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IntroductionInflammatory bowel disease (IBD) is a multi-organ autoimmune disease that commonly affects the gastrointestinal tract, but can also affect other organs throughout the body. Less is known, however, about kidney involvement in IBD. Although IBD has been associated with chronic kidney disease (CKD) and end-stage renal disease (ESRD), these results have been inconsistent. The present study analyzed the prevalence of concurrent CKD and ESRD in patients with IBD.MethodsPubMed, Cochrane, Web of Science, and Embase were searched for studies published through October 2023 on IBD patients with concurrent CKD or ESRD. Outcomes included the incidence rates and odds ratios (OR) of concurrent CKD and ESRD in IBD patients. The quality of included studies was assessed using the Newcastle-Ottawa Scale, and sequential sensitivity was analyzed. Publication bias was evaluated using Egger’s test.ResultsNine studies were included in this meta-analysis. The combined results of eight studies, which included 239,042 IBD patients, showed that the prevalence of CKD in IBD patients was 5% (95% confidence interval [CI]: 1–9%). The combined results of two studies, which included 40,341 IBD patients, showed that the prevalence of ESRD in IBD patients was 0.2% (95% CI: −0.08–0.12%). The combined results of six case–control studies reported that the risk of CKD was significantly higher in patients with than without IBD (OR 1.36, 95% CI: 1.08–1.70, p = 0.008).ConclusionAlthough studies have shown an increased risk of CKD in IBD, due to the small number of included studies and high heterogeneity across studies, it is not enough to definitively conclude that CKD is more common in patients with IBD. But patients with IBD should be regularly monitored for CKD.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/.

Background and aimsInflammatory bowel disease (IBD) is a common chronic inflammatory bowel disease characterized by diarrhea and abdominal pain. Recently human metabolites have been found to help explain the underlying biological mechanisms of diseases of the intestinal system, so we aimed to assess the causal relationship between human blood metabolites and susceptibility to IBD subtypes.MethodsWe selected a genome-wide association study (GWAS) of 275 metabolites as the exposure factor, and the GWAS dataset of 10 IBD subtypes as the outcome, followed by univariate and multivariate analyses using a two-sample Mendelian randomization study (MR) to study the causal relationship between exposure and outcome, respectively. A series of sensitivity analyses were also performed to ensure the robustness of the results.ResultsA total of 107 metabolites were found to be causally associated on univariate analysis after correcting for false discovery rate (FDR), and a total of 9 metabolites were found to be significantly causally associated on subsequent multivariate and sensitivity analyses. In addition we found causal associations between 7 metabolite pathways and 6 IBD subtypes.ConclusionOur study confirms that blood metabolites and certain metabolic pathways are causally associated with the development of IBD subtypes and their parenteral manifestations. The exploration of the mechanisms of novel blood metabolites on IBD may provide new therapeutic ideas for IBD patients.

Abstract Single cell chromatin accessibility profiling and transcriptome sequencing are the most widely used technologies for single-cell genomics. Here, we present Microwell-seq3, a high-throughput and facile platform for high-sensitivity single-nucleus chromatin accessibility or full-length transcriptome profiling. The method combines a preindexing strategy and a penetrable chip-in-a-tube for single nucleus loading and DNA amplification and therefore does not require specialized equipment. We used Microwell-seq3 to profile chromatin accessibility in more than 200,000 single nuclei and the full-length transcriptome in ~50,000 nuclei from multiple adult mouse tissues. Compared with the existing polyadenylated transcript capture methods, integrative analysis of cell type-specific regulatory elements and total RNA expression uncovered comprehensive cell type heterogeneity in the brain. Gene regulatory networks based on chromatin accessibility profiling provided an improved cell type communication model. Finally, we demonstrated that Microwell-seq3 can identify malignant cells and their specific regulons in spontaneous lung tumors of aged mice. We envision a broad application of Microwell-seq3 in many areas of research.

BackgroundLimited studies have investigated the relationship between systemic oxidative stress and inflammatory bowel disease (IBD). The purpose of this study was to explore the relationship between oxidative balance score (OBS) and IBD.MethodsWe included 175,808 participants from the UK Biobank database from 2006 to 2010. OBS scores were calculated based on 22 lifestyle and dietary factors. Multiple variable Cox proportional regression models, as well as gender stratification and subgroup analysis, were utilized to investigate the relationship between OBS and IBD.ResultsThere is a significant negative correlation between OBS and the occurrence of IBD, ulcerative colitis (UC), and Crohn’s disease (CD). Additionally, OBS is significantly negatively correlated with intestinal obstruction in CD patients. Gender stratified analysis suggest a significant correlation between OBS and CD in female patients, particularly pronounced in those under 60 years old. Sensitivity analysis indicates a significant negative correlation between lifestyle-related OBS and diet-related OBS with the occurrence of CD in females, diet-related OBS is negatively correlated with CD in males.ConclusionOBS showed a significant negative correlation with IBD, especially in female CD patients. This study underscores the importance of antioxidant diet and lifestyle, which may provide a greater advantage for female CD patients.

