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Cochlear implantation (CI) offers a dependable treatment for sensorineural hearing loss, with precision electroacoustic stimulation parameters showing great potential in improving auditory outcomes in CI patients. Here, we report the attachment of MXene into CI systems which effectively mimic the neural electrode interface due to MXene's excellent electrical conductivity and biocompatibility. Low-frequency short-term biphasic electrical pulses emitted by the MXenes-based CI promoted the outgrowth of spiral ganglion neuron (SGN) neurites and growth cones, substantially boosting the calcium activity in SGNs. This study lays a theoretical foundation for the precision medicine approaches in CI patient care, and informs the selection of materials for cochlear implant electrode materials in the future.

Excessive underground train-induced vibration becomes a serious environmental problem in cities. To investigate the vibration transfer from an underground train to a building nearby, an explicit-integration time-domain, three-dimensional finite element model is developed. The underground train, track, tunnel, soil layers and a typical multi-story building nearby are all fully coupled in this model. The complex geometries involving the track components and the building are all modelled in detail, which makes the simulation of vibration transfer more realistic from the underground train to the building. The model is validated with in-situ tests data and good agreements have been achieved between the numerical results and the experimental results both in time domain and frequency domain. The proposed model is applied to investigate the vibration transfer along the floors in the building and the influences of the soil stiffness on the vibration characteristics of the track-tunnel-soil-building system. It is found that the building vibration induced by an underground train is dominant at the frequency determined by the P2 resonance and influenced by the vibration modes of the building. The vertical vibration in the building decreases in a fluctuant pattern from the foundation to the top floor due to loss of high frequency contents and local modes. The vibration levels in different rooms at a same floor can be different due to the different local stiffness. A room with larger space thus smaller local stiffness usually has higher vibration level. Softer soil layers make the tunnel lining and the building have more low frequency vibration. The influence of the soil stiffness on the amplification scale along the floors of the building is found to be nonlinear and frequency-dependent, which needs to be further investigated.

Abstract Soil biogenic components are subject to continuous sequestration, and export from soils into the surrounding air and water environments. However, the processes involving the stability or lability of their mineral states remain still unclear. To assess these issues, we have measured various biogenic components in a number of agricultural, forest, grassland, and deep soils, as well as desert sands from Inner Mongolia, both in the solid state and liquid extracts. The contents of soil organic carbon (SOC) and soil total nitrogen (STN) were higher in soils than in sands, whilst those of soil total sulfur (STS) and inorganic carbon were higher in sands and deeper soils. The significant positive correlations found between STS and SOC, and STN, and their significant negative correlations with pH and δ13C-SOC in all soils suggest a pH-dependent sequestration of C, N, and S. The decreased stability of organo-mineral complexes at acidic pH, resulting from the acidification of humic substance (HS) functionalities, leads to a higher availability of nutrients that facilitates the sequestration of soil organic matter (SOM). Conversely, an increase in pH enhances the stability of organo-mineral complexes by promoting negatively charged HS functionalities, which reduces the availability of nutrients and the sequestration of SOM. The δ13C-SOC enrichment in desert sands (-17.63 to -7.10‰) and its depleted values in soils (-24.9 to -18.8‰) suggest the occurrence of C sequestration in desert, via uptake of enriched atmospheric CO2 (-8.4‰). The fluorescence spectra of humic substance components and their molecular weights in sands were typically different from those of soils. The predominant relatively low molecular weight (MW) ( 25 − 15 kDa) of water-extracted (labile state: LS) components of all soils suggest, respectively, their involvement in organo-mineral complexes and for export into the surrounding environment. The quantities of LS and CS soil components differ significantly on dependence of soil characteristics, implying their corresponding lability or stability in soils. These findings will provide useful input for the management of the corresponding soil/sand ecosystems.

Abstract Residue-free and highly efficient techniques for drinking water disinfection are urgently needed. Herein, we report an electrochemical water disinfection system equipped with atomically precise Ag28 nanoclusters (NCs) as electrode materials. The deployment of these Ag28 NCs not only provides sufficient electrosorption sites for intelligent microbe enrichment but also ensures high-efficiency dual-mode microbial killing through the in situ electrocatalytic production of residue-free reactive oxygen species (ROS) and the inherent antimicrobial activity of Ag28 NCs. Moreover, the design of the system enables a cyclical “alive microbe capture–killing–dead microbe desorption” process for continuous water disinfection. On this basis, this water disinfection system is efficient against broad-spectrum microbes (with >99.99% antimicrobial activity), durable (with a performance reduction of only 0.75% over 40 cycles and 99.90% antimicrobial efficiency for over 5 h of continuous operation), versatile (i.e., other NCs can be used), scalable (with water productivity of 213.33 L h−1 m− 2), energy efficient (with a low energy consumption of 4.91 Wh m− 3; 1.04 Wh m− 3 without the pumping cost) and applicable for various real water samples. This study may open new avenues for global water disinfection techniques.

Ulva prolifera, as the dominant species of the green macro-algal bloom, was used as the raw material to prepare cellulose (UPC) by alkali extraction and bleaching treatment with a yield of 23.61%. Nanocelluloses of UPCNC-S, UPCNC-H, and UPCNC-T were prepared using sulfuric acid hydrolysis, hydrochloric acid hydrolysis, and TEMPO oxidation methods, respectively. The structure and micro-morphology of the prepared nanocelluloses were characterized and compared based on yield, fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), particle size, zeta potential, and chromaticity value. The results showed that the yields of the nanocelluloses prepared by three methods were 10.07% of UPCNC-S, 32.48% of UPCNC-H, and 26.63% of UPCNC-T, respectively. All three methods did not damage the crystal form and the structure of the cellulose showed, an increase in crystallinity and reached 72.11% (UPCNC-S), 77.16% (UPCNC-H), and 66.53% (UPCNC-T). The thermal stability of nanocellulose UPCNC-S produced by sulfuric acid was to the weakest, while that of UPCNC-H was the optimal. In terms of morphological features, both UPCNC-T and UPCNC-H exhibited short-shaped morphology, with particle sizes concentrated around 430 nm and 610 nm, respectively. In addition to the short rod structure, partially spherical nanocellulose was produced by sulfuric acid hydrolysis, with the smallest particle sizes ranging from 300 nm to 400 nm. The Zeta potential values of the three types of nanocellulose were all less than −30 mV, indicating good stability in suspension. Besides, the color of UPCNC-S was slightly yellowish with the lowest whiteness value, while UPCNC-H and UPCNC-T both showed the whitish appearance. In summary, the nanocellulose prepared from Ulva prolifera in this study exhibited excellent characteristics such as high crystallinity, good dispersion, and small particle sizes, which would provide a theoretical basis for the high-value utilization of Ulva prolifera.

To develop the fermented food of Porphyra yezoensis, monascus and compound yeast and lactic acid bacteria were used to ferment Porphyra yezoensis. The active ingredients of Porphyra yezoensis during fermentation were determined, and their antioxidant, hypoglycemic and antihypertensive activities were evaluated. Results showed that the total phenol and flavonoid contents of M. purpureus fermented P. yezoensis (MF), M. purpureus and L. plantarum co-fermented P. yezoensis (MLF), M. purpureus and S. cerevisiae co-fermented P. yezoensis (MYF) significantly increased with fermentation time (P

Abstract Recent studies have uncovered that TIPE2 is involved in the development of cancer. However, less research has been conducted on the role of TIPE2 in melanoma. Our study aims to elucidate the mechanism of action of TIPE2 in the development of melanoma. We examined TIPE2 expression in paracarcinoma tissue and melanoma tissues and found that TIPE2 expression was downregulated in melanoma tissue compared with paracarcinoma tissue. Overexpression of TIPE2 significantly inhibited the proliferation of melanoma cells in vitro and even inhibited tumor formation in vivo. The CCK8 assay results indicated that TIPE2 overexpression suppressed the proliferation of melanoma cells. The colony-forming ability and wound healing ability of TIPE2-overexpressing melanoma cells were significantly reduced compared with those of control cells. Moreover, immunohistochemistry experiments using a nude mouse tumor model showed consistent results. TIPE2 inhibited the phosphorylation of MEK and ERK. In summary, TIPE2 suppresses the proliferation and migration of melanoma cells by affecting proliferation-related factors and possibly by regulating the MEK/ERK pathway. TIPE2 could be used to inhibit melanoma growth and is a potential drug target for future drug development.

