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Abstract Background The site-specific tissue properties of knee cartilage may play an essential role in knee joint mechanical function, and mitigate joint injury and cartilage degeneration. The present study aimed to determine the significance of tissue inhomogeneity in knee joint contact mechanics using a porcine model. Methods Finite element models were developed for a porcine knee with intact and total meniscectomy conditions to simulate whole-joint compression-relaxation tests under a 1.2-mm ramp-compression at 0.01, 0.1, or 1 mm/s. Two reference benchmarks were introduced for the implementation of poromechanical material properties of fibril-reinforced cartilage: Benchmark II consisted of 17 sets of cartilage properties, each for a region in the knee, representing site-specific inhomogeneity averaged from cartilage indentation maps of 14 porcine knees. Benchmark I was comprised of a single set of properties by taking the average properties of 17 regions in Benchmark II, assuming tissue homogeneity. To validate the modeling method, the reference benchmarks were used to produce results against whole-joint compression test data. Results Both benchmarks were able to approximate experimental force-compression data obtained from the same knee with intact menisci and total meniscectomy, provided that the average properties from 14 knees were appropriately scaled to account for individual joint differences. Noticeable differences in stress and pressure distributions were observed between the benchmarks. For instance, benchmark I generated higher peak contact and fluid pressures in the medial tibial cartilage, but benchmark II produced the higher ones in the lateral tibial cartilage. The load sharing asymmetry between the lateral and medial compartments was reduced in benchmark II which was more pronounced for higher compression rates. On the other hand, benchmark II produced a more uniform stress distribution or lower maxima. Meniscectomy caused a slight shift of the contact centers in the tibial plateaus as compared to the intact joint. Conclusion The modeling results demonstrated substantial differences in loading distributions in the joint between the homogeneous and nonhomogeneous models represented by the two benchmarks, indicating the role of tissue inhomogeneity in the joint contact mechanics. Region-dependent tissue properties may need to be implemented in joint mechanical modeling to evaluate the site of cartilage prone to injury or degeneration.

Abstract Background Transfer RNA-derived small RNAs (tsRNAs), including tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs), constitute a novel class of small noncoding RNAs (sncRNAs). tsRNAs have been linked to tumorigenesis and the progression of carcinogenesis; however, the precise molecular mechanism through which tRFs act in gastric cancer (GC) remains unknown. Methods tRF-Tyr is a potential GC tumor suppressor that was identified through high-throughput sequencing technology. The expression and subcellular localization of tRF-Tyr in GC were detected by via qRT‒PCR and FISH. RNA pull-down, mass spectrometry, RNA immunoprecipitation (RIP), dual-luciferase reporter and rescue assays were performed to explore the regulatory mechanisms through which tRF-Tyr acts in GC. Results tRF-Tyr was significantly downregulated and the downregulation of its mainly concentrated in the nuclei of GC cells. Functionally, tRF-Tyr inhibited the proliferation, invasiveness and migration of GC cells and promoted GC cells apoptosis in vitro; meanwhile, tRF-Tyr inhibited tumor growth in vivo. Mechanistically, tRF-Tyr bound directly to the hnRNPD protein and competitively inhibited the binding of hnRNPD to the c-Myc 3′UTR, thereby, regulating the c-Myc/Bcl2/Bax pathway and ultimately inhibiting the progression of GC. Conclusions This study focused on a novel GC suppressor, tRF-Tyr, and revealed a previously undiscovered mechanism that tRF-Tyr inhibits tumor progression by targeting hnRNPD. These findings provide new insight into the involvement of tRFs in GC and suggest a novel target for GC treatment.

Abstract Aging is an inevitable physiological process in organisms, and the development of tumors is closely associated with cellular senescence. This article initially examines the role of cellular senescence in tumorigenesis, emphasizing the correlation between telomere length—a marker of cellular senescence—and tumor risk. Concurrently, the study explores the expression levels of senescence-associated markers, such as p16, p53, and mTOR, in the context of tumor development. Additionally, the study investigates the impact of tumors on cellular and organismal senescence, including the effects on immune system function and metabolic processes. Ultimately, the discussion explores the potential application of anti-aging strategies in tumor therapy and considers the possibility of utilizing senescence mechanisms as a novel therapeutic approach for tumors. This research provides novel insights into the complex interplay between senescence and tumor development, suggesting potential strategies for future preventative measures and therapeutic interventions.

Abstract The gut microbiota is a complex and dynamic ecosystem that plays a crucial role in human health and disease, including obesity, diabetes, cardiovascular diseases, neurodegenerative diseases, inflammatory bowel disease, and cancer. Chronic inflammation is a common feature of these diseases and is closely related to angiogenesis (the process of forming new blood vessels), which is often dysregulated in pathological conditions. Inflammation potentially acts as a central mediator. This abstract aims to elucidate the connection between the gut microbiota and angiogenesis in various diseases. The gut microbiota influences angiogenesis through various mechanisms, including the production of metabolites that directly or indirectly affect vascularization. For example, short-chain fatty acids (SCFAs) such as butyrate, propionate, and acetate are known to regulate immune responses and inflammation, thereby affecting angiogenesis. In the context of cardiovascular diseases, the gut microbiota promotes atherosclerosis and vascular dysfunction by producing trimethylamine N-oxide (TMAO) and other metabolites that promote inflammation and endothelial dysfunction. Similarly, in neurodegenerative diseases, the gut microbiota may influence neuroinflammation and the integrity of the blood–brain barrier, thereby affecting angiogenesis. In cases of fractures and wound healing, the gut microbiota promotes angiogenesis by activating inflammatory responses and immune effects, facilitating the healing of tissue damage. In cancer, the gut microbiota can either inhibit or promote tumor growth and angiogenesis, depending on the specific bacterial composition and their metabolites. For instance, some bacteria can activate inflammasomes, leading to the production of inflammatory factors that alter the tumor immune microenvironment and activate angiogenesis-related signaling pathways, affecting tumor angiogenesis and metastasis. Some bacteria can directly interact with tumor cells, activating angiogenesis-related signaling pathways. Diet, as a modifiable factor, significantly influences angiogenesis through diet-derived microbial metabolites. Diet can rapidly alter the composition of the microbiota and its metabolic activity, thereby changing the concentration of microbial-derived metabolites and profoundly affecting the host's immune response and angiogenesis. For example, a high animal protein diet promotes the production of pro-atherogenic metabolites like TMAO, activating inflammatory pathways and interfering with platelet function, which is associated with the severity of coronary artery plaques, peripheral artery disease, and cardiovascular diseases. A diet rich in dietary fiber promotes the production of SCFAs, which act as ligands for cell surface or intracellular receptors, regulating various biological processes, including inflammation, tissue homeostasis, and immune responses, thereby influencing angiogenesis. In summary, the role of the gut microbiota in angiogenesis is multifaceted, playing an important role in disease progression by affecting various biological processes such as inflammation, immune responses, and multiple signaling pathways. Diet-derived microbial metabolites play a crucial role in linking the gut microbiota and angiogenesis. Understanding the complex interactions between diet, the gut microbiota, and angiogenesis has the potential to uncover novel therapeutic targets for managing these conditions. Therefore, interventions targeting the gut microbiota and its metabolites, such as through fecal microbiota transplantation (FMT) and the application of probiotics to alter the composition of the gut microbiota and enhance the production of beneficial metabolites, present a promising therapeutic strategy.