BackgroundThe Oxidative Balance Score (OBS) is commonly used to assess oxidative stress and provides a comprehensive evaluation of dietary and lifestyle-related exposures. However, there is limited research on the association between OBS and colorectal cancer (CRC), its subsites, and complications. The objective of this study was to assess the relationship between OBS and the risk of CRC, its subsites, and common complications in a large prospective cohort study.MethodsWe included data from 175,808 participants in the UK Biobank data sample repository from 2006 to 2010. We evaluated OBS using a scoring system based on 22 dietary and lifestyle factors. Multiple adjustments, including multivariate Cox proportional hazard regression, gender stratification, subgroup analysis, and sensitivity analysis, were performed to fully explore the relationship between OBS and CRC, its subsites, and complications. The mediation analysis was conducted to investigate whether serum albumin, uric acid, and neutrophil levels mediate the relationship between OBS and CRC.ResultsAfter adjusting for potential confounding factors, a significant negative correlation was found between OBS and the risk of CRC and its subsites (proximal colon cancer, distal colon cancer, and rectal cancer). This correlation was particularly pronounced in male CRC patients. Serum albumin, uric acid, and neutrophil count, which are biomarkers, were found to have a significant mediating effect between OBS and CRC.ConclusionOur study suggests that higher exposure to antioxidants assessed through OBS (diet and lifestyle rich in antioxidants) may decrease the occurrence of CRC and its subsites.

Background and aimsInflammatory bowel disease (IBD), mainly categorized into Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic relapsing gastrointestinal disorder that significantly impairs patients’ quality of life. IBD patients often experience comorbidities such as anxiety and depression, and the underlying mechanisms and treatment strategies remain areas of investigation.MethodsWe conducted a Mendelian randomization(MR) analysis utilizing brain image derived phenotypes (IDP) from the UK Biobank database to investigate the causal relationships between IBD and alterations in brain structural morphology and connectivity of neural tracts. This study aimed to identify biological evidence linking IBD to psychiatric disorders such as anxiety and depression.ResultsSpecifically, the volume of grey matter in the Left Frontal Orbital Cortex exhibited a negative association with the onset of Crohn’s disease (odds ratio (OR) [95% confidence interval (CI)]: 0.315[0.180~0.551], adjusted P=0.001), while the volume of the superior frontal cortex in the right hemisphere showed a positive correlation with the development of Ulcerative colitis (OR [95% CI]: 2.285[1.793~2.911], adjusted P

Abstract Tumor heterogeneity and its drivers impair tumor progression and cancer therapy. Single‐cell RNA sequencing is used to investigate the heterogeneity of tumor ecosystems. However, most methods of scRNA‐seq amplify the termini of polyadenylated transcripts, making it challenging to perform total RNA analysis and somatic mutation analysis.Therefore, a high‐throughput and high‐sensitivity method called snHH‐seq is developed, which combines random primers and a preindex strategy in the droplet microfluidic platform. This innovative method allows for the detection of total RNA in single nuclei from clinically frozen samples. A robust pipeline to facilitate the analysis of full‐length RNA‐seq data is also established. snHH‐seq is applied to more than 730 000 single nuclei from 32 patients with various tumor types. The pan‐cancer study enables it to comprehensively profile data on the tumor transcriptome, including expression levels, mutations, splicing patterns, clone dynamics, etc. New malignant cell subclusters and exploring their specific function across cancers are identified. Furthermore, the malignant status of epithelial cells is investigated among different cancer types with respect to mutation and splicing patterns. The ability to detect full‐length RNA at the single‐nucleus level provides a powerful tool for studying complex biological systems and has broad implications for understanding tumor pathology.

Abstract A deeper understanding of genetic regulation and functional mechanisms underlying genetic associations with complex traits and diseases is impeded by cellular heterogeneity and linkage disequilibrium. To address these limits, we introduce Huatuo, a framework to decode genetic variation of gene regulation at cell type and single-nucleotide resolutions by integrating deep-learning-based variant predictions with population-based association analyses. We apply Huatuo to generate a comprehensive cell type-specific genetic variation landscape across human tissues and further evaluate their potential roles in complex diseases and traits. Finally, we show that Huatuo’s inferences permit prioritizations of driver cell types associated with complex traits and diseases and allow for systematic insights into the mechanisms of phenotype-causal genetic variation.