Abstract Oxford Nanopore Technologies (ONT) offers ultrahigh-throughput multi-sample sequencing but only provides barcode kits that enable up to 96-sample multiplexing. We present TDFPS-Designer, a new toolkit for nanopore sequencing barcode design, which creates significantly more barcodes: 137 with a length of 20 base pairs, 410 at 24 bp, and 1779 at 30 bp, far surpassing ONT’s offerings. It includes GPU-based acceleration for ultra-fast demultiplexing and designs robust barcodes suitable for high-error ONT data. TDFPS-Designer outperforms current methods, improving the demultiplexing recall rate by 20% relative to Guppy, without a reduction in precision.

Background: Bariatric surgery induces significant weight loss, increases insulin sensitivity, and improves dyslipidemia. As one of the most widely performed bariatric surgeries, laparoscopic sleeve gastrectomy (LSG) is thought to improve the metabolic profile along with weight loss. The objective of this study was to evaluate longitudinal changes in the serum metabolite levels after LSG and elucidate the underlying mechanisms of metabolic improvement. Methods: Clinical metabolic parameters and serum samples were collected preoperatively and at 1, 3, and 6 months postoperatively from nine patients with obesity undergoing LSG. Serum metabolites were measured using a non-targeted metabolic liquid chromatography–mass spectrometry method. Results: During the 1, 3, and 6 months postoperative follow-up, the body mass index, HOMA-IR, and liver fat content showed a gradual descending trend. A total of 328 serum metabolites were detected, and 38 were differentially expressed. The up-regulated metabolites were mainly enriched in ketone body metabolism, alpha-linolenic acid and linoleic acid metabolism, pantothenate and CoA biosynthesis, glycerolipid metabolism, and fructose and mannose degradation, while the down-regulated metabolites were closely related to caffeine metabolism, oxidation of branched-chain fatty acids, glutamate metabolism, and homocysteine degradation. Notably, nine metabolites (oxoglutarate, 2-ketobutyric acid, succinic acid semialdehyde, phthalic acid, pantetheine, eicosapentaenoate, 3-hydroxybutanoate, oxamic acid, and dihydroxyfumarate) showed persistent differential expression at 1, 3, and 6 months follow-up. Some were found to be significantly associated with weight loss, insulin resistance improvement, and liver fat content reduction. Conclusions: This finding may provide a new perspective for revealing novel biomarkers and mechanisms of metabolic improvement in obesity and related comorbidities.

Abstract Using the Kreuzer-Skarke database of 4-dimensional reflexive polytopes, we systematically constructed a new database of orientifold Calabi-Yau threefolds with h 1,1(X) ≤ 12. Our approach involved non-trivial ℤ2 involutions, incorporating both divisor exchanges and multi-divisor reflections acting on the Calabi-Yau threefolds. Each proper involution results in an orientifold Calabi-Yau threefolds and we constructed 320, 386, 067 such examples. We developed a novel algorithm that significantly reduces the complexity of determining all the fixed loci under the involutions, and clarifies the types of O-planes. Our results show that under proper involutions, the majority of cases end up with O3/O7-plane systems, and most of these further admit a naive Type IIB string vacua. Additionally, a new type of free action was determined. We also computed the smoothness and the splitting of Hodge numbers in the ℤ2-orbifold limit for these orientifold Calabi-Yau threefolds.

Abstract Osteopetrosis is an inherited metabolic disease, characterized by increased bone density and narrow marrow cavity. Patients with severe osteopetrosis exhibit abnormal bone brittleness, anemia, and infection complications, which commonly cause death within the first decade of life. Pathologically, osteopetrosis impairs not only the skeletal system, but also the hemopoietic and immune systems during development, while the underlying osteoimmunological mechanisms remain unclear. Osteoclastic mutations are regarded as the major causes of osteopetrosis, while osteoclast non-autonomous theories have been proposed in recent years with unclear underlying mechanisms. Retinoic acid (RA), the metabolite of Vitamin A, is an essential requirement for skeletal and hematopoietic development, through the activation of retinoic acid signaling. RA can relieve osteopetrosis symptoms in some animal models, while its effect on bone health is still controversial and the underlying mechanisms remain unclear. In this study, we constructed an osteoblast-specific inhibitory retinoic acid signaling mouse model and surprisingly found it mimicked the symptoms of osteopetrosis found in clinical cases: dwarfism, increased imperfectly-formed trabecular bone deposition with a reduced marrow cavity, thin cortical bone with a brittle skeleton, and hematopoietic and immune dysfunction. Micro-CT, the three-point bending test, and histological analysis drew a landscape of poor bone quality. Single-cell RNA sequencing (scRNA-seq) of the femur and RNA-seq of osteoblasts uncovered an atlas of pathological skeletal metabolism dysfunction in the mutant mice showing that osteogenesis was impaired in a cell-autonomous manner and osteoclastogenesis was impaired via osteoblast-osteoclast crosstalk. Moreover, scRNA-seq of bone marrow and flow cytometry of peripheral blood, spleen, and bone marrow uncovered pathology in the hematopoietic and immune systems in the mutant mice, mimicking human osteopetrosis. Results showed that hematopoietic progenitors and B lymphocyte differentiation were affected and the osteoblast-dominated cell crosstalk was impaired, which may result from transcriptional impairment of the ligands Pdgfd and Sema4d. In summary, we uncovered previously unreported pathogenesis of osteopetrosis-like disorder in mice with skeletal, hematopoietic, and immune system dysfunction, which was induced by the inhibition of retinoic acid signaling in osteoblasts, and sheds new insights into a potential treatment for osteopetrosis.

Abstract Previous studies have yielded inconsistent results regarding the association between chronic kidney disease (CKD) and the risk of cognitive impairment (CI). This study aimed to investigate the longitudinal association of CKD with CI risk in the Chinese middle-aged and older population. A total of 16,515 CI-free participants 45 years of age or older including 15,595 without CKD and 920 with CKD were followed from 2011 until 2018 (median [interquartile range]: 7 [5.5-7]) to detect incident CI. Over the follow-up, 648 participants developed CI. Data were analyzed using multi-adjusted Cox proportional hazard regression and Laplace regression. The incidence rate (IR) of CI was significantly higher in individuals with CKD at 11.46 per 1,000 person-years (95% confidence interval [CI], 8.90 to 14.76) than in those without CKD at 6.38 per 1,000 person-years (95% CI, 5.89 to 6.92). Compared to those without CKD, the hazard ratios of those with CKD was 1.56 (95% CI, 1.19 to 2.04) for CI. Participants with CKD in the middle-aged group (45–54 years) exhibited a heightened risk of CI in age-stratified analyses. CKD accelerated the onset of CI by 1.24 years (10th percentile difference [PD]; 95% CI, -2.03 to -0.43, p

