SCTC: inference of developmental potential from single-cell transcriptional complexity.

Inferring the developmental potential of single cells from scRNA-Seq data and reconstructing the pseudo-temporal path of cell development are fundamental but challenging tasks in single-cell analysis. Although single-cell transcriptional diversity (SCTD) measured by the number of expressed genes per cell has been widely used as a hallmark of developmental potential, it may lead to incorrect estimation of differentiation states in some cases where gene expression does not decrease monotonously during the development process. In this study, we propose a novel metric called single-cell transcriptional complexity (SCTC), which draws on insights from the economic complexity theory and takes into account the sophisticated structure information of scRNA-Seq count matrix. We show that SCTC characterizes developmental potential more accurately than SCTD, especially in the early stages of development where cells typically have lower diversity but higher complexity than those in the later stages. Based on the SCTC, we provide an unsupervised method for accurate, robust, and transferable inference of single-cell pseudotime. Our findings suggest that the complexity emerging from the interplay between cells and genes determines the developmental potential, providing new insights into the understanding of biological development from the perspective of complexity theory.

Virome Analysis of Aconitum carmichaelii Reveals Infection by Eleven Viruses, including Two Potentially New Species.

Aconitum carmichaelii is a herbaceous herb indigenous to China that has been cultivated for traditional medicine for centuries. Virus-like symptoms of A. carmichaelii plants were observed on leaves in some A. carmichaelii plantations in Zhanyi and Wuding Counties, Yunnan Province, southwest China. High-throughput sequencing (HTS) was performed on 28 symptomatic plants, and the results revealed infection with 11 viruses, including 2 novel viruses and 9 previously described viruses: Aconitum amalgavirus 1 (AcoAV-1), aconite virus A (AcVA), cucumber mosaic virus (CMV), currant latent virus (CuLV), apple stem grooving virus (ASGV), chilli veinal mottle virus (ChiVMV), tomato spotted wilt orthotospovirus (TSWV), tobacco vein distorting virus (TVDV), and potato leafroll virus (PLRV). Two novel viruses tentatively named Aconitum potyvirus 1 and Aconitum betapartitivirus 1, were supported by sequence and phylogenetic analysis results of their genomes. We proposed the names Potyvirus aconiti and Betapartitivirus aconiti. RT-PCR assays of 142 plants revealed the predominance and widespread distribution of CMV, AcVA, and AcoPV-1 in plantations. The detection of isolates of CuLV, ASGV, ChiVMV, TSWV, TVDV, and PLRV infections for the first time in A. carmichaelii expands their known host ranges.

[Clinical Effect of Surgical Reconstruction of Extracranial Vertebral Artery].

Objective To evaluate the effect of surgical reconstruction of extracranial vertebral artery and to summarize the experience. Methods The clinical data of 15 patients undergoing surgical reconstruction of extracranial vertebral artery from September 2018 to June 2022 were collected.The operation methods,operation duration,intraoperative blood loss,operation complications,and relief of symptoms were retrospectively analyzed. Results Eleven patients underwent vertebral artery (V1 segment) to common carotid artery transposition,two patients underwent endarterectomy of V1 segment,two patients underwent V3 segment to external carotid artery bypass or transposition.The operation duration,intraoperative blood loss,and blocking time of common carotid artery varied within 120-340 min,50-300 ml,and 12-25 min,with the medians of 240 min,100 ml,and 16 min,respectively.There was no cardiac accident,cerebral hyperperfusion syndrome,cerebral hemorrhage or lymphatic leakage during the perioperative period.One patient suffered from cerebral infarction and three patients suffered from incomplete Horner's syndrome after the operation.During the follow-up (4-45 months,median of 26 months),there was no anastomotic stenosis,new cerebral infarction or cerebral ischemia. Conclusion Surgical reconstruction of extracranial vertebral artery is safe and effective,and individualized reconstruction strategy should be adopted according to different conditions.

Current Situation of Methamphetamine Abuse and Related Research Progress.

