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【Objective】 The Huaibei Plain in central China is a major agricultural production area where winter wheat often experiences drought during its growing season. This study analyses the spatiotemporal variation in drought during the winter wheat growing season in this region. 【Method】 The analysis was based on meteorological data measured from 1957 to 2018. We used the crop water deficit index (CWDI) during the wheat growing season as a proxy for drought, analysing its inter-annual variation, spatial distribution, fluctuation patterns, occurrence rates, and spatial frequency distribution across different areas in the region. 【Result】 ① Throughout the wheat growing season, ten-day water demand and water supply both showed an initial decrease followed by an increase. Effective precipitation per ten-day period was less than 10 mm, while soil-surface evaporation increased by 260% from mid-March to late May. ② During the growing season, water supply and demand were balanced in Fuyang, Bengbu, and Mengcheng, but not in Dangshan, Bozhou, and Suzhou. Suzhou had the greatest fluctuation in CWDI, while Bengbu had the least. ③ From 1957 to 2018, drought occurrence during the winter wheat growing season increased by approximately 1.5 times, with 2010 experiencing the most widespread and severe droughts. ④ Spatially, drought severity increased from the South to the North, with Dangshan, characterized by fluvo-aquic soil, experiencing more severe droughts than areas with Shajiang Mollisol. Over time, the center with high-frequency of moderate drought shifted northward toward Bozhou and Suzhou. Extreme droughts were rare in this region. 【Conclusion】 Drought severity during the winter wheat growing season in the Huaibei Plain has increased from 1957 to 2018. Water supply and demand are imbalanced in regions such as Dangshan and Suzhou, where supplemental irrigation is needed.

Abstract Complement activation is involved in idiopathic membranous nephropathy (IMN). We aimed to investigate the relationship of serum complement cleavage factor Bb with IMN progression, and to establish a model for early prediction of kidney outcomes. We measured serum factor Bb in a retrospective cohort of 449 IMN patients at the time of kidney biopsy. Cox regression analysis showed that higher levels of serum factor Bb were independently associated with IMN progression event defined as end-stage renal disease or ≥ 40% decline in estimated glomerular filtration rate. Patients in the middle and highest tertiles of serum factor Bb had respectively 2.1-, and 2.6-fold higher risk for disease progression compared with those in the lowest tertile. We developed an optimized prognostic nomogram model incorporating age, log serum anti-PLA2R antibody, log serum Bb, proteinuria and tubular atrophy/interstitial fibrosis. The model demonstrated good predictive ability with a concordance index of 0.77 (bootstrap-corrected of 0.76) for predicting 3-, and 5-year kidney survival. Calibration curves and decision curve analysis confirmed the model’s good calibration and clinical utility. Our findings suggest that serum factor Bb may serve as an essential prognostic indicator of IMN. The novel nomogram model may offer important guidance on the management of this patient population.

In this study, on the basis of single factor experiments, the effects of raw material mass concentration, ethanol volume fraction, ultrasonic power, extraction temperature, and extraction time on the lipase inhibition activity of mulberry leaves extract were investigated in combination with response surface methodology to optimize the ultrasonic-assisted extraction process of the lipase-inhibiting components of mulberry leaves. Meanwhile, the active ingredients of mulberry leaves extract were analyzed by UPLC-Q-TOF HRMS. The results showed that the optimal extraction process parameters for the lipase-inhibiting components of mulberry leaves were as follows: The mass concentration of raw material was 0.05 g/mL, volume fraction of ethanol was 70%, ultrasonic power was 195 W, extraction temperature was 31 ℃ and the extraction time was 40 min. Under these conditions, the lipase inhibition rate of mulberry leaves extract was 39.68%. A total of 1067 compounds were identified. Flavonoids and phenolic acids accounted for the highest proportion, containing 203 and 201 compounds, respectively. These compounds might be the material basis for the lipase inhibiting activity of mulberry leaves extract. In this study, the ultrasonic-assisted extraction process of mulberry leaves was optimized to improve the extraction efficiency of the lipase-inhibiting active components, and the main active ingredients were analyzed. The results may provide a reference for the functional application of mulberry leaves in improving lipid metabolism and the development of health food.

Abstract Objective To compare therapeutic outcomes of predicted proliferative and nonproliferative hepatocellular carcinoma (HCC) after microwave ablation (MWA) using a previously developed imaging-based predictive model, the SMARS score. Methods This multicenter retrospective study included consecutive 635 patients with unresectable HCC who underwent MWA between August 2013 and September 2020. Patients were stratified into predicted proliferative and nonproliferative phenotypes according to the SMARS score. Overall survival (OS) and recurrence-free survival (RFS) were compared between the predicted proliferative and nonproliferative HCCs before and after propensity score matching (PSM). OS and RFS were also compared between the two groups in subgroups of tumor size smaller than 30 mm and tumor size 30–50 mm. Results The SMARS score classified 127 and 508 patients into predicted proliferative and nonproliferative HCCs, respectively. The predicted proliferative HCCs exhibited worse RFS but equivalent OS when compared with nonproliferative HCCs before (p < 0.001 for RFS; p = 0.166 for OS) and after (p < 0.001 for RFS; p = 0.456 for OS) matching. Regarding subgroups of tumor size smaller than 30 mm (p = 0.098) and tumor size 30–50 mm (p = 0.680), the OSs were similar between the two groups. However, predicted proliferative HCCs had worse RFS compared to nonproliferative HCCs in the subgroup of tumor size 30–50 mm (p < 0.001), while the RFS did not differ in the subgroup of tumor size smaller than 30 mm (p = 0.141). Conclusion Predicted proliferative HCCs have worse RFS than nonproliferative ones after MWA, especially in tumor size larger than 30 mm. However, the phenotype of the tumor may not affect the OS. Critical relevance statement Before performing microwave ablation for hepatocellular carcinoma, the tumor phenotype should be considered because it may affect the therapeutic outcome. Key Points Proliferative hepatocellular carcinoma (HCC) may be identified using the SMARS score, an imaging-based predictive model. SMARS predicted proliferative HCCs have worse recurrence-free and equivalent overall survival compared to nonproliferative HCC after microwave ablation. Tumor phenotype should be considered before performing microwave ablation. Graphical Abstract

As China’s electricity market reform progresses， market-based customers can not only participate in medium-to-long-term markets but also engage in the spot market based on their electricity procurement needs. The decomposition strategy for long-term contract energy is directly related to electricity purchasing decisions in the spot market. To rationalize curve decomposition of medium-to-long-term energy of market-based customers and reduce their overall electricity costs， this paper proposes a curve decomposition strategy for medium-to-long term contract energy of market-based customers considering price uncertainty in spot market. Drawing upon information gap decision theory （IGDT）， it proposes two types of uncertainty analysis models—risk-averse models and risk-seeking models—to establish a quantitative relationship between the total electricity costs of market-based customers and the accuracy of spot market price predictions. Case study results demonstrate that the proposed strategy can effectively support energy decomposition decisions for customers while considering price uncertainty in spot market.

Abstract The successful accomplishment of the first telomere-to-telomere human genome assembly, T2T-CHM13, marked a milestone in achieving completeness of the human reference genome. The upcoming era of genome study will focus on fully phased diploid genome assembly, with an emphasis on genetic differences between individual haplotypes. Most existing sequencing approaches only achieved localized haplotype phasing and relied on additional pedigree information for further whole-chromosome scale phasing. The short-read-based Strand-seq method is able to directly phase single nucleotide polymorphisms (SNPs) at whole-chromosome scale but falls short when it comes to phasing structural variations (SVs). To shed light on this issue, we developed a Nanopore sequencing platform-based Strand-seq approach, which we named NanoStrand-seq. This method allowed for de novo SNP calling with high precision (99.52%) and acheived a superior phasing accuracy (0.02% Hamming error rate) at whole-chromosome scale, a level of performance comparable to Strand-seq for haplotype phasing of the GM12878 genome. Importantly, we demonstrated that NanoStrand-seq can efficiently resolve the MHC locus, a highly polymorphic genomic region. Moreover, NanoStrand-seq enabled independent direct calling and phasing of deletions and insertions at whole-chromosome level; when applied to long genomic regions of SNP homozygosity, it outperformed the strategy that combined Strand-seq with bulk long-read sequencing. Finally, we showed that, like Strand-seq, NanoStrand-seq was also applicable to primary cultured cells. Together, here we provided a novel methodology that enabled interrogation of a full spectrum of haplotype-resolved SNPs and SVs at whole-chromosome scale, with broad applications for species with diploid or even potentially polypoid genomes.

