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Abstract Achalasia is a rare motility disorder of the esophagus caused by the gradual degeneration of myenteric neurons. Immune-mediated ganglionitis has been proposed to underlie the loss of myenteric neurons. Here, we measure the immune cell transcriptional profile of paired lower esophageal sphincter (LES) tissue and blood samples in achalasia and controls using single-cell RNA sequencing (scRNA-seq). In achalasia, we identify a pattern of expanded immune cells and a specific transcriptional phenotype, especially in LES tissue. We show C1QC+ macrophages and tissue-resident memory T cells (TRM), especially ZNF683+ CD8+ TRM and XCL1+ CD4+ TRM, are significantly expanded and localized surrounding the myenteric plexus in the LES tissue of achalasia. C1QC+ macrophages are transcriptionally similar to microglia of the central nervous system and have a neurodegenerative dysfunctional phenotype in achalasia. TRM also expresses transcripts of dysregulated immune responses in achalasia. Moreover, inflammation increases with disease progression since immune cells are more activated in type I compared with type II achalasia. Thus, we profile the immune cell transcriptional landscape and identify C1QC+ macrophages and TRM as disease-associated immune cell subsets in achalasia.

Background and Aims: Accurate recognition of endoscopic instruments facilitates quantitative evaluation and quality control of endoscopic procedures. However, no relevant research has been reported. In this study, we aimed to develop a computer-assisted system, EndoAdd, for automated endoscopic surgical video analysis based on our dataset of endoscopic instrument images. Methods: Large training and validation datasets containing 45,143 images of 10 different endoscopic instruments and a test dataset of 18,375 images collected from several medical centers were used in this research. Annotated image frames were used to train the state-of-the-art object detection model, YOLO-v5, to identify the instruments. Based on the frame-level prediction results, we further developed a hidden Markov model to perform video analysis and generate heatmaps to summarize the videos. Results: EndoAdd achieved high accuracy (>97%) on the test dataset for all 10 endoscopic instrument types. The mean average accuracy, precision, recall, and F1-score were 99.1%, 92.0%, 88.8%, and 89.3%, respectively. The area under the curve values exceeded 0.94 for all instrument types. Heatmaps of endoscopic procedures were generated for both retrospective and real-time analyses. Conclusions: We successfully developed an automated endoscopic video analysis system, EndoAdd, which supports retrospective assessment and real-time monitoring. It can be used for data analysis and quality control of endoscopic procedures in clinical practice.

BackgroundEndoscopic biopsy is the pivotal procedure for the diagnosis of gastric cancer. In this study, we applied whole-slide images (WSIs) of endoscopic gastric biopsy specimens to develop an endoscopic gastric biopsy assistant system (EGBAS).MethodsThe EGBAS was trained using 2373 WSIs expertly annotated and internally validated on 245 WSIs. A large-scale, multicenter test dataset of 2003 WSIs was used to externally evaluate EGBAS. Eight pathologists were compared with the EGBAS using a man-machine comparison test dataset. The fully manual performance of the pathologists was also compared with semi-manual performance using EGBAS assistance.ResultsThe average area under the curve of the EGBAS was 0·979 (0·958-0·990). For the diagnosis of all four categories, the overall accuracy of EGBAS was 86·95%, which was significantly higher than pathologists (P< 0·05). The EGBAS achieved a higher κ score (0·880, very good κ) than junior and senior pathologists (0·641 ± 0·088 and 0·729 ± 0·056). With EGBAS assistance, the overall accuracy (four-tier classification) of the pathologists increased from 66·49 ± 7·73% to 73·83 ± 5·73% (P< 0·05). The length of time for pathologists to manually complete the dataset was 461·44 ± 117·96 minutes; this time was reduced to 305·71 ± 82·43 minutes with EGBAS assistance (P = 0·00).ConclusionsThe EGBAS is a promising system for improving the diagnosis ability and reducing the workload of pathologists.

Crystalline borates have received great attention due to their various structures and wide applications. For a long time, the corner-sharing B–O unit is considered a basic rule in borate structural chemistry. The Dy4B6O15 synthesized under high-pressure is the first oxoborate with edge-sharing [BO4] tetrahedra, while the KZnB3O6 is the first ambient pressure borate with the edge-sharing [BO4] tetrahedra. The edge-sharing connection modes greatly enrich the structural chemistry of borates and are expected to expand new applications in the future. In this review, we summarize the recent progress in crystalline borates with edge-sharing [BO4] tetrahedra. We discuss the synthesis, fundamental building blocks, structural features, and possible applications of these edge-sharing borates. Finally, we also discuss the future perspectives in this field.