Polysomnography (PSG) measures brain activity during sleep via electroencephalography (EEG) using six leads. Artifacts caused by movement or loose leads distort EEG measurements. We developed a method to automatically identify such artifacts in a PSG EEG trace. After preprocessing, we extracted power levels at frequencies of 0.5–32.5 Hz with multitaper spectral analysis using 4 s windows with 3 s overlap. For each resulting 1 s segment, we computed segment-specific correlations between power levels for all pairs of leads. We then averaged all pairwise correlation coefficients involving each lead, creating a time series of segment-specific average correlations for each lead. Our algorithm scans each averaged time series separately for “bad” segments using a local moving window. In a second pass, any segment whose averaged correlation is less than a global threshold among all remaining good segments is declared an outlier. We mark all segments between two outlier segments fewer than 300 s apart as artifact regions. This process is repeated, removing a channel with excessive outliers in each iteration. We compared artifact regions discovered by our algorithm to expert-assessed ground truth, achieving sensitivity and specificity of 80% and 91%, respectively. Our algorithm is an open-source tool, either as a Python package or a Docker.

The failure of a filament eruption caused by magnetic reconnection between the erupting filament and the overlying magnetic field has been previously proposed in numerical simulations. It is, however, rarely observed. In this study, we report a reconnection between an erupting filament and its overlying coronal loops that results in the failure of the filament eruption. On 2023 September 24, a filament was located in active region 13445. It slowly rose, quickly erupted, rapidly decelerated, then finally stopped, with an untwisting motion. As a failed eruption, the event is associated with an M4.4 flare but no coronal mass ejection. During the eruption, the filament became bright, and the overlying loops appeared first in the high-temperature channels. They have average temperatures of ∼12.8 and ∼9.6 MK, respectively, indicating that both of them were heated. Two sets of new loops, separately connecting the filament endpoints and the overlying loop footpoints, then formed. Subsequently, the heated overlying loops were seen sequentially in the low-temperature channels, showing the cooling process, which is also supported by the light curves. Plasmoids formed and propagated bidirectionally along the filament and the overlying loops, indicating the presence of plasmoid instability. These results suggest that reconnection occurs between the erupting filament and the overlying loops. The erupting filament eventually disappeared, with the appearance of more newly formed loops. We propose that the reconnection between the erupting filament and the overlying loops ruins the filament completely, hence resulting in the failed eruption.

Abstract Recent studies have highlighted the biological significance of cuproptosis in disease occurrence and development. However, it remains unclear whether cuproptosis signaling also has potential impacts on tumor initiation and prognosis of gastric cancer (GC). In this study, 16 cuproptosis‐related genes (CRGs) transcriptional profiles were harnessed to perform the regularized latent variable model‐based clustering in GC. A cuproptosis signature risk scoring (CSRS) scheme, based on a weighted sum of principle components of the CRGs, was used to evaluate the prognosis and risk of individual tumors of GC. Four distinct cuproptosis signature‐based clusters, characterized by differential expression patterns of CRGs, were identified among 1136 GC samples across three independent databases. The four clusters were also associated with different clinical outcomes and tumor immune contexture. Based on the CSRS, GC patients can be divided into CSRS‐High and CSRS‐Low subtypes. We found that DBT, MTF1, and ATP7A were significantly elevated in the CSRS‐High subtype, while SLC31A1, GCSH, LIAS, DLAT, FDX1, DLD, and PDHA1 were increased in the CSRS‐Low subtype. Patients with CSRS‐Low score were characterized by prolonged survival time. Further analysis indicated that CSRS‐Low score also correlated with greater tumor mutation burden (TMB) and higher mutation rates of significantly mutated genes (SMG) in GC. In addition, the CSRS‐High subtype harbored more significantly amplified focal regions related to tumorigenesis (3q27.1, 12p12.1, 11q13.3, etc.) than the CSRS‐Low tumors. Drug sensitivity analyses revealed the potential compounds for the treatment of gastric cancer with CSRS‐High score, which were experimentally validated using GC cells. This study highlights that cuproptosis signature‐based subtyping is significantly associated with different clinical features and molecular landscape of GC. Quantitative evaluation of the CSRS of individual tumors will strengthen our understanding of the occurrence and development of cuproptosis and the treatment progress of GC.

Abstract Malignant tumours of the digestive system cover a wide range of diseases that affect the health of people to a large extent. Angiogenesis is indispensable in the development, and metastasis of tumours, mainly in two ways: occupation or formation. Vessels can provide nutrients, oxygen, and growth factors for tumours to encourage growth and metastasis, so cancer progression depends on simultaneous angiogenesis. Recently, exosomes have been proven to participate in the angiogenesis of tumours. They influence angiogenesis by binding to tyrosine kinase receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 with different affinities, regulating Yap-VEGF pathway, Akt pathway or other signaling pathway. Additionally, exosomes are potential therapeutic vectors that can deliver many types of cargoes to different cells. In this review, we summarize the roles of exosomes in the angiogenesis of digestive system tumours and highlight the clinical application prospects, directly used as targers or delivery vehicles, in antiangiogenic therapy.

Abstract Organoids are established through in vitro 3D culture, and they can mimic the structure and physiological functions of organs or tissues in vivo. Organoids have attracted much attention in recent years. They can provide a reliable technology platform for cancer research and treatment and are a valuable preclinical model for academic research and personalized medicine. A number of studies have confirmed that organoids have great application prospects in new drug development, drug screening, tumour mechanism research, and precision medicine. In this review, we mainly focus on recent advances in the application of organoids in cancer research. We also discussed the opportunities and challenges facing organoids, hoping to indicate directions for the development of organoids in the future.

Abstract Background Tumor mutational load (TML) has emerged as a potential biomarker for multiple solid tumors. However, data on its prognostic impact on upper gastrointestinal (UGI) cancer are limited. Therefore, the aim of this systematic review and meta‐analysis was to assess the prognostic value of TML for the survival of patients with UGI cancer. Method A comprehensive search of the PubMed, Embase, Cochrane Library, and Web of Science databases was conducted up to February 13, 2023. Eleven studies met our inclusion criteria. Hazard ratios (HRs) for progression‐free survival and overall survival and their 95% confidence intervals (CIs) were calculated. Subsequently, the combined HR and its 95% CI were calculated for UGI tract cancers in the high and low TML groups. I2 statistics and p‐values were used to evaluate heterogeneity. Publication bias, sensitivity, and subgroup analyses were performed to determine sources of heterogeneity. Results In total, 932 patients with UGI tract cancer from 11 publications were included. The high TML group treated with immunotherapy showed significantly improved overall survival (HR = 0.68; 95% CI: 0.53, 0.86; p = .001) and progression‐free survival (HR = 0.74; 95% CI: 0.58, 0.95; p = .020) compared with the low TML group. Conclusion Our study demonstrated that patients with UGI tumors and higher TML have a better prognosis with immunotherapy, suggesting that TML is a promising predictive biomarker for immunotherapy. Registration The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO Registration No: CRD42023405596).

Abstract Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has recently emerged as a novel tumor suppressor. Researchers have observed that LHPP plays a crucial role in inhibiting proliferation, growth, migration, invasion, and cell metabolism across various cancers. Nevertheless, the specific functions and underlying mechanisms of LHPP as a tumor suppressor in gastric cancer (GC) require further exploration. The expression of LHPP was assessed in human GC specimens and cell lines. Various assays were employed to evaluate the impact of LHPP on GC cells. RNA sequencing and Gene Set Enrichment Analysis were conducted to unravel the mechanism through which LHPP regulates GC cell behavior. Additionally, xenograft nude mouse models were utilized to investigate the in vivo effects of LHPP. The findings indicate that LHPP, functioning as a tumor suppressor, is downregulated in both GC tissues and cells. LHPP emerges as an independent risk factor for GC patients, and its expression level exhibits a positive correlation with patient prognosis. LHPP exerts inhibitory effects on the adhesion and proliferation of GC cells by suppressing the expression of insulin‐like growth factor 1 receptor (IGF1R) and modulating downstream signaling pathways. Consequently, LHPP holds potential as a biomarker for targeted therapy involving IGF1R inhibition in GC patients.

