SPOP Mutations or ERG Rearrangements Result in Enhanced Levels of ERG to Promote Cell Invasion in Prostate Cancer.

In this issue, An et al. (2015) and Gan et al. (2015) reveal that the CRL3(SPOP) ubiquitin ligase mediates the degradation of the transcription factor ERG and that translocations of ERG or mutations in SPOP prevent CRL3(SPOP)-dependent degradation of ERG in prostate cancer cells.

Single-cell transcriptional diversity of neonatal umbilical cord blood immune cells reveals neonatal immune tolerance.

The characteristics of neonatal immune cells display intrinsic differences compared with adult immune cells. Therefore, a comprehensive analysis of key gene expression regulation is required to understand the response of the human fetal immune system to infections. Here, we applied single-cell RNA sequencing (scRNA-seq) and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) to systematically profile umbilical cord blood (UCB) nucleated cells and peripheral blood mononuclear cells (PBMCs) to identify their composition and differentially expressed genes. The immune cells in neonatal UCB demonstrated the expression of key genes, such as HBG2, NFKBIA, JUN, FOS, and TNFAIP3. In contrast, natural killer and T cells, which are constituents of adult PBMCs, exhibited high cytotoxic gene expression. Furthermore, we obtained similar results from the data of scATAC-seq by identifying the status of chromatin accessibility of key genes. Therefore, scRNA-seq and scATAC-seq of neonatal UCB nucleated cells and adult PBMCs could serve as an invaluable resource for elucidating the regulatory mechanisms of responses of distinct immune cell types and further identifying the differences between neonatal and adult immune responses to predict the potential underlying mechanism for neonatal immune tolerance.

Suppression of MIR31HG affects the functional properties of thyroid cancer cells depending on the miR-761/MAPK1 axis.

BACKGROUND: Thyroid cancer is the most prevalent endocrine malignancy. Long non-coding RNA (lncRNA) MIR31HG is abnormally expressed in thyroid cancer tissues. However, the precise, critical role of MIR31HG in thyroid cancer development remains unclear. METHODS: MIR31HG, microRNA (miR)-761 and mitogen-activated protein kinase 1 (MAPK1) were quantified by quantitative real-time PCR (qRT-PCR) and immunoblotting. Cell viability, proliferation, apoptosis, invasion and migration abilities were evaluated by MTS, 5-Ethynyl-2'-Deoxyuridine (EdU), flow cytometry, transwell and wound-healing assays, respectively. Dual-luciferase reporter assays were used to validate the direct relationship between miR-761 and MIR31HG or MAPK1. RESULTS: MIR31HG was overexpressed in human thyroid cancer, and its overexpression predicted poor prognosis. Suppression of MIR31HG impeded cell proliferation, invasion and migration, as well as promoted cell apoptosis in vitro, and diminished the growth of xenograft tumors in vivo. Mechanistically, MIR31HG targeted and regulated miR-761. Moreover, miR-761 was identified as a molecular mediator of MIR30HG function in regulating thyroid cancer cell behaviors. MAPK1 was established as a direct and functional target of miR-761 and MAPK1 knockdown phenocopied miR-761 overexpression in impacting thyroid cancer cell behaviors. Furthermore, MIR31HG modulated MAPK1 expression by competitively binding to miR-761 via the shared binding sequence. CONCLUSION: Our findings demonstrate that MIR31HG targets miR-761 to regulate the functional behaviors of thyroid cancer cells by upregulating MAPK1, highlighting a strong rationale for developing MIR31HG as a novel therapeutic target against thyroid cancer.

Direct Ink Writing of Li1.3 Al0.3 Ti1.7 (PO4 )3 -Based Solid-State Electrolytes with Customized Shapes and Remarkable Electrochemical Behaviors.

All-solid-state lithium batteries have received extensive attention due to their high safety and promising energy density and are considered as the next-generation electrochemical energy storage system. However, exploring solid-state electrolytes in customized geometries without sacrificing the ionic transport is significant yet challenging. Herein, various 3D printable Li1.3 Al0.3 Ti1.7 (PO4 )3 (LATP)-based inks are developed to construct ceramic and hybrid solid-state electrolytes with arbitrary shapes as well as high conductivities. The obtained inks show suitable rheological behaviors and can be successfully extruded into solid-state electrolytes using the direct ink writing (DIW) method. As-printed free-standing LATP ceramic solid-state electrolytes deliver high ionic conductivity up to 4.24 × 10-4  S cm-1 and different shapes such as "L", "T," and "+" can be easily realized without sacrificing high ionic transport properties. Moreover, using this printing method, LATP-based hybrid solid-state electrolytes can be directly printed on LiFePO4 cathodes for solid-state lithium batteries, where a high discharge capacity of 150 mAh g-1 at 0.5 C is obtained. The DIW strategy for solid-state electrolytes demonstrates a new way toward advanced solid-state energy storage with the high ionic transport and customized manufacturing ability.

