ST-CellSeg: Cell segmentation for imaging-based spatial transcriptomics using multi-scale manifold learning.

Spatial transcriptomics has gained popularity over the past decade due to its ability to evaluate transcriptome data while preserving spatial information. Cell segmentation is a crucial step in spatial transcriptomic analysis, as it enables the avoidance of unpredictable tissue disentanglement steps. Although high-quality cell segmentation algorithms can aid in the extraction of valuable data, traditional methods are frequently non-spatial, do not account for spatial information efficiently, and perform poorly when confronted with the problem of spatial transcriptome cell segmentation with varying shapes. In this study, we propose ST-CellSeg, an image-based machine learning method for spatial transcriptomics that uses manifold for cell segmentation and is novel in its consideration of multi-scale information. We first construct a fully connected graph which acts as a spatial transcriptomic manifold. Using multi-scale data, we then determine the low-dimensional spatial probability distribution representation for cell segmentation. Using the adjusted Rand index (ARI), normalized mutual information (NMI), and Silhouette coefficient (SC) as model performance measures, the proposed algorithm significantly outperforms baseline models in selected datasets and is efficient in computational complexity.

The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance.

BACKGROUND: Trachypithecus leucocephalus, the white-headed langur, is a critically endangered primate that is endemic to the karst mountains in the southern Guangxi province of China. Studying the genomic and transcriptomic mechanisms underlying its local adaptation could help explain its persistence within a highly specialized ecological niche. RESULTS: In this study, we used PacBio sequencing and optical assembly and Hi-C analysis to create a high-quality de novo assembly of the T. leucocephalus genome. Annotation and functional enrichment revealed many genes involved in metabolism, transport, and homeostasis, and almost all of the positively selected genes were related to mineral ion binding. The transcriptomes of 12 tissues from three T. leucocephalus individuals showed that the great majority of genes involved in mineral absorption and calcium signaling were expressed, and their gene families were significantly expanded. For example, FTH1 primarily functions in iron storage and had 20 expanded copies. CONCLUSIONS: These results increase our understanding of the evolution of alkali tolerance and other traits necessary for the persistence of T. leucocephalus within an ecologically unique limestone karst environment.

MRI and 18F-FDG PET/CT findings of a giant cell tumor of the tendon sheath of the knee joint (pigmented villonodular synovitis): A case report and literature review.

We present a case of a 33-year-old female hospitalized with a 3-month history of right knee pain when squatting. Her physical examination showed no resting pain or local skin fever. Magnetic resonance imaging (MRI) showed multiple nodular long T1 and short T2 abnormal signal shadows in the popliteal fossa region. A patchy T2 high signal shadow was found in the soft tissue around the right knee.Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) revealed multiple soft tissue density nodules around and within the right knee joint (largest 20x13mm) with a maximum standardized uptake value (SUVmax) of 10.5 and a delayed SUVmax of 12.0. The subsequent histopathologic examination confirmed the diagnosis of a diffuse giant cell tumor of the tendon sheath (GCTTS) and pigmented villonodular synovitis(PVNS).

MitoQ Modulates Lipopolysaccharide-Induced Intestinal Barrier Dysfunction via Regulating Nrf2 Signaling.