This study investigates the influence of molybdenum (Mo) doping on the local atomic structure, morphology, and electrical properties of amorphous germanium telluride (GeTe) thin films. Structural and morphological studies show that Mo-doping inhibits the crystallization of amorphous GeTe thin films. Moreover, the crystallization temperature of the GeTe thin film increases from 197 to 317 °C with increasing Mo dopant concentration. The electrical properties of Mo-doped GeTe thin films are discussed in terms of the capacitance–voltage characteristics in temperatures range 27–357 °C. The optical bandgap values decrease from 0.67 to 0.55 eV when increasing Mo doping in GeTe thin film. Mo integration significantly impacts the Ge–Te bond lengths and structural symmetry, increasing the degree of disorder in amorphous GeTe thin films. This study demonstrates the effectiveness of Mo doping in enhancing the thermal stability of the amorphous phase of GeTe for its envisioned memory and brain-inspired computing applications.

ObjectiveSignificant differences have been discovered between subtypes of Crohn’s disease (CD) and ulcerative colitis (UC). The role of gut microbiota in promoting the onset of UC and CD is established, but conclusions regarding subtype-specific analyses remain limited.MethodsThis study aims to explore the influence of gut microbiota on subtypes of UC and CD, offering novel insights into the pathogenesis and treatment of UC and CD.Two-sample Mendelian randomization (MR) analysis was employed to examine the causal relationship between subtypes of UC and CD and gut microbiota composition. Gut microbiota data were sourced from the International Consortium MiBioGen, while UC and CD data were obtained from FINNGEN. Eligible single nucleotide polymorphisms (SNPs) were selected as instrumental variables. Multiple analytical approaches such as inverse variance-weighted (IVW), MR-Egger regression, weighted median, weighted mode, and MR-RAPS were utilized. Sensitivity analyses including MR-Egger intercept test, Cochran’s Q test, and leave-one-out analysis were conducted for quality control. Subsequently, we employed multivariable IVW, MR-Egger, weighted median, and LASSO regression methods to identify independently significant genera or families and conducted sensitivity analyses.ResultsWe have determined that Hungatella, Acidaminococcaceae, and 15 other microbial taxa act as protective factors for various CD and UC subtypes, while Terrisporobacter, Anaerostipes, and 23 other microbial taxa are associated with increased risk for different CD and UC subtypes. Furthermore, through multivariable MR analysis, we have identified significant genera or families with independent effects.ConclusionOur study confirms a causal relationship between dysbiosis of gut microbiota and the occurrence of CD and UC subtypes. Furthermore, it validates etiological distinctions among different subtypes of CD and UC. A novel approach to adjunctive therapy involving distinct UC or CD subtypes may involve the use of probiotics and represents a potential avenue for future treatments.

To realize the automatic sorting of eggs, the sorting models are established in this paper by using the visible-near infrared spectroscopy technique and taking the eggshell colour, integrity, as well as the feeding mode as sorting indexes. A variety of methods are selected to remove the noise and systematic error by preprocess the spectral information. The backpropagation neural network (BP), the Principal Component Analysis (PCA) coupled with BP and the Soft Independent Modeling of Class Analogy (SIMCA) sorting method are used to identify the eggshell colours (white, pink, green), eggshell integrity (intact, cracked) and laying hen feeding mode (caged and cage-free) by their characteristic band, respectively. The prediction correlation coefficient (Rv), the prediction mean square error (RMSEP), the prediction standard error (SEP), the recognition rate ([Formula: see text]) and the rejection rate ([Formula: see text]) are used to evaluate the established models. The results show that the established classification models have high prediction accuracy and small errors. The non-destructive testing (NDT) technology has great potential for large-scale intelligent laying hen farms.

The Mexican axolotl is a well-established tetrapod model for regeneration and development. Here the authors report a scRNA-seq method to profile neotenic, metamorphic and limb development stages, highlighting unique perturbation patterns of cell type-related gene expression throughout metamorphosis.

Single-cell RNA sequencing technology offers a unique opportunity to dissect cell heterogeneity of animals. Here, the authors construct a Xenopus cell landscape including larval and adult organs to dissect cell heterogeneity of the amphibian.