【Objective】 Drought is a significant abiotic stress affecting agricultural production in many regions of China. This study investigates the spatiotemporal variations in drought during the growing seasons of summer maize in the Huaibei Plain. 【Method】 The analysis was based on the drought severity index (DSI) from 2010 to 2019 calculated using metrological data measured from weather stations across the region. We focused on the top 0-10 cm soil layer and the root zone from the soil surface to the depth of 50 cm. The M-K test and the Kriging spatial interpolation were used to analyze the spatiotemporal variation in droughts over the region at different time scales. 【Result】 ① Since 2016, the severity and frequency of droughts have both significantly increased in the areas of Dangshan, Mengcheng, and Qiaocheng, while decreased in the area of Fuyang. In Suzhou, droughts mainly occurred in 2010—2012 and 2019. Compared to seasonal scale, some drought events exhibited greater severity and higher frequency at the ten-day scale with unpredictable onset. ②The highest average annual drought index and frequency both occurred during the sowing-emergence stage, reaching moderate level or above, with the frequencies exceeding 40%. Severe droughts or worse at both timescales occurred in northern Dangshan and central Mengcheng and Suzhou. The frequency of the 0-10 cm soil-layer droughts was higher in the southwest, while the frequency of 0-50 cm soil-layer droughts was higher in the east and north than in other areas. ③ At the ten-day scale, the periods with the highest drought severity in each growing season mostly started in the early stage of sowing - emergence, emergence - jointing, and the mid-stage of jointing - tasseling. Severe droughts occurred primarily in August and September. 【Conclusion】 Since 2016, there has been a significant increase in drought severity and frequency for summer maize in the Huaibei Plain, particularly during the sowing seedling stage. Severe droughts were observed at uncertain ten-day scales, with increased drought frequency.

Abstract Background To compare the diagnostic performance of the Node-RADS scoring system and lymph node (LN) size in preoperative LN assessment for rectal cancer (RC), and to investigate whether the selection of size as the primary criterion whereas morphology as the secondary criterion for LNs can be considered the preferred method for clinical assessment. Methods Preoperative CT data of 146 RC patients treated with radical resection surgery were retrospectively analyzed. The Node-RADS score and short-axis diameter of size-prioritized LNs and the morphology-prioritized LNs were obtained. The correlations of Node-RADS score to the pN stage, LNM number and lymph node ratio (LNR) were investigated. The performances on assessing pathological lymph node metastasis were compared between Node-RADS score and short-axis diameter. A nomogram combined the Node-RADS score and clinical features was also evaluated. Results Node-RADS score showed significant correlation with pN stage, LNM number and LNR (Node-RADS of size-prioritized LN: r = 0.600, 0.592, and 0.606; Node-RADS of morphology-prioritized LN: r = 0.547, 0.538, and 0.527; Node-RADSmax: r = 0.612, 0.604, and 0.610; all p

Abstract Comprehensive single-cell metabolic profiling is critical for revealing phenotypic heterogeneity and elucidating the molecular mechanisms underlying biological processes. However, single-cell metabolomics remains challenging because of the limited metabolite coverage and inability to discriminate isomers. Herein, we establish a single-cell metabolomics platform for in-depth organic mass cytometry. Extended single-cell analysis time guarantees sufficient MS/MS acquisition for metabolite identification and the isomers discrimination while online sampling ensures the high-throughput of the method. The largest number of identified metabolites (approximately 600) are achieved in single cells and fine subtyping of MCF-7 cells is first demonstrated by an investigation on the differential levels of 3-hydroxybutanoic acid among clusters. Single-cell transcriptome analysis reveals differences in the expression of 3-hydroxybutanoic acid downstream antioxidative stress genes, such as metallothionein 2 (MT2A), while a fluorescence-activated cell sorting assay confirms the positive relationship between 3-hydroxybutanoic acid and target proteins; these results suggest that the heterogeneity of 3-hydroxybutanoic acid provides cancer cells with different ability to resist surrounding oxidative stress. Our method paves the way for deep single-cell metabolome profiling and investigations on the physiological and pathological processes that occur during cancer.

Abstract Immunotherapy has revolutionized the treatment of cancer. However, its efficacy remains to be optimized. There are at least two major challenges in effectively eradicating cancer cells by immunotherapy. Firstly, cancer cells evade immune cell killing by down-regulating cell surface immune sensors. Secondly, immune cell dysfunction impairs their ability to execute anti-cancer functions. Radiotherapy, one of the cornerstones of cancer treatment, has the potential to enhance the immunogenicity of cancer cells and trigger an anti-tumor immune response. Inspired by this, we fabricate biofunctionalized liposome-like nanovesicles (BLNs) by exposing irradiated-cancer cells to ethanol, of which ethanol serves as a surfactant, inducing cancer cells pyroptosis-like cell death and facilitating nanovesicles shedding from cancer cell membrane. These BLNs are meticulously designed to disrupt both of the aforementioned mechanisms. On one hand, BLNs up-regulate the expression of calreticulin, an “eat me” signal on the surface of cancer cells, thus promoting macrophage phagocytosis of cancer cells. Additionally, BLNs are able to reprogram M2-like macrophages into an anti-cancer M1-like phenotype. Using a mouse model of malignant pleural effusion (MPE), an advanced-stage and immunotherapy-resistant cancer model, we demonstrate that BLNs significantly increase T cell infiltration and exhibit an ablative effect against MPE. When combined with PD-1 inhibitor (α-PD-1), we achieve a remarkable 63.6% cure rate (7 out of 11) among mice with MPE, while also inducing immunological memory effects. This work therefore introduces a unique strategy for overcoming immunotherapy resistance.

Constructing an ecological network is crucial to maintaining ecosystem stability, optimizing ecological space, and ensuring regional ecological security. Using circuit theory, the study integrated habitat condition, ecosystem function, and landscape structure to construct ecological network in Ulanqab. The ecological networks consist of four basic components, including sources, resistance surfaces, corridors and nodes. Ecological sources refer to patches with high habitat quality, while the resistance to species movement between patches is named as ecological resistance surfaces, the important corridors for movement between patches are referred to as ecological corridors, and the vital spots in ecological network are referred to ecological nodes. In addition, the drivers affecting these changes were also analyzed using geographical detector. The results indicated that the area of ecological sources dropped by 19.1 % and the area of high value of ecological resistance surfaces increased from 2000 and 2020. The length of ecological corridors increased by 793.80 km. Mean annual precipitation is the main natural factor influencing the ecological network, and land use intensity and human footprint are the main anthropogenic factors. Our findings suggest that in this region, urban developing should minimize the encroachment on grasslands, forests and waters. Additionally, the availability of water resources should be considered in the planning and implementation of ecological restoration and protection. The findings of the study offer reasonable suggestions for the protection and restoration of priority regions, as well as a scientific foundation optimization and sustainable development of the regional ecological network.

Summary: Our understanding of human fetal cerebellum development during the late second trimester, a critical period for the generation of astrocytes, oligodendrocytes, and unipolar brush cells (UBCs), remains limited. Here, we performed single-cell RNA sequencing (scRNA-seq) in human fetal cerebellum samples from gestational weeks (GWs) 18–25. We find that proliferating UBC progenitors distribute in the subventricular zone of the rhombic lip (RLSVZ) near white matter (WM), forming a layer structure. We also delineate two trajectories from astrogenic radial glia (ARGs) to Bergmann glial progenitors (BGPs) and recognize oligodendrogenic radial glia (ORGs) as one source of primitive oligodendrocyte progenitor cells (PriOPCs). Additionally, our scRNA-seq analysis of the trisomy 21 fetal cerebellum at this stage reveals abnormal upregulated genes in pathways such as the cell adhesion pathway and focal adhesion pathway, which potentially promote neuronal differentiation. Overall, our research provides valuable insights into normal and abnormal development of the human fetal cerebellum.