Drug problem is a major social and public security problem in the world. Drug abuse poses a great threat to economic development, social stability and public health. In recent years, synthetic drugs represented by methamphetamine have surpassed traditional drugs such as morphine, heroin, ketamine and become one of the most abused drugs in the world. In order to solve the problem of drug abuse, it is of great theoretical value and practical significance to carry out all-round and multi-level scientific research on drug-related issues. Based on the current situation of drug abuse, this article reviews research progresses on the epidemiology of methamphetamine abuse, the monitoring technology, the basic researches on toxicity damage, the withdrawal drug screening, the related clinical comorbidity and the testing technologies, comprehensively presenting the development trend of methamphetamine abuse related issues.

Cancer stem-like cells with hybrid epithelial/mesenchymal phenotype leading the collective invasion.

Collective invasion of cancer cells is the key process of circulating tumor cell (CTC) cluster formation, and greatly contributes to metastasis. Cancer stem-like cells (CSC) have a distinct advantage of motility for metastatic dissemination. To verify the role of CSC in the collective invasion, we performed 3D assays to investigate the collective invasion from cancer cell spheroids. The results demonstrated that CSC can significantly promote both collective and single-cell invasion. Further study showed that CSC prefer to move outside and lead the collective invasion. More interestingly, approximately 60% of the leader CSC in collective invasion co-expressed both epithelial and mesenchymal genes, while only 4% co-expressed in single invasive CSC, indicating that CSC with hybrid epithelial/mesenchymal phenotype play a key role in cancer cell collective invasion.

High-throughput cell migration assay under combinatorial chemical environments by a novel 24-well-plate based device.

The quantitative studies of cell proliferation and migration under different chemical environments are important for both scientists and clinicians searching for new therapeutics. In this study, we developed a new device to pattern several types of cells in 24-well-plate and demonstrated its' application in cancer cell proliferation and migration assay. The new device combined 3D-printed-silica-part for multi cell types loading with PDMS-through-hole-layer-part for cell micro-patterning which was matched with commercial 24-well-plate. This 24-well-plate based device is flexible and feasible in many applications and can be used in one piece or multi pieces. Besides the application for two types of cells proliferation and migration assay in one chemical condition, as a demonstration, the migration behaviors of four types of cells under 24 types of EGF + bFGF combinatorial conditions were studied. We believed this device could be widely used in clinical searching for new anti-cancer therapeutics and other related studies.

Construction and Preclinical Evaluation of a 124/131I-Labeled Radiotracer for the Detection of Mesothelin-Overexpressing Cancer.

Mesothelin is a molecular biomarker of many types of solid cancers, which may represent a highly promising new target in the development of cancer-targeted diagnostic agents. A human anti-mesothelin antibody with a low molecular weight, ET210sc, was applied; this antibody has potent affinity and can penetrate tissue quickly and stably without causing immunoreactions. We developed a new 124/131I-labeled radiotracer of ET210sc. The 124/131I-labeled ET210sc radiotracer showed excellent radiochemical quality (with over 99% radiolabeling yield, 0.07 GBq/µmol specific activity) and remarkable stability in phosphate-buffered saline (>95% at 3 days). The radiotracer retained its potent affinity (dissociation constant, Kd = 0.101 nM). The radiotracer specifically bound to mesothelin-positive cells in vitro. Interestingly, the radiotracer exhibited significant positive-to-negative tumor uptake ratios (1.5:1) 3 days postinjection. The estimated absorbed doses of each organ (e.g., 0.704 mGy/MBq for the rectum; 0.341 mGy/MBq for the spleen) met the medical safety standards for further clinical applications. Our findings provide an initial proof of concept for the potential use of 124/131I-labeled ET210sc radiotracers to detect mesothelin-overexpressing cancer. 124I-ET210sc is proposed to be an ideal imaging agent for further clinical applications.

Electrochemical Detection and Point-of-Care Testing for Circulating Tumor Cells: Current Techniques and Future Potentials.

Circulating tumor cells (CTCs) are tumor cells that escaped from the primary tumor or the metastasis into the blood and they play a major role in the initiation of metastasis and tumor recurrence. Thus, it is widely accepted that CTC is the main target of liquid biopsy. In the past few decades, the separation of CTC based on the electrochemical method has attracted widespread attention due to its convenience, rapidness, low cost, high sensitivity, and no need for complex instruments and equipment. At present, CTC detection is not widely used in the clinic due to various reasons. Point-of-care CTC detection provides us with a possibility, which is sensitive, fast, cheap, and easy to operate. More importantly, the testing instrument is small and portable, and the testing does not require specialized laboratories and specialized clinical examiners. In this review, we summarized the latest developments in the electrochemical-based CTC detection and point-of-care CTC detection, and discussed the challenges and possible trends.