BACKGROUND: Gut barrier dysfunction with alterant mucosal permeability during sepsis is a challenge problem in clinical practice. Intestinal epithelial cells (IECs) are strongly involved in mucosal oxidative stress and inflammatory response. The current study aimed at investigating the effect of MitoQ, a mitochondrial targeted antioxidant, in the treatment of intestinal injury and its potential mechanism during sepsis. METHODS: 30 minutes before sepsis induction by lipopolysaccharide (LPS) treatment, mice were treated with MitoQ. Intestinal histopathology, mucosal permeability, inflammatory cytokines, and mucosal barrier proteins were evaluated in the present study. RESULTS: MitoQ pretreatment significantly decreased the levels of plasma diamine oxidase, D-lactate, and intestinal histological damage and markedly restored the levels of tight junction proteins (ZO-1 and occludin) following LPS challenge. Furthermore, MitoQ inhibited the LPS-induced intestinal oxidative stress and inflammatory response, evidenced by increased levels of intestinal superoxide dismutase and glutathione, and decreased levels of intestinal IL-1, IL-6, TNF-α, and nitric oxide levels. Mechanically, we found that MitoQ inhibited the oxidative stress via activating nuclear factor E2-related factor 2 (Nrf2) signaling pathway and its downstream antioxidant genes, including HO-1, NQO-1, and GCLM. CONCLUSIONS: MitoQ exerts antioxidative and anti-inflammatory effects against sepsis-associated gut barrier injury by promoting Nrf2 signaling pathway.

Comparison of gallium-68 somatostatin receptor and 18F-fluorodeoxyglucose positron emission tomography in the diagnosis of neuroendocrine tumours: A systematic review and meta-analysis.

OBJECTIVE: A meta-analysis was performed to compare the diagnostic performance of gallium-68 (18Ga) somatostatin receptor positron emission tomography (68Ga-SSTR PET) and fluorine-18-fluorodeoxyglucose (18F-FDG) PET in patients with neuroendocrine tumours (NET) and whether the two imaging modalities can be mutually substituted in clinical work. METHODS: We performed electronic literature searches of the MEDLINE, PubMed, Embase and Cochrane Library databases for English-language articles from the earliest available date of indexing through 30 July 2019. We calculated the pooled sensitivity, specificity and diagnostic odds ratios (DOR) with 95% confidence intervals (95% CI) of 68Ga-SSTR PET and 18F-FDG PET in NET. We drew a summary receiver operator characteristic (SROC) curve and calculated the area under the curve (AUC) to measure the accuracy of 68Ga-SSTR PET and 18F-FDG PET in patients or lesions with NET. RESULTS: Thirty studies comprising 3401 patients and 5793 lesions with NET were included in this meta-analysis. The pooled sensitivity, sensitivity, DOR and AUC for 68Ga-SSTR PET or PET/computed tomography (CT) in the diagnosis of NET, based on lesion patient, were 0.92(0.89-0.95), 0.91(0.83-0.95),119(51-282) and 0.96(0.94-0.98), and based on lesion, were 0.95(0.86-0.98), 0.93(0.83-0.97), 229(43-1205) and 0.98(0.96-0.99), respectively. The pooled sensitivity, sensitivity, DOR and AUC for 18F-FDG PET or PET/CT in NET were 0.70(0.41-0.89), 0.97(0.70-1.00), 67(7-612) and 0.94(0.92-0.96), respectively, when analyzed on a per-patient basis.The pooled sensitivities of 68Ga-SSTR PET/CT were 0.923 (95% CI: 0.884-0.952), 0.902 (0.862-0.934) and 0.578 (0.482-0.669) in the G1(ki67,≤2%), G2(ki67,>3%,≤20% and G3(ki67,>20%) groups based on patients with NET, respectively. The pooled sensitivities of 18F-FDG PET/CT were 0.378 (0.319-0.440), 0.554 (0.492-0.615) and 0.712 (0.633-0.783) in the G1, G2 and G3 groups based on patients with NET, respectively. CONCLUSION: The 68Ga-SSTR PET has highly sensitive and had a greater diagnostic value than 18F-FDG PET for patients with NET. Fluorine-18-FDG PET, however, had significant specificity than 68Ga-SSTR PET. The 68Ga-SSTR has high sensitivity in G1/G2 NET, while 18F-FDG has a low positive rate. In G3 NET, however, the opposite is true. Therefore, the 68Ga-SSTR PET and 18F-FDG PET modalities are complementary rather than substitutive in clinical practice.

Exploration of Doubly Thermal Phase Transition Process of PDEGA-b-PDMA-b-PVCL in Water.