Abstract Single-cell whole-genome sequencing methods have undergone great improvements over the past decade. However, allele dropout, which means the inability to detect both alleles simultaneously in an individual diploid cell, largely restricts the application of these methods particularly for medical applications. Here, we develop a new single-cell whole-genome sequencing method based on third-generation sequencing (TGS) platform named Refresh-seq (restriction fragment ligation-based genome amplification and TGS). It is based on restriction endonuclease cutting and ligation strategy in which two alleles in an individual cell can be cut into equal fragments and tend to be amplified simultaneously. As a new single-cell long-read genome sequencing method, Refresh-seq features much lower allele dropout rate compared with SMOOTH-seq. Furthermore, we apply Refresh-seq to 688 sperm cells and 272 female haploid cells (secondary polar bodies and parthenogenetic oocytes) from F1 hybrid mice. We acquire high-resolution genetic map of mouse meiosis recombination at low sequencing depth and reveal the sexual dimorphism in meiotic crossovers. We also phase the structure variations (deletions and insertions) in sperm cells and female haploid cells with high precision. Refresh-seq shows great performance in screening aneuploid sperm cells and oocytes due to the low allele dropout rate and has great potential for medical applications such as preimplantation genetic diagnosis.

Abstract Major depressive disorder (MDD) is a serious mental illness, characterized by disturbances of gut microbiome, it is required to further explore how the carbohydrate-active enzymes (CAZymes) were changed in MDD. Here, using the metagenomic data from patients with MDD (n = 118) and heath controls (HC, n = 118), we found that the whole CAZymes signatures of MDD were significantly discriminated from that in HC. α-diversity indexes of the two groups were also significantly different. The patients with MDD were characterized by enriched Glycoside Hydrolases (GHs) and Polysaccharide Lyases (PLs) relative to HC. A panel of makers composed of 9 CAZymes mainly belonging to GHs enabled to discriminate the patients with MDD and HC with AUC of 0.824. In addition, this marker panel could classify blinded test samples from the two groups with an AUC of 0.736. Moreover, we found that baseline 4 CAZymes levels also could predict the antidepressant efficacy after adjusted confounding factors and times of depressive episode. Our findings showed that MDD was associated with disturbances of gut CAZymes, which may help to develop diagnostic and predictive tools for depression.

Abstract Background Glioblastoma (GBM) is the most common malignant tumor of the central nervous system. It is an aggressive tumor characterized by rapid proliferation, diffuse tumor morphology, and poor prognosis. Unfortunately, current treatments, such as surgery, radiotherapy, and chemotherapy, are unable to achieve good outcomes. Therefore, there is an urgent need to explore new treatment targets. A detailed mechanistic exploration of the role of the nuclear pore transporter KPNB1 in GBM is lacking. This study demonstrated that KPNB1 regulated GBM progression through a transcription factor YBX1 to promote the expression of post-protrusion membrane protein NLGN3. This regulation was mediated by the deubiquitinating enzyme USP7. Methods A tissue microarray was used to measure the expression of KPNB1 and USP7 in glioma tissues. The effects of KPNB1 knockdown on the tumorigenic properties of glioma cells were characterized by colony formation assays, Transwell migration assay, EdU proliferation assays, CCK-8 viability assays, and apoptosis analysis using flow cytometry. Transcriptome sequencing identified NLGN3 as a downstream molecule that is regulated by KPNB1. Mass spectrometry and immunoprecipitation were performed to analyze the potential interaction between KPNB1 and YBX1. Moreover, the nuclear translocation of YBX1 was determined with nuclear-cytoplasmic fractionation and immunofluorescence staining, and chromatin immunoprecipitation assays were conducted to study DNA binding with YBX1. Ubiquitination assays were performed to determine the effects of USP7 on KPNB1 stability. The intracranial orthotopic tumor model was used to detect the efficacy in vivo. Results In this study, we found that the nuclear receptor KPNB1 was highly expressed in GBM and could mediate the nuclear translocation of macromolecules to promote GBM progression. Knockdown of KPNB1 inhibited the progression of GBM, both in vitro and in vivo. In addition, we found that KPNB1 could regulate the downstream expression of Neuroligin-3 (NLGN3) by mediating the nuclear import of transcription factor YBX1, which could bind to the NLGN3 promoter. NLGN3 was necessary and sufficient to promote glioma cell growth. Furthermore, we found that deubiquitinase USP7 played a critical role in stabilizing KPNB1 through deubiquitination. Knockdown of USP7 expression or inhibition of its activity could effectively impair GBM progression. In vivo experiments also demonstrated the promoting effects of USP7, KPNB1, and NLGN3 on GBM progression. Overall, our results suggested that KPNB1 stability was enhanced by USP7-mediated deubiquitination, and the overexpression of KPNB1 could promote GBM progression via the nuclear translocation of YBX1 and the subsequent increase in NLGN3 expression. Conclusion This study identified a novel and targetable USP7/KPNB1/YBX1/NLGN3 signaling axis in GBM cells.

Abstract Background The development of radioresistance seriously hinders the efficacy of radiotherapy in lung cancer. However, the underlying mechanisms by which radioresistance occurs are still incompletely understood. The N6-Methyladenosine (m6A) modification of RNA is involved in cancer progression, but its role in lung cancer radioresistance remains elusive. This study aimed to identify m6A regulators involved in lung cancer radiosensitivity and further explore the underlying mechanisms to identify therapeutic targets to overcome lung cancer radioresistance. Methods Bioinformatic mining was used to identify the m6A regulator IGF2BP2 involved in lung cancer radiosensitivity. Transcriptome sequencing was used to explore the downstream factors. Clonogenic survival assays, neutral comet assays, Rad51 foci formation assays, and Annexin V/propidium iodide assays were used to determine the significance of FBW7/IGF2BP2/SLC7A5 axis in lung cancer radioresistance. Chromatin immunoprecipitation (ChIP)-qPCR analyses, RNA immunoprecipitation (RIP) and methylated RNA immunoprecipitation (MeRIP)-qPCR analyses, RNA pull-down analyses, co-immunoprecipitation analyses, and ubiquitination assays were used to determine the feedback loop between IGF2BP2 and SLC7A5 and the regulatory effect of FBW7/GSK3β on IGF2BP2. Mice models and tissue microarrays were used to verify the effects in vivo. Results We identified IGF2BP2, an m6A “reader”, that is overexpressed in lung cancer and facilitates radioresistance. We showed that inhibition of IGF2BP2 impairs radioresistance in lung cancer both in vitro and in vivo. Furthermore, we found that IGF2BP2 enhances the stability and translation of SLC7A5 mRNA through m6A modification, resulting in enhanced SLC7A5-mediated transport of methionine to produce S-adenosylmethionine. This feeds back upon the IGF2BP2 promoter region by further increasing the trimethyl modification at lysine 4 of histone H3 (H3K4me3) level to upregulate IGF2BP2 expression. We demonstrated that this positive feedback loop between IGF2BP2 and SLC7A5 promotes lung cancer radioresistance through the AKT/mTOR pathway. Moreover, we found that the ubiquitin ligase FBW7 functions with GSK3β kinase to recognize and degrade IGF2BP2. Conclusions Collectively, our study revealed that the m6A “reader” IGF2BP2 promotes lung cancer radioresistance by forming a positive feedback loop with SLC7A5, suggesting that IGF2BP2 may be a potential therapeutic target to control radioresistance in lung cancer.

Abstract The desert ecosystem of the Qinghai–Tibet Plateau (QTP) is an important component of China's desert ecosystem. Studying the mechanisms shaping the taxonomic, phylogenetic, and functional beta diversity of plant communities in the QTP desert will help us to promote scientific conservation and management of the region's biodiversity. This study investigated the effects of environmental (including altitude, climate factors, and soil factors) and geographic distances on three facets of beta diversity as well as their turnover and nestedness components based on field survey data. The results showed that turnover components dominate the three facets of beta diversity. However, the turnover contributions to phylogenetic and functional beta diversity were lower than for taxonomic beta diversity. Environmental distance had a greater influence than geographic distance, with the former uniquely explaining 15.2%–22.8% of beta diversity and the latter explaining only 1.7%–2.4%. Additionally, the explanatory power of different factors for beta diversity differed between herbs and shrubs, with environmental distance being more important for the latter. Distance‐based redundancy analysis suggested that soil total potassium content had a substantial impact on the beta diversity of three dimensions, with mean temperature of the coldest month and soil total phosphorus content having a substantial impact on taxonomic and functional beta diversity as well. Our results support that environmental sorting plays a predominant role in shaping plant community composition across QTP desert ecosystems. To maintain the plant diversity of this region, it is crucial to prioritize the conservation of its diverse environmental conditions and actively mitigate its degradation by anthropogenic pressures.