Abstract Background Hepatic cavernous hemangioma is the most common type of benign liver tumor. Although ruptures and hemorrhages of hepatic hemangioma are rare complications, they are associated with high mortality. Most practitioners only pay more attention to abdominal hemorrhages caused by the rupture of hepatic hemangiomas. However, spontaneous intracapsular hemorrhages can often be neglected and poorly understood. Case presentation A 65-year-old man was referred to our institution with right upper quadrant pain, which had occurred suddenly and without a history of recent trauma. The blood test results were normal. Magnetic resonance imaging (MRI) of the abdomen showed a cystic mass in the right liver lobe. Considering the possibility of hepatic cystadenoma with hemorrhage, the patient underwent a right hepatic lobectomy. The pathological findings unexpectedly revealed intratumoral hemorrhage of hepatic hemangioma. The patient recovered well and was discharged eight days after surgery. Conclusions Intracapsular hemorrhage of hepatic cavernous hemangioma is challenging to diagnose and has a high potential risk of rupture. MRI is beneficial for diagnosing subacute internal hemorrhage cases, and it is recommended to undergo surgery for patients with a definitive diagnosis.

Abstract Background Aberrant expression of ubiquitin-specific peptide 22 (USP22) has been detected in various cancers. This study aimed to investigate the role of USP22 and the underlying mechanism in human gastric cancer. Methods The expression pattern of USP22 in human gastric cancer was detected in a tissue microarray containing 88 pairs of gastric cancer tissue and adjacent normal tissue samples from patients with primary gastric cancer using immunohistochemical staining. The correlation of USP22 expression with clinical characteristics of patients, as well as their prognostic values in the overall survival of patients, were evaluated. USP22-overexpressing SGC7901 and USP22-silencing AGS cells were used to explore the role of USP22 in gastric cancer cell behavior in vitro and in vivo. Chromatin immunoprecipitation was performed to identify differentially expressed genes induced by USP22 overexpression. Western blot analysis was conducted to detect the activation of RAS/ERK and PI3K/AKT signaling in USP22-overexpressing SGC7901 cells and xenograft tumor tissues. Knockdown of RAS activator son of sevenless 1 (SOS1) was performed to investigate the role of SOS1 in USP22-regulated gastric cancer cell behavior and RAS signaling both in vitro and in vivo. Results USP22 protein expression was significantly increased in human gastric cancer tissues, compared with adjacent normal tissues, and was positively correlated with local tumor stage. Gain- and loss-of-function assays showed that USP22 promoted gastric cancer cell growth and cell cycle transition while suppressing apoptosis in vitro. Consistent results were observed in a xenograft mouse model. Chromatin immunoprecipitation revealed that the overexpression of USP22 induced the upregulation of RAS activator son of sevenless 1 (SOS1) in SGC7901 cells. Western blot analysis showed that USP22 overexpression also induced activation of the RAS/ERK and PI3K/AKT pathways in SGC7901 cells and xenograft tumor tissues. Furthermore, SOS1 silencing could reverse the effects of USP22 on gastric cancer cell behavior and RAS signaling both in vitro and in vivo. Conclusions Our results suggest that USP22 acts as an oncogene in gastric cancer in a SOS1-dependent manner, identifying the USP22/SOS1/RAS axis as a potential therapeutic target in gastric cancer.

Organic matter application was one of the suitable ways to improve soil nitrogen availability in saline soils. In this study, two soils of different levels of total soluble salts, 2.45 g kg−1 (LS) and 4.03 g kg−1 (HS), were used in a pot experiment with eight treatments: bio-organic fertilizer (prepared with cow dung) and farmyard manure (fowl manure) each at three dosages (3350, 6700, and 13,400 kg ha−1), chemical fertilizer control (DAP: 1675 kg ha−1), no fertilizer blank. At the same time, an indoor nitrogen mineralization incubation experiment with the same treatments without alfalfa planting was carried out. We aimed to explore the effects of the types and application amounts of organic fertilizers on soil nitrogen mineralization in saline soils and to improve its quality and finally realize its sustainable utilization. The main conclusions are as follows: the biomass of alfalfa treated with medium dose of organic fertilizer was higher than that of alfalfa treated with low or high dose of organic fertilizer. Compared with farmyard manure, bio-organic manure was more effective in increasing the biomass of alfalfa. The nitrogen uptake of alfalfa in high-dose treatment was significantly higher than that in low-dose treatment. The effects of the fertilizer treatments on soil nitrogen availability were in the increasing order of: medium dose, high or low dose of fertilizer treatment, single chemical fertilizer, and fertilizer free treatments by principal component analysis. For possible potential application, medium dosage of bio-organic fertilizer was recommended to apply in the region with saline fluvo-aquic soil.

