphere.

This study investigated the effect of removing proteins, lipids and starch on the structure, physicochemical properties and digestion properties of rice flour (with 30% moisture) treated with heat moisture treatment (HMT). According to the results, HMT caused the adhesion and agglomeration of the rice flour, promoted the binding between starch, protein and lipid molecular chains and led to the formation of complexes (especially starch-lipid complexes), which hindered the removal of non-starch components. Compared to the untreated rice flour, the HMT treated lipid-removal rice flour had small changes in their crystallinity, gelatinization temperature and viscosity property. After removing protein, the crystallinity, peak viscosity, final viscosity, breakdown and starch digestibility were sharply increased. In particular, the peak viscosity increased from 811 cP to 1746 cP and the enthalpy change increased from 5.33 J/g to 10.18 J/g. These findings are helpful in understanding the contribution of removing endogenous proteins and lipids to the physicochemical changes of HMT treated rice flour during its heating process and thus can be helpful in controlling the quality of rice flour through HMT.

Abstract Background Thymic clear cell carcinoma is a rare mediastinal neoplasm, with only 25 reported cases to date. We report a case of a 45-year-old man with thymic clear cell carcinoma. We think imaging and laboratory tests may be helpful for differential diagnosis. Case presentation A 45-year-old male was admitted to a local hospital for chest distress with cardiopalmus. CT showed a mediastinal mass. Laboratory examination results were all in the normal range. Histologically, the tumor cells had a clear cytoplasm, and immunohistochemically, the tumor cells were positive for epithelial markers. We performed abdominal and pelvic CT and further examined serum levels of thyroxine, parathyroid hormone and AFP postoperatively, which were normal. The patient received postoperative radiotherapy, and CT showed left adrenal metastasis at 20 months after surgery. Conclusion Thymic clear cell carcinoma is a rare malignant neoplasm. Adrenal metastasis can occur. Patients undergo thymectomy with chemotherapy or with radiotherapy have better outcoming. Metastasis, direct invasion of parathyroid carcinoma and other primary tumors in the mediastinum should be excluded. Immunohistochemical markers, imaging and laboratory examination can help to exclude metastasis.

Underwater target detection is an essential topic in the applications of underwater exploration. However, underwater target detection faces serious challenges, such as complex scattering, low visibility, and target clutter. Here a polarization-enhanced underwater multiple material target detection method is proposed to address these challenges. The similarity principle of locally backscattered polarization features is utilized to suppress the influence of backscattered light. Our target detection model combines polarization gradient and edge detection techniques to optimize the detection process, enabling superior target detection and feature extraction. Experimental results indicate that our method has significantly enhanced the detection performance in multiple (overlapping or nonoverlapping) material targets, especially in high turbid underwater scattering environments. This research provides a promising new approach for polarized target detection in underwater environments and opens up new possibilities for underwater multiple-material target detection.

The use of a Controller Area Network (CAN) bus in the automotive industry for connecting electronic control units (ECUs) poses security vulnerabilities due to the lack of built-in security features. Intrusion Detection Systems (IDSs) have emerged as a practical solution for safeguarding the CAN bus. However, developing an effective IDS for in-vehicle CAN buses encounters challenges in achieving high precision for detecting attacks and meeting real-time requirements with limited computational resources. To address these challenges, we propose a novel method for anomaly detection on CAN data using windowed Hamming distance. Our approach utilizes sliding windows and Hamming distance to extract features from time series data. By creating benchmark windows that span at least one cycle of data, we compare newly generated windows with recorded benchmarks using the Hamming distance to identify abnormal CAN messages. During the experimental phase, we conduct extensive testing on both the public car-hack dataset and a proprietary dataset. The experimental results indicate that our method achieves an impressive accuracy of up to 99.67% in detecting Denial of Service (DoS) attacks and an accuracy of 98.66% for fuzzing attacks. In terms of two types of spoofing attacks, our method achieves detection accuracies of 99.48% and 99.61%, respectively, significantly outperforming the methods relying solely on the Hamming distance. Furthermore, in terms of detection time, our method significantly reduces the time consumption by nearly 20-fold compared to the approach using deep convolutional neural networks (DCNN), decreasing it from 6.7 ms to 0.37 ms.