Background: The potential significance of immunoinflammatory factors in the prognosis of individuals afflicted with coronavirus disease 2019 (COVID-19) is worthy of examination. The systemic immune-inflammatory index (SII), a recently developed immunoinflammatory metric based on the enumeration of neutrophils, platelets, and lymphocytes in blood samples, holds promise for elucidating this relationship. Consequently, in order to explore any possible correlation between the SII levels at admission and the in-hospital mortality of patients with COVID-19, we undertook a thorough systematic review and meta-analysis. Methods: In pursuit of accomplishing the aim of this meta-analysis, an extensive search was conducted to seek out pertinent observational studies featuring longitudinal follow-up across PubMed, Cochrane Library, Embase and the Web of Science databases. The I2 statistic was utilized to estimate the extent of heterogeneity and the Cochrane Q test was employed to evaluate heterogeneity between studies. The synthesis of outcomes involved the use of random-effects models, accounting for the possible influence of heterogeneity. Results: Our analysis included sixteen studies, encompassing 10,007 hospitalized COVID-19 patients. Among them, 1801 patients (18.0 %) succumbed during hospitalization. The pooled results indicated that a high SII at admission was substantially linked to a higher risk of all-cause mortality (risk ratio [RR]: 2.41, 95 % confidence interval: 1.78 to 3.24, p

Soil microorganisms play a crucial role in wetland ecosystems, but the specific mechanisms underlying their diversity and network stability across lakeshore wetlands, as well as their importance in microbial ecology, are still poorly understood. Here, we analyzed the biogeographical pattern and network stability of lakeshore wetland microbial communities across a regional scale, and identified the primary factors that influence their composition. The results revealed that α-diversity of wetland bacteria decreased linearly with increasing longitude and latitude, whereas the α-diversity of fungal showed an increasing trend in lakeshore wetlands. Species richness was the principal way that the biogeographical pattern of α-diversity was expressed. The β-diversity of soil microbial in lakeshore wetlands has a significant geographical attenuation pattern. Fungal communities were influenced by stochastic spatial diffusion, while bacterial communities were influenced by deterministic environmental filtration as they transition from semi-arid to arid regions. Community network stability was specifically determined by bacterial and fungal diversity. Structural equation modelling revealed that spatial distance and climate indirectly affect bacterial diversity by influencing soil and plant diversity, which in turn affects feedback network stability. These findings show that the geographical pattern of soil microbial diversity in lakeshore wetlands influences network stability at the spatial scale, offering insights into the adaptation of wetland ecosystem diversity and stability at the regional level.

[Objective] Numerous external interference signals exist in urban rail transit wireless communication system, posing a significant threat to operational safety. Targeting the issue of low identification accuracy due to the radiation source RF (radio frequency) characteristics susceptible to noise and interference, it is necessary to propose an individual identification method for communication radiation sources based on enhanced diagonal integral bispectrum. This method provides an effective new approach to ensuring the security of rail transit wireless communication systems. [Method] The data processing procedure and principles of DCLIB (diagonal-correlation local-integral bispectrum) are analyzed. The calculations for bispectrum transformation, enhanced diagonal integral bispectrum calculation, division of adaptive bispectrum integration interval, and radiation source identification method based on residual networks are explained. Simulation experiments are conducted using actual Wi-Fi (wireless fidelity) devices to analyze and compare the identification performance of the DCLIB method with that of other radiation source identification methods. [Result & Conclusion] The DCLIB method first estimates the bispectrum of communication radiation source signals and utilizes the autocorrelation characteristics of each parallel line on the sub-diagonals to form new spectral information for the enhancement of the signal subtle features. Subsequently, the method adaptively selects a reasonable spectral signal integration interval based on the spectral signal strength, reducing both noise impact and algorithm computational complexity. Thus, an enhanced diagonal integral bispectrum is obtained. The proposed DCLIB signal is then used as the RF fingerprint feature of the radiation source, and individual source identification is achieved using a deep residual network. Simulation identification experiments based on actual Wi-Fi devices demonstrate that the DCLIB method achieves the highest identification accuracy and exhibits excellent noise-resistance performance.

Abstract Background Apatinib, a highly selective VEGFR2 inhibitor, significantly improved efficacy versus placebo as a third- and later-line treatment for advanced gastric cancer in phase 2 and 3 trials. This prospective, single-arm, multicenter phase IV AHEAD study was conducted to verify the safety and efficacy of apatinib in patients with advanced or metastatic gastric or gastroesophageal adenocarcinoma after at least two lines of systematic therapy in clinical practice settings. Methods Patients with advanced gastric cancer who had previously failed at least two lines of chemotherapy received oral apatinib until disease progression, death or unacceptable toxicity. The primary endpoint was safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Adverse events were summarized by the incidence rate. Median OS and PFS were estimated using the Kaplan–Meier method. ORR, DCR, OS at 3 and 6 months, and PFS at 3 and 6 months were calculated, and their 95% CIs were estimated according to the Clopper-Pearson method. Results Between May 2015 and November 2019, a total of 2004 patients were enrolled, and 1999 patients who received at least one dose of apatinib were assessed for safety. In the safety population, 87.9% of patients experienced treatment-related adverse events (TRAEs), with the most common hypertension (45.2%), proteinuria (26.5%), and white blood cell count decreased (25.3%). Additionally, 51% of patients experienced grade ≥ 3 TRAEs. Fatal TRAEs occurred in 57 (2.9%) patients. No new safety concerns were reported. Among the 2004 patients included in the intention-to-treat population, the ORR was 4.4% (95% CI, 3.6–5.4%), and DCR was 35.8% (95% CI, 33.7–38.0%). The median PFS was 2.7 months (95% CI 2.2–2.8), and the median OS was 5.8 months (95% CI 5.4–6.1). Conclusions The findings in the AHEAD study confirmed the acceptable and manageable safety profile and clinical benefit of apatinib in patients with advanced gastric cancer as a third- or later-line of treatment. Trial registration This study was registered with ClinicalTrials.gov NCT02426034. Registration date was April 24, 2015.

Abstract Disturbed gut microbiota is a potential factor in the pathogenesis of major depressive disorder (MDD), yet whether gut microbiota dysbiosis is associated with the severity of MDD remains unclear. Here, we performed shotgun metagenomic profiling of cross-sectional stool samples from MDD (n = 138) and healthy controls (n = 155). The patients with MDD were divided into three groups according to Hamilton Depression Rating Scale 17 (HAMD-17), including mild (n = 24), moderate (n = 72) and severe (n = 42) individuals, respectively. We found that microbial diversity was closely related to the severity of MDD. Compared to HCs, the abundance of Bacteroides was significantly increased in both moderate and severe MDD, while Ruminococcus and Eubacterium depleted mainly in severe group. In addition, we identified 99 bacteria species specific to severity of depression. Furthermore, a panel of microbiota marker comprising of 37 bacteria species enabled to effectively distinguish MDD patients with different severity. Together, we identified different perturbation patterns of gut microbiota in mild-to-severe depression, and identified potential diagnostic and therapeutic targets.

ABSTRACTRadiotherapy could regulate systemic antitumor immunity, while the immune state in the tumor microenvironment (TME) also affects the efficacy of radiotherapy. We have found that higher CD8+ T cell infiltration is associated with longer overall survival of lung adenocarcinoma and melanoma patients receiving radiotherapy. 8-Gray radiation increased the transcriptional levels of chemokines in tumor cells in vitro. However, it was not sufficient to induce significant lymphocyte infiltration in vivo. Dipeptidyl peptidase 4 (DPP4) has been reported to inactivate chemokines via post-translational truncation. Single-cell sequencing revealed that dendritic cells (DCs) had a higher DPP4 expression among other cells in the TME and upregulated DPP4 expression after radiation. Combining a DPP4 inhibitor with radiotherapy could promote chemokines expression and T cell infiltration in the TME, enhancing the antitumor effect of radiotherapy. Moreover, this therapy further enhanced the therapeutic efficacy of anti-PD-1. In this study, we demonstrated the underlying mechanism of why radiotherapy failed to induce sufficient T cell infiltration and proposed an effective strategy to promote T cell infiltration and sensitize radiotherapy. These findings demonstrate the translational value of DPP4 inhibition as a complementary approach to enhance the efficacy of radiotherapy and the combination of radiotherapy with immunotherapy.