[Clinical features and chest CT findings of coronavirus disease 2019 in infants and young children].

OBJECTIVE: To study the clinical features and chest CT findings of coronavirus disease 2019 (COVID-19) in infants and young children. METHODS: A retrospective analysis was performed for the clinical data and chest CT images of 9 children, aged 0 to 3 years, who were diagnosed with COVID-19 by nucleic acid detection between January 20 and February 10, 2020. RESULTS: All 9 children had an epidemiological history, and family clustering was observed for all infected children. Among the 9 children with COVID-19, 5 had no symptoms, 4 had fever, 2 had cough, and 1 had rhinorrhea. There were only symptoms of the respiratory system. Laboratory examination showed no reductions in leukocyte or lymphocyte count. Among the 9 children, 6 had an increase in lymphocyte count and 2 had an increase in leukocyte count. CT examination showed that among the 9 children, 8 had pulmonary inflammation located below the pleura or near the interlobar fissure and 3 had lesions distributed along the bronchovascular bundles. As for the morphology of the lesions, 6 had nodular lesions and 7 had patchy lesions; ground glass opacity with consolidation was observed in 6 children, among whom 3 had halo sign, and there was no typical paving stone sign. CONCLUSIONS: Infants and young children with COVID-19 tend to have mild clinical symptoms and imaging findings not as typical as those of adults, and therefore, the diagnosis of COVID-19 should be made based on imaging findings along with epidemiological history and nucleic acid detection. Chest CT has guiding significance for the early diagnosis of asymptomatic children.

Exploring the inhibitory effect of membrane tension on cell polarization.

Cell polarization toward an attractant is influenced by both physical and chemical factors. Most existing mathematical models are based on reaction-diffusion systems and only focus on the chemical process occurring during cell polarization. However, membrane tension has been shown to act as a long-range inhibitor of cell polarization. Here, we present a cell polarization model incorporating the interplay between Rac GTPase, filamentous actin (F-actin), and cell membrane tension. We further test the predictions of this model by performing single cell measurements of the spontaneous polarization of cancer stem cells (CSCs) and non-stem cancer cells (NSCCs), as the former have lower cell membrane tension. Based on both our model and the experimental results, cell polarization is more sensitive to stimuli under low membrane tension, and high membrane tension improves the robustness and stability of cell polarization such that polarization persists under random perturbations. Furthermore, our simulations are the first to recapitulate the experimental results described by Houk et al., revealing that aspiration (elevation of tension) and release (reduction of tension) result in a decrease in and recovery of the activity of Rac-GTP, respectively, and that the relaxation of tension induces new polarity of the cell body when a cell with the pseudopod-neck-body morphology is severed.

Radiation tolerance of La-doped nanocrystalline steel under heavy-ion irradiation at different temperatures.

Nanostructured materials have great potential for use as structural materials in advanced nuclear reactors due to the high density of grain boundaries that can serve as sinks to absorb irradiation-induced defects. In the present study, the irradiation tolerance of a La-doped nanocrystalline 304 austenitic stainless steel (NC-La) with a grain size of about 40 nm was investigated under an irradiation of 6 MeV Au ions to 1.5 × 1016 ions cm-2 at 600 °C and room temperature. Compared to its coarse-grained counterpart, in La-doped nanocrystalline steel no visible voids were observed at high-temperature irradiation, and no significant difference in extended defects, such as irradiation-induced dislocation loops or clusters, were found between irradiated and unirradiated areas at room temperature irradiation. Furthermore, the nano grain remains stable under irradiation, and no significant grain growth occurs at both irradiation temperatures. The excellent irradiation tolerance of the La-doped nanocrystalline alloys is attributed to the abundant grain boundaries and enhanced stability of nano grains induced by the Zener pinning effect and La segregation on grain boundaries. This study therefore demonstrates the superior irradiation tolerance of the La-doped nanocrystalline steel.

A parallel and quantitative cell migration assay using a novel multi-well-based device.