Alpha–proton differential flow ( V _α _p ) of coronal mass ejections (CMEs) and solar wind from the Sun to 1 au and beyond could influence the instantaneous correspondence of absolute abundances of alpha particles (He ^2+ /H ^+ ) between the solar corona and interplanetary space as the abundance of a coronal source can vary with time. Previous studies based on Ulysses and Helios showed that V _α _p is negligible within CMEs from 5 to 0.3 au, similar to slow solar wind (

Abstract Gut microbiota is closely related to human health and disease because, together with their metabolites, gut microbiota maintain normal intestinal peristalsis. The use of antibiotics or opioid anesthetics, or both, during surgical procedures can lead to dysbiosis and affect intestinal motility; however, the underlying mechanisms are not fully known. This review aims to discuss the effect of gut microbiota and their metabolites on postoperative intestinal motility, focusing on regulating the enteric nervous system, 5-hydroxytryptamine neurotransmitter, and aryl hydrocarbon receptor.

Background The characteristics of and relationship between sleep apnoea and hypoventilation in patients with muscular dystrophy (MD) remain to be fully understood.Methods We analysed 104 in-laboratory sleep studies of 73 patients with MD with five common types (DMD—Duchenne, Becker MD, CMD—congenital, LGMD—limb-girdle and DM—myotonic dystrophy). We used generalised estimating equations to examine differences among these types for outcomes.Results Patients in all five types had high risk of sleep apnoea with 53 of the 73 patients (73%) meeting the diagnostic criteria in at least one study. Patients with DM had higher risk of sleep apnoea compared with patients with LGMD (OR=5.15, 95% CI 1.47 to 18.0; p=0.003). Forty-three per cent of patients had hypoventilation with observed prevalence higher in CMD (67%), DMD (48%) and DM (44%). Hypoventilation and sleep apnoea were associated in those patients (unadjusted OR=2.75, 95% CI 1.15 to 6.60; p=0.03), but the association weakened after adjustment (OR=2.32, 95% CI 0.92 to 5.81; p=0.08). In-sleep average heart rate was about 10 beats/min higher in patients with CMD and DMD compared with patients with DM (p=0.0006 and p=0.02, respectively, adjusted for multiple testing).Conclusion Sleep-disordered breathing is common in patients with MD but each type has its unique features. Hypoventilation was only weakly associated with sleep apnoea; thus, high clinical suspicion is needed for diagnosing hypoventilation. Identifying the window when respiratory muscle weakness begins to cause hypoventilation is important for patients with MD; it enables early intervention with non-invasive ventilation—a therapy that should both lengthen the expected life of these patients and improve its quality.Cite Now

Introduction Gastric cancer (GC) diagnosed in the elderly population has become a serious public health problem worldwide. Given the combined effects of frailty and the consequences of cancer treatment, older individuals with GC are more likely than young patients to suffer from postoperative complications and poor clinical outcomes. Nutrition, functional capacity and psychological state-based multimodal prehabilitation, which is dominated by Enhanced Recovery After Surgery (ERAS) pathway management, has been shown to reduce postoperative complications, promote functional recovery and decrease hospitalisation time in certain malignancies. However, no previous studies have investigated the clinical application of multimodal prehabilitation in frail older patients with GC.Methods and analysis The study is a prospective, multicentre randomised controlled trial in which a total of 368 participants who meet the inclusion criteria will be randomised into either a prehabilitation group or an ERAS group. The prehabilitation group will receive multimodal prehabilitation combined with ERAS at least 2 weeks before the gastrectomy is performed, including physical and respiratory training, nutritional support, and therapy and psychosocial treatment. The ERAS group patients will be treated according to the ERAS pathway. All interventions will be supervised by family members. The primary outcome measures are the incidence and severity of postoperative complications. Secondary outcomes include survival, functional capacity and other short-term postoperative outcomes. Overall, the multimodal prehabilitation protocol may improve functional capacity, reduce the surgical stress response and concomitant systemic inflammation, and potentially modulate the tumour microenvironment to improve short-term and long-term clinical outcomes and patients’ quality of life.Ethics and dissemination All procedures and participating centres of this study were approved by their respective ethics committees (QYFYKYLL 916111920). The final study results will be published separately in peer-reviewed journals.Trial registration number NCT05352802.

DNASE1L3, an enzyme highly expressed in DCs, is functionally important for regulating autoimmune responses to self-DNA and chromatin. Deficiency of DNASE1L3 leads to development of autoimmune diseases in both humans and mice. However, despite the well-established causal relationship between DNASE1L3 and immunity, little is known about the involvement of DNASE1L3 in regulation of antitumor immunity, the foundation of modern antitumor immunotherapy. In this study, we identify DNASE1L3 as a potentially new regulator of antitumor immunity and a tumor suppressor in colon cancer. In humans, DNASE1L3 is downregulated in tumor-infiltrating DCs, and this downregulation is associated with poor patient prognosis and reduced tumor immune cell infiltration in many cancer types. In mice, Dnase1l3 deficiency in the tumor microenvironment enhances tumor formation and growth in several colon cancer models. Notably, the increased tumor formation and growth in Dnase1l3-deficient mice are associated with impaired antitumor immunity, as evidenced by a substantial reduction of cytotoxic T cells and a unique subset of DCs. Consistently, Dnase1l3-deficient DCs directly modulate cytotoxic T cells in vitro. To our knowledge, our study unveils a previously unknown link between DNASE1L3 and antitumor immunity and further suggests that restoration of DNASE1L3 activity may represent a potential therapeutic approach for anticancer therapy.

The vast majority of severe (Type 0) spinal muscular atrophy (SMA) cases are caused by homozygous deletions of survival motor neuron 1 (SMN1). We report a case in which the patient has two copies of SMN1 but clinically presents as Type 0 SMA. The patient is an African American male carrying a homozygous maternally inherited missense variant (c.796T>C) in a cis-oriented SMN1 duplication on one chromosome and an SMN1 deletion on the other chromosome (genotype: 2*+0). Initial extensive genetic workups including exome sequencing were negative. Deletion analysis used in the initial testing for SMA also failed to detect SMA as the patient has two copies of SMN1. Because of high clinical suspicion, SMA diagnosis was finally confirmed based on full-length SMN1 sequencing. The patient was initially treated with risdiplam and later gene therapy with onasemnogene abeparvovec at 5 months without complications. The patient’s muscular weakness has stabilized with mild improvement. The patient is now 28 months old and remains stable and diffusely weak, with stable respiratory ventilatory support. This case highlights challenges in the diagnosis of SMA with a non-deletion genotype and provides a clinical example demonstrating that disruption of functional SMN protein polymerization through an amino acid change in the YG-box domain represents a little known but important pathogenic mechanism for SMA. Clinicians need to be mindful about the limitations of the current diagnostic approach for SMA in detecting non-deletion genotypes.