Abstract Background Colorectal carcinomas (CRCs) arise from premalignant precursors in an adenoma-carcinoma sequence, in which adenoma with high-grade dysplasia (HGD) and early-stage carcinoma are defined as advanced neoplasia. A limited number of studies have evaluated the long-term outcomes of endoscopic submucosal dissection (ESD) for advanced colorectal neoplasia. This study aimed to assess the efficacy and safety of ESD for advanced colorectal neoplasia as well as the long-term outcomes, including local recurrence and metastasis. Methods We analyzed data collected from 610 consecutive patients with 616 advanced colorectal neoplasia lesions treated with ESD between January 2007 and December 2013. Clinical, endoscopic, and histological data were collected over a median follow-up period of 58 months to determine tumor stage and type, resection status, complications, tumor recurrence, and distant metastasis. Results The overall rates of en bloc resection, histological complete resection, and major complications were 94.3%, 89.4%, and 2.3%, respectively. Hybrid ESD was an independent factor of piecemeal resection. Tumor location in the colon was associated with increased risk of ESD-related complications. During the follow-up period, all patients remained free of metastasis. However, local recurrence occurred in 4 patients (0.8%); piecemeal resection was a risk factor. Conclusions ESD is effective and safe for resection of advanced colorectal neoplasia, with a high en bloc resection rate and favorable long-term outcomes. ESD is indicated for the treatment of HGD and early-stage CRC to obtain curative resection and reduce local recurrence rate.

The complete mitochondrial genome of the stellate puffer (Arothron stellatus) was first determined in this study. It was a 16,475 bp circular molecule and consisted of 37 genes with typical gene order in vertebrate mitogenome. Its nucleotide content was 29.0% A, 32.0% C, 15.9% G and 23.1% T. This mitogenome had 30 bp short intergenic spaces located in 12 gene junctions and 28 bp overlaps located in 7 gene junctions. In the protein-coding genes, two start codons (GTG and ATG) and two stop codons (TAG and TAA/TA/T) were found. The 22 tRNA genes ranged from 64 bp (tRNA-Cys) to 74 bp (tRNA-Leu1 and tRNA-Lys). The phylogenetic result showed that Takifugu xanthopterus was most closely related to the reef-related A. stellatus among all Tetraodontiformes species.

Abstract Background Additional surgery is recommended when early colorectal cancer (ECRC) is resected by non-curative endoscopic submucosal dissection (ESD) and there is significant risk of lymph node metastasis (LNM). The aim of this study was to investigate the efficacy and safety of additional surgery after non-curative ESD for ECRC and evaluate long-term outcomes. Methods Patients with ECRC who underwent ESD and additional surgery between July 2007 and November 2013 were identified. Histology and patient data were collected during an average period of more than 5 years to determine tumor stage and type, resection status, complications, tumor recurrence, and distant metastasis. Results Fifty-one patients who underwent additional surgery were eligible for analysis. Overall, regional LNM was detected in 5 patients (9.8%) and presence of lymphovascular infiltration was a significant risk factor. Surgery-related complications occurred in 3 patients (5.9%). During a median follow-up period of 59 months, no metastasis or local recurrence was observed. Three patients died of other diseases and no CRC-related deaths took place. Conclusions Additional surgery after non-curative ESD for ECRC is effective and safe and should be encouraged to foster curative treatment and better long-term outcomes.

This paper proposes a physics-based model of flat-band capacitance Cfb for metal oxide thin-film transistors, in which the influences of free carriers and electrons trapped in deep/tail states are taken into account. Hereinto, a parameter Ls is introduced to characterize the screening length in the metal oxide semiconductor, which is similar to the extrinsic Debye length (Ld) for conventional MOS structure. Based on the proposed model, the flat-band voltage Vfb can be consequently determined as the gate voltage corresponding to Cgs equal to Cfb. It is shown that the value of Vfb determined by the proposed model is consistent with that extracted from experimental data of I-V and C-V or the simulated results of 2D device simulator ATLAS. Moreover, we investigate the effect of the parameters of density of states on the flat band capacitance and Cgs-Vgs characteristics of metal oxide TFTs by ATLAS in details. It is found that both tail states and deep states should be simultaneously taken into account for determining the flat band capacitance and flat band voltage of metal oxide TFTs. The proposed model for the flat band capacitance of metal oxide TFTs is expected to be useful for device characterization since it is analytical and physically meaningful.