ObjectiveTo compare computed tomography (CT)- and magnetic resonance imaging (MRI)-based multiparametric radiomics models and validate a multi-modality, multiparametric clinical-radiomics nomogram for individual preoperative prediction of lymph node metastasis (LNM) in rectal cancer (RC) patients.Methods234 rectal adenocarcinoma patients from our retrospective study cohort were randomly selected as the training (n = 164) and testing (n = 70) cohorts. The radiomics features of the primary tumor were extracted from the non-contrast enhanced computed tomography (NCE-CT), the enhanced computed tomography (CE-CT), the T2-weighted imaging (T2WI) and the gadolinium contrast-enhanced T1-weighted imaging (CE-TIWI) of each patient. Three kinds of models were constructed based on training cohort, including the Clinical model (based on the clinical features), the radiomics models (based on NCE-CT, CE-CT, T2WI, CE-T1WI, CT, MRI, CT combing with MRI) and the clinical-radiomics models (based on CT or MRI radiomics model combing with clinical data) and Clinical-IMG model (based on CT and MRI radiomics model combing with clinical data). The performances of the 11 models were evaluated via the area under the receiver operator characteristic curve (AUC), accuracy, sensitivity, and specificity in the training and validation cohort. Differences in the AUCs among the 11 models were compared using DeLong’s test. Finally, the optimal model (Clinical-IMG model) was selected to create a radiomics nomogram. The performance of the nomogram to evaluate clinical efficacy was verified by ROC curves and decision curve analysis (DCA).ResultsThe MRI radiomics model in the validation cohort significantly outperformed than CT radiomics model (AUC, 0.785 vs. 0.721, p

Common reed (Phragmites australis) is a widespread grass species that exhibits a high degree of intraspecific variation for functional traits along environmental gradients. However, the mechanisms underlying intraspecific variation and adaptation strategies in response to environmental gradients on a regional scale remain poorly understood. In this study, we measured leaf, stem, and root traits of common reed in the lakeshore wetlands of the arid and semi-arid regions of the Inner Mongolia Plateau aiming to reveal the regional-scale variation for functional traits in this species, and the corresponding potentially influencing factors. Additionally, we aimed to reveal the ecological adaptation strategies of common reed in different regions using the plant economics spectrum (PES) theory. The results showed that functional-trait variation followed significant latitudinal and longitudinal patterns. Furthermore, we found that these variations are primarily driven by temperature-mediated climatic differences, such as aridity, induced by geographical distance. In contrast, soil properties and the combined effects of climate and soil had relatively minor effects on such properties. In the case of common reed, the PES theory applies to the functional traits at the organ, as well as at the whole-plant level, and different ecological adaptation strategies across arid and semi-arid regions were confirmed. The extent of utilization and assimilation of resources by this species in arid regions was a conservative one, whereas in semi-arid regions, an acquisition strategy prevailed. This study provides new insights into intraspecific variations for functional traits in common reed on a regional scale, the driving factors involved, and the ecological adaptation strategies used by the species. Moreover, it provided a theoretical foundation for wetland biodiversity conservation and ecological restoration.

Abstract Bone marrow mesenchymal stromal/stem cells (MSCs) are a heterogeneous population that can self-renew and generate stroma, cartilage, fat, and bone. Although a significant progress has been made toward recognizing about the phenotypic characteristics of MSCs, the true identity and properties of MSCs in bone marrow remain unclear. Here, we report the expression landscape of human fetal BM nucleated cells (BMNCs) based on the single-cell transcriptomic analysis. Unexpectedly, while the common cell surface markers such as CD146, CD271, and PDGFRa used for isolating MSCs were not detected, LIFR+PDGFRB+ were identified to be specific markers of MSCs as the early progenitors. In vivo transplantation demonstrated that LIFR+PDGFRB+CD45-CD31-CD235a- MSCs could form bone tissues and reconstitute the hematopoietic microenvironment (HME) effectively in vivo. Interestingly, we also identified a subpopulation of bone unipotent progenitor expressing TM4SF1+CD44+CD73+CD45-CD31-CD235a-, which had osteogenic potentials, but could not reconstitute HME. MSCs expressed a set of different transcription factors at the different stages of human fetal bone marrow, indicating that the stemness properties of MSCs might change during development. Moreover, transcriptional characteristics of cultured MSCs were significantly changed compared with freshly isolated primary MSCs. Our cellular profiling provides a general landscape of heterogeneity, development, hierarchy, microenvironment of the human fetal BM-derived stem cells at single-cell resolution.

Although chromosomal mosaic embryos detected by trophectoderm (TE) biopsy offer healthy embryos available for transfer, high-resolution postnatal karyotyping and chromosome testing of the transferred embryos are insufficient. Here, we applied single-cell multi-omics sequencing for seven infants with blastula chromosomal mosaicism detected by TE biopsy. The chromosome ploidy was examined by single-cell genome analysis, with the cellular identity being identified by single-cell transcriptome analysis. A total of 1616 peripheral leukocytes from seven infants with embryonic chromosomal mosaicism and three control ones with euploid TE biopsy were analyzed. A small number of blood cells showed copy number alterations (CNAs) on seemingly random locations at a frequency of 0%−2.5% per infant. However, none of the cells showed CNAs that were the same as those of the corresponding TE biopsies. The blastula chromosomal mosaicism may be fully self-corrected, probably through the selective loss of the aneuploid cells during development, and the transferred embryos can be born as euploid infants without mosaic CNAs corresponding to the TE biopsies. The results provide a new reference for the evaluations of transferring chromosomal mosaic embryos in certain situations.

The effects of hot pressing pressure, sintering temperature and Y2O3 content on the hardness, the density, the flexural strength and the fracture morphology of the iron-based matrix were studied by orthogonal test, and the better sintering process parameters were obtained. On this basis, the iron-based diamond tool containing Y2O3 was prepared, and its fracture morphology, wear resistance and sharpness were detected and analyzed.The results show that the order of factors affecting the relative density and the hardness of the iron-based binder matrix containing Y2O3 is Y2O3 content, followed by the sintering temperature and the hot pressing pressure, and the influencing factor order of the flexural strength is sintering temperature, Y2O3 content and hot pressing pressure. Y2O3 can promote the densification of iron-based diamond matrix structure and reduces its sintering temperature. Under the better sintering process with sintering temperature of 780 ℃ and hot pressing pressure of 51 kN, an appropriate amount of Y2O3 can reduce the porosity of diamond tools, improve the bonding condition, and enhance the holding ability of binder to diamond abrasive particles.

Ecological integrity can satisfactorily reflect the comprehensive quality of ecosystems and has become a useful tool for evaluating the ecological environment. Ecological integrity evaluation has been widely applied in various ecosystems. Conducted in the Alxa League, the study established an ecological integrity index based on ecosystem structure, function and resilience and evaluated the ecological integrity of the study area in 1990, 2000, 2010 and 2020. Using hotspots spatial analyses, we analyzed the temporal and spatial variation of ecological integrity index during the study period. The main contributing factors affecting ecological integrity were identified with the help of the geographical detector model. Our results showed that: (1) Ecosystem structure, function and resilience in the Alxa League had obvious spatial heterogeneity and barely changed from 1990 to 2020. (2) Half of the area had a poor ecological integrity index, and the decrease in ecological integrity mainly occurred in the Alxa Left Banner. (3) Among the factors affecting the ecological integrity index, land use intensity was the major driving factor, and desertification was a key reason leading to the decrease. Ecological integrity evaluation can increase public awareness of desert conditions and guide policy makers to make reasonable and sustainable policies or strategies to protect and restore desert ecosystems.