Understanding of phase transition mechanism of thermoresponsive polymers is the basis for the rational design of smart materials with predictable properties. Linear ABC triblock terpolymer poly(di(ethylene glycol)ethyl ether acrylate)-b-poly(N,N-dimethylacrylamide)-b-poly(N-vinylcaprolactam) (PDEGA-b-PDMA-b-PVCL) was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. The doubly thermal phase transition of PDEGA-b-PDMA-b-PVCL in aqueous solution was investigated by a combination of nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), turbidimetry, and dynamic light scattering (DLS). The terpolymer self-assembles into micelles with PDEGA being the core-forming block during the first lower critical solution temperature (LCST) transition corresponding to PDEGA, which is followed by a second LCST transition corresponding to PVCL, resulting in the formation of micellar aggregates. The PDMA middle segment plays an important role as an isolation zone to prevent cooperative dehydration of the PDEGA and PVCL segments, and therefore, two independent LCST transitions corresponding to PDEGA and PVCL were observed. Furthermore, FT-IR with perturbation correlation moving window (PCMW) and two-dimensional spectroscopy (2DCOS) was applied to elucidate the two-step phase transition mechanism of this terpolymer. It was observed that the CH, ester carbonyl, and ether groups of PDEGA change prior to the CH and amide carbonyl groups of PVCL, further supporting that the two phase transitions corresponding to PDEGA and PVCL indeed occur without mutual interferences.

Effects of white matter microstructure lesions on language and memory function in magnetic resonance imaging-negative temporal lobe epilepsy determined by diffusion tensor imaging.

OBJECTIVES: This study was conducted to investigate the associations between white matter lesions and language and memory dysfunctions in patients with magnetic resonance imaging (MRI)-negative temporal lobe epilepsy. MATERIALS AND METHODS: This study included 26 patients with temporal lobe epilepsy, who did not have significant findings on conventional MRI scanning, and 17 healthy subjects as control. Diffusion tensor imaging data was obtained with a 3Tesla (T) MRI scanner. Neuropsychological scores of language and memory functions were measured. One-way analysis of variance was used to analyze abnormal fractional anisotropy and mean diffusivity values. Correlations were performed to evaluate the relationship between fractional anisotropy/mean diffusivity of each fiber tract and neuropsychological measures. Regression analysis was performed to determine the contribution of each fiber tract to cognitive performance. RESULTS: Our data showed significantly decreased neuropsychological scores in the left and right temporal lobe epilepsy groups compared with control; it however, failed to show a statistical difference between the two groups. For the left temporal lobe epilepsy group, the mean diffusivity of the left parahippocampal and cingulate cortex, right arcuate fasciculus, and left fornix were significantly higher than control. Fractional anisotropy of the right fornix and mean diffusivity of the left uncinate fasciculus were significantly related to confrontational naming scores. There were significant correlations between the fractional anisotropy of the left fornix and verbal delayed memory scores and between the fractional anisotropy of the left fornix and nonverbal delayed memory scores. The mean diffusivity of left fractional anisotropy and the fractional anisotropy of the left uncinate fasciculus were significantly related to confrontational naming and verbal fluency scores, and seizure frequency was significantly related to nonverbal delayed memory scores. CONCLUSIONS: Language and memory function impairment was correlated with white matter structural integrity.

Noncardiogenic stroke patients with metabolic syndrome have more border-zone infarction and intracranial artery stenosis.