The widespread use of non-renewable phosphate fertilizers in agriculture poses a significant pollution threat to soil, necessitating the exploration of sustainable alternatives for phosphate fertility. Releasing phytate phosphorus through microbial phytases presents an eco-friendly solution for sustainable phosphate fertility in agriculture. This study directly inoculated dual-domain β-propeller alkaline phytase (phyHT) derived from Bacillus sp. HJB17 into the soil. The study analyzed the impact of inoculated phyHT on the physicochemical properties of the soil, assessed the variations in enzyme activity of phyHT within the soil, and examined the effects of the treated soil on wheat growth. Additionally, the study explored the enhancement of the available phosphorus in the soil through the inoculation of phyHT in both crop residues and organic fertilizer. PhyHT exhibited the highest catalytic activity at 37 °C and pH 8.0. After soil adsorption, phyHT maintained stable enzymatic activity. PhyHT markedly boosted the available phosphorus in the soil while reducing the soil phytate content by about 20%, increasing the phosphorus levels and enhancing soil fertility. PhyHT effectively degraded phytates in an organic fertilizer and crop residues, increasing the available phosphorus. PhyHT supplementation enhanced growth, biomass, and phosphorus content in both the shoot and root weights of Triticum aestivum. This study establishes phyHT as a viable and eco-friendly method to enhance phosphorus fertility in soil. The direct application of microbial phytases can serve as a sustainable source of phosphate fertility in soil.

Type 2 diabetic osteoporosis (T2DOP) is a common complication in diabetic patients that seriously affects their health and quality of life. The pathogenesis of T2DOP is complex, and there are no targeted governance means in modern medicine. Citri Reticulatae Pericarpium (CRP) is a traditional Chinese medicine that has a long history and has been used in the treatment of osteoporosis diseases. However, the molecular mechanism for the CRP treatment of T2DOP is not clear. Therefore, this study aimed to explore the underlying mechanisms of CRP for the treatment of T2DOP by using network pharmacology and molecular modeling techniques. By retrieving multiple databases, we obtained 5 bioactive compounds and 63 common targets of bioactive compounds with T2DOP, and identified AKT 1, TP 53, JUN, BCL 2, MAPK 1, NFKB 1, and ESR 1 as the core targets of their PPI network. Enrichment analysis revealed that these targets were mainly enriched in the estrogen signaling pathway, TNF signaling pathway, and AGE-RAGE signaling pathway in diabetics, which were mainly related to oxidative stress and hormonal regulation. Molecular docking and molecular dynamics simulations have shown the excellent binding effect of the bioactive compounds of CRP and the core targets. These findings reveal that CRP may ameliorate T2DOP through multiple multicomponent and multitarget pathways.

Abstract The Pinatubo eruption in 1991 injected 10–20 Tg SO2 into the stratosphere, which formed sulfate aerosols through oxidation. Our modeling results show that volcanic heating significantly perturbs the heterogeneous and homogeneous chemistry including NOx and HOx catalytic cycles in the tropical stratosphere. The simulated tropical chemical ozone tendency is positive at 20 mb while negative at 10 mb in the tropics. The simulated ozone chemical tendency is of the same magnitude as the dynamical ozone tendency caused by the accelerated tropical upwelling, but with the opposite sign. Our study finds that the tropical ozone chemical tendency due to homogeneous chemistry becomes more important than heterogeneous chemistry 3 months after eruption. Sensitivity simulations further suggest that the tropical ozone tendency through heterogeneous chemistry is saturated when the injected amount exceeds 2 Tg.

The oil and gas potential of the Yan'an Formation in the Ordos Basin has yet to be fully tapped. In this study, the pore structure, mobile fluid saturation, and water flooding micro-mechanism of the Yan'an Formation sandstone are systematically studied through the application of a series of rock physics and fluid experiments. The results show that there is a good positive correlation between porosity and permeability, and the reservoirs are divided into types Ⅰ, Ⅱ, and Ⅲ. Mercury injection tests show that the average pore throat radius of the oil-bearing reservoir ranges from 1 to 7 μm. The displacement pressure of the Yan'an Formation is also relatively low, and it decreases from 0.1 MPa to 0.01 MPa as the rock porosity increases from 11% to 18%. NMR tests show that small (diameter