To solve problems of the low yields and dark color of Sargassum horneri polysaccharides which were produced according to the traditional extraction method under the high-temperature and alkalic condition, this study attempted to produce S. horneri polysaccharides at a lower alkaline treatment temperature of 60 ℃ and optimize the process parameters by the response surface methodology. The combined scores of alginate and fucoidan yields and whiteness index (WI) were used as assessment indices to identify the optimal process condition. Under the optimal extraction condition, the concentration of NaClO addition was changed to investigate its effect on various characteristics of the produced alginate and fucoidan. The results showed that the polysaccharide comprehensive score was significantly correlated with the alkaline concentration, the extraction time, and the dosage of NaClO (P

Abstract Chronic Kidney Disease (CKD) stands as a substantial challenge within the global health landscape. The elevated metabolic demands essential for sustaining normal kidney function have propelled an increasing interest in unraveling the intricate relationship between mitochondrial dysfunction and CKD. However, the authentic causal relationship between these two factors remains to be conclusively elucidated. This study endeavors to address this knowledge gap through the Mendelian Randomization (MR) method. We utilized large-scale QTL datasets (including 31,684 eQTLs samples, 1980 mQTLs samples, and 35,559 pQTLs samples) to precisely identify key genes related to mitochondrial function as exposure factors. Subsequently, we employed GWAS datasets (comprising 480,698 CKD samples and 1,004,040 eGFRcrea samples) as outcome factors. Through a comprehensive multi-level analysis (encompassing expression, methylation, and protein quantification loci), we evaluated the causal impact of these genes on CKD and estimated glomerular filtration rate (eGFR). The integration and validation of diverse genetic data, complemented by the application of co-localization analysis, bi-directional MR analysis, and various MR methods, notably including inverse variance weighted, have collectively strengthened our confidence in the robustness of these findings. Lastly, we validate the outcomes through examination in human RNA sequencing datasets encompassing various subtypes of CKD. This study unveils significant associations between the glycine amidinotransferase (GATM) and CKD, as well as eGFR. Notably, an augmentation in GATM gene and protein expression corresponds to a diminished risk of CKD, whereas distinct methylation patterns imply an increased risk. Furthermore, a discernible reduction in GATM expression is observed across diverse pathological subtypes of CKD, exhibiting a noteworthy positive correlation with GFR. These findings establish a causal relationship between GATM and CKD, thereby highlighting its potential as a therapeutic target. This insight lays the foundation for the development of potential therapeutic interventions for CKD, presenting substantial clinical promise.

Abstract The 2-oxoglutarate dehydrogenase complex (OGDHc) orchestrates a critical reaction regulating the TCA cycle. Although the structure of each OGDHc subunit has been solved, the architecture of the intact complex and inter-subunit interactions still remain unknown. Here we report the assembly of native, intact OGDHc from Sus scrofa heart tissue using cryo-electron microscopy (cryo-EM), cryo-electron tomography (cryo-ET), and subtomogram averaging (STA) to discern native structures of the whole complex and each subunit. Our cryo-EM analyses revealed the E2o cubic core structure comprising eight homotrimers at 3.3-Å resolution. More importantly, the numbers, positions and orientations of each OGDHc subunit were determined by cryo-ET and the STA structures of the core were resolved at 7.9-Å with the peripheral subunits reaching nanometer resolution. Although the distribution of the peripheral subunits E1o and E3 vary among complexes, they demonstrate a certain regularity within the position and orientation. Moreover, we analyzed and validated the interactions between each subunit, and determined the flexible binding mode for E1o, E2o and E3, resulting in a proposed model of Sus scrofa OGDHc. Together, our results reveal distinctive factors driving the architecture of the intact, native OGDHc.

Abstract Background Alterations in DNA methylation (DNAm) have been observed in patients with fatty liver, but whether they are cause or consequence remains unknown. The study aimed to investigate longitudinal association of epigenome-wide DNAm with liver fat content (LFC) in Chinese participants, and explore their temporal relationships. Methods Data were obtained from 2 waves over a four-year time period of the Shanghai Changfeng Study (discovery, n = 407 and replication, n = 126). LFC and peripheral blood DNAm were repeatedly measured using quantitative hepatic ultrasonography and the 850 K Illumina EPIC BeadChip, respectively. Longitudinal and cross-sectional epigenome-wide association studies (EWASs) were conducted with linear mixed model and linear regression model, respectively. Meta-analysis was performed using METAL. Cross-lagged panel analysis (CLPA) was carried out to infer temporal relationships between the significant CpGs and LFC. Results Longitudinal EWAS identified cg11024682 (SREBF1), cg06500161 (ABCG1), cg16740586 (ABCG1), cg15659943 (ABCA1) and cg00163198 (SNX19) significantly associated with LFC with P

Abstract Background This study investigated the clinical value of breast magnetic resonance imaging (MRI) radiomics for predicting axillary lymph node metastasis (ALNM) and to compare the discriminative abilities of different combinations of MRI sequences. Methods This study included 141 patients diagnosed with invasive breast cancer from two centers (center 1: n = 101, center 2: n = 40). Patients from center 1 were randomly divided into training set and test set 1. Patients from center 2 were assigned to the test set 2. All participants underwent preoperative MRI, and four distinct MRI sequences were obtained. The volume of interest (VOI) of the breast tumor was delineated on the dynamic contrast-enhanced (DCE) postcontrast phase 2 sequence, and the VOIs of other sequences were adjusted when required. Subsequently, radiomics features were extracted from the VOIs using an open-source package. Both single- and multisequence radiomics models were constructed using the logistic regression method in the training set. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and precision of the radiomics model for the test set 1 and test set 2 were calculated. Finally, the diagnostic performance of each model was compared with the diagnostic level of junior and senior radiologists. Results The single-sequence ALNM classifier derived from DCE postcontrast phase 1 had the best performance for both test set 1 (AUC = 0.891) and test set 2 (AUC = 0.619). The best-performing multisequence ALNM classifiers for both test set 1 (AUC = 0.910) and test set 2 (AUC = 0.717) were generated from DCE postcontrast phase 1, T2-weighted imaging, and diffusion-weighted imaging single-sequence ALNM classifiers. Both had a higher diagnostic level than the junior and senior radiologists. Conclusions The combination of DCE postcontrast phase 1, T2-weighted imaging, and diffusion-weighted imaging radiomics features had the best performance in predicting ALNM from breast cancer. Our study presents a well-performing and noninvasive tool for ALNM prediction in patients with breast cancer.

Abstract The complexity of brain activity reflects its ability to process information, adapt to environmental changes, and transition between states. However, it remains unclear how schizophrenia (SZ) affects brain activity complexity, particularly its dynamic changes. This study aimed to investigate the abnormal patterns of brain activity complexity in SZ, their relationship with cognitive deficits, and the impact of antipsychotic medication. Forty-four drug-naive first-episode (DNFE) SZ patients and thirty demographically matched healthy controls (HC) were included. Functional MRI-based sliding window analysis was utilized for the first time to calculate weighted permutation entropy to characterize complex patterns of brain activity in SZ patients before and after 12 weeks of risperidone treatment. Results revealed reduced complexity in the caudate, putamen, and pallidum at baseline in SZ patients compared to HC, with reduced complexity in the left caudate positively correlated with Continuous Performance Test (CPT) and Category Fluency Test scores. After treatment, the complexity of the left caudate increased. Regions with abnormal complexity showed decreased functional connectivity, with complexity positively correlated with connectivity strength. We observed that the dynamic complexity of the brain exhibited the characteristic of spontaneous, recurring “complexity drop”, potentially reflecting transient state transitions in the resting brain. Compared to HC, patients exhibited reduced scope, intensity, and duration of complexity drop, all of which improved after treatment. Reduced duration was negatively correlated with CPT scores and positively with clinical symptoms. The results suggest that abnormalities in brain activity complexity and its dynamic changes may underlie cognitive deficits and clinical symptoms in SZ patients. Antipsychotic treatment partially restores these abnormalities, highlighting their potential as indicators of treatment efficacy and biomarkers for personalized therapy.