Regulation of the CRL4(Cdt2) ubiquitin ligase and cell-cycle exit by the SCF(Fbxo11) ubiquitin ligase.

F-box proteins and DCAF proteins are the substrate binding subunits of the Skp1-Cul1-F-box protein (SCF) and Cul4-RING protein ligase (CRL4) ubiquitin ligase complexes, respectively. Using affinity purification and mass spectrometry, we determined that the F-box protein FBXO11 interacts with CDT2, a DCAF protein that controls cell-cycle progression, and recruits CDT2 to the SCF(FBXO11)complex to promote its proteasomal degradation. In contrast to most SCF substrates, which exhibit phosphodegron-dependent binding to F-box proteins, CDK-mediated phosphorylation of Thr464 present in the CDT2 degron inhibits recognition by FBXO11. Finally, our results show that the functional interaction between FBXO11 and CDT2 is evolutionary conserved from worms to humans and plays an important role in regulating the timing of cell-cycle exit.

Perceptions of workplace heat exposure and adaption behaviors among Chinese construction workers in the context of climate change.

BACKGROUND: Workplace heat exposure can cause a series of heat-related illnesses and injuries. Protecting workers especially those undertake work outdoors from the risk of heat strain is a great challenge for many workplaces in China under the context of climate change. The aim of this study is to investigate the perceptions and adaptation behaviors of heat exposure among construction workers and to provide evidence for the development of targeted heat adaptation strategies nationally and internationally. METHODS: In 2020, we conducted a cross-sectional online questionnaire survey via WeChat Survey Star in China, using a purposive snowball sampling approach. A total of 326 construction workers submitted completed questionnaires. The perceptions of workplace heat exposure were measured using seven indicators: concerns over high temperature, perception of high temperature injury, attitudes towards both heat-related training and regulations, adjustment of working habits during heat, heat prevention measures in the workplace, and reduction of work efficiency. Bivariate and multivariate regression analyses were used to identify the factors significantly associated with workers' heat perceptions and behavioral responses. RESULTS: 33.3% of the respondents were moderately or very concerned about heat exposure in the workplace. Less than half of the workers (43.8%) were worried about heat-related injuries. Workers who have either experienced work-related injuries (OR = 1.30, 95% CI 1.03-1.62) or witnessed injuries to others during high temperatures (OR = 1.12, 95% CI 1.02-1.27) were more concerned about heat exposure compared to other workers. Most respondents (63.5%) stated that their work efficiency declined during extremely hot weather. The factors significantly associated with a reduction of work efficiency included undertaking physically demanding jobs (OR = 1.28, 95% CI 1.07-1.54) and witnessing other workers' injuries during high temperatures (OR = 1.26, 95% CI 1.11-1.43). More than half of the workers were willing to adjust their work habits to adapt to the impact of high temperatures (81.6%). The internet was the most common method to obtain heat prevention information (44.7%), and the most frequently used heat prevention measure was the provision of cool drinking water (64.8%). CONCLUSIONS: Chinese construction workers lack heat risk awareness and are not well prepared for the likely increasing heat exposure in the workplace due to global warming. Therefore, there is a need to improve their awareness of heat-related injuries, strengthen high temperature related education and training, and update the current heat prevention policies to ensure compliance and implementation.

Visualization of individual microRNA molecules in fixed cells and tissues using target-primed padlock probe assay.

MicroRNAs (miRNAs) are key regulators of gene expression at the posttranscriptional level. Precisely profiling of miRNA expression will help us to better understand their roles in normal and diseased cells and tissues. Here we describe in situ miRNA detection by padlock probing and miRNA target-primed rolling circle amplification. We optimized our protocol and showed it can be applied to both fixed cells and tissue sections. The method can be used in basic research and potentially in clinical diagnostics in the future.

mTOR generates an auto-amplification loop by triggering the ßTrCP- and CK1α-dependent degradation of DEPTOR.