Cell migration assays for different chemical environments are important for both scientists and clinicians searching for new therapeutics. In this study, we developed a multi-well-based microfluidic chip that has multiple units for different conditions. In each unit, cells can be patterned and then released to observe their migration. Automatic image analysis and model-based data processing were developed to describe the integrated cell migration assay precisely and quickly. As a demonstration, the migration behaviors of two types of cells in eight chemical conditions were studied. The results showed that supplementation with transforming growth factor-ß(TGF-ß) significantly promoted the migration of MCF-7 and MCF-10 A cells compared to several growth factors, such as Epidermal Growth Factor(EGF) and basic fibroblast growth factor(bFGF), as well as a control sample. Cells can migrate particularly fast with two or more mixed supplementary factors, such as TGF-ß + bFGF + EGF, which indicated a synergy effect. Thus, this chip could be used to quantitatively observe cancer cell migration and demonstrated great potential for use in quantitative migration studies and chemical screening.

Protective effect of melatonin on cigarette smoke-induced restenosis in rat carotid arteries after balloon injury.

Vascular restenosis after the interventional angioplasty remains the main obstacle to a favorable long-term patency. Many researches suggest cigarette smoking is one of the most important causes of restenosis. This study was designed to investigate whether melatonin could protect against the cigarette smoke-induced restenosis in rat carotid arteries after balloon injury. Three groups of male rats (normal condition, cigarette smoke exposed, cigarette smoke exposed, and melatonin injected) were used in this study. An established balloon-induced carotid artery injury was performed, and the carotid arteries were harvested from these three groups 14 days later. The ratio of intima to media, the infiltration of inflammatory cells, the expression of inflammatory cytokines (NF-κB, IL-1ß, IL-6, TNF-α, MCP-1), adhesion molecules (ICAM-1, VCAM-1), and eNOS were measured. The results showed that cigarette smoke exposure aggravated the stenosis of the lumen, promoted the infiltration of inflammatory cells and induced the expression of the inflammatory cytokines and adhesion molecules after the balloon-induced carotid artery injury. Moreover, cigarette smoke exposure can inhibit the expression of eNOS. Particularly, we surprised that melatonin could minimize this effect caused by cigarette smoke. These results suggested that melatonin could prevent the cigarette smoke-induced restenosis in rat carotid arteries after balloon injury and the mechanism of its protective effect may be the inhibition of the inflammatory reaction. This also implies melatonin has the potential therapeutic applicability in prevention of restenosis after the vascular angioplasty in smokers.

Wnt-induced secreted protein 1/CCN4 in liver fibrosis both in vitro and in vivo.

BACKGROUND: Wnt-induced secreted protein-1 (WISP-1/CCN4) is a member of the CCN family growth factors, and its role in liver fibrosis is largely unknown. METHODS: For in vitro, hepatic stellate cells (HSCs) were isolated from Sprague-Dawley rats. Expression of WISP-1 during progressive activation of cultured rat HSCs was analyzed by qRT-PCR. The effects of TNF-a and TGF-beta1 on WISP-1 expression were analyzed in stellate cell lines HSC-T6 and LX-2. The effect of exogenous WISP-1 protein on LX-2 proliferation was examined. For in vivo, expressions of WISP-1 in fibrotic liver of a carbon tetrachloride (CCl4)-induced fibrosis rat model were analyzed by qRT-PCR and immunohistochemistry. RESULTS: In vitro, WISP-1 was increasingly expressed during progressive activation of cultured rat HSCs. WISP-1 was significantly induced in HSC-T6 cells by TNF-a and in LX-2 cells by TGF-beta1. Recombinant WISP-1 protein promoted LX-2 proliferation in a dose-dependent manner. In vivo, both mRNA and protein expression levels of WISP-1 were increased significantly in experimental hepatic fibrosis model. CONCLUSIONS: Our results showed the upregulation of WISP-1 in both in vitro and in vivo liver fibrosis models, and WISP-1 stimulated the proliferation of HSCs in vitro. These results may be helpful to elucidate the exact role of WISP-1 in liver fibrogenesis.

A novel algorithm combining finite state method and genetic algorithm for solving crude oil scheduling problem.