Accurate prediction of peptide spectra is crucial for improving the efficiency and reliability of proteomic analysis, as well as for gaining insight into various biological processes. In this study, we introduce Deep MS Simulator (DMSS), a novel attention-based model tailored for forecasting theoretical spectra in mass spectrometry. DMSS has undergone rigorous validation through a series of experiments, consistently demonstrating superior performance compared to current methods in forecasting theoretical spectra. The superior ability of DMSS to distinguish extremely similar peptides highlights the potential application of incorporating our predicted intensity information into mass spectrometry search engines to enhance the accuracy of protein identification. These findings contribute to the advancement of proteomics analysis and highlight the potential of the DMSS as a valuable tool in the field.

Abstract Non-muscle myosin heavy chain IIA (MYH9), a member of the non-muscle myosin II (NM II) family, is widely expressed in cells. The interaction of MYH9 with actin in the cytoplasm can hydrolyze ATP, completing the conversion of chemical energy to mechanical motion. MYH9 participates in various cellular processes, such as cell adhesion, migration, movement, and even signal transduction. Mutations in MYH9 are often associated with autosomal dominant platelet disorders and kidney diseases. Over the past decade, tumor-related research has gradually revealed a close relationship between MYH9 and the occurrence and development of tumors. This article provides a review of the research progress on the role of MYH9 in cancer regulation. We also discussed the anti-cancer effects of MYH9 under special circumstances, as well as its regulation of T cell function. In addition, given the importance of MYH9 as a key hub in oncogenic signal transduction, we summarize the current therapeutic strategies targeting MYH9 as well as the ongoing challenges.

Abstract Pseudouridine widely affects the stability and function of RNA. However, our knowledge of pseudouridine properties in tumors is incomplete. We systematically analyzed pseudouridine synthases (PUSs) expression, genomic aberrations, and prognostic features in 10907 samples from 33 tumors. We found that the pseudouridine-associated pathway was abnormal in tumors and affected patient prognosis. Dysregulation of the PUSs expression pattern may arise from copy number variation (CNV) mutations and aberrant DNA methylation. Functional enrichment analyses determined that the PUSs expression was closely associated with the MYC, E2F, and MTORC1 signaling pathways. In addition, PUSs are involved in the remodeling of the tumor microenvironment (TME) in solid tumors, such as kidney and lung cancers. Particularly in lung cancer, increased expression of PUSs is accompanied by increased immune checkpoint expression and Treg infiltration. The best signature model based on more than 112 machine learning combinations had good prognostic ability in ACC, DLBC, GBM, KICH, MESO, THYM, TGCT, and PRAD tumors, and is expected to guide immunotherapy for 19 tumor types. The model was also effective in identifying patients with tumors amenable to etoposide, camptothecin, cisplatin, or bexarotene treatment. In conclusion, our work highlights the dysregulated features of PUSs and their role in the TME and patient prognosis, providing an initial molecular basis for future exploration of pseudouridine. Studies targeting pseudouridine are expected to lead to the development of potential diagnostic strategies and the evaluation and improvement of antitumor therapies.

Abstract The yield of pearl millet, a resilient cereal crop crucial for African food security, is severely impacted by the root parasitic weed Striga hermonthica, which requires host-released hormones, called strigolactones (SLs), for seed germination. Herein, we identify four SLs present in the Striga-susceptible line SOSAT-C88-P10 (P10) but absent in the resistant 29Aw (Aw). We generate chromosome-scale genome assemblies, including four gapless chromosomes for each line. The Striga-resistant Aw lacks a 0.7 Mb genome segment containing two putative CARLACTONOIC ACID METHYLTRANSFERASE1 (CLAMT1) genes, which may contribute to SL biosynthesis. Functional assays show that P10CLAMT1b produces the SL-biosynthesis intermediate methyl carlactonoate (MeCLA) and that MeCLA is the precursor of P10-specific SLs. Screening a diverse pearl millet panel confirms the pivotal role of the CLAMT1 section for SL diversity and Striga susceptibility. Our results reveal a reason for Striga susceptibility in pearl millet and pave the way for generating resistant lines through marker-assisted breeding or direct genetic modification.

Abstract Background With the fast pace of modern life, people have less time for meals, but few studies have examined the association between the habit of fast eating and metabolic diseases. Objective Combining the results of the current study and the prior ones, we aimed to investigate the possible relationship between fast eating and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD). Methods This is a sub-analysis of a multicenter cross-sectional study of 1965 participants investigated the association between fast eating and MASLD in Chinese. Fast eating was defined as meal time less than five minutes and participants were divided into three categories based on their self-reported frequency of fast eating: ≤1 time/month, ≤1 time/week and ≥2 times/week. We further conducted a literature search for available studies published before November, 2023 as well as a meta-analysis to investigate the association between fast eating and MASLD. Results The proportion of MASLD was 59.3%, 50.5%, and 46.2% in participants with fast eating ≥2 times/week, ≤1 time/week and ≤1 time/month, respectively (P for trend

Abstract Complicated peripheral nerve injuries or defects, especially at branching sites, remain a prominent clinical challenge after the application of different treatment strategies. Current nerve grafts fail to match the expected shape and size for delicate and precise branched nerve repair on a case-by-case basis, and there is a lack of geometrical and microscale regenerative navigation. In this study, we develop a sugar painting-inspired individualized multilevel epi-/peri-/endoneurium-mimetic device (SpinMed) to customize natural cues, featuring a selectively protective outer sheath and an instructive core, to support rapid vascular reconstruction and consequent efficient neurite extension along the defect area. The biomimetic perineurium dictates host-guest crosslinking in which new vessels secrete multimerin 1 binding to the fibroin filler surface as an anchor, contributing to the biological endoneurium that promotes Schwann cell homing and remyelination. SpinMed implantation into rat sciatic nerve defects yields a satisfactory outcome in terms of structural reconstruction, with sensory and locomotive function restoration. We further customize SpinMed grafts based on anatomy and digital imaging, achieving rapid repair of the nerve trunk and branches superior to that achieved by autografts and decellularized grafts in a specific beagle nerve defect model, with reliable biosafety. Overall, this intelligent art-inspired biomimetic design offers a facile way to customize sophisticated high-performance nerve grafts and holds great potential for application in translational regenerative medicine.