Abstract Gastric cancer (GC) is a high-incidence cancer worldwide. Most patients are diagnosed at an advanced stage, by which time they have limited treatment options and poor prognosis. Early diagnosis and precise treatment are important. In the past few years, emerging research has been conducted on the use of non-invasive liquid biopsy, with its advantages of minimal invasiveness and repeated sampling, to monitor tumor occurrence and recurrence in real time and to evaluate prognosis and treatment response. Many studies have demonstrated the potential of liquid biopsy in GC, and the detection of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating free DNA (cfDNA), and exosomes has achieved gratifying results. In this review, we summarize evolving technologies for and information regarding liquid biopsy, the most recently discovered GC liquid biopsy biomarkers, and ongoing clinical trials and discuss the challenges and application prospects of liquid biopsy in GC.

Earlier studies have shown that less than one-third of coronal mass ejections (CMEs) possess the archetypical three-part (bright core, dark cavity, and bright front) structure in the outer corona (e.g., 2–6 R _⊙ ). In the traditional opinion, the core, cavity, and front correspond to the erupted filament, magnetic flux rope (MFR), and plasma pileup along the MFR border, respectively. Recent studies have demonstrated that nearly 100% of normal CMEs have a three-part structure in the inner corona (

The elemental abundance of interplanetary coronal mass ejections (ICMEs) and solar wind near 1 au is often adopted to represent the abundance in the corresponding coronal sources. However, the absolute abundance of heavy ions (relative to hydrogen) near 1 au might be different from the coronal abundance due to the ion–proton differential speed ( V _ip ). To illustrate the V _ip characteristics and explore whether it influences the absolute abundance analysis for ICMEs and solar wind, we perform a statistical study on the V _ip for He ^2+ , C ^5+ , O ^6+ , and Fe ^10+ in both ICMEs and solar wind based on measurements of Advanced Composition Explorer. The results show that the V _ip is negligible within ICMEs and slow solar wind (< 400 km s ^−1 ), while obvious in the intermediate (400–600 km s ^−1 ) and fast wind (> 600 km s ^−1 ). Previous studies showed that the V _ip in ICMEs keeps negligible during propagation from 0.3 to 5 au, but in solar wind it increases with the decreasing heliocentric distance. Therefore, it might be questionable to infer the absolute abundance of coronal sources through in situ abundance near 1 au for solar wind. Fortunately, the ion–oxygen (O ^6+ ) differential speed ( V _io ) is negligible for He ^2+ , C ^5+ , and Fe ^10+ within both ICMEs and solar wind, and previous studies suggested that the V _io does not vary significantly with the heliocentric distance. This indicates that various heavy ions always flow at the same bulk speed and their relative abundance (relative to oxygen) near 1 au can represent the coronal abundance for both ICMEs and solar wind.

Solar magnetic flux rope (MFR) plays a central role in the physics of coronal mass ejections (CMEs). It mainly includes a cold filament at typical chromospheric temperatures (∼10,000 K) and a hot channel at high coronal temperatures (∼10 MK). The warm MFR at quiescent coronal temperatures of a million Kelvin is, however, rarely reported. In this study, using multiwavelength images from the Atmospheric Imaging Assembly (AIA) on board the Solar Dynamic Observatory and Extreme Ultraviolet Imager (EUVI) on board the Solar Terrestrial Relations Observatory-A, we present an eruption of a warm channel that represents an MFR with quiescent coronal temperatures (∼0.6–2.5 MK). On 2022 May 8, we observed the failed eruption of a hot channel, with the average temperature and emission measure (EM) of 10 MK and 1.1 × 10 ^28 cm ^−5 , using AIA high-temperature images in the active region (AR) 13007. This failed eruption was associated with a C8.2 flare, with no CME. Subsequently, we observed a warm channel that appeared in AIA and EUVI low-temperature images rather than in AIA high-temperature images. It then erupted and transformed into a semicircular shape. An associated C2.1 flare, along with the signatures of magnetic reconnection in AIA high-temperature images, were identified. Additionally, we observed a CME associated with this event. Compared with the hot channel, the warm channel is cooler and rarer with the average temperature and EM of 1.7 (1.6) MK and 2.0 × 10 ^26 (2.3 × 10 ^26 ) cm ^−5 . All the results suggest an unambiguous observation of the million-Kelvin warm MFR that erupted as a CME and fill a gap in the temperature domain of coronal MFRs.

Coronal rain (CR) is a crucial part of the mass cycle between the corona and chromosphere. It includes flare-driven CR and two types of quiescent CR, along nonflaring active region closed loops and along open structures, separately, labeled as type I, type II, and type III CR, respectively. Among them, type I and type III CR are generally associated with magnetic reconnection. In this study, employing data taken by the Solar Dynamics Observatory and the Solar Upper Transition Region Imager on 2022 October 11, we report three types of CR during an interchange reconnection between open and closed magnetic field structures above the southeastern solar limb. The open and closed structures converge, with the formation of the current sheet at the interface, and reconnect. The newly formed closed and open structures then recede from the reconnection region. During the reconnection, coronal condensation occurs along the reconnecting closed loops and falls toward the solar surface along both loop legs, as type II CR. Subsequently, condensation happens in the newly formed closed loops and moves down toward the solar surface along both loop legs, as type I CR. Magnetic dips of the reconnecting open structures form during the reconnection. In the dips, condensation occurs and propagates along the open structures toward the solar surface as type III CR. Our results suggest that the reconnection rate may be crucial for the formation of type I and type III CR during reconnection.

Abstract Background Harmonic ACE +7 Shears with Advanced Hemostasis is an upgraded ultrasonic device, an ultrasonic surgical and electrosurgical system (USES). The study aimed to evaluate the economic and clinical effectiveness of the USES compared with the conventional ultrasonic scalpel (CUS) in gastrectomy. Methods We conducted a single-center, retrospective cohort study using the electronic medical records in China. We collected intraoperative and postoperative data from gastric cancer patients who underwent the endoscope-assisted distal gastrectomy from 2018 to June 30, 2019. Procedure-related costs were estimated. We used linear regression by controlling a set of covariates to assess the effect of USES on outcomes. Result Out of 87 eligible patients, the USES group (40 patients) and CUS group (47 patients) were comparable in terms of age, medical history and stages of cancer. Compared with the CUS, the USES saved 4.27 hemoclips per person (95% CI 0.57–7.97, p

Abstract At present, it is commonly believed that tRFs and tiRNAs are formed by the specific and selective shear of tRNAs under certain pressure stimulation, rather than by random degradation of tRNA. tRFs and tiRNAs have been reported to contribute to the biological process of a variety of human cancers. However, the evidence for the mechanisms of tRFs and tiRNAs in the occurrence and development of gastric cancer (GC) is still insufficient. Here, we aimed to explore the carcinogenic roles of tRFs and tiRNAs in GC with RNA-sequencing technique, and found a novel 3’tRNA-derived fragment tRF-Val was significantly upregulated in GC tissues and cell lines. tRF-Val expression was positively correlated with tumor size and the depth of tumor invasion in GC tissues. Functionally, tRF-Val promoted proliferation and invasion, and inhibited apoptosis in GC cells. Mechanistically, tRF-Val directly bound to the chaperone molecule EEF1A1, mediated its transport into the nucleus and promoted its interaction with MDM2 (a specific p53 E3 ubiquitin ligase), thus inhibiting the downstream molecular pathway of p53 and promoting GC progression. These findings provided a new potential therapeutic target for GC and a new explanation for the occurrence of GC.