Abstract Myelodysplastic syndrome with myelofibrosis (MDS-MF) has been associated with an inferior prognosis compared with MDS without MF. However, MDS-MF is not listed independently as a subtype of MDS, and its clinical and genetic characteristics remain poorly understood. We retrospectively compared 53 patients with MDS-MF (44 MF grade 1/MF1; 9 MF grade 2–3/MF2 − 3) and 31 with de novo MDS without MF (MDS). The leukemic transformation risks of both MDS-MF2 − 3 and MDS-MF1 were increased compared with the MDS group. To identify the potential mechanisms responsible for the leukemic transformation of MDS-MF, we performed single-cell sequencing for one MDS-MF2 − 3 patient before and after leukemic transformation to explore the variations in gene expression levels. In addition to upgraded expression levels of acute myeloid leukemia-related genes during leukemic transformation, expression levels of some inflammation-related genes (such as S100s, RNASE3, and CYBB) were also increased, and inflammation-related pathways were up-regulated. These results suggest that inflammation-related genes and pathways may play an important role in the leukemic transformation of MDS-MF.

Abstract Background Acute myeloid leukemia (AML) is a fatal hematopoietic malignancy and has a prognosis that varies with its genetic complexity. However, there has been no appropriate integrative analysis on the hierarchy of different AML subtypes. Methods Using Microwell-seq, a high-throughput single-cell mRNA sequencing platform, we analyzed the cellular hierarchy of bone marrow samples from 40 patients and 3 healthy donors. We also used single-cell single-molecule real-time (SMRT) sequencing to investigate the clonal heterogeneity of AML cells. Results From the integrative analysis of 191727 AML cells, we established a single-cell AML landscape and identified an AML progenitor cell cluster with novel AML markers. Patients with ribosomal protein high progenitor cells had a low remission rate. We deduced two types of AML with diverse clinical outcomes. We traced mitochondrial mutations in the AML landscape by combining Microwell-seq with SMRT sequencing. We propose the existence of a phenotypic “cancer attractor” that might help to define a common phenotype for AML progenitor cells. Finally, we explored the potential drug targets by making comparisons between the AML landscape and the Human Cell Landscape. Conclusions We identified a key AML progenitor cell cluster. A high ribosomal protein gene level indicates the poor prognosis. We deduced two types of AML and explored the potential drug targets. Our results suggest the existence of a cancer attractor.

Abstract Recently, single-cell RNA-seq technologies have been rapidly updated, leading to a revolution in biology. We previously developed Microwell-seq, a cost-effective and high-throughput single cell RNA sequencing(scRNA-seq) method with a very simple device. Most cDNA libraries are sequenced using an expensive Illumina platform. Here, we present the first report showing combined Microwell-seq and BGI MGISEQ2000, a less expensive sequencing platform, to profile the whole transcriptome of 11,883 individual mouse adult adrenal gland cells and identify 18 transcriptionally distinct clusters. Moreover, we performed a single-cell comparative analysis of human and mouse adult adrenal glands to reveal the conserved genetic networks in these mammalian systems. These results provide new insights into the sophisticated adrenal gland hierarchy and provide a benchmark, low-cost strategy for high-throughput single-cell RNA study.

Zebrafish have been found to be a premier model organism in biological and regeneration research. However, the comprehensive cell compositions and molecular dynamics during tissue regeneration in zebrafish remain poorly understood. Here, we utilized Microwell-seq to analyze more than 250,000 single cells covering major zebrafish cell types and constructed a systematic zebrafish cell landscape. We revealed single-cell compositions for 18 zebrafish tissue types covering both embryo and adult stages. Single-cell mapping of caudal fin regeneration revealed a unique characteristic of blastema population and key genetic regulation involved in zebrafish tissue repair. Overall, our single-cell datasets demonstrate the utility of zebrafish cell landscape resources in various fields of biological research.

Enchondroma (EC) is a common benign bone tumor. It has the risk of malignant transformation to Chondrosarcoma (CS). However, the underlying mechanism is unclear. The gene expression profile of EC and CS was obtained from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using GEO2R. We conducted the enrichment analysis and constructed the gene interaction network using the DEGs. We found that the epithelial-mesenchymal transition (EMT) and the VEGFA-VEGF2R signaling pathway were more active in CS. The CD8+ T cell immunity was enhanced in CS I. We believed that four genes (MFAP2, GOLM1, STMN1, and HN1) were poor predictors of prognosis, while two genes (CAB39L and GAB2) indicated a good prognosis. We have revealed the mechanism in the tumor progression and identified the key genes that predicted the prognosis. This study provided new ideas for the diagnosis and treatment of EC and CS.