DEPTOR is a recently identified inhibitor of the mTOR kinase that is highly regulated at the posttranslational level. In response to mitogens, we found that DEPTOR was rapidly phosphorylated on three serines in a conserved degron, facilitating binding and ubiquitylation by the F box protein ßTrCP, with consequent proteasomal degradation of DEPTOR. Phosphorylation of the ßTrCP degron in DEPTOR is executed by CK1α after a priming phosphorylation event mediated by either the mTORC1 or mTORC2 complexes. Blocking the ßTrCP-dependent degradation of DEPTOR via ßTrCP knockdown or expression of a stable DEPTOR mutant that is unable to bind ßTrCP results in mTOR inhibition. Our findings reveal that mTOR cooperates with CK1α and ßTrCP to generate an auto-amplification loop to promote its own full activation. Moreover, our results suggest that pharmacologic inhibition of CK1 may be a viable therapeutic option for the treatment of cancers characterized by activation of mTOR-signaling pathways.

FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas.

BCL6 is the product of a proto-oncogene implicated in the pathogenesis of human B-cell lymphomas. By binding specific DNA sequences, BCL6 controls the transcription of a variety of genes involved in B-cell development, differentiation and activation. BCL6 is overexpressed in the majority of patients with aggressive diffuse large B-cell lymphoma (DLBCL), the most common lymphoma in adulthood, and transgenic mice constitutively expressing BCL6 in B cells develop DLBCLs similar to the human disease. In many DLBCL patients, BCL6 overexpression is achieved through translocation (~40%) or hypermutation of its promoter (~15%). However, many other DLBCLs overexpress BCL6 through an unknown mechanism. Here we show that BCL6 is targeted for ubiquitylation and proteasomal degradation by a SKP1­CUL1­F-box protein (SCF) ubiquitin ligase complex that contains the orphan F-box protein FBXO11 (refs 5, 6). The gene encoding FBXO11 was found to be deleted or mutated in multiple DLBCL cell lines, and this inactivation of FBXO11 correlated with increased levels and stability of BCL6. Similarly, FBXO11 was either deleted or mutated in primary DLBCLs. Notably, tumour-derived FBXO11 mutants displayed an impaired ability to induce BCL6 degradation. Reconstitution of FBXO11 expression in FBXO11-deleted DLBCL cells promoted BCL6 ubiquitylation and degradation, inhibited cell proliferation, and induced cell death. FBXO11-deleted DLBCL cells generated tumours in immunodeficient mice, and the tumorigenicity was suppressed by FBXO11 reconstitution. We reveal a molecular mechanism controlling BCL6 stability and propose that mutations and deletions in FBXO11 contribute to lymphomagenesis through BCL6 stabilization. The deletions/mutations found in DLBCLs are largely monoallelic, indicating that FBXO11 is a haplo-insufficient tumour suppressor gene.

Carotid artery intima-media thickness associated with prognosis of intracranial branch atheromatous disease.

BACKGROUND AND PURPOSE: Small deep brain infarcts are often caused by two different vascular pathologies: branch atheromatous disease (BAD) and lipohyalinotic degeneration (LD). In this study, we compare the clinical characteristics of BAD and LD and investigate the role of C-reactive protein (CRP), homocysteine (Hcy), and carotid artery intima-media thickness (IMT) in the prognosis of patients with BAD and LD. METHODS: Of 262 adult patients with small deep infarcts, 104 were considered BAD and 158 were considered LD. Data compared included clinical information, prevalence of lacune and leukoaraiosis, Hcy, CRP, carotid artery IMT, deterioration during admission, and recurrence of ischemic stroke (IS) within 1 year. RESULTS: Patients with LD have severe leukoaraiosis and higher prevalence of lacune and intracerebral hemorrhage compared with those with BAD. Patients with BAD have higher initial National Institutes of Health Stroke Scale scores and incidence of progressive motor deficits compared with those with LD; CRP is associated with the progression in both groups. There is no statistical difference of recurring risk of IS within 1 year between the two groups; by multivariable logistic regression analysis, carotid artery IMT was an independent risk factor for recurrence of IS in 1 year in patients with BAD. CONCLUSION: BAD as an independent clinical entity has different clinical and radiological characteristics compared with LD. Carotid artery IMT is an independent risk factor for recurrence of IS in patients with BAD.

Angiogenesis contributes to the neuroprotection induced by hyperbaric oxygen preconditioning against focal cerebral ischemia in rats.