Abstract Purpose Acute appendicitis usually requires immediate surgical treatment, but appendectomies were difficult for some patients with severe periappendiceal adhesions. We investigated risk factors of intraoperative adhesions to help surgeons make better treatment plans for appendicitis. Methods We retrospectively analyzed 186 cases diagnosed with acute appendicitis and underwent surgery in Shandong Provincial Hospital affiliated to Shandong First Medical University between January 2018 and December 2019. According to the degree of intraoperative adhesions, they were divided into mild, moderate and severe groups. Then, we analyzed a number of preoperative factors contributed to adhesions, suppuration and perforation during appendectomy in 186 patients. Results Contrast to the moderate group (MoG) and the mild group (MiG), the severe degree of adhesions group (SG) had a higher intraoperative perforation and suppuration rate, a greater likelihood of conversion to open and more postoperative complications. Multivariable logistic regression analysis showed that recurrent appendicitis and high neutrophil percentage were independently associated with periappendiceal adhesions. The preoperative ultrasonography (US) revealed periappendiceal fluid and high neutrophil percentage were independently associated with appendix suppuration. A high preoperative neutrophil percentage was independently associated with appendix perforation. Conclusions Recurrent appendicitis and preoperative high neutrophil percentage were risk factors of periappendiceal adhesions; preoperative US revealed periappendiceal fluid and high neutrophil percentage were risk factors of appendix suppuration; and a high preoperative neutrophil percentage was a risk factor of appendix perforation.

Abstract Background A novel multidimensional inflammatory and nutritional assessment system named the Naples prognostic score could serve as an independent prognostic indicator. However, its significance in patients with high- and intermediate-risk gastrointestinal stromal tumours remains unclear. Methods We performed this retrospective cohort study based on a prospectively collected database of gastrointestinal stromal tumours (GISTs) between March 2010 and December 2019. The Kaplan–Meier method and log-rank test were used for survival analyses. Least absolute shrinkage and selection operator (LASSO) and Cox proportional hazards regression analysis was used for univariate and multivariate analyses. Time-dependent receiver operating characteristic curves were generated to evaluate the discriminatory ability of the prognostic scoring systems. Differences in the areas under the curve were further compared. Results A total of 405 patients with regular follow-up were included and analysed in this study. Significant differences in progression-free survival and overall survival were observed between the groups (P < 0.001). Multivariate analysis demonstrated that the NPS was a significant predictor of poor progression-free survival (1 vs 0, HR = 4.622, P = 0.001; 2 vs 0, HR = 12.770, P < 0.001) and overall survival (2 vs 0, HR = 5.535, P = 0.002). Furthermore, time-dependent AUC analyses showed that the NPS was more accurate than other haematologic prognostic systems. Conclusions The present study demonstrates that the NPS could independently predict disease progression and survival among patients with high- and intermediate-risk GISTs. The NPS might be regarded and applied as one of the most convenient and effective preoperative risk stratification tools in the future, which should be validated by large-scale multicentre prospective cohort studies.

Abstract Background Gastric cancer (GC) is one of the most common malignancies, and an increasing number of studies have shown that its pathogenesis is regulated by various miRNAs. In this study, we investigated the role of miR-875-5p in GC. Methods The expression of miR-875-5p was detected in human GC specimens and cell lines by miRNA qRT–PCR. The effect of miR-875-5p on GC proliferation was determined by Cell Counting Kit-8 (CCK-8) proliferation and 5-ethynyl-2′-deoxyuridine (EdU) assays. Migration and invasion were examined by transwell migration and invasion assays as well as wound healing assays. The interaction between miR-875-5p and its target gene upstream stimulatory factor 2(USF2) was verified by dual luciferase reporter assays. The effects of miR-875-5p in vivo were studied in xenograft nude mouse models. Related proteins were detected by western blot. Results The results showed that miR-875-5p inhibited the proliferation, migration and invasion of GC cells in vitro and inhibited tumorigenesis in vivo. USF2 was proved to be a direct target of miR-875-5p. Knockdown of USF2 partially counteracted the effects of miR-875-5p inhibitor. Overexpression of miR-875-5p could inhibit proliferation, migration and invasion and suppress the TGF-β signalling pathway by downregulating USF2. Conclusions MiR-875-5p can inhibit the progression of GC by directly targeting USF2. And in the future, miR-875-5p is expected to be a potential target for GC diagnosis and treatment.

Hepatectomy is an effective surgical method for the treatment of liver diseases, but intraoperative bleeding and postoperative liver function recovery are still key issues. This study aims to develop a composite hydrogel dressing with excellent hemostatic properties, biocompatibility, and ability to promote liver cell regeneration. The modified gelatin matrix (GelMA, 10%) was mixed with equal volumes of sodium alginate-dopamine (Alg-DA) at concentrations of 0.5%, 1%, and 2%. Then a cross-linking agent (0.1%) was added to prepare different composite hydrogels under UV light, named GelMA/Alg-DA-0.5, GelMA/Alg-DA-1 and GelMA/Alg-DA-2, respectively. All the prepared hydrogel has a porous structure with a porosity greater than 65%, and could be stabilized in a gel state after being cross-linked by ultraviolet light. Physicochemical characterization showed that the elastic modulus, water absorption, adhesion, and compressibility of the composite hydrogels were improved with increasing Alg-DA content. Furthermore, the prepared hydrogel exhibits in vitro degradability, excellent biocompatibility, and good hemostatic function. Among all tested groups, the group of GelMA/Alg-DA-1 hydrogel performed the best. To further enhance its application potential in the field of liver regeneration, adipose-derived mesenchymal stem cell exosomes (AD-MSC-Exo) were loaded into GelMA/Alg-DA-1 hydrogel. Under the same conditions, GelMA/Alg-DA-1/Exo promoted cell proliferation and migration more effectively than hydrogels without extracellular vesicles. In conclusion, the prepared GelMA/Alg-DA-1 composite hydrogel loaded with AD-MSC-Exo has great application potential in liver wound hemostasis and liver regeneration.

Semaphorin 4D (SEMA4D) is considered a new antitumor target closely related to immune cells. However, understanding the role of SEMA4D in the tumor microenvironment (TME) is limited. In this study, we explored the expression and immune cell infiltration patterns of SEMA4D using multiple bioinformatics datasets and analyzed the relationship between SEMA4D expression with immune checkpoints, tumor mutational load (TMB), microsatellite instability (MSI) and immune function. We detected that SEMA4D is overexpressed in many tumors types, widely enriched in immune cells, and closely associated with TILs, MSI, TMB, as well as T-cell exhaustion-associated immune checkpoints, and thus can broadly affect the immune microenvironment. We further verified the overexpression of SEMA4D in tumor and its distribution in TME by immunohistochemistry, RT-qPCR and flow cytometry, and confirmed that decreased expression of SEMA4D can lead to recovery of T cell exhaustion. In conlusion, this study provides a more comprehensive perspective of SEMA4D regulation of tumor immunity, which provide a new option for cancer immunotherapy.