Mn-Cu high damping alloy is a twin-type damping alloy. Owing to its martensite twin structure at room temperature, it can convert vibration energy into heat energy, thereby reducing vibration. Although essentially a nonlinear elastic material, Mn-Cu damping alloys are treated as linear elastic materials in current engineering practice. However, introducing a constant damping coefficient alone will produce significant errors when modeling vibration reduction characteristics of the material, especially under impact loading. In this study, vibration test was performed on Mn-Cu damping alloy cantilever beam subjected to an impact load and deviation between the test result and the one of existing modeling method was analyzed. A generalized fractional-order Maxwell model was established to describe the nonlinear constitutive relation of the Mn-Cu damping alloy. Then, the model was extended to the three-dimensional state and a secondary development was performed. Finally, various applications for the damping alloy were explored and the effects of the damping alloy on the vibration characteristics of composite cantilever beam structures subjected to impact loads were investigated with the aim of better understanding the dynamic characteristics and improving the effectiveness of vibration reduction applications using Mn-Cu damping alloy in the future.

Abstract Background Human pluripotent stem cells (hPSCs) provide powerful models for studying cellular differentiations and unlimited sources of cells for regenerative medicine. However, a comprehensive single-cell level differentiation roadmap for hPSCs has not been achieved. Results We use high throughput single-cell RNA-sequencing (scRNA-seq), based on optimized microfluidic circuits, to profile early differentiation lineages in the human embryoid body system. We present a cellular-state landscape for hPSC early differentiation that covers multiple cellular lineages, including neural, muscle, endothelial, stromal, liver, and epithelial cells. Through pseudotime analysis, we construct the developmental trajectories of these progenitor cells and reveal the gene expression dynamics in the process of cell differentiation. We further reprogram primed H9 cells into naïve-like H9 cells to study the cellular-state transition process. We find that genes related to hemogenic endothelium development are enriched in naïve-like H9. Functionally, naïve-like H9 show higher potency for differentiation into hematopoietic lineages than primed cells. Conclusions Our single-cell analysis reveals the cellular-state landscape of hPSC early differentiation, offering new insights that can be harnessed for optimization of differentiation protocols.

Variation in gene expression is an important feature of mouse embryonic stem cells (ESCs). However, the mechanisms responsible for global gene expression variation in ESCs are not fully understood. We performed single-cell mRNA-seq analysis of mouse ESCs and uncovered significant heterogeneity in ESCs cultured in serum. We define highly variable gene clusters with distinct chromatin states and show that bivalent genes are prone to expression variation. At the same time, we identify an ESC-priming pathway that initiates the exit from the naive ESC state. Finally, we provide evidence that a large proportion of intracellular network variability is due to the extracellular culture environment. Serum-free culture reduces cellular heterogeneity and transcriptome variation in ESCs.

To better describe its constitutive relation, we need a new constitutive equation for an important nonlinear elastic material, Mn-Cu damping alloy. In this work, we studied the nonlinear and hysteretic characteristics of the stress-strain curve of the M2052 alloy with the uniaxial cyclic tensile test with constant strain rate. The strain rate and amplitude correlations of M2052 resembled those of nonlinear viscoelastic material. Therefore, we created a new constitutive equation for the M2052 damping alloy by modifying the fractional Maxwell model, and we used the genetic algorithm to carry out numerical fitting with MATLAB. By comparing with the experimental data, we confirmed that the new constitutive equation could accurately depict the nonlinear constitutive relation and hysteretic property of the damping alloy. Taken together, this new constitutive equation for Mn-Cu damping alloy based on the fractional Maxwell model can serve as an effective tool for further studies of the constitutive relation of the Mn-Cu damping alloys.

A gas chromatography-mass spectrometry (GC-MS) method was established for the determination of 18 preservatives compounds (methyl chloride isothiazolinone, etc.) in infant cosmetics. The cosmetic samples were extracted with 0.1 mg/mL ascorbic acid methanol as the solvent, separated on an Agilent DB-5 MS chromatographic column (30 m×0.25 mm×0.25 μm) by temperature programming with split injection technique, analyzed by GC-MS, and then quantified by an external standard curve. The results indicate that the effective separation and determination of 18 preservatives can be realized within 20 minutes. The method has good linear relationship with the correlation coefficients (R) greater than 0.998, the limits of detection (LOD) are in the ranges of 0.15-1.50 μg/kg, and the average recoveries at three spiked levels are in the range of 76.7%-104.9%. The method is accurate, rapid, simple, and quite suitable for the simultaneous determination of 18 preservatives in infant cosmetics. [ABSTRACT FROM AUTHOR]

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