Ischemic stroke is one of the leading causes of mortality and disability worldwide. Previous studies have indicated that hyperbaric oxygen preconditioning (HBO-PC) can induce neuroprotection against focal cerebral ischemia. However, the underlying mechanisms are still not fully understood, and the optimal regimen for preconditioning must be confirmed. In the present study, we designed eight preconditioning regimens and compared their neuroprotective effects. Hyperbaric oxygen preconditioning every other day for there sessions exhibited the best neuroprotective effect; the infarct volume was reduced by almost 50% at 48 h after middle cerebral artery occlusion. We also found that HBO-PC significantly increased the microvessel density and the CD31-positive cells in the penumbra at 72 h after stroke. These results indicate that angiogenesis is involved in the neuroprotection induced by HBO-PC. Moreover, we explored the roles of HIF-1α and angiogenic factors in the angiogenesis process induced by HBO-PC. The results from western blotting demonstrated that protein expression of Ang-2 in the HBO-PC group was significantly increased. In conclusion, HBO-PC reduced brain injury and improved neurological function after focal cerebral ischemia, as partly mediated by the increased microvessel density in the penumbra, and this effect may result from the upregulation of Ang-2.

Pathogenesis and management of low-pressure hydrocephalus: A narrative review.

Patients diagnosed with low-pressure hydrocephalus typically present with enlarged ventricles and unusually low intracranial pressure, often measuring below 5 cmH2O or even below atmospheric pressure. This atypical presentation often leads to low recognition and diagnostic rates. The development of low-pressure hydrocephalus is believed to be associated with a decrease in the viscoelasticity of brain tissue or separation between the ventricular and subarachnoid spaces. Risk factors for low-pressure hydrocephalus include subarachnoid hemorrhage, aqueduct stenosis, prior cranial radiotherapy， ventricular shunting, and cerebrospinal fluid leaks. For potential low-pressure hydrocephalus, diagnostic criteria include neurological symptoms related to hydrocephalus, an Evans index >0.3 on imaging, ICP ≤ 5 cm H2O, symptom improvement with negative pressure drainage, and exclusion of ventriculomegaly caused by neurodegenerative diseases. The pathogenesis and pathophysiological features of low-pressure hydrocephalus differ significantly from other types of hydrocephalus, making it challenging to restore normal ventricular morphology through conventional drainage methods. The primary treatment options for low-pressure hydrocephalus involve negative pressure drainage and third ventriculostomy. With appropriate treatment, most patients can regain their previous neurological function. However, in most cases, permanent shunt surgery is still necessary. Low-pressure hydrocephalus is a rare condition with a high rate of underdiagnosis and mortality. Early identification and appropriate intervention are crucial in reducing complications and improving prognosis.

Intracranial pressure monitoring in patients with spontaneous intracerebral hemorrhage: a systematic review with meta-analysis.

OBJECTIVE: To describe the potential effects of Intracranial pressure monitoring on the outcome of patients with spontaneous intracerebral hemorrhage. DESIGN: Systematic review with meta-analysis. SETTING: Observational and interventional studies published up to May 30th, 2024, were considered for inclusion. We investigated the effects of increased Intracranial pressure and intracranial pressure monitoring on relevant clinical outcomes. POPULATION: Patients with spontaneous intracerebral hemorrhage treated with intracranial pressure monitoring. MAIN OUTCOME MEASURES: The primary outcome was mortality at 6 months and in-hospital mortality. The secondary outcome was poor neurological function outcome at 6 months. RESULTS: This analysis compares in-hospital and 6-month mortality rates between patients with intracranial pressure monitoring (ICPm) and those without (no ICPm). Although the ICPm group had a lower in-hospital mortality rate, it was not statistically significant (24.9% vs. 34.1%; OR 0.51, 95% CI 0.20 to 1.31, p=0.16). Excluding patients with intraventricular hemorrhage (IVH) revealed a significant reduction in in-hospital mortality for the ICPm group (23.5% vs. 43%; OR 0.39, 95% CI 0.29 to 0.53, p < 0.00001). For 6-month mortality, the ICPm group showed a significant reduction (32% vs. 39.6%; OR 0.76, 95% CI 0.61 to 0.94, p=0.01), with the effect being more pronounced after excluding IVH patients (29.1% vs. 47.2%; OR 0.45, 95% CI 0.34 to 0.60, p<0.0001). However, there were no statistically significant differences in 6-month functional outcomes between the groups. Increased ICP was associated with higher 3-month mortality (OR 1.12, 95% CI 1.07 to 1.18, p < 0.00001) and lower likelihood of good functional outcomes (OR 1.11, 95% CI 1.04 to 1.18, p < 0.00001). CONCLUSIONS: Elevated ICP is associated with increased mortality and poor prognosis in ICH patients. Although continuous intracranial pressure monitoring may reduce short-term mortality rates in specific subgroups of ICH patients, it does not improve neurological functional outcomes. While potential patient populations may benefit from ICP monitoring, more research is needed to screen suitable populations for ICP monitoring.