AimTo investigate the effect of intravenous dexamethasone administration on postoperative enteral nutrition tolerance in patients following gastrointestinal surgery.MethodsBased on the previous results of a randomized controlled study to explore whether intravenous administration of dexamethasone recovered gastrointestinal function after gastrointestinal surgery, we used the existing research data from 1 to 5 days post operation in patients with enteral nutrition tolerance and nutrition-related analyses of the changes in serum indices, and further analyzed the factors affecting resistance to enteral nutrition.ResultThe average daily enteral caloric intake was significantly higher in patients receiving intravenous administration of dexamethasone during anesthesia induction than in controls (8.80 ± 0.92 kcal/kg/d vs. 8.23 ± 1.13 kcal/kg/d, P = 0.002). Additionally, intravenous administration of 8 mg dexamethasone during anesthesia induction can reduce the changes in postoperative day (POD) 3, POD5, and preoperative values of serological indices, including ΔPA, ΔALB, and ΔRBP (P < 0.05). In the subgroup analysis, dexamethasone significantly increased the average daily enteral nutrition caloric intake in patients undergoing enterotomy (8.98 ± 0.87 vs. 8.37 ± 1.17 kcal/kg/d, P = 0.010) or in female patients (8.94 ± 0.98 vs. 8.10 ± 1.24 kcal/kg/d, P = 0.019). The changes of serological indexes (ΔPA, ΔALB, and ΔRBP) in the dexamethasone group were also significantly different on POD3 and POD5 (P < 0.05). In addition, multivariate analysis showed that dexamethasone use, surgical site, and age might influence enteral nutrition caloric tolerance.ConclusionPostoperative enteral nutrition tolerance was significantly improved in patients receiving intravenous administration of dexamethasone during anesthesia induction, especially in patients following enterotomy surgery, with significant improvements in average daily enteral caloric intake, PA levels, ALB levels, and RBP levels.Clinical trial registrationhttp://www.chictr.org.cn, identifier: ChiCTR1900024000.

Diffuse type gastric cancer was identified with relatively worse prognosis than other Lauren’s histological classification. Integrin β1 (ITGB1) was a member of integrin family which played a markedly important role in tumorigenesis and progression. However, the influence of ITGB1 in diffuse gastric cancer (DGC) remains uncertain. Here, we leveraged the transcriptomic and proteomic data to explore the association between ITGB1 expression and clinicopathologic information and biological process in DGC. Cell phenotype experiments combined with quantitative-PCR (q-PCR) and western blotting were utilized to identify the potential molecular mechanism underling ITGB1.Transcriptomics and proteomics both revealed that the higher ITGB1 expression was significantly associated with worse prognosis in DGC, but not in intestinal GC. Genomic analysis indicated that the mutation frequency of significantly mutated genes of ARID1A and COL11A1, and mutational signatures of SBS6 and SBS15 were markedly increased in the ITGB1 low expression subgroup. The enrichment analysis revealed diverse pathways related to dysregulation of ITGB1 in DGC, especially in cell adhesion, proliferation, metabolism reprogramming, and immune regulation alterations. Elevated activities of kinase-ROCK1, PKACA/PRKACA and AKT1 were observed in the ITGB1 high-expression subgroup. The ssGSEA analysis also found that ITGB1 low-expression had a higher cuproptosis score and was negatively correlated with key regulators of cuproptosis, including FDX1, DLAT, and DLST. We further observed that the upregulated expression of mitochondrial tricarboxylic acid (TCA) cycle in the ITGB1 low-expression group. Reduced expression of ITGB1 inhibited the ability of cell proliferation and motility and also potentiated the cell sensitive to copper ionophores via western blotting assay. Overall, this study revealed that ITGB1 was a protumorigenic gene and regulated tumor metabolism and cuproptosis in DGC.

Abstract Integrative expression Quantitative Trait Loci (eQTL) analysis found that rs8180040 was significantly associated with Coiled-coil domain containing 12 (CCDC12) in colon adenocarcinoma (COAD) patients. Immunohistochemical staining and western blotting confirmed CCDC12 was highly expressed in COAD tissues, which was consistent with RNA-Seq data from the TCGA database. Knockdown of CCDC12 could significantly reduce proliferation, migration, invasion, and tumorigenicity of colon cancer cells, while exogenous overexpression of CCDC12 had the opposite effect. Four plex Isobaric Tags for Relative and Absolute Quantitation assays were performed to determine its function and potential regulatory mechanism and demonstrated that overexpression of CCDC12 would change proteins on the adherens junction pathway. Overexpressed Snail and knocked down CCDC12 subsequently in SW480 cells, and we found that overexpression of Snail did not significantly change CCDC12 levels in SW480 cells, while knockdown of CCDC12 reduced that of Snail. CCDC12 plays a significant role in tumorigenesis, development, and invasion of COAD and may affect the epithelial to mesenchymal transformation process of colon cancer cells by regulating the Snail pathway.

Abstract Background Gastric cancer, which is the fifth most common malignancy and the third most common cause of cancer-related death, is particularly predominant in East Asian countries, such as China, Japan and Korea. It is a serious global health issue that causes a heavy financial burden for the government and family. To our knowledge, there are few reports of multicentre randomized controlled trials on the utilization of CT angiography (CTA) for patients who are histologically diagnosed with gastric cancer before surgery. Therefore, we planned this RCT to verify whether the utilization of CTA can change the short- and long-term clinical outcomes. Method The GISSG 20–01 study is a multicentre, prospective, open-label clinical study that emphasises the application of CTA for patients who will undergo laparoscopic gastrectomy to prove its clinical findings. A total of 382 patients who meet the inclusion criteria will be recruited for the study and randomly divided into two groups in a 1:1 ratio: the CTA group (n = 191) and the non-CTA group (n = 191). Both groups will undergo upper abdomen enhanced CT, and the CTA group will also receive CT angiography. The primary endpoint of this trial is the volume of blood loss. The second primary endpoints are the number of retrieved lymph nodes, postoperative recovery course, hospitalization costs, length of hospitalization days, postoperative complications, 3-year OS and 3-year DFS. Discussion It is anticipated that the results of this trial will provide high-level evidence and have clinical value for the application of CTA in laparoscopic gastrectomy. Trial registration ClinicalTrials.gov , NCT04636099. Registered November 19, 2020

Abstract Mutations in five different genes encoding connexin channels cause eleven clinically defined human skin diseases. Keratitis ichthyosis deafness (KID) syndrome is caused by point mutations in the GJB2 gene encoding Connexin 26 (Cx26) which result in aberrant activation of connexin hemichannels. KID syndrome has no cure and is associated with bilateral hearing loss, blinding keratitis, palmoplantar keratoderma, ichthyosiform erythroderma and a high incidence of childhood mortality. Here, we have tested whether a topically applied hemichhanel inhibitor (flufenamic acid, FFA) could ameliorate the skin pathology associated with KID syndrome in a transgenic mouse model expressing the lethal Cx26-G45E mutation. We found that FFA blocked the hemichannel activity of Cx26-G45E in vitro, and substantially reduced epidermal pathology in vivo, compared to untreated, or vehicle treated control animals. FFA did not reduce the expression of mutant connexin hemichannel protein, and cessation of FFA treatment allowed disease progression to continue. These results suggested that aberrant hemichannel activity is a major driver of skin disease in KID syndrome, and that the inhibition of mutant hemichannel activity could provide an attractive target to develop novel therapeutic interventions to treat this incurable disease.