The retention of gel system in porous media results in the reduction of porosity and permeability. However, the length of the current experiment models (sandpack or core sample) are in the range of centimeter scale, which is too short to track the full movement path of gel particles. In this work, a series of gel flooding experiments were conducted on 2.5-m long slim sandpack models. Seven fluid collection/pressure monitoring points were equally distributed along the length of the slim sandpack to track the movement of gel particles during the flooding process. We quantified the adsorption capacity, adsorption velocity, and mechanical shear effect of polymer/cross-linking agent along the flowing direction. In addition, we also employed scanning electron microscope (SEM) equipment to observe the morphology of the gel and the pore structure along the flooding direction, which provides good evidences of the adsorption retention and mechanical shear effects. Results show that most of the polymers and cross-linking agent were adsorbed on the region near the inlet. We emphasized the advantages of using long sandpack/core to track the full movement path of the gel system. In addition, the morphology of the original gel system showed a network characteristic of hexagonal structure, which was dragged to an elongated structure or even totally broke when it was transported through the porous medium. This work provides the fundamental understandings of the dynamic adsorption behaviors of gel system, which could be useful for optimizing the components of gel system, selection of target oil reservoirs and their operational parameters during gel flooding in enhancing oil recovery.

While competing endogenous RNAs (ceRNAs) play pivotal roles in various diseases, the proliferation and differentiation of keratinocytes are becoming a research focus in psoriasis. Therefore, the three commitment points for S phase entry (CP1–3) cell cycle model has pointed to a new research direction in these areas. However, it is unclear what role ceRNA regulatory mechanisms play in the interaction between keratinocytes and the immune system in psoriasis. In addition, the ceRNA network-based screening of potential therapeutic agents for psoriasis has not been explored. Therefore, we used multiple bioinformatics approaches to construct a ceRNA network for psoriasis, identified CTGF as the hub gene, and constructed a ceRNA subnetwork, after which validation datasets authenticated the results' accuracy. Subsequently, we used multiple online databases and the single-sample gene-set enrichment analysis algorithm, including the CP1–3 cell cycle model, to explore the mechanisms accounting for the increased proliferation and differentiation of keratinocytes and the possible roles of the ceRNA subnetwork in psoriasis. Next, we performed cell cycle and cell trajectory analyses based on a single-cell RNA-seq dataset of psoriatic skin biopsies. We also used weighted gene co-expression network analysis and single-gene batch correlation analysis-based gene set enrichment analysis to explore the functions of CTGF. Finally, we used the Connectivity Map to identify MS-275 (entinostat) as a novel treatment for psoriasis, SwissTargetPrediction to predict drug targets, and molecular docking to investigate the minimum binding energy and binding sites of the drug to target proteins.

Using glutinous rice flour and surimi as main raw materials, surimi-starch chips were prepared by pressure difference puffing technology. Using hardness, brittleness, puffing rate, color and sensory scores as evaluation indicators, the effects of surimi addition, fat addition, salt addition, sugar addition and drying time on the quality of surimi-starch chips were discussed. The results showed that with the increasing of surimi content, the expansion rate of crisps decreased and the hardness increased. With the increasing of oil content, the expansion rate and whiteness of crisps increased. With the increasing of sugar content, the whiteness of crisps increased. With the increasing of salt content, the puffing rate of chips decreased. Under different drying time, the puffing rate, texture, color and sensory of chips changed significantly. Finally, the process parameters of surimi-starch chips were 25% surimi addition, 5% fat addition, 1.2% salt addition, 1.2% sugar addition, and 3.5 h of drying.

Based on the community radiative transfer model, ensemble tree-based random forest algorithm, and extreme gradient boosting tree algorithm, this study established a random forest retrieval model (RF) and an extreme gradient boosting tree retrieval model (XGBoost) for the microwave land surface emissivity by using ERA5 reanalysis data and the observed brightness temperature of 10.65 GHz vertical polarization from FY3C Microwave Radiation Imager-I. In addition, an optimized Bayesian regularized neural network retrieval model (M2_30NN) has also been established on the basis of the original neural network land surface emissivity retrieval model (M1_20NN). The results show that compared with the simulated brightness temperature of the original land surface emissivity, the simulated brightness temperature of the land surface emissivity from each retrieval model is not only significantly improved in the correlation coefficient with the observed brightness temperature (5.92% (M1_20NN), 4.23% (M2_30NN), 14.21% (RF), 13.07% (XGBoost)), but also in the evaluation indexes of root mean square error, mean absolute error and explained variance regression score in the training datasets. Furthermore, in terms of testing datasets and spatiotemporal independence test datasets, the retrieval results of RF and XGBoost models can capture the spatial distribution patterns that are consistent with observations well, and also show great numerical improvement compared with the original model. In general, the XGBoost retrieval model is the best, followed by the RF retrieval model.