Study on the thawing characteristics of beef in ultrasound combined with plasma-activated water.

The effects of deionized water thawing (DT), plasma-activated water thawing (PT), ultrasound (150 W, 40 kHz) combined with deionized water thawing (UDT), and ultrasound combined with plasma-activated water thawing (UPT) on the thawing characteristics and the physicochemical properties of the beef were investigated. The results showed that the UPT group had a faster thawing rate (38 % higher compared to the PT group) and good bactericidal ability (75 % higher compared to the UDT group), and had no adverse effect on the color and pH value of the beef. Plasma-activated water (PAW) can maintain the stability of the beef fiber, improve the water holding capacity (WHC), inhibit lipid oxidation, and reduce the loss of soluble substances such as protein. Therefore, UPT thawing is a promising meat thawing technology, which provides practical guidance and methods for the wide application of UPT in the field of meat thawing.

Tumor-induced osteomalacia combined with increased bone resorption postoperatively: A case report.

RATIONALE: Rare tumor-induced osteomalacia (TIO) usually resulted in bone pain, fragility fractures and muscle weakness in clinical, which is caused by the reduced phosphate reabsorption, thus impaired mineralization of the bone matrix and free energy transfer. The specific problems in postsurgical patients are obscure although surgical removal of the tumor is the only definitive treatment. Here, we documented a female TIO patient who suffered more severe bone pain and muscle spasms post-operation. Further, we presented and discussed our explanation for the unexpected symptoms. PATIENT CONCERNS: The main symptoms were whole-body pain and muscle weakness. The patient also presented with osteoporosis and multiple fractures. DIAGNOSIS: Elevated serum fibroblast growth factor 23 (FGF23) level and hypophosphatemia indicated the diagnosis of TIO. Positron emission tomography (PET)/computed tomography (CT) with 68 Ga-DOTATATE located the tumor in the dorsolateral part of the left foot. Histopathological examinations confirmed the diagnosis. INTERVENTIONS: The tumor was surgically removed immediately after the diagnosis of TIO and localization of the tumor. Postoperatively, calcium carbonate supplement treatment was continued. OUTCOMES: Two days after surgery, the serum FGF23 level was decreased to the normal range. Five days after surgery, N-terminal propeptide of type I procollagen and ß-CrossLaps (ß-CTx) had a remarkable increase. A month after surgery, the patient N-terminal propeptide of type I procollagen and ß-CTx levels were decreased obviously, and serum FGF23, phosphate and 24h urinary phosphate were in the normal range. LESSONS: We report a female patient who presented with osteoporosis and fractures. She was found with an elevation of FGF23 and diagnosis with TIO after PET/CT scanning. After surgically removing the tumor, the patient experienced more severe bone pain and muscle spasms. Active bone remodeling might be the reason for the symptoms. Further study will reveal the specific mechanism for this abnormal bone metabolism.

Comparative analysis of bile metabolic profile in patients with biliary obstruction complicated by Clonorchis sinensis infection.

Background: Clonorchiasis is an important foodborne parasitic disease. However, eggs of Clonorchis sinensis (C. sinensis) cannot be detected in feces during biliary obstruction. Moreover, many diseases can cause biliary obstruction, such as gallstones, adenocarcinoma, cholangiocarcinoma and Ascaris lumbricoides infection. Therefore, it is of great significance to distinguish between patients of biliary obstruction and biliary obstruction with C. sinensis infection. Methods: A total of 48 biliary obstruction patients were enrolled, including 23 infected with C. sinensis (C. sinensis) (OB+C.s) and 25 non-infected subjects (OB). The bile samples were collected by endoscopic retrograde cholangiopancreatography and analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS). Additionally, multivariate statistical analysis methods were employed to identify differential metabolites. Next, bile amino acid levels were determined by targeted metabolomics analysis. Result: A total of 146 and 132 significant metabolites were identified in electrospray ionization (ESI)+ and ESI- modes, respectively. The levels of amino acids (asparagine, glutamate, ornithine) and polyamines (spermidine and spermine) were significantly changed. Targeted analysis showed that the levels of amino acids (such as L-arginine, L-glutamine, L-lysine, L-propionic, and L-tyrosine) were lower in OB+C.s patients compared to those in OB patients. Marked metabolic pathways were involved in "Glutathione metabolism", "Caffeine metabolism", "Alanine, aspartate and glutamate metabolism", "Arginine and proline metabolism", "Purine metabolism", "Beta-Alanine metabolism", and "D-glutamine and D-glutamate metabolism". Conclusion: These results show that there were significant differences between OB+C.s and OB patients, especially in amino acids. The metabolic signature and perturbations in metabolic pathways may help to better distinguish OB+C.s and OB patients.