The quantitative relationship between land use/cover change (LUCC) within basins, lake water environmental factors, and water quality has long been a popular research area. In this study, we investigated three typical basins (Ulansuhai Basin, Daihai Basin, and Dalinor Basin) in arid and semi-arid areas of China. The assessment was based on the China Land Cover Dataset (CLCD), which was used to calculate the land use dynamic degree index and Markov transfer matrix. Moreover, an econometric analysis model and a hybrid evolutionary algorithm (HEA) model were used to explore the quantitative relationship between LUCC and environmental factors on the lake water quality. The results showed that the LUCC of the three lake basins was dominated by cultivated land and grassland over the past 20 years. In all of the basins, grassland and water area were converted into cultivated land, water area decreased to varying degrees, and impervious surface area increased continuously. Moreover, the concentration of TN and TP were generally proportional to chemical oxygen demand concentration (COD), biochemical oxygen demand concentration (BOD5), and dissolved oxygen concentration (DO), but inversely proportional to water depth and transparency; the relationship between Nutrient concentration and pH was usually related to the ecological threshold. On the basin scale, the grassland and forestland played positive roles in improving water quality, while cultivated land and impervious surface were the main factors contributing to water pollution. Overall, this study provides a scientific theoretical basis for the rational utilization of land resources, improvement of lake water quality, and ecological protection of typical lake basins in arid and semi-arid regions.

Abstract Small bowel adenocarcinomas (SBAs) are rare malignant tumors with a high mortality rate, and their molecular characteristics are still largely unexplored. Here we performed single-cell RNA sequencing for tumor samples from 12 SBA patients and predicted drug candidates for SBA. We identified four prevalent subtypes of malignant cells with distinct signatures including cell cycle program, mitochondria program, metabolism program and epithelial–mesenchymal transition (EMT) program. The progression relationships of these four subtypes of malignant cells were also revealed, which started from the cell cycle program, through the mitochondria program and then progressing into either the metabolism program or the EMT program. Importantly, ligand–receptor interaction pairs were found to be specifically enriched in pairs of EMT-program malignant cells and highly exhausted CD8+ T cells, suggesting that cancer cell subpopulations with EMT features may contribute most to the exhaustion of T cells. We also showed that the duodenal subtype of SBA exhibited molecular features more similar to gastric cancer whereas jejunal subtype of SBA more similar to colorectal cancer. Especially, we predicted specific drugs for SBA based on differential gene expression signatures between malignant cells and normal epithelial cells of SBA, and verified more potent inhibitory effects of volasertib and tozasertib for SBA cancer cells than conventional drugs of SBA at the same concentration, which provides new clues for treatments of SBA. In summary, our study provides a blueprint of the molecular signatures of both tumor cells and tumor microenvironment cells in SBA and reveals potential targets and drug candidates for its clinical treatments.

Abstract Background Colorectal cancer (CRC) ranks as the second-leading cause of cancer-related death worldwide with metastases being the main cause of cancer-related death. Here, we investigated the genomic and transcriptomic alterations in matching adjacent normal tissues, primary tumors, and metastatic tumors of CRC patients. Methods We performed whole genome sequencing (WGS), multi-region whole exome sequencing (WES), simultaneous single-cell RNA-Seq, and single-cell targeted cDNA Sanger sequencing on matching adjacent normal tissues, primary tumors, and metastatic tumors from 12 metastatic colorectal cancer patients (n=84 for genomes, n=81 for exomes, n=9120 for single cells). Patient-derived tumor organoids were used to estimate the anti-tumor effects of a PPAR inhibitor, and self-renewal and differentiation ability of stem cell-like tumor cells. Results We found that the PPAR signaling pathway was prevalently and aberrantly activated in CRC tumors. Blocking of PPAR pathway both suppressed the growth and promoted the apoptosis of CRC organoids in vitro, indicating that aberrant activation of the PPAR signaling pathway plays a critical role in CRC tumorigenesis. Using matched samples from the same patient, distinct origins of the metastasized tumors between lymph node and liver were revealed, which was further verified by both copy number variation and mitochondrial mutation profiles at single-cell resolution. By combining single-cell RNA-Seq and single-cell point mutation identification by targeted cDNA Sanger sequencing, we revealed important phenotypic differences between cancer cells with and without critical point mutations (KRAS and TP53) in the same patient in vivo at single-cell resolution. Conclusions Our data provides deep insights into how driver mutations interfere with the transcriptomic state of cancer cells in vivo at a single-cell resolution. Our findings offer novel knowledge on metastatic mechanisms as well as potential markers and therapeutic targets for CRC diagnosis and therapy. The high-precision single-cell RNA-seq dataset of matched adjacent normal tissues, primary tumors, and metastases from CRCs may serve as a rich resource for further studies.

Abstract Background Lung cancer, one of the most common malignant tumors, exhibits high inter- and intra-tumor heterogeneity which contributes significantly to treatment resistance and failure. Single-cell RNA sequencing (scRNA-seq) has been widely used to dissect the cellular composition and characterize the molecular properties of cancer cells and their tumor microenvironment in lung cancer. However, the transcriptomic heterogeneity among various cancer cells in non-small cell lung cancer (NSCLC) warrants further illustration. Methods To comprehensively analyze the molecular heterogeneity of NSCLC, we performed high-precision single-cell RNA-seq analyses on 7364 individual cells from tumor tissues and matched normal tissues from 19 primary lung cancer patients and 1 pulmonary chondroid hamartoma patient. Results In 6 of 16 patients sequenced, we identified a significant proportion of cancer cells simultaneously expressing classical marker genes for two or even three histologic subtypes of NSCLC—adenocarcinoma (ADC), squamous cell carcinoma (SCC), and neuroendocrine tumor (NET) in the same individual cell, which we defined as mixed-lineage tumor cells; this was verified by both co-immunostaining and RNA in situ hybridization. These data suggest that mixed-lineage tumor cells are highly plastic with mixed features of different types of NSCLC. Both copy number variation (CNV) patterns and mitochondrial mutations clearly showed that the mixed-lineage and single-lineage tumor cells from the same patient had common tumor ancestors rather than different origins. Moreover, we revealed that patients with high mixed-lineage features of different cancer subtypes had worse survival than patients with low mixed-lineage features, indicating that mixed-lineage tumor features were associated with poorer prognosis. In addition, gene signatures specific to mixed-lineage tumor cells were identified, including AKR1B1. Gene knockdown and small molecule inhibition of AKR1B1 can significantly decrease cell proliferation and promote cell apoptosis, suggesting that AKR1B1 plays an important role in tumorigenesis and can serve as a candidate target for tumor therapy of NSCLC patients with mixed-lineage tumor features. Conclusions In summary, our work provides novel insights into the tumor heterogeneity of NSCLC in terms of the identification of prevalent mixed-lineage subpopulations of cancer cells with combined signatures of SCC, ADC, and NET and offers clues for potential treatment strategies in these patients.

Summary: Cell-free DNA (cfDNA) in spent embryo culture media (SECM) provides prospects for noninvasive preimplantation genetic testing. Here, we present a post-bisulfite-adapter-tagging (PBAT)-based whole-genome DNA methylation sequencing protocol (SECM-PBAT) for human SECM cfDNA analysis. We describe steps for SECM lysis, bisulfite conversion and purification, preamplification by random priming, tagging adapter II, and library establishment. We then detail library quality control, sequencing, and bioinformatics analysis. This approach simultaneously detects chromosome aneuploidy and deduces the proportional contributions of cellular components.For complete details on the use and execution of this protocol, please refer to Chen et al. (2021).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

In order to compare and analyze the chloroplast (cp) genomes of tomato germplasms and understand their phylogenetic relationships, the cp genomes of 29 tomato germplasms were sequenced and analyzed in this study. The results showed highly conserved characteristics in structure, number of gene and intron, inverted repeat regions, and repeat sequences among the 29 cp genomes. Moreover, single-nucleotide polymorphism (SNP) loci with high polymorphism located at 17 fragments were selected as candidate SNP markers for future studies. In the phylogenetic tree, the cp genomes of tomatoes were clustered into two major clades, and the genetic relationship between S. pimpinellifolium and S. lycopersicum was very close. In addition, only rps15 showed the highest average KA/KS ratio in the analysis of adaptive evolution, which was strongly positively selected. It may be very important for the study of adaptive evolution and breeding of tomato. In general, this study provides valuable information for further study of phylogenetic relationships, evolution, germplasm identification, and molecular marker-assisted selection breeding of tomato.