BackgroundPatients with tumors generally present with accompanying activation of the coagulation system, which may be related to tumor stage. To our knowledge, few studies have examined the activation of the coagulation system in reference to lymph node metastasis within gastric cancer. This study aimed to investigate the correlation between multiple coagulation-related factors and lymph node metastasis in patients with gastric cancer after excluding the influence of tumor T stage.Materials and methodsWe retrospectively evaluated the relationship between lymph node metastasis and coagulation-related factors in 516 patients with T4a stage gastric cancer. We further analyzed influencing factors for lymph node metastasis and verified the predictive value of maximum amplitude (MA, a parameter of thromboelastography which is widely used to assess the strength of platelet-fibrinogen interaction in forming clots) in reference to lymph node metastasis.ResultsPlatelet counts (P=0.011), fibrinogen levels (P=0.002) and MA values (P=0.006) were statistically significantly higher in patients with T4a stage gastric cancer presenting with lymph node metastasis than in those without lymph node metastasis. Moreover, tumor N stage was statistically significantly and positively correlated with platelet count (P

Previous survey studies reported that coronal mass ejections (CMEs) can exhibit various structures in white-light coronagraphs, and ∼30% of them have the typical three-part feature in the high corona (e.g., 2–6 R _⊙ ), which has been taken as the prototypical structure of CMEs. It is widely accepted that CMEs result from eruption of magnetic flux ropes (MFRs), and the three-part structure can be understood easily by means of the MFR eruption. It is interesting and significant to answer why only ∼30% of CMEs have the three-part feature in previous studies. Here we conduct a synthesis of the CME structure in the field of view (FOV) of K-Coronagraph (1.05–3 R _⊙ ). In total, 369 CMEs are observed from 2013 September to 2022 November. After inspecting the CMEs one by one through joint observations of the Atmospheric Imaging Assembly, K-Coronagraph, and LASCO/C2, we find 71 events according to the criteria: (1) limb event; (2) normal CME, i.e., angular width ≥30°; (3) K-Coronagraph caught the early eruption stage. All (or more than 90% considering several ambiguous events) of the 71 CMEs exhibit the three-part feature in the FOV of K-Coronagraph, while only 30%–40% have the feature in the C2 FOV (2–6 R _⊙ ). For the first time, our studies show that 90%–100% and 30%–40% of normal CMEs possess the three-part structure in the low and high corona, respectively, which demonstrates that many CMEs can lose the three-part feature during their early evolutions, and strongly supports that most (if not all) CMEs have the MFR structures.

The formation of filaments/prominences is still a debated topic. Many different processes have been proposed: levitation, injection of cool plasma, merging filaments, and cooling plasma in hot loops. We take the opportunity to make a multiwavelength analysis of the formation of an active-region filament, combining several UV and EUV observations including the new Ne vii 465 Å filtergrams provided by the Solar Upper Transition Region Imager on board the Space Advanced Technology satellite. The filament is mainly observed at the limb for 3 hr. It is progressively formed through a series of stages, including emergence and cooling of hot loops, reconnection between small filaments, material transfer in a large filament channel, and reconnection between filaments and emerged hot loops. From the observations at 465 Å, we find that the new-formed filaments show bright structures as in 304 Å, while the long-lived stable filaments display dark morphology as in 211 Å. This suggests that the plasma around 0.5 MK would be an essential component of new-formed filaments and the material temperature in filaments would be variable during their evolution. The filament formed by the recombination of two filaments and an emerged hot loop finally erupts. After reconnection, the final filament shows a highly twisted structure of both bright and dark strands, which is surrounded by several weak and dispersive looplike structures. This eruptive filament has a complex multichannel topology and covers a wide range of temperatures.

Abstract As oncogenes and tumor suppressor genes, long non-coding RNAs (lncRNAs) regulate the biological behavior of gastric cancer (GC) cells such as proliferation, invasion, and metastasis through various signal pathways. At present, although numerous lncRNAs that significantly influence the development and progression of GC have been identified, a considerable number of them have not been found and studied yet. In this study, we identified a new lncRNA derived from pseudogenes WFDC21P, which have not been reported in any previous GC study. LncRNA WFDC21P was significantly upregulated in GC cells and tissues, and clinically associated with the pathological stages of advanced GC. WFDC21P promoted proliferation and metastasis of GC cells both in vitro and in vivo. LncRNA WFDC21P was directly bound to GTPase Ran and it promoted the activity of the Akt/GSK3β/β-catenin pathway. Forkhead Box P3 (FOXP3), as a transcription factor of WFDC21P, was directly bound to the promoter region and it positively regulated the transcription of WFDC21P. This finding may provide a novel biomarker and therapeutic target for GC.

Abstract Background Biological tissues consist of heterogenous populations of cells. Because gene expression patterns from bulk tissue samples reflect the contributions from all cells in the tissue, understanding the contribution of individual cell types to the overall gene expression in the tissue is fundamentally important. We recently developed a computational method, CDSeq, that can simultaneously estimate both sample-specific cell-type proportions and cell-type-specific gene expression profiles using only bulk RNA-Seq counts from multiple samples. Here we present an R implementation of CDSeq (CDSeqR) with significant performance improvement over the original implementation in MATLAB and an added new function to aid cell type annotation. The R package would be of interest for the broader R community. Result We developed a novel strategy to substantially improve computational efficiency in both speed and memory usage. In addition, we designed and implemented a new function for annotating the CDSeq estimated cell types using single-cell RNA sequencing (scRNA-seq) data. This function allows users to readily interpret and visualize the CDSeq estimated cell types. In addition, this new function further allows the users to annotate CDSeq-estimated cell types using marker genes. We carried out additional validations of the CDSeqR software using synthetic, real cell mixtures, and real bulk RNA-seq data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project. Conclusions The existing bulk RNA-seq repositories, such as TCGA and GTEx, provide enormous resources for better understanding changes in transcriptomics and human diseases. They are also potentially useful for studying cell–cell interactions in the tissue microenvironment. Bulk level analyses neglect tissue heterogeneity, however, and hinder investigation of a cell-type-specific expression. The CDSeqR package may aid in silico dissection of bulk expression data, enabling researchers to recover cell-type-specific information.

Abstract Background Human cancer cell line profiling and drug sensitivity studies provide valuable information about the therapeutic potential of drugs and their possible mechanisms of action. The goal of those studies is to translate the findings from in vitro studies of cancer cell lines into in vivo therapeutic relevance and, eventually, patients’ care. Tremendous progress has been made. Results In this work, we built predictive models for 453 drugs using data on gene expression and drug sensitivity (IC50) from cancer cell lines. We identified many known drug-gene interactions and uncovered several potentially novel drug-gene associations. Importantly, we further applied these predictive models to ~ 17,000 bulk RNA-seq samples from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database to predict drug sensitivity for both normal and tumor tissues. We created a web site for users to visualize and download our predicted data ( https://manticore.niehs.nih.gov/cancerRxTissue ). Using trametinib as an example, we showed that our approach can faithfully recapitulate the known tumor specificity of the drug. Conclusions We demonstrated that our approach can predict drugs that 1) are tumor-type specific; 2) elicit higher sensitivity from tumor compared to corresponding normal tissue; 3) elicit differential sensitivity across breast cancer subtypes. If validated, our prediction could have relevance for preclinical drug testing and in phase I clinical design.

Abstract Gastric cancer (GC) is a common tumour that affects humans worldwide, is highly malignant and has a poor prognosis. Small extracellular vesicles (sEVs), especially exosomes, are nanoscale vesicles released by various cells that deliver bioactive molecules to recipient cells, affecting their biological characteristics, changing the tumour microenvironment and producing long-distance effects. In recent years, many studies have clarified the mechanisms by which sEVs function with regard to the initiation, progression, angiogenesis, metastasis and chemoresistance of GC. These molecules can function as mediators of cell-cell communication in the tumour microenvironment and might affect the efficacy of immunotherapy. Due to their unique physiochemical characteristics, sEVs show potential as effective antitumour vaccines as well as drug carriers. In this review, we summarize the roles of sEVs in GC and highlight the clinical application prospects in the future.