Objective: Acute myeloid leukemia (AML) is primarily a malignant disorder affecting the elderly. We aimed to compare the outcomes of different treatment patterns in elderly AML patients and to propose a prognostic scoring system that could predict survival and aid therapeutic decisions. Methods: Patients aged ≥ 60 years who had been diagnosed with AML at 7 hospitals in China were enrolled (n = 228). Treatment patterns included standard chemotherapy, low intensity therapy, and best supportive care (BSC). Results: The early mortality rates were 31%, 6.8%, and 6.3% for the BSC, low intensity therapy, and standard chemotherapy groups, respectively. The complete remission rate of the standard chemotherapy group was higher than that of the low intensity therapy group. The median overall survival (OS) was 561 days and 222 days for the standard chemotherapy and low intensity therapy groups, respectively, and were both longer than that of the BSC group (86 days). Based on multivariate analyses, we defined a prognostic scoring system that enabled classification of patients into 3 risk groups, in an attempt to predict the OS of patients receiving chemotherapies and low intensity therapies. Low and intermediate risk patients benefited more from standard chemotherapies than from low intensity therapies. However, the median OS was comparable between standard chemotherapies and low intensity therapies in high risk patients. Conclusions: Our prognostic scoring system could predict survival and help select appropriate therapies for elderly AML patients. Standard chemotherapy is important for elderly AML patients, particularly for those categorized into low and intermediate risk groups.

We examine the impact of party organisation construction of accounting firms on audit quality. We find that although there is no relationship between the party membership status of auditors and audit quality, the audit quality of party-member auditors significantly improves after accounting firms strengthen party organisation construction. Additional analyses show that the positive impact of auditor party membership on audit quality does not generate a contagious effect in the presence of party organisation construction. Moreover, cross-section results show that the impact of party organisation construction on audit quality is more pronounced in Non-Big4 audit firms, and in audit firms having a higher proportion of party-member partners/employees. Finally, we find that party organisation construction of accounting firms plays a more significant role in improving audit quality in state-owned firms. We believe our paper to be the first to investigate the governance role of party organisation construction in accounting firms.

Abstract One of the obstacles in studying the pathogenesis of hypertrophic cardiomyopathy (HCM) is the poor availability of myocardial tissue samples at the early stages of disease development. This has been addressed by the advent of induced pluripotent stem cells (iPSCs), which allow us to differentiate patient-derived iPSCs into cardiomyocytes (iPSC-CMs) in vitro. In this review, we summarize different approaches to establishing iPSC models and the application of genome editing techniques in iPSC. Because iPSC-CMs cultured at the present stage are immature in structure and function, researchers have attempted several methods to mature iPSC-CMs, such as prolonged culture duration, and mechanical and electrical stimulation. Currently, many researchers have established iPSC-CM models of HCM and employed diverse methods for performing measurements of cellular morphology, contractility, electrophysiological property, calcium handling, mitochondrial function, and metabolism. Here, we review published results in humans to date within the growing field of iPSC-CM models of HCM. Although there is no unified consensus, preliminary results suggest that this approach to modeling disease would provide important insights into our understanding of HCM pathogenesis and facilitate drug development and safety testing.