BACKGROUND: Little is known about the clinical character of stroke patients with metabolic syndrome (MetS) in Chinese population. In this hospital-based cross-sectional study, we elucidated the prevalence of MetS among patients with acute noncardiogenic cerebral infarction from south China, the topographic infarction patterns in magnetic resonance imaging, and vascular angiography findings of stroke patients with MetS. METHODS: The patients with acute noncardiogenic stroke were clinically evaluated including waistline circumference, blood pressure, glycemia, serum triglyceride, high-density lipoprotein cholesterol level, magnetic resonance imaging, and angiography evaluation, including magnetic resonance angiography, computed tomography angiography, or digital subtraction angiography for intracranial (IC) and extracranial arteries. According to the National Cholesterol Education Program Adult Treatment Panel III criterion, the patients were classified into the MetS and non-MetS groups. RESULTS: Among 222 patients studied, the prevalence of MetS was 54.5%, and there were more women in the MetS group than in the non-MetS group (P < .05). Frequency of all the individual factors of MetS was higher in the MetS group than in the non-MetS group (P < .05). The lesion pattern of border-zone (BZ) infarction was more prevalent in MetS patients (P < .05). The frequency of IC artery stenosis was higher in the MetS group than in the non-MetS group (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.0-3.0). After adjustment for age and gender, IC stenosis was significantly associated with large waistline circumference (OR, .95; 95% CI, .91-.99). CONCLUSIONS: According to our findings, MetS was of high prevalence in noncardiogenic stroke patients in China, and female patients were more likely to have MetS. The MetS patients tended to have more BZ infarctions and more IC artery stenosis than the non-MetS stroke patients.

The concomitant use of the renin-angiotensin system inhibitors and survival outcomes of patients with pancreatic adenocarcinoma: an analysis from a tertiary center.

Background: The limited efficacy of chemotherapy in improving survival in pancreatic ductal adenocarcinoma (PDAC) necessitates the exploration of novel strategies to overcome treatment resistance. Objectives: This study aimed to investigate the impact of combining renin-angiotensin system (RAS) blockers with chemotherapy on survival outcomes in patients with PDAC. Design: Patients with PDAC were enrolled in the retrospective study. Methods: We analyzed patients with PDAC (n = 384) at our institution between 2014 and 2021. Survival outcomes, including event-free survival (EFS) and overall survival (OS), were analyzed according to the concomitant use of RAS blockers. Results: Among the 384 patients in the study, 70 (18.2%) concomitantly received angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Patients in the ACEI/ARB group, characterized by older age and more comorbidities, displayed a significantly superior 12-month EFS rate (22.86% versus 13.69%, p = 0.008) compared to the non-ACEI/ARB group, while OS remained similar between the groups. In the multivariate analysis, the use of ACEI/ARB was associated with better 12-month EFS (hazards ratio = 0.71, 95% confidence interval: 0.52-0.96; p = 0.024). Poor performance, advanced disease status, and higher CA19-9 levels were associated with poor survival outcomes. Conclusion: Concomitant use of ACEIs/ARBs in patients with pancreatic cancer resulted in significantly better 12-month EFS. Age, performance status, disease status, and higher CA19-9 levels were independent predictors of survival. The combination strategy might provide better treatment outcomes in patients with PDAC.

N6-methyladenosine RNA methylation regulators contribute to the progression of prostate cancer.