Abstract Cochlear implants can directly activate the auditory system’s primary sensory neurons, the spiral ganglion neurons (SGNs), via circumvention of defective cochlear hair cells. This bypass restores auditory input to the brainstem. SGN loss etiologies are complex, with limited mammalian regeneration. Protecting and revitalizing SGN is critical. Tissue engineering offers a novel therapeutic strategy, utilizing seed cells, biomolecules, and scaffold materials to create a cellular environment and regulate molecular cues. This review encapsulates the spectrum of both human and animal research, collating the factors contributing to SGN loss, the latest advancements in the utilization of exogenous stem cells for auditory nerve repair and preservation, the taxonomy and mechanism of action of standard biomolecules, and the architectural components of scaffold materials tailored for the inner ear. Furthermore, we delineate the potential and benefits of the biohybrid neural interface, an incipient technology in the realm of implantable devices. Nonetheless, tissue engineering requires refined cell selection and differentiation protocols for consistent SGN quality. In addition, strategies to improve stem cell survival, scaffold biocompatibility, and molecular cue timing are essential for biohybrid neural interface integration. Graphical Abstract

DNA barcodes, short and unique DNA sequences, play a crucial role in sample identification when processing many samples simultaneously, which helps reduce experimental costs. Nevertheless, the low quality of long-read sequencing makes it difficult to identify barcodes accurately, which poses significant challenges for the design of barcodes for large numbers of samples in a single sequencing run. Here, we present a comprehensive study of the generation of barcodes and develop a tool, PRO, that can be used for selecting optimal barcode sets and demultiplexing. We formulate the barcode design problem as a combinatorial problem and prove that finding the optimal largest barcode set in a given DNA sequence space in which all sequences have the same length is theoretically NP-complete. For practical applications, we developed the novel method PRO by introducing the probability divergence between two DNA sequences to expand the capacity of barcode kits while ensuring demultiplexing accuracy. Specifically, the maximum size of the barcode kits designed by PRO is 2,292, which keeps the length of barcodes the same as that of the official ones used by Oxford Nanopore Technologies (ONT). We validated the performance of PRO on a simulated nanopore dataset with high error rates. The demultiplexing accuracy of PRO reached 98.29% for a barcode kit of size 2,922, 4.31% higher than that of Guppy, the official demultiplexing tool. When the size of the barcode kit generated by PRO is the same as the official size provided by ONT, both tools show superior and comparable demultiplexing accuracy.

Abstract Objectives To develop an innovative magnetic resonance imaging (MRI)-based PUMCH (Peking Union Medical College Hospital) classification system aimed at standardising the diagnosis of congenital cervical malformations (CCMs) by identifying their distinctive MRI features. Methods Seventy-nine consecutive patients with CCM underwent pre-treatment pelvic MRI; three experienced gynaecological radiologists retrospectively analysed these images. Qualitative assessments included Rock et al’s classification; PUMCH classification; haematometra; cervical signal features; ovarian endometriosis; haematosalpinx; and uterine, vaginal, urinary, and musculoskeletal malformations. Quantitative assessments involved the uterine volume, sagittal cervical length, and maximum ovarian cross-sectional area. The surgical treatment types were also recorded. Statistical methods were used to incorporate differences in clinical features and surgical methods into our classification. Results Morphologically, CCMs were categorised into three types: type I (53%) was characterised by the presence of a cervix with visible cervical canals; type II (23%) featured an existing cervix with concealed cervical canals; and type III (24%) indicated cervical aplasia, which involves a blind end in the lower part of the uterine corpus. Haematometra was significantly more prevalent in patients with type I CCM than in those with type II (p

Abstract With the flourishing of spatial omics technologies, alignment and stitching of slices becomes indispensable to decipher a holistic view of 3D molecular profile. However, existing alignment and stitching methods are unpractical to process large-scale and image-based spatial omics dataset due to extreme time consumption and unsatisfactory accuracy. Here we propose SANTO, a coarse-to-fine method targeting alignment and stitching tasks for spatial omics. SANTO firstly rapidly supplies reasonable spatial positions of two slices and identifies the overlap region. Then, SANTO refines the positions of two slices by considering spatial and omics patterns. Comprehensive experiments demonstrate the superior performance of SANTO over existing methods. Specifically, SANTO stitches cross-platform slices for breast cancer samples, enabling integration of complementary features to synergistically explore tumor microenvironment. SANTO is then applied to 3D-to-3D spatiotemporal alignment to study development of mouse embryo. Furthermore, SANTO enables cross-modality alignment of spatial transcriptomic and epigenomic data to understand complementary interactions.

Abstract We study a nearly critical superfluid system from two complementary approaches. Within the first approach, we formulate a Schwinger-Keldysh effective field theory (EFT) for the system when it is located slightly above the critical temperature. The dynamical variables in the EFT construction are two scalars: a neutral scalar associated with the conserved U(1) charge, and a complex scalar describing the order parameter. The set of symmetries, particularly the dynamical Kubo-Martin-Schwinger (KMS) symmetry and chemical shift symmetry, strictly constrains the form of EFT action. Within the second approach, using the holographic Schwinger-Keldysh technique, we derive the effective action for a “microscopic” holographic superfluid, confirming the EFT construction. A systematic inclusion of non-Gaussianity is one highlight of present study.

In order to establish the standard preparation methodology for bioactive polysaccharide of fucoidan, this study carried out the research of preparation method of fucoidan from Saccharina japonica. Three extraction methods, high temperature pressure extraction (HPE), acid extraction (AE), and microwave extraction at 400 W (M400 W), 500 W (M500 W), and 600 W (M600 W) were selected. Subsequently, two precipitation methods, calcium chloride precipitation (CP) and ethanol precipitation (GAP) were used to remove alginate followed by finally precipitation of fucoidan with high concentration ethanol. Fucoidan extracts prepared in totally ten different conditions were collected, of which the contents of total sugar, total phenols, protein, uronic acid, and sulfate groups were analyzed. Meanwhile their antioxidant activities including Fe3+ reduction ability, ABTS+ and DPPH free radical scavenging ability were determined. The correlation analysis was conducted based on the above determined results to discover the relationship between preparation methods and fucoidan qualities. Accordingly, the preparation methods for fucoidan of high yield, high purity, and excellent antioxidant activities were selected. Results showed that the yields of fucoidan by acid extraction with calcium precipitation (AE-CP) and microwave extraction with calcium precipitation (M400 W-CP, M500 W-CP, M600 W-CP) were 3.821%, 3.516%, 3.376%, and 2.998%, respectively. Meanwhile, the sulfate content was 17.734%, 23.872%, 23.376%, and 22.149%, respectively. Their protein and total phenol content were below 1%, the uronic acid content was below 10%, and the Trolox equivalent (ABTS+ radical scavenging ability) was 5.637, 5.336, 6.567, and 5.616 μg/mg, respectively. Thus, the above four preparation conditions were ideal for processing of fucoidan, among which the method of microwave extraction followed by calcium precipitation showed advantages of short processing time and low solvent consumption that met the requirement of the environmental-friendly processing. This study systematically investigated the effects of preparation methods on the yield and quality of fucoidan, which provided a practical preparation methodology for fucoidan from Saccharina japonica with high yield, purity and antioxidant activity.

Abstract Recent advancements in genome assembly have greatly improved the prospects for comprehensive annotation of Transposable Elements (TEs). However, existing methods for TE annotation using genome assemblies suffer from limited accuracy and robustness, requiring extensive manual editing. In addition, the currently available gold-standard TE databases are not comprehensive, even for extensively studied species, highlighting the critical need for an automated TE detection method to supplement existing repositories. In this study, we introduce HiTE, a fast and accurate dynamic boundary adjustment approach designed to detect full-length TEs. The experimental results demonstrate that HiTE outperforms RepeatModeler2, the state-of-the-art tool, across various species. Furthermore, HiTE has identified numerous novel transposons with well-defined structures containing protein-coding domains, some of which are directly inserted within crucial genes, leading to direct alterations in gene expression. A Nextflow version of HiTE is also available, with enhanced parallelism, reproducibility, and portability.

Abstract Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs.

