DeepRisk network: an AI-based tool for digital pathology signature and treatment responsiveness of gastric cancer using whole-slide images.

BACKGROUND: Digital histopathology provides valuable information for clinical decision-making. We hypothesized that a deep risk network (DeepRisk) based on digital pathology signature (DPS) derived from whole-slide images could improve the prognostic value of the tumor, node, and metastasis (TNM) staging system and offer chemotherapeutic benefits for gastric cancer (GC). METHODS: DeepRisk is a multi-scale, attention-based learning model developed on 1120 GCs in the Zhongshan dataset and validated with two external datasets. Then, we assessed its association with prognosis and treatment response. The multi-omics analysis and multiplex Immunohistochemistry were conducted to evaluate the potential pathogenesis and spatial immune contexture underlying DPS. RESULTS: Multivariate analysis indicated that the DPS was an independent prognosticator with a better C-index (0.84 for overall survival and 0.71 for disease-free survival). Patients with low-DPS after neoadjuvant chemotherapy responded favorably to treatment. Spatial analysis indicated that exhausted immune clusters and increased infiltration of CD11b+CD11c+ immune cells were present at the invasive margin of high-DPS group. Multi-omics data from the Cancer Genome Atlas-Stomach adenocarcinoma (TCGA-STAD) hint at the relevance of DPS to myeloid derived suppressor cells infiltration and immune suppression. CONCLUSION: DeepRisk network is a reliable tool that enhances prognostic value of TNM staging and aid in precise treatment, providing insights into the underlying pathogenic mechanisms.

3-Hydroxy-3-methylglutaryl-CoA synthase 2 facilitates erectile dysfunction via inhibiting autophagy by enhancing the mammalian target of rapamycin pathway in type 1 diabetic mellitus rats.

BACKGROUND: The relationship between erectile dysfunction (ED) and type 1 diabetes mellitus (T1DM) is currently a hot topic of medical research. It has been reported that autophagy plays a crucial role in causing erectile dysfunction in T1DM. Recent research has shown that mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) is strongly linked to the development of T1DM. However, the specific mechanism by which it regulates the erectile function is not yet fully understood. OBJECTIVES: To investigate whether HMGCS2 affects erectile function in type 1 diabetic rats by regulating autophagy in corpus cavernosum endothelial