A hybrid optimization algorithm combining finite state method (FSM) and genetic algorithm (GA) is proposed to solve the crude oil scheduling problem. The FSM and GA are combined to take the advantage of each method and compensate deficiencies of individual methods. In the proposed algorithm, the finite state method makes up for the weakness of GA which is poor at local searching ability. The heuristic returned by the FSM can guide the GA algorithm towards good solutions. The idea behind this is that we can generate promising substructure or partial solution by using FSM. Furthermore, the FSM can guarantee that the entire solution space is uniformly covered. Therefore, the combination of the two algorithms has better global performance than the existing GA or FSM which is operated individually. Finally, a real-life crude oil scheduling problem from the literature is used for conducting simulation. The experimental results validate that the proposed method outperforms the state-of-art GA method.

[Research advances in endotension after endovascular abdominal aneurysm repair].

When more abdominal aortic aneurysms are repaired by endovascular approaches, the post-operative endotension without endoleak increase along with the extended follow-up. An early detection of such endotension and a proper differentiation from endoleaks are particularly important for the treatment decision-making. This article reviews the mechanism, diagnosis, and management of endotension.

Comparison of endovascular aortic repair and open surgical repair for ruptured abdominal aortic aneurysm.

OBJECTIVE: To compare the clinical efficacies of endovascular aortic repair(EVAR)and open surgical repair(OSR)for ruptured abdominal aortic aneurysm(rAAA). METHODS: The clinical data of 28 rAAA patients undergoing emergent treatment between February 2002 and February 2013 in PUMC Hospital were retrospectively reviewed. Among them 13 cases were treated by EVAR and 15 cases by OSR. RESULTS: Before the surgery,the general conditions,comorbidities,and hemodynamics were not significantly different between these two groups(all P>0.05),although the EVAR group had significantly higher mean age than OSR group(P=0.041). In the perioperative period,the EVAR group showed significantly lower 30-day mortality(P=0.044),less blood loss(P=0.005),less blood transfusion(P=0.003),less infusion quantity(P=0.000),shorter length of procedure(P=0.001),and shorter hospital stay(P=0.020). Also,the EVAR group had no severe perioperative complications and showed superior 1-year follow up survival(P<0.05). CONCLUSIONS: EVAR is an effective treatment for rAAA and can improve the clinical outcomes. EVAR may be adopted as the first-line treatment for rAAA,especially for the aged.

[Establishment and functional identification of a stable cell line overexpression heme oxygenase-1].

OBJECTIVE: To establish a stable cell line overexpression heme oxygenase-1 (HO-1) mediated by a modified lentivirus system and identify its function. METHODS: The HO-1 gene was amplified by polymerase chain reaction and cloned into the modified pLentiLox3.7 expression vectors. The recombinant plasmids were transfected into HEK293T cells and the HO-1 was detected by Western blot. The recombinant plasmids were transfected into HEK293T cells to produce the viruses, with the helping plasmids including plp1, plp2, and VSVG. HEK293T cells were infected by the viruses and the cells that can express HO-1 were identified by Western blot. The reactive oxygen species were detected in the HO-1-overexpression HEK293T cells and the normal cells after the adding of hydrogen peroxide. The same experiment was performed with human umbilical vein endothelial cells. RESULTS: The stable cell line that can overexpress HO-1 was established, which was verified by Western blot. The reactive oxygen species in the HO-1-overexpression HEK293T cells and human umbilical vein endothelial cells decreased obviously after exposure to hydrogen peroxide. CONCLUSIONS: The lentivirus-carrying HO-1 was successfully packaged and the stable cell line overexpression HO-1 was established. HO-1 can play a protective role in the course of oxidative damage.

[CT and MRI findings in patients with autoimmune pancreatitis].