Prostate cancer (PCa) is one of the most common epithelial malignant tumors and the fifth leading cause of cancer death in men. An increasing number of studies have demonstrated that N6-methyladenosine (m6A) plays a crucial role in tumorigenesis and tumor development. However, little is known about the role and levels of common m6A regulators and m6A levels in PCa. In this study, we analyzed the characteristic expression of m6A regulators in PCa and castration-resistant prostate cancer (CRPC). UALCAN and cBioPortal were used to estimate the clinical value and genetic alterations of m6A regulators, respectively. The correlation between m6A regulators and androgen receptor (AR) was assessed using Gene Expression Profiling Interactive Analysis (GEPIA) by Pearson correlation statistics. Total m6A levels were detected in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice and PCa cell lines. Results showed that the expression of methyltransferase-like 3 (METTL3) and YTH domain family members, namely, YTHDC2, YTHDF1, and YTHDF2 were generally upregulated in PCa, whereas those of fat mass and obesity-associated protein (FTO), AlkB homolog 5 (ALKBH5), and methyltransferase-like 14 (METTL14) were downregulated. The expression of METTL3, METTL14, Wilms' tumor 1-associating protein (WTAP), YTHDC2, YTHDF1, and YTHDF2 were remarkably higher in CRPC with lymph node metastasis than that in CRPC with bone metastasis, whereas ALKBH5, FTO, and YTHDF3 significantly decreased in CRPC with lymph node metastasis tissues. YTHDF1, YTHDF2, and YTHDC2 were positively correlated with the Gleason grades of PCa, and METTL14, FTO, and ALKBH5 were negatively associated with the Gleason classification. M6A regulators were positively correlated with AR. Patients with a genomic alteration of m6A were associated with poor disease-free survival (DFS). The total m6A levels in TRAMP mice increased dramatically compared with those in tumor-free mice, and m6A levels in LNCaP cell lines were higher than DU145 and PC3 cell lines. In summary, METTL3, METTL14, ALKBH5, FTO, YTHDC2, YTHDF1, and YTHDF2 were abnormally expressed in PCa and related to Gleason classification. Changes in m6A levels maybe contributed to the development and progression of PCa.

Redefining Remission Induction Chemotherapy Ineligibility by Early Mortality in De Novo Acute Myeloid Leukemia.

The therapeutic strategies for acute myeloid leukemia (AML) patients ineligible for remission induction chemotherapy have been improving in the past decade. Therefore, it is important to define ineligibility for remission induction chemotherapy. We retrospectively assessed 153 consecutive adult de novo AML patients undergoing remission induction chemotherapy and defined early mortality as death within the first 60 days of treatment. The 153 patients were stratified into the early mortality group (n = 29) and the non-early mortality group (n = 124). We identified potential factors to which early mortality could be attributed, investigated the cumulative incidence of early mortality for each aspect, and quantified the elements. The early mortality rate in our study cohort was 19.0%. Age ≥ 65 years (odds ratio (OR): 3.15; 95% confidence interval (CI): 1.05-9.44; p = 0.041), Eastern Cooperative Oncology Group performance status ≥ 2 (OR: 4.87; 95% CI: 1.77-13.41; p = 0.002), and lactate dehydrogenase ≥ 1000 IU/L (OR: 4.20; 95% CI: 1.57-11.23; p = 0.004) were the risk factors that substantially increased early mortality in AML patients. Patients with two risk factors had a significantly higher early mortality rate than those with one risk factor (68.8% vs. 20.0%; p < 0.001) or no risk factors (68.8% vs. 9.2%; p < 0.001). In conclusion, older age, poor clinical performance, and a high tumor burden were risks for early mortality in AML patients receiving remission induction chemotherapy. Patients harboring at least two of these three factors should be more carefully assessed for remission induction chemotherapy.

Magnetic silicon fullerene.

A metal-encapsulating silicon fullerene, Eu@Si(20), has been predicted by density functional theory to be by far the most stable fullerene-like silicon structure. The Eu@Si(20) structure is a dodecahedron with D(2h) symmetry in which the europium atom occupies the center site. The calculated results show that the europium atom has a large magnetic moment of nearly 7.0 Bohr magnetons. In addition, it was found that a stable "pearl necklace" nanowire, constructed by concatenating a series of Eu@Si(20) units, with the central europium atom, retains the high spin moment. The magnetic structure of the nanowire indicates potential applications in the fields of spintronics and high-density magnetic storage.

A new class of boron nanotube.

The configurations, stability and electronic structures of a new class of boron sheet and related boron nanotubes are predicted within the framework of density functional theory. This boron sheet is sparser than those of recent proposals. Our theoretic results show that the stable boron sheet remains flat and is metallic. There are bands similar to the pi-bands in graphite near the Fermi level. Stable nanotubes with various diameters and chiral vectors can be rolled from the sheet. Within our study, only the thin (8, 0) nanotube with a band gap of 0.44 eV is semiconducting, while all the other thicker boron nanotubes are metallic, independent of their chirality. It indicates the possibility, in the design of nanodevices, to control the electronic transport properties of the boron nanotube through the diameter.