Background: Sepsis causes acute kidney injury (AKI) in critically ill patients, although the mechanisms underlying the pathophysiology are not fully understood. SUMO-specific proteases 3 (SENP3), a member of the deSUMOylating enzyme family, is known as a redox sensor and could regulate multiple cellular signaling pathways. However, the role of SENP3 in septic AKI remains unclear. Objectives: The purpose of this study was to investigate the role of SENP3 in lipopolysaccharide (LPS)-induced AKI model. Methods: C57BL/6 mice were given intraperitoneal injection of LPS (10 mg/kg). NRK-52E cells were treated with LPS in vitro. The SENP3 protein expression was analyzed by Western blotting. The levels of reactive oxygen species (ROS) in cells were measured using DCFH-DA. SENP3-siRNA or SENP3-plasmid was, respectively, transfected into NRK-52E cells to knock down or overexpress the SENP3 expression. Western blotting was performed to analyze the protein expression of cleaved caspase 3, cytochrome c, and dynamin-related protein 1 (Drp1). The mitochondrial membrane potential was measured using JC-1 assay kit. Co-immunoprecipitation was used to determine the interaction of Drp1 and SMUO2/3. Results: SENP3 protein expression was obviously increased in renal tissues from the mouse model of LPS-induced AKI. Accordingly, SENP3 expression was upregulated in NRK-52E cells treated with LPS in a ROS-dependent manner in vitro. Knockdown of SENP3 dramatically ameliorated LPS-induced apoptosis of NRK-52E cells, whereas overexpression of SENP3 further aggravated LPS-induced apoptosis of NRK-52E cells. Mechanistically, SENP3 triggered Drp1 recruitment to mitochondria by increasing the deSUMOylation of Drp1. Conclusion: SENP3 aggravated renal tubular epithelial cell apoptosis in LPS-induced AKI via Drp1 deSUMOylation manner.

Abstract The evolution of discharge dynamics in N2–SF6 mixtures under long‐term repetitive submicrosecond pulses is investigated based on pulse‐sequence resolved electrical and optical diagnostics. The effects of gas pressure, pulse repetition frequency (PRF), and SF6 concentration on discharge evolutions are determined. The number of applied pulses before breakdown is shown to non‐linearly decrease with increasing PRF for all included gas pressures and SF6 concentrations. A higher SF6 concentration is favourable for increasing relative insulation capability under repetitive pulses. Unexpected complexities of discharge evolutions under repetitive pulses are reported for the first time for the discharge mechanism transition when a strong electronegative gas is introduced. A pulse‐to‐pulse progressive streamer (first discharge)‐to‐precursor (before breakdown) transition is observed in an N2–SF6 mixture under positive repetitive pulses and is less dependent on gas pressure than traditional scenarios. The formation of a precursor section is jointly supported by electrical and optical signatures. The discharge mechanism transition and the detour phenomenon under repetitive pulses are discussed based on the effects of space charges on the spatial distribution of the electric field strength.

Abstract The long culture duration of patient-derived organoids (PDOs) have severely limited their clinical applications. The aim of this study was to determine the effect of lactate supplementation on the growth, genetic profiles and drug sensitivities of PDOs from hepatopancreatobiliary tumors. LM3, Huh7, Panc02, and RBE cell lines were cultured as organoids in the presence or absence of lactate, and total protein was extracted to measure the expression of α-enolase (ENO1), hypoxia-inducible factor-1α (HIF1α), AKT, and PI3 kinase (PI3K). Thirteen hepatopancreatobiliary tumor specimens were collected during surgical resection and cultured as PDOs with or without l-lactate. Hematoxylin and eosin (H&E) staining and immunohistochemical staining were performed on the original tissues and PDOs to compare their pathological structures, and their genetic profiles were analyzed by whole-exome sequencing (WES). The sensitivity of the PDOs to gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, ivosidenib, infigratinib, and lenvatinib were evaluated in terms of cell viability. Peripheral blood mononuclear cells (PBMCs) were isolated and co-cultured with PDOs to test the sensitivity of PDOs to tislelizumab. The addition of 20 mM lactate significantly promoted the growth of LM3 and Huh 7 organoids by 217% and 36%, respectively, compared to the control group, and the inhibition of lactate transporter decreased their growth. The HIF1α/ENO1/AKT/PI3K pathway was also activated by lactate. The inhibition of enolase also partly decreased the growth of organoids treated with lactate. Furthermore, 20 mM lactate increased the viability of 9 PDOs from 135% to 317% without affecting their pathological features. The genetic similarity, in terms of single nucleotide variations, insertions, and deletions, between original tissues and lactate-treated PDOs ranged from 83.2% to 94.1%, and that between the untreated and lactate-treated PDOs was at least 93.2%. Furthermore, the addition of lactate did not significantly change the dose–response curves of the PDOs to chemotherapeutic drugs, targeted drugs, and immune checkpoint inhibitor, especially for the drugs to which the cells were sensitive. Thus, lactate can be added to the culture medium of PDOs to promote their growth without altering their genetic profiles and drug sensitivities.