Abstract The dynamics of proteins are crucial for understanding their mechanisms. However, computationally predicting protein dynamic information has proven challenging. Here, we propose a neural network model, RMSF-net, which outperforms previous methods and produces the best results in a large-scale protein dynamics dataset; this model can accurately infer the dynamic information of a protein in only a few seconds. By learning effectively from experimental protein structure data and cryo-electron microscopy (cryo-EM) data integration, our approach is able to accurately identify the interactive bidirectional constraints and supervision between cryo-EM maps and PDB models in maximizing the dynamic prediction efficacy. Rigorous 5-fold cross-validation on the dataset demonstrates that RMSF-net achieves test correlation coefficients of 0.746 ± 0.127 at the voxel level and 0.765 ± 0.109 at the residue level, showcasing its ability to deliver dynamic predictions closely approximating molecular dynamics simulations. Additionally, it offers real-time dynamic inference with minimal storage overhead on the order of megabytes. RMSF-net is a freely accessible tool and is anticipated to play an essential role in the study of protein dynamics.

Abstract Large language models (LLMs) are seen to have tremendous potential in advancing medical diagnosis recently, particularly in dermatological diagnosis, which is a very important task as skin and subcutaneous diseases rank high among the leading contributors to the global burden of nonfatal diseases. Here we present SkinGPT-4, which is an interactive dermatology diagnostic system based on multimodal large language models. We have aligned a pre-trained vision transformer with an LLM named Llama-2-13b-chat by collecting an extensive collection of skin disease images (comprising 52,929 publicly available and proprietary images) along with clinical concepts and doctors’ notes, and designing a two-step training strategy. We have quantitatively evaluated SkinGPT-4 on 150 real-life cases with board-certified dermatologists. With SkinGPT-4, users could upload their own skin photos for diagnosis, and the system could autonomously evaluate the images, identify the characteristics and categories of the skin conditions, perform in-depth analysis, and provide interactive treatment recommendations.

Abstract During early embryonic development, the transition from totipotency to pluripotency is a fundamental and critical process for proper development. However, the regulatory mechanisms governing this transition remain elusive. Here, we conducted a comprehensive genome-wide CRISPR/Cas9 screen to investigate the 2-cell-like cells (2CLCs) phenotype in mouse embryonic stem cells (mESCs). This effort led to the identification of ten regulators that play a pivotal role in determining cell fate during this transition. Notably, our study revealed Mdm2 as a significant negative regulator of 2CLCs, as perturbation of Mdm2 resulted in a higher proportion of 2CLCs. Mdm2 appears to influence cell fate through its impact on cell cycle progression and H3K27me3 epigenetic modifications. In summary, the results of our CRISPR/Cas9 screen have uncovered several genes with distinct functions in regulating totipotency and pluripotency at various levels, offering a valuable resource for potential targets in future molecular studies.

Objective: To improve the contents of various hypoglycemic components in natural mulberry leaves, different fermentation-promoting substances were added to mulberry leaf shoots during their fermentation by means of that drawn on the experience of traditional black tea fermentation process. Method: Based on the single factor experiments, orthogonal optimization test was carried out to determine the optimal addition amount using cellulase, pectinase and tea polyphenols as influencing factors, and the contents of total alkaloids, total flavonoids and total polysaccharides in mulberry leaves as comprehensive evaluation indicators. Results: Compared with natural fermentation, the contents of total alkaloids, total flavonoids and total polysaccharides in mulberry leaves fermented by additives were increased by 61.84%, 45.02% and 28.68%, when the addition amounts of cellulase, pectinase and tea polyphenols were 0.6%, 0.8% and 0.9%, respectively. And their contents were 115.12%, 80.19% and 54.81% higher than those in natural mulberry leaves, respectively. Conclusion: The contents of hypoglycemic components in natural mulberry leaves can be improved by adding substances that promote fermentation, which lays a foundation for its subsequent effective utilization in hypoglycemia.

Abstract With the fast‐growing and evolving omics data, the demand for streamlined and adaptable tools to handle bioinformatics analysis continues to grow. In response to this need, Automated Bioinformatics Analysis (AutoBA) is introduced, an autonomous AI agent designed explicitly for fully automated multi‐omic analyses based on large language models (LLMs). AutoBA simplifies the analytical process by requiring minimal user input while delivering detailed step‐by‐step plans for various bioinformatics tasks. AutoBA's unique capacity to self‐design analysis processes based on input data variations further underscores its versatility. Compared with online bioinformatic services, AutoBA offers multiple LLM backends, with options for both online and local usage, prioritizing data security and user privacy. In comparison to ChatGPT and open‐source LLMs, an automated code repair (ACR) mechanism in AutoBA is designed to improve its stability in automated end‐to‐end bioinformatics analysis tasks. Moreover, different from the predefined pipeline, AutoBA has adaptability in sync with emerging bioinformatics tools. Overall, AutoBA represents an advanced and convenient tool, offering robustness and adaptability for conventional multi‐omic analyses.

Abstract Cholangiocarcinoma (CCA) was identified as a malignant tumor with rising incidence and mortality rates, and the roles of long noncoding RNA (lncRNA) in CCA remained not entirely clear. In this study, LINC00511 had high expression in CCA, which was closely related to poor prognosis. Knockdown of LINC00511 significantly inhibited cell malignant biological behaviors. It also affected the stemness of CCA, evidenced by decreased SOX2 protein expression. Moreover, the study revealed the interaction of LINC00511, YTHDF2, and SOX2 in CCA. Specifically, LINC00511 facilitated the formation of a complex with YTHDF2 on SOX2 mRNA, which uniquely enhances the mRNA's stability through m6A methylation sites. This stabilization appears crucial for maintaining malignant behaviors in CCA cells. Additionally, LINC00511 modulated SOX2 expression via the PI3K/AKT signaling pathway. Meanwhile, SOX2 can also promote LINC00511 expression as an upstream transcription factor, thereby confirming a positive feedback loop formed by LINC00511, YTHDF2, and SOX2, which plays a significant role in the occurrence and development of CCA. Finally, the study successfully constructed two patient‐derived xenograft models, revealing the vital role of LINC00511 in CCA development. In summary, this research provides a comprehensive understanding of the role of LINC00511 in the pathogenesis of CCA.

AimTo evaluate the real-life effectiveness and safety of hydrogen inhalation (HI) therapy as an additional treatment in Chinese adults with hypertension.MethodsThis observational, retrospective clinical study included hypertensive patients receiving routine antihypertensives with or without HI initiation from 2018 to 2023. Participants were assigned to the HI group or non-HI group (control group) after propensity score matching. The changes in mean systolic blood pressure (SBP) level during the 24-week follow-up period in different groups were examined primarily. The secondary outcome was the changes in diastolic blood pressure (DBP) and blood pressure (BP) control rate during the study. Several subgroup and sensitivity analyses were performed to confirm the robustness of our main findings. Adverse event (AE) was also assessed in patients of both groups.ResultsIn total, we selected 2,364 patients into the analysis. Both mean SBP and DBP levels significantly decreased in the HI group compared to control group at each follow-up visit with the between group difference of −4.63 mm Hg (95% CI, −6.51 to −2.74) at week 8, −6.69 mm Hg (95% CI, −8.54 to −4.85) at week 16, −7.81 mm Hg (95% CI, −9.57 to −6.04) at week 24 for SBP, and −1.83 mm Hg (95% CI, −3.21 to −0.45) at week 8, −2.57 mm Hg (95% CI, −3.97 to −1.17) at week 16, −2.89 mm Hg (95% CI, −4.24 to −1.54) at week 24 for DBP. Patients in the HI group were more likely to attain controlled BP at the follow-up period with odds ratio of 1.44 (95% CI, 1.21–1.72) at week 8, 1.90 (95% CI, 1.59–2.27) at week 16, and 2.24 (95% CI, 1.87–2.68) at the end. The trends of subgroup and sensitivity analyses were mostly consistent with the main analysis. The incidences of AEs were similar between the HI group and control group with all p-value >0.05.ConclusionThe HI therapy is related to significant amelioration in BP levels with acceptable safety profile in Chinese hypertensive adults after 24 weeks of treatment, building a clinical ground for further research to evaluate the antihypertensive effect of HI therapy.