Au42: a possible ground-state noble metallic nanotube.

A large hollow tubelike Au(42) is predicted as a new ground-state configuration based on the scalar relativistic density functional theory. The shape of this new Au(42) cluster is similar to a (5,5) single-wall gold nanotube, the two ends of which are capped by half of a fullerenelike Au(32). In the same way, a series of Au(n) (n = 37, 42, 47, 52, 57, 62, 67, 72, ..., Delta n = 5) tubelike structures has been constructed. The highest occupied molecular orbital-lowest unoccupied molecular orbital gaps suggested a significant semiconductor-conductor alternation in n is an element of [32,47]. Similar to the predictions and speculation of Daedalus [D. E. H. Jones, New Sci. 32, 245 (1966); E. Osawa, Superaromaticity (Kagaku, Kyoto, 1970), Vol. 25, pp. 854-863; Z. Yoshida and E. Osawa, Aromaticity Chemical Monograph (Kagaku Dojin, Kyoto, Japan, 1971), Vol. 22, pp. 174-176; D. A. Bochvar and E. G. Gal'pern, Dokl. Akad. Nauk SSSR 209, 610 (1973)], here a large hollow ground-state gold nanotube was predicted theoretically.

Preoperative evaluation of neurovascular relationship in trigeminal neuralgia by three-dimensional fast low angle shot (3D-FLASH) and three-dimensional constructive interference in steady-state (3D-CISS) MRI sequence.

OBJECTIVE: The purpose of the study was to evaluate the value of high-resolution three-dimensional fast low angle shot (3D-FLASH) and three-dimensional constructive interference in steady-state (3D-CISS) MRI sequence solely or the combination of both in the visualization of neurovascular relationship in patients with trigeminal neuralgia (TN). METHODS: 65 patients with unilateral TN underwent 3D-FLASH and 3D-CISS imaging were retrospectively studied. Neurovascular relationship at the intracisternal segment of trigeminal nerve was reviewed by two experienced neuroradiologist, who was blinded to the clinical details. The imaging results were compared with the operative findings in all patients. RESULTS: The accuracy and positive rates of the 3D-FLASH + CISS imaging (98.46, 92.31%) in judging the symptomatic side according to the presence of vascular contacts were higher than those of 3D-CISS (90.77%, 84.62) or 3D-FLASH (89.23, 83.08%) sequence. In addition, the statistical analysis showed the sensitivity and accuracy of 3D-FLASH + CISS imaging was higher than that of 3D-FLASH (p < 0.05). The 3D-FLASH + CISS imaging was more accurate in determining the type of offending vessel than 3D-CISS or 3D-FLASH imaging. CONCLUSION: The retrospective study demonstrates that the combination of 3D-FLASH with 3D-CISS sequence well delineates the relationship between intracisternal segment of trigeminal nerve and adjacent vessels in terms of increased positive rates and accuracy. Advances in knowledge: The study firstly dealt with the combination of 3D-CISS and 3D-FLASH imaging in TN.

Band structures and transport properties of zigzag graphene nanoribbons with antidot arrays.

We study the band and transport features of zigzag graphene nanoribbon with an antidot lattice. It is found that an antidot lattice could turn semi-metal graphene into a semiconductor. The size of the band gap can be tuned by the position of the antidots and the distance D between the two nearest antidots. For a finite superlattice with N antidots and a large D, a group of (N - 1) splitting resonant peaks and transmission-blockade regions appear alternately in the conductance spectrum. This indicates the formation of minibands and minigaps. In addition, Fano resonances can be observed when the antidots are localized near one edge of the nanoribbon. These features provide potential applications for graphene-based electronic and optoelectronic devices.