Influence of electrohydrodynamics on the drying characteristics and physicochemical properties of garlic.

Electrohydrodynamic (EHD) drying, natural air drying (AD) and hot air drying (HAD) were used to comprehensively study the drying characteristics and physicochemical properties of garlic, and low-field nuclear magnetic resonance (NMR), infrared spectroscopy, scanning electron microscopy and other technologies were used as detection methods. In terms of drying characteristics, HAD has the largest effective diffusion coefficient of moisture and the shortest average drying time. EHD-treated garlic slices had the most attractive color, the highest rehydration rate, the most stable cell structure, the highest content of active ingredients, and the most stable protein secondary structure. Therefore, electrohydrodynamic drying is a promising garlic slice drying technology and provides an effective method for the large-scale production of high-quality garlic.

Influence of electrohydrodynamics on the drying characteristics and volatile components of iron stick yam.

The drying characteristics, rehydration capacity, color, infrared spectra and volatile components of iron stick yam slices were investigated under different alternating current (AC) voltages (13, 17, 21 kV), hot air drying (HAD) (60 °C) and natural drying (AD) by electrohydrodynamic (EHD) drying and HAD experimental devices. The results showed that slices of iron stick yam dried the quickest with HAD, which also had the fastest drying rate; while drying the slices of iron stick yam with EHD led to a better rehydration capacity, higher brightness L* and whiteness, a more stable protein secondary structure, and a greater variety and content of volatile components compared with AD and HAD. These finding indicated that EHD is a more promising method for drying iron stick yam.

Profiles of biliary microbiota in biliary obstruction patients with Clonorchis sinensis infection.

Background: Clonorchis sinensis (C. sinensis) is a epidemiologically significant food-borne parasite, causing several hepatobiliary diseases. Biliary microbiota community structure might be influenced by infection with pathogens. However, the biliary microbiome of biliary obstruction patients infected with C. sinensis is still an unexplored aspect. Methods: A total of 50 biliary obstruction patients were enrolled, including 24 infected with C. sinensis and 26 non-infected subjects. The bile samples were collected by Endoscopic Retrograde Cholangiopancretography. Biliary microbiota alteration was analyzed through high-throughput 16S ribosomal RNA (rRNA) gene sequencing. Results: Our findings revealed that there was significant increase in both richness and diversity, as well as changes in the taxonomic composition of the biliary microbiota of C. sinensis infected patients. At the phylum level, C. sinensis infection induced Proteobacteria increased and Firmicutes reduced. At the genus level, the relative abundance of Pseudomonas and Staphylococcus increased significantly, while Enterococcus decreased prominently in infected groups (P < 0.05). The PICRUSt analysis further showed remarkably different metabolic pathways between the two groups. Conclusion: C. sinensis infection could modify the biliary microbiota, increasing the abundance and changing the phylogenetic composition of bacterial in biliary obstruction patients. This study may help deepen the understanding of the host-biliary microbiota interplay with C. sinensis infection on the background of biliary obstruction and provide new insights into understanding the pathogenesis of clonorchiasis.

Single-cell chromatin accessibility profiling of cell-state-specific gene regulatory programs during mouse organogenesis.

In mammals, early organogenesis begins soon after gastrulation, accompanied by specification of various type of progenitor/precusor cells. In order to reveal dynamic chromatin landscape of precursor cells and decipher the underlying molecular mechanism driving early mouse organogenesis, we performed single-cell ATAC-seq of E8.5-E10.5 mouse embryos. We profiled a total of 101,599 single cells and identified 41 specific cell types at these stages. Besides, by performing integrated analysis of scATAC-seq and public scRNA-seq data, we identified the critical cis-regulatory elements and key transcription factors which drving development of spinal cord and somitogenesis. Furthermore, we intersected accessible peaks with human diseases/traits-related loci and found potential clinical associated single nucleotide variants (SNPs). Overall, our work provides a fundamental source for understanding cell fate determination and revealing the underlying mechanism during postimplantation embryonic development, and expand our knowledge of pathology for human developmental malformations.