Abstract Background The objective of the study was to detect the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1) in gastric cancer (GC) specimens and analyse the associations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis. Methods All of the 94 patients in this study were GC patients who underwent surgical resection. KK-LC-1 protein expression in GC tissue was detected by immunohistochemistry. This report applies the histological score (H-score) to evaluate KK-LC-1 expression. To calculate this indicator, the number of positive cells in each section and their staining intensity were converted to corresponding values. The expression of KK-LC-1 in the cytoplasm of cancer and normal tissues was scored to obtain their respective H values. The chi-square test, Kaplan-Meier method and Cox regression were used to analyse the linear association between KK-LC-1 expression and clinicopathological data and prognosis. Results In the cytoplasm, KK-LC-1 expression in tumour tissues was significantly higher than that in normal tissues (P

The molecular determinants of differential responses of different cancer cells to methionine restriction are poorly understood. Here the authors show that hepatocyte nuclear factor 4α regulates sulfur amino acid metabolism and dictates the sensitivity of liver cancer to this dietary manipulation.

Abstract Background The incidence of gastric cancer in East Asia is much higher than the international average. Therefore, improving the prognosis of patients and establishing effective clinical pathways are important topics for the prevention and treatment of gastric cancer. At present, the enhanced recovery after surgery (ERAS) pathway is widely used in the field of gastric surgery. Many randomized controlled trial (RCT) studies have proven that the ERAS regimen can improve the short-term clinical outcomes of patients with gastric cancer. However, a prospective study on the effect of the ERAS pathway on the prognosis of patients with gastric cancer has not yet been reported. This trial aims to confirm whether the ERAS pathway can improve the disease-free survival and overall survival of patients undergoing laparoscopic-assisted radical resection for distal gastric cancer. Methods/design This study is a prospective, multicentre RCT. This experiment will consist of two groups – an experimental group and a control group – randomly divided in a 1:1 ratio. The perioperative period of the experimental group will be managed according to the ERAS pathway and that of the control group will be managed according to the traditional management mode. An estimated 400 patients will be enrolled. The main endpoint for comparison is the 3-year overall survival and disease-free survival between the two groups. Discussion The results of this RCT should clarify whether the ERAS pathway is superior to traditional treatment on inflammatory indexes, short-term clinical outcome and survival for laparoscopic-assisted radical resection of distal gastric cancer. It is hoped that our data will provide evidence that the ERAS pathway improves survival in patients with gastric cancer. Trial registration Chinese Clinical Trial Registry, CHiCTR1900022438 . Registered on 11 April 2019.

BackgroundCancer is a major disease burden to society. Increasing evidence has indicated that low skeletal muscle mass is linked with cancer prognosis. The purpose of the study is to determine the impact of preoperative low skeletal muscle mass (LSMM) on complications and survival of patients who undergo laparoscopic gastrectomy for gastric cancer (GC).MethodsThis study retrospectively collected patients undergoing laparoscopic gastrectomy for GC between January 2017 and December 2018. Tumor staging was performed according to the American Joint Committee on Cancer 8th edition. The third lumbar psoas index (PMI) was assessed by computed tomography (CT) within 15 days before surgery. Postoperative complications were classified according to Clavien-Dindo classification and dichotomized into none vs any (Clavien-Dindo score, ≥1). Using propensity score matching (1:1) to obtain 2 well-balanced cohorts for available variables influencing clinical outcomes, comparing the postoperative complications and 3-year overall survival (OS) between LSMM group and non-LSMM group.ResultsA total of 386 patients, 226 were matched for analyses. The average patient age was 57.31 ± 10.33 years; 75.65% (n = 292) were men and 24.35% (n = 94) were women. A total of 249 (64.51%) patients were diagnosed with LSMM. Compared with the non-LSMM group, the LSMM group manifested significantly shorter 3-year OS (58.14% vs 71.95%, p = 0.034). However, the incidence of postoperative complications was no difference between two groups after matching. After stratification based on the pT stage of the tumor, statistically significant difference in the 3-year OS rates of the advance GC cohort between the two groups were observed.ConclusionsLSMM predicts a poor prognosis for patients with advance GC and it is not associated with postoperative complications.

IntroductionAbdominal cocoon is a unique peritoneal disease that is frequently misdiagnosed. The occurrence of the abdominal cocoon with a jejuno-ileo-colonic fistula has not been previously reported.Case PresentationWe admitted a 41-year-old female patient with an abdominal cocoon and a jejuno-ileo-colonic fistula. She was admitted to our hospital for the following reasons: “the menstrual cycle is prolonged for half a year, and fatigue, palpitations, and shortness of breath for 2 months”. On the morning of the 4th day of admission, the patient experienced sudden, severe, and intolerable abdominal pain after defecating. An emergency abdominal CT examination revealed intestinal obstruction. Surgery was performed, and the small intestine and colon were observed to be conglutinated and twisted into a mass surrounded by a fibrous membrane, and an enteroenteric fistula was observed between the jejunum, ileum, and sigmoid colon. We successfully relieved the intestinal obstruction and performed adhesiolysis. The patient was discharged from our hospital on the 6th postoperative day, then she recovered and was discharged from Feicheng People's Hospital after another 11 days of conservative treatment, and she recovered well-during the 2-month follow-up period.ConclusionAbdominal cocoon coexisting with a jejuno-ileo-colonic fistula is very rare. During the process of abdominal cocoon treatment, the patient's medical history should be understood in detail before the operation, and the abdominal organs should be carefully evaluated during the operation to avoid missed diagnoses.

Polypyrimidine tract binding protein 3 (PTBP3) plays a critical role in post-transcriptional regulation. The role of PTBP3 in various human tumours was explored and analysed in this study based on the Cancer Genome Atlas and Gene Expression Omnibus datasets. PTBP3 was highly expressed in most tumours, such as breast invasive carcinoma, colon adenocarcinoma and hepatocellular carcinoma. PTBP3 overexpression generally predicts poor overall survival and disease-free survival in patients with adrenocortical carcinoma, lung squamous cell carcinoma, and pancreatic adenocarcinoma. However, low PTBP3 expression predicts poor prognosis in kidney renal clear cell carcinoma. We also explored PTBP3 genetic alterations in different tumour tissues. The result found that the frequency of PTBP3 alteration (>4%) was the highest in uterine tumours with “mutation” as the primary type. Furthermore, we found a significant correlation between PTBP3 expression and tumour mutational burden and microsatellite instability in various human tumours, and found that PTBP3 expression was positively correlated with TMB in ACC, STAD, PAAD, LUAD, and SARC. Two enhanced phosphorylation levels of S30 and S426 in colon cancer, ovarian cancer, and uterine corpus endometrial carcinoma were found. Further analysis indicated that PTBP3 expression was positively correlated with the cancer-associated fibroblasts for most tumour types. This study also found a relationship between immune checkpoints and N6-methyladenosine-related markers and PTBP3 expression. Moreover, the “mRNA surveillance pathway” and “RNA degradation” were involved in the functional mechanisms of PTBP3. These results provide new insights for molecular studies, and integrative analysis provided a framework for determining the predictive, prognostic, and therapeutic relevance of PTBP3 in cancer patients.

An Extreme Ultraviolet (EUV) jet that occurred around 22:30 on July 2, 2012 was observed by the Atmospheric Imaging Assembly (AIA) on-board the Solar Dynamics Observatory (SDO). There were two phases of the jet. In Phase 1, two blobs were observed. In Phase 2, the intensity of the jet was almost coherent initially. One minute later, three blobs were formed at the same time in the jet, and the width of the jet changed after the formation of these blobs. The formation and evolution processes of the blobs in these two phases are analyzed in this paper. The physical parameters of the blobs are determined. The measured width of the blobs is 0.8 − 2.3 Mm, and the apparent velocities of the blobs are from 59 km s−1 to 185 km s−1. The formation mechanism of the blobs is likely to be tear-mode instability.