Cisplatin is a widely used chemotherapy drug; however, it induces both acute and chronic kidney diseases (CKD) in patients with cancer. The pathogenesis of cisplatin-induced CKD is unclear, and effective renoprotective approaches are not available. Here, we report that repeated low-dose cisplatin (RLDC) treatment of C57BL/6 mice induced chronic cellular senescence in kidney tubules, accompanied with tubular degeneration and profibrotic phenotype transformation that culminated in maladaptive repair and renal fibrosis. Suppression of tubular senescence by senolytic drugs ABT-263 and Fisetin attenuated renal fibrosis and improved tubular repair, as indicated by restoration of tubular regeneration and renal function. In vitro, RLDC also induced senescence in mouse proximal tubular (BUMPT) cells. ABT-263 eliminated senescent BUMPT cells following RLDC treatment, reversed the profibrotic phenotype of the cells, and increased their clonogenic activity. Moreover, ABT-263 alleviated the paracrine effect of RLDC-treated BUMPT cells on fibroblasts for fibrosis. Consistently, knockdown of p16 suppressed post-RLDC senescence and fibrotic changes in BUMPT cells and alleviated their paracrine effects on renal fibroblast proliferation. These results indicate that persistent induction of tubular senescence plays an important role in promoting cisplatin-induced CKD. Targeting senescent tubular cells may be efficient for improvement of kidney repair and for the prevention and treatment of cisplatin-induced CKD.

The presence of senescent cells is associated with renal fibrosis. This study aims to investigate the effect of albumin-induced premature senescence on tubulointerstitial fibrosis and its possible mechanism in vitro. Different concentrations of bovine serum albumim (BSA) with or without si-p21 are used to stimulate HK-2 cells for 72 h, and SA-β-gal activity, senescence-associated secretory phenotypes (SASPs), LaminB1 are used as markers of senescence. Immunofluorescence staining is performed to characterize the G2/M phase arrest between the control and BSA groups. Alterations in the DNA damage marker γ-H2AX, fibrogenesis, and associated proteins at the G2/M phase, such as p21, p-CDC25C and p-CDK1, are evaluated. Compared with those in the control group, the SA-β-gal activity, SASP, and γ-H2AX levels are increased in the BSA group, while the level of LaminB1 is decreased. Meanwhile, HK-2 cells blocked at the G2/M phase are significantly increased under the stimulation of BSA, and the levels of p21, p-CDC25C and p-CDK1, as well as fibrogenesis are also increased. When p21 expression is inhibited, the levels of p-CDC25C and p-CDK1 are decreased and the G2/M phase arrest is improved, which decreases the production of fibrogenesis. In conclusion, BSA induces renal tubular epithelial cell premature senescence, which regulates the G2/M phase through the CDC25C/CDK1 pathway, leading to tubulointerstitial fibrosis.

Abstract Intercellular adhesion molecule 1 (ICAM-1) related long noncoding RNA (ICR) is on the antisense strand of ICAM-1 and regulates ICAM-1 expression. ICAM-1 is involved in renal tubulointerstitial injury; however, the expression and clinical implication of ICR are not determined in IgA nephropathy (IgAN). We compared renal ICR levels in 337 IgAN patients with those of 89 biopsy controls, and a markedly increased ICR level was observed in IgAN patients. By Cox proportional hazards models, higher levels of renal ICR were independently associated with disease progression event defined as end-stage renal disease or ≥ 40% decline in estimated glomerular filtration rate. Patients in the highest tertile of renal ICR had a 3.5-fold higher risk for disease progression compared with those in the lowest tertile. The addition of renal ICR to a model with traditional risk factors improved risk prediction of disease progression (net reclassification index: 0.31 [95% CI 0.01–0.50]; integrated discrimination index: 0.10 [95% CI 0.04–0.16]). Inhibition of ICR by transfection with plasmids containing ICR shRNA significantly reduced expression of collagen I and α-SMA, and phosphorylation of Akt and mTOR in TGF-β1- treated HK-2 cells. Our findings suggest that renal ICR might be an independent predictor of IgAN progression and contribute to renal fibrosis.

Gonadal somatic cells are the main players in gonad development and are important for sex determination and germ cell development. Here, using a time-series single-cell RNA sequencing (scRNA-seq) strategy, we analyzed fetal germ cells (FGCs) and gonadal somatic cells in human embryos and fetuses. Clustering analysis of testes and ovaries revealed several novel cell subsets, including POU5F1+SPARC+ FGCs and KRT19+ somatic cells. Furthermore, our data indicated that the bone morphogenetic protein (BMP) signaling pathway plays cell type-specific and developmental stage-specific roles in testis development and promotes the gonocyte-to-spermatogonium transition (GST) in late-stage testicular mitotic arrest FGCs. Intriguingly, testosterone synthesis function transitioned from fetal Sertoli cells to adult Leydig cells in a stepwise manner. In our study, potential interactions between gonadal somatic cells were systematically explored and we identified cell type-specific developmental defects in both FGCs and gonadal somatic cells in a Turner syndrome embryo (45, XO). Our work provides a blueprint of the complex yet highly ordered development of and the interactions among human FGCs and gonadal somatic cells.

Abstract Background Patient-derived organoid culture is a powerful system for studying the molecular mechanisms of cancers, especially colorectal cancer (CRC), one of the most prevalent cancers worldwide. There are two main types of 3D culture methods for colonic cells, but the similarities and differences between gene expression patterns in different culture media remain largely unexplored. Results Here, we establish patient-derived organoids from colorectal cancer patients and perform single-cell RNA-Seq for pairwise samples from seven patients for both organoids and their corresponding tumor and normal tissues in vivo. We find that organoids derived from tumor tissues faithfully recapitulate the main gene expression signatures of cancer cells in vivo. On the other hand, organoids derived from normal tissues exhibited some tumor-like features at the whole transcriptome level but retained normal genomic features, such as CNVs, point mutations, and normal global DNA methylation levels, for both cultural media. More importantly, we show that conditioned medium outperforms chemical-defined medium in long-term culture of tumor epithelial cells. Finally, we mutually exchange the culture medium for the organoids and find that after interchanging the medium, the organoid cells basically maintain the transcriptome characteristics of the original medium. Conclusions Our work gives a thorough evaluation of both the cultural conditions and the biological features of organoids of CRC patients.

The wireless communication system is used to provide dispatching, control, communication and other services for rail transit operations. In practice, interference from other wireless communication systems will affect the normal operation of trains, so it is an urgent problem to study the interference detection algorithms for rail transit applications. In this paper, the fourth-order cyclic cumulant (FOCC) of signals with different modulation modes is analyzed for the narrow-band wireless communications system of rail transit. Based on the analysis results, an adjacent-frequency interference detection algorithm is proposed according to the FOCC of the received signal within the predetermined cyclic frequency range. To detect interference with the same carrier frequency, a same-frequency interference detection algorithm using the relationship between the FOCC and the received power is proposed. The performance of the proposed detection algorithms in terms of correct rate and computational complexity is analyzed and compared with the traditional second-order statistical methods. Simulation results show that when an interference signal coexists with the expected signal, the correct rates of the adjacent-frequency and the same-frequency interference detection algorithms are greater than 90% when the signal-to-noise ratio (SNR) is higher than 2 dB and −4 dB, respectively. Under the practical rail transit wireless channel with multipath propagation and the Doppler effect, the correct rates of the adjacent-frequency and the same-frequency interference detection algorithms are greater than 90% when the SNR is higher than 3 dB and 7 dB, respectively. Compared with the existing second-order statistical methods, the proposed method can detect both the adjacent-frequency and the same-frequency interference when the interference signals coexist with the expected signal. Although the computational complexity of the proposed method is increased, it is acceptable in the application of rail transit wireless communication interference detection.