Drawing upon a comprehensive dataset encompassing Chinese publicly traded enterprises across the two-decade span from 2000 to 2020, this article analyzes the effects of external economic policy variations on the productivity of Chinese enterprises. The consequences show that when facing the aggravation of external variations in economic policy, enterprises prefer to enhance total factor productivity and labor productivity to reduce the risk caused by the expansion of external uncertainty. Moreover, the greater the degree of internationalization of an enterprise, the higher its vulnerability to variations in external economic policies. The mechanism test shows that for enterprises that only participate in domestic circulation, external economic policy fluctuations improve productivity by affecting the operating environment; however, when enterprises join in the dual circulation, the fluctuations will promote productivity by affecting the scale of enterprises’ overseas business instead. First published online 6 November 2024

Objective: Non-alcoholic fatty liver disease (NAFLD) is deemed as an emerging global epidemic, whereas the underlying pathogenic mechanism remains to be clarified. We aimed to systemically analyze all the NAFLD-related gene expression datasets from published human-based studies, by which exploring potential key factors and mechanisms accounting for the pathogenesis of NAFLD. Methods: Robust rank aggregation (RRA) method was used to integrate NAFLD-related gene expression datasets. For fatty liver study, adeno-associated virus (AAV) delivery and genetic knockout mice were used to create IGFBP2 (Insulin-like growth factor binding protein 2) gain- or loss-of function models. Western blot, Co-immunoprecipitation (Co-IP), immunofluorescent (IF) staining, luciferase assay, molecular docking simulation were performed to reveal the IGFBP2-EGFR-STAT3 axis involved. Key axis protein levels in livers from healthy donors and patients with NAFLD were assessed via immunohistochemical staining. Results: By using RRA method, the present study identified IGFBP2 being the most significantly down-regulated gene in all NAFLD subjects. The decreased IGFBP2 expression was further confirmed in the liver tissues from patients and animal models of NAFLD. IGFBP2 deficiency aggravated hepatic steatosis and NASH phenotypes and promoted lipogenic gene expression both in vivo and in vitro. Mechanistically, IGFBP2 directly binds to and regulates EGFR, whereas blockage of the IGFBP2-EGFR complex by knockdown of IGFBP2 resulted in the EGFR-STAT3 pathway activation, which in turn promoted the promoter activity of Srebf1. By using molecular docking simulation and protein-protein interaction analysis, the sequence of 233-257 amino acids in IGFBP2 was characterized as a key motif responding for its specific binding to EGFR and the protective effect against hepatic steatosis. Conclusions: The current study has, for the first time, identified IGFBP2 as a novel protector against hepatosteatosis. The protective effect is mediated by its specific interaction with EGFR and thereby suppressing the EGFR-STAT3 pathway. Therefore, pharmaceutically targeting the IGFBP2-EGFR-STAT3 axis may provide a theoretical basis for for the treatment of NAFLD/NASH and the associated diseases.

Heated cigarettes are becoming trendy due to their advantage of not burning the tobacco material and thus reducing the amount of harmful ingredients released, while being able to leave the nicotine and tar content of the smoke untouched. However, the high temperature of the smoke as it enters the human mouth can affect the user experience. Therefore, the development of adsorption cooling materials for use in heated cigarettes is gradually becoming a hot topic. In this work, an adsorption cooling material based on embossed rod powder was prepared. It was found that compared with the commercial Yoga cooling material, the embossed rod powder based adsorption cooling material was able to reduce the maximum smoke temperature to 45.16 °C. In addition, it reduced the adsorption of nicotine by the cooling material, and increased the glycerol and nicotine content in the cooled smoke, which effectively promoted the taste of the smoke. Furthermore, the molecular simulation results found that the higher specific surface area and rich microscopic pore structure could increase the heat conduction area of the high-temperature flue gas, which enhanced the heat transfer effect of the flue gas. Finally, the periodic characteristic velocity pulsation destroyed the boundary layer formed by the fluid in the wall region, which increased the convective heat transfer effect between the fluid and the particles. The optimum sample 03 had the largest specific surface area and the lowest crystallinity, and thus had the best cooling effect. This work could provide some reference significance for the development of cooling materials for heating cigarettes.

Object: This study aims to evaluate the value of super resolution (SR) technology in augmenting the quality of digestive endoscopic images. Methods: In the retrospective study, we employed two advanced SR models, i.e., SwimIR and ESRGAN. Two discrete datasets were utilized, with training conducted using the dataset of the First Affiliated Hospital of Soochow University (12,212 high-resolution images) and evaluation conducted using the HyperKvasir dataset (2,566 low-resolution images). Furthermore, an assessment of the impact of enhanced low-resolution images was conducted using a 5-point Likert scale from the perspectives of endoscopists. Finally, two endoscopic image classification tasks were employed to evaluate the effect of SR technology on computer vision (CV). Results: SwinIR demonstrated superior performance, which achieved a PSNR of 32.60, an SSIM of 0.90, and a VIF of 0.47 in test set. 90 % of endoscopists supported that SR preprocessing moderately ameliorated the readability of endoscopic images. For CV, enhanced images bolstered the performance of convolutional neural networks, whether in the classification task of Barrett's esophagus (improved F1-score: 0.04) or Mayo Endoscopy Score (improved F1-score: 0.04). Conclusions: SR technology demonstrates the capacity to produce high-resolution endoscopic images. The approach enhanced clinical readability and CV models’ performance of low-resolution endoscopic images.

The emergence of metacommunity theory has provided a framework for studying the spatial structure of biological communities. To unravel the underlying driving mechanisms of macroinvertebrate metacommunity structure and diversity, this paper evaluates macroinvertebrate data from a water body in eastern China using variance decomposition and stratified partitioning. The results suggest that spatial processes dominate macroinvertebrate metacommunity structure, while the combined effects of spatial processes, aquatic environment, and geoclimatic factors also explain part of the macroinvertebrate community structure. Spatial processes, aquatic environment, and geoclimatic factors significantly influenced macroinvertebrate alpha diversity and indirectly influenced beta diversity through alpha diversity. Therefore, the significant effects of spatial processes and geoclimatic variables cannot be ignored in biological assessments, especially biodiversity assessments. Our findings elucidate the metacommunity dynamics in the region and provide crucial information for conservation planning in riverine ecosystems.

Climate anomalies such as drought may lead to cascading effects on river ecosystems, ultimately resulting in the change of aquatic biocenosis. Here, we investigated functional assemblies of fish communities at three sites below the Gezhouba Dam of the middle Yangtze River in China before and during a drought event from 2021 to 2022. As the drought proceeded, the richness of the fish functional groups decreased, and the abundance of demersal/invertivore species increased. These changes might indicate adaptive responses of fish communities to the reduction in water volume and shrinkage in habitat areas. The shifts in functional structure also caused fish communities to become more similar during the drought. The null model based on functional traits showed a distance effect of the fish community assembly rules. The communities close to the dam were structured more stochastically under drought stress, which may be attributed to the impact of ecological operation by cascade hydro-junctions. In contrast, the communities far away from the dam were structured by environmental filtering. Our results support the hypothesis that the natural hydrological regime is the main force driving the spatiotemporal dynamic of riverine fish assemblages, and the drought stress on fish communities may need more attention to cope with future biodiversity loss under global climate changes.