The mitochondrial genome of Bregmaceros macclellandii was elucidated and analyzed for the first time in this study. It had a double-stranded DNA molecule with 17,319 bp in length and was made up of 37 genes (13 protein-coding genes, 2 rRNA genes, and 22 tRNA genes), and one control region. Phylogenetic analysis of 18 included species indicated that B. macclellandii was clustered closely with Coelorinchus kishinouyei and Ventrifossa garmani.

The frequency-domain and time-domain characteristics of adaptive interference cancellation system were ana-lyzed,when interference signal had nonzero bandwidth.The nonzero bandwidth interference signal made the system a time-variation system.When the bandwidth was far less than the center frequency,the interference cancellation system could be approximated as an adaptive comb filter.The average convergence speed of the system was proportional to the overall reference signal gain,and the interference cancellation ratio (ICR) decreased with the increase of the bandwidth.The theoretical and simulation analyses of couple time delay matching reveal that the precise time delay matching can improve ICR significantly.

In the application of the Lambert W function, the surface potential for amorphous oxide semiconductor thin-film transistors (AOS TFTs) under the subthreshold region is approximated by an asymptotic equation only considering the tail states. While the surface potential under the above-threshold region is approximated by another asymptotic equation only considering the free carriers. The intersection point between these two asymptotic equations represents the transition from the weak accumulation to the strong accumulation. Therefore, the gate voltage corresponding to the intersection point is defined as threshold voltage of AOS TFTs. As a result, an analytical expression for the threshold voltage is derived from this novel definition. It is shown that the threshold voltage achieved by the proposed physics-based model is agreeable with that extracted by the conventional linear extrapolation method. Furthermore, we find that the free charge per unit area in the channel starts increasing sharply from the threshold voltage point, where the concentration of the free carriers is a little larger than that of the localized carriers. The proposed model for the threshold voltage of AOS TFTs is not only physically meaningful but also mathematically convenient, so it is expected to be useful for characterizing and modeling AOS TFTs.

Prenatal organophosphate exposure elicits long-term brain cytoarchitecture and cognitive function impairments, but the mechanism underlying the onset and development of neural progenitors remain largely unclear. Using precise positioned brain slices, we observed an alternated cleavage plane bias that emerged in the mitotic neural progenitors of embryonal neocortex with diazinion (DZN) and chlorpyrifos (CPF) pretreatment. In comparison with the control, DZN and CPF treatment induced decrease of vertical orientation, increase of oblique orientation, and increase of horizontal orientation. That is, the cleavage plane orientation bias had been rotated from vertical to horizontal after DZN and CPF treatment. Meanwhile, general morphology and mitotic index of the progenitors were unchanged. Acephate (ACP), another common organophosphate, had no significant effects on the cleavage plane orientation, cell morphology and mitotic index. These results represent direct evidence for the toxicity mechanism in onset multiplication of neural progenitors.

As a minimally invasive technique, endoscopic resection may benefit patients diagnosed with early stage gastrointestinal neuroendocrine tumors (NETs). However, no studies have yet been published in which endoscopic submucosal dissection (ESD) has been applied for gastric NETs. For the first time a research group in China applied ESD to remove gastric NETs, and indicated that ESD should be considered for treatment of eligible gastric NETs because the technique shows a high histologically complete resection rate, provides accurate histopathological evaluation, has a low complication rate, and can be performed within a reasonable timeframe.

BackgroundAfter positive selection, the newly generated single positive (SP) thymocytes migrate to the thymic medulla, where they undergo negative selection to eliminate autoreactive T cells and functional maturation to acquire immune competence and egress capability.Methodology/principal findingsTo elucidate the genetic program underlying this process, we analyzed changes in gene expression in four subsets of mouse TCRαβ(+)CD4(+)CD8(-) thymocytes (SP1 to SP4) representative of sequential stages in a previously defined differentiation program. A genetic signature of the migration of thymocytes was thus revealed. CCR7 and PlexinD1 are believed to be important for the medullary positioning of SP thymocytes. Intriguingly, their expression remains at low levels in the newly generated thymocytes, suggesting that the cortex-medulla migration may not occur until the SP2 stage. SP2 and SP3 cells gradually up-regulate transcripts involved in T cell functions and the Foxo1-KLF2-S1P(1) axis, but a number of immune function-associated genes are not highly expressed until cells reach the SP4 stage. Consistent with their critical role in thymic emigration, the expression of S1P(1) and CD62L are much enhanced in SP4 cells.ConclusionsThese results support at the molecular level that single positive thymocytes undergo a differentiation program and further demonstrate that SP4 is the stage at which thymocytes acquire the immunocompetence and the capability of emigration from the thymus.