Abstract The epigenomic abnormality of pancreatic ductal adenocarcinoma (PDAC) has rarely been investigated due to its strong heterogeneity. Here, we used single-cell multiomics sequencing to simultaneously analyze the DNA methylome, chromatin accessibility and transcriptome in individual tumor cells of PDAC patients. We identified normal epithelial cells in the tumor lesion, which have euploid genomes, normal patterns of DNA methylation, and chromatin accessibility. Using all these normal epithelial cells as controls, we determined that DNA demethylation in the cancer genome was strongly enriched in heterochromatin regions but depleted in euchromatin regions. There were stronger negative correlations between RNA expression and promoter DNA methylation in cancer cells compared to those in normal epithelial cells. Through in-depth integrated analyses, a set of novel candidate biomarkers were identified, including ZNF667 and ZNF667-AS1, whose expressions were linked to a better prognosis for PDAC patients by affecting the proliferation of cancer cells. Our work systematically revealed the critical epigenomic features of cancer cells in PDAC patients at the single-cell level.

Abstract Background Circulating cell-free DNA (cfDNA) can be released when myocardial damage occurs. Methods Here, we used the methylated CpG tandem amplification and sequencing (MCTA-seq) method for analyzing dynamic changes in heart-derived DNA in plasma samples from myocardial infarction (MI) patients. Results We identified six CGCGCGG loci showing heart-specific hypermethylation patterns. MCTA-seq deconvolution analysis combining these loci detected heart-released cfDNA in MI patients at hospital admission, and showed that the prominently elevated total cfDNA level after percutaneous coronary intervention (PCI) was derived from both the heart and white blood cells. Furthermore, for the top marker CORO6, we developed a digital droplet PCR (ddPCR) assay that clearly detected heart damage signals in cfDNA of MI patients at hospital admission. Conclusions Our study provides insights into MI pathologies and developed a new ddPCR assay for detecting myocardial damage in clinical applications.

Abstract Soil freeze–thaw processes lead to high nitrous oxide (N2O) emissions and exacerbate the greenhouse effect. The wetlands of the Inner Mongolia Plateau are in the pronounced seasonal freeze–thaw zone, but the effect of spring thaw on N2O emissions and related microbial mechanisms is still unclear. We investigated the effects of different periods (freeze, freeze–thaw, and thaw) on soil bacterial community diversity and composition and greenhouse gas emissions during the spring freeze–thaw in the XiLin River riparian wetlands in China by amplicon sequencing and static dark box methods. The results showed that the freeze–thaw periods predominantly impact on the diversity and composition of the bacterial communities. The phyla composition of the soil bacteria communities of the three periods is similar in level, with Proteobacteria, Chloroflexi, Actinobacteria, and Acidobacteria dominating the microbial communities. The alpha‐diversity of bacterial communities in different periods varies that the freezing period is higher than that of the freeze–thaw period (p

The emerging method of microwave (MW) heating was adopted to synthesize a phase pure La0.7Na0.3MnO3 from their oxide precursors. The MW power (P) used for heating the sample was varied from P = 1000 W to 1600 W to examine the effect of MW power on its physical properties. A well-crystalline single phase La0.7Na0.3MnO3 was achieved in 20 min of MW irradiation with P = 1600 W. The obtained grain sizes at P = 1000 W have grown bigger and densified while increasing the P = 1600 W. Growth in the grains was reflected in the resistivity of La0.7Na0.3MnO3 prepared at high P. As the P increases from 1000 W to 1600 W, the resistivity decreases drastically and the metal–insulator transition also becomes sharp at a temperature very close to TC whereas the ferromagnetic Curie temperature (TC) is least affected. The sample prepared at low P showed larger microwave absorption than the sample prepared under high P. These findings were correlated and discussed with the structural and morphological features acquired by microwave irradiation with different powers.

The spatial distribution and heterogeneity of soil and vegetation, as the root of the maintenance of ecosystem services in the riparian zone, play a decisive role in the ecological functions of the riverscape. In this study, a field survey of wetland plant communities and soil sampling were conducted in both longitudinal and lateral dimensions from the perspective of the riverscape of the Ulgai River, a typical inland river on the Mongolian Plateau. The diversity of wetland plant communities, soil physicochemical properties, and the correlations between them were systematically analyzed. The results showed that a total of 87 species belonging to 65 genera and 24 families of plants were present, with Asteraceae, Poaceae, and Cyperaceae as the main families. The plant composition and species diversity in the riparian zone at different dimensions showed obvious spatial patterns of succession. Although the correlation coefficient and significance of the physicochemical properties of river length and river width in the study area were different, most correlations remained consistent, among which soil moisture, soil pH, and total carbon were correlated with many physicochemical factors. The soil ammonium and nitrate nitrogen along the river length direction and electrical conductivity and organic carbon content along the river width direction were the main limiting factors affecting the diversity and distribution of plant species in the riparian zone based on the redundancy analysis. This study provides a theoretical basis for the continuous improvement of the current soil quality and the restoration of the degraded wetland ecosystems of inland rivers in arid and semi-arid regions, as well as a new perspective for the study of riverscape ecology.

Green farming is the inevitable path to solving the problem of pasture ecological protection and a fundamental guarantee to realize the high-quality development of grassland animal husbandry. This study explores the differences in green farming behaviors of different operating agents in grassland pastoral areas. The mechanism of the formation of the differences is based on 274 working agents’ survey data from Xilin Gol league pastoral areas in Inner Mongolia, China, by constructing the Logit model and Fairlie decomposition method. The results show that family ranch is the primary operating agent of green farming in China’s grassland pastoral areas. The green farming behavior is 2.115 times more extreme than that of traditional pastoralists. Differences in the intensity of green farming behavior of the operating agents were significantly and positively correlated with differences in their ecological consciousness and differences in resource endowment. Differences in ecological consciousness and participation in training were the key factors contributing to the differences in the intensity of green farming behavior among the operators, with ecological consciousness contributing 51.34% and participation in training contributing 46.65% to the differences in the intensity of green farming behaviors. Therefore, to enhance the effective transformation of traditional pastoralists’ green farming behavior, we should guide them to raise ecological consciousness, focus on the role of resource endowment, and gradually form a new grassland animal husbandry development where green farming behavior fully landed.

A clear understanding of the spatiotemporal evolution and driving factors of ecosystem service value (ESV) and the landscape ecological risk index (ERI) can effectively link human well-being and ecosystem security, which is essential for sustainable ecosystem management. Based on multitemporal land use data (1990, 2000, 2010, and 2018), the spatiotemporal evolution of ESV and the ERI in the Ulan Buh Desert was evaluated. The driving forces of ESV and the ERI were quantitatively evaluated by the Geodetector model. The results show that 1) from 1990 to 2018, total ESV in the Ulan Buh Desert increased from 7.00×108 yuan to 11.09×108 yuan. Low-ESV areas accounted for approximately 72.28% of the study area. High-ESV and moderate-high-ESV areas were mainly distributed along the Yellow River and the northeastern region. 2) During the study period, the ecological risk of the Ulan Buh Desert generally decreased; only the ecological risk of the northeastern region improved significantly, and high-risk areas were mainly distributed across sand dunes located in the middle of the desert. 3) There was a negative correlation between ESV and the ERI in the study area, and the main relationship was low value-high risk. 4) Driving force analysis results show that natural and human impact factors jointly affected the spatiotemporal differentiation of ESV and the ERI in the Ulan Buh Desert. Among the influencing factors, the interaction between the distance to a highway and annual precipitation had the strongest impact. The implementation of relevant policies in the study area should be guided by ESV and the ERI, and the protection and restoration of various ecosystems in the study area must be strengthened.

Abstract Background The cognitive impairment pattern of deficit schizophrenia (DS) is centered on an impaired attention function. Previous studies have suggested that the exploratory eye movement (EEM) tests reflect attention deficits in patients with schizophrenia. However, no study has investigated the characteristics of eye movement in DS in the Chinese Han population. This study aimed to investigate the pattern of eye movement characteristics in DS patients and to examine whether eye movement characteristic is associated with serious negative symptoms and cognitive decline in this schizophrenia subtype. Methods A total of 86 male patients [37 DS and 49 non-deficit schizophrenia (NDS)] and 80 healthy controls (HC) participated in this study. Clinical symptoms were assessed using the Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS). Cognitive function was assessed using the Mattis Dementia Rating Scale (MDRS-2). Eye movement data of subjects were collected using an eye movement tracking analyzer. Results There were significant differences in the overall eye movement data and cognitive test scores among the three groups (all P