Abstract Ulcerative colitis (UC) is characterized by an abnormal immune response, and the pathogenesis lacks clear understanding. The cGAS-STING pathway is an innate immune signaling pathway that plays a significant role in various pathophysiological processes. However, the role of the cGAS-STING pathway in UC remains largely unclear. In this study, we obtained transcriptome sequencing data from multiple publicly available databases. cGAS-STING related genes were obtained through literature search, and differentially expressed genes (DEGs) were analyzed using R package limma. Hub genes were identified through protein–protein interaction (PPI) network analysis and module construction. The ConsensuClusterPlus package was utilized to identify molecular subtypes based on hub genes. The therapeutic response, immune microenvironment, and biological pathways of subtypes were further investigated. A total of 18 DEGs were found in UC patients. We further identified IFI16, MB21D1 (CGAS), TMEM173 (STING) and TBK1 as the hub genes. These genes are highly expressed in UC. IFI16 exhibited the highest diagnostic value and predictive value for response to anti-TNF therapy. The expression level of IFI16 was higher in non-responders to anti-TNF therapy. Furthermore, a cluster analysis based on genes related to the cGAS-STING pathway revealed that patients with higher gene expression exhibited elevated immune burden and inflammation levels. This study is a pioneering analysis of cGAS-STING pathway-related genes in UC. These findings provide new insights for the diagnosis of UC and the prediction of therapeutic response.

Phenotypic differences between diploid parents and their allotriploid offspring are common in aquaculture breeding. Some allotriploid populations exhibit rapid growth rates and increased body weight, which are significant for supporting fisheries development. Understanding the genetic mechanisms underlying these traits is crucial for implementing diverse breeding strategies to achieve high production in fish farming. Here, we collected the following fish species for our study: red crucian carp (Carassius auratus red var., 2nRR), common carp (Cyprinus carpio L., 2nCC), and two allotriploids (3nR2C and 3 nRC2). These allotriploids were obtained through backcrossing an allotetraploid of C. auratus red var. × C. carpio L. (4nR2C2, ♂) with C. auratus red var. and C. carpio L. (♀), respectively. These allotriploids demonstrated faster growth rates compared to their diploid inbred parents, contributing to the Chinese fisheries industry for several decades. We conducted a systematic comparison of mitochondrial DNA (mtDNA) copy numbers in the liver and muscle tissues of 2nRR, 2nCC, 3nR2C, and 3 nRC2 under different seasons. When entering winter (low water temperature: 13 °C), the triploid fish (3nR2C and 3 nRC2) exhibited lower mtDNA copy numbers in the muscle, indicating a reduction in individual activity and energy expenditure to facilitate weight maintenance when food availability is limited. Furthermore, we analysed the expression levels of three nuclear-regulated mitochondrial genes (tfam, tfb1m, and tfb2m) and observed an imbalance of allelic expression in tfam and tfb1m in the two triploid fish. These findings enhance our understanding of the molecular regulatory mechanisms underlying growth trait differences among fish with different ploidy levels.

The Dongsheng Coalfield in Ordos is a Jurassic coal bearing formation, and the 2-2 and 3-1 coal seams in many deep mining areas can be mined in the whole area, and the spacing of coal seams is small. This paper takes Yingpanhao Coal Mine as a geological prototype, and constructs a numerical model of the research area through FLAC3D and UDEC numerical simulation software to study the surface movement deformation and the evolution law of stress field caused by mining coal seams 2-2 and 3-1. The results show that repeated mining in multiple coal seams will cause the central projection of the subsidence basin to move toward the direction of lower coal seam, and then approach the central projection of the initial mining of the upper coal seam, and ultimately cross it; after the two coal seams were continuously mined, the maximum subsidence value of the surface is less than the sum of the maximum subsidence values caused by mining the two coal seams separately, and the subsidence coefficient of the coal seam repeated mining is less than the initial mining subsidence coefficient; coal pillar dislocation is closely related to surface movement parameters, the staggered coefficient is related to the surface subsidence coefficient, horizontal movement coefficient, and the tangent of the main influencing angle in a logarithmic normal function, concave parabolic function, and convex parabolic function, respectively; as common factors, pillar staggered distance and width-depth ratio have coupling effects on the ratio of characteristic parameters of primary mining and repeated mining in coal seam; in addition, with the increase of pillar staggered distance, the surface subsidence basin area decreases first and then increases, and the contours of horizontal movement near the basin evolve from ellipse to shuttle; the optimal staggered distance of multi-coal seam mining in this study area is 30 m based on the empirical formula of pressure relief distance, the surface damage degree and the relief effect of staggered mining.

Abstract Background Obesity is a global public health concern linked to chronic diseases such as cardiovascular disease and type 2 diabetes (T2D). Emerging evidence suggests that epigenetic modifications, particularly DNA methylation, may contribute to obesity. However, the molecular mechanism underlying the longitudinal change of BMI has not been well-explored, especially in East Asian populations. Methods This study performed a longitudinal epigenome-wide association analysis of DNA methylation to uncover novel loci associated with BMI change in 533 individuals across two Chinese cohorts with repeated DNA methylation and BMI measurements over four years. Results We identified three novel CpG sites (cg14671384, cg25540824, and cg10848724) significantly associated with BMI change. Two of the identified CpG sites were located in regions previously associated with body shape and basal metabolic rate. Annotation of the top 20 BMI change-associated CpGs revealed strong connections to obesity and T2D. Notably, these CpGs exhibited active regulatory roles and located in genes with high expression in the liver and digestive tract, suggesting a potential regulatory pathway from genome to phenotypes of energy metabolism and absorption via DNA methylation. Cross-sectional and longitudinal EWAS comparisons indicated different mechanisms between CpGs related to BMI and BMI change. Conclusion This study enhances our understanding of the epigenetic dynamics underlying BMI change and emphasizes the value of longitudinal analyses in deciphering the complex interplay between epigenetics and obesity.

Abstract Background Aldehyde dehydrogenases (ALDHs) are a family of enzymes that catalyze the oxidation of aldehyde molecules into the corresponding carboxylic acid, regulate the balance of aldehydes and protect plants from the poisoning caused by excessive accumulation of aldehydes; however, this gene family has rarely been studied in cotton. Results In the present study, genome-wide identification was performed, and a total of 114 ALDH family members were found in three cotton species, Gossypium hirsutum, Gossypium arboreum and Gossypium raimondii. The ALDH genes were divided into six subgroups by evolutionary analysis. ALDH genes in the same subgroup showed similar gene structures and conserved motifs, but some genes showed significant differences, which may result in functional differences. Chromosomal location analysis and selective pressure analysis revealed that the ALDH gene family had experienced many fragment duplication events. Cis-acting element analysis revealed that this gene family may be involved in the response to various biotic and abiotic stresses. The RT‒qPCR results showed that the expression levels of some members of this gene family were significantly increased under salt stress conditions. Gohir.A11G040800 and Gohir.D06G046200 were subjected to virus-induced gene silencing (VIGS) experiments, and the sensitivity of the silenced plants to salt stress was significantly greater than that of the negative control plants, suggesting that Gohir.A11G040800 and Gohir.D06G046200 may be involved in the response of cotton to salt stress. Conclusions In total, 114 ALDH genes were identified in three Gossypium species by a series of bioinformatics analysis. Gene silencing of the ALDH genes of G. hirsutum revealed that ALDH plays an important role in the response of cotton to salt stress.