OBJECTIVE: To evaluate computed tomography (CT) and magnetic resonance imaging (MRI) findings in patients with autoimmune pancreatitis (AIP). METHODS: The imaging findings of pancreas and extra-pancreas in 24 patients with AIP were retrospectively reviewed. Among them, CT scan was performed in 18 patients, MRI in 11, and bGth CT and MRI in 10. RESULTS: The pancreas showed diffuse enlargement (25%, 6/24), focal enlargement (37. 5%, 9/24), combined enlargement (25%, 6/24) ,and no enlargement (12. 5%, 9/24). Unenhanced CT showed hypoattenuation in AIP area (n = 2) . After intravenous injection of contrast medium, 17 patients showed abnormal contrast enhancement in the affected pancreatic parenchyma, including hypoattenuation during the arterial phase (50%, 9/18) and hyper attenuation during the delayed phase (94. 4%, 17/18). Precontrast MRI showed abnormal signal intense (n =9), including hypointense on T1-weight images (T1 WI) (n = 7), hyperintense (n = 7) and hypointense (n = 2) on T2-weight images (TIWI). Enhanced MRI demonstrated abnormal contrast enhancement within lesions (n = 11), including hypoattenuation during the arterial phase (81. 8%, 9/11) and good enhancement during the delayed phase (100%, 11111). A capsule-like rim was seen around pancreas (37. 5%, 9/24), among which CT detected in 6 out of 18 patients and MRI found in 7 out of 11 patients.The main pancreatic duct lumen within lesions has no visualization (100%, 24/24) and upstream dilation of the main pancreatic duct (n = 8) , ranging from 2. 2 to 4. 5 mm(mean 3. 1 0. 47 mm) in diameter. Narrowing of the common bile duct was shown in 14 patients. Miscellaneous findings were: infiltration of extrapancreatic vein (n = 9) and artery (n = 1); mild fluid collection around pancreas (n = 2); pseudocysts (n = 3). Fourteen patients also presented one or more of the following extrapancreatic imaging findings: narrowing of the intra-hepatic bile duct or hilar duct (n = 5); thickening of gallbladder wall (n = 5); fibrosis in mesenteric (n = 2), in retroperitoneal (n = 2) and in ligamentum teres hepatis (n = 1); renal involvement (n = 3); peri-pancreatic or para-aortic lymphadenopathy (n = 10); and ulcerative colitis (n = 3). CONCLUSION: AIP display some characteristic CT and MRI imaging features: sausage-like change of the pancreas; capsule-like rims around lesions; delayed contrast enhancement in the affected pancreatic parenchyma; segment or diffuse pancreatic duct stenosis but mild upstream dilation and extrapancreatic organs involvement. CT and MRI findings combining with serological tests and pancreas biopsy can assist physicians to make accurate and timely diagnosis.

Primary anaplastic lymphoma kinase-positive large B-cell lymphoma of the left bulbar conjunctiva: A case report.

BACKGROUND: Anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (LBCL) is an aggressive and rare variant of diffuse LBCL. Herein, we report an uncommon case of stage IE extranodal ALK-positive LBCL initially originating in the bulbar conjunctiva. CASE SUMMARY: A 63-year-old woman presented with a mass in the left bulbar conjunctiva that had persisted for six months, accompanied by swelling and pain that had persisted for 3 d. Eye examination revealed an 8 mm slightly elevated pink mass in the lower conjunctival sac of the left eye. Microscopically, the tumor was composed of large immunoblastic and plasmablastic large lymphoid cells with scattered anaplastic or multinucleated large cells. Immunophenotypically, the neoplastic cells were positive for ALK, CD10, CD138, Kappa, MUM1, BOB.1, OCT-2, CD4, CD45, EMA, CD79a, CD38, and AE1/AE3, and negative for CD20, PAX5, Lambda, BCL6, CD30 and all other T-cell antigens. The results of gene rearrangement tests showed monoclonal IGH/IGK/IGL and TCRD rearrangements. Fluorescence in situ hybridization studies did not reveal any BCL2, BCL6 or MYC rearrangements. Furthermore, Epstein-Barr virus was not detected by in situ hybridization in the lesions. Based on the histopathological and imaging examinations, the neoplasm was classified as stage IE ALK-positive LBCL. No further treatments were administered. At the 6, 15, and 21 mo postoperative follow-up visits, the patient was in good condition, without obvious discomfort. This case represents the first example of primary extranodal ALK-positive LBCL presenting as a bulbar conjunctival mass, which is extremely rare and shares morphological and immunohistochemical features with a variety of other neoplasms that can result in misdiagnosis. CONCLUSION: Awareness of the condition presented in this case report is necessary for early and accurate diagnosis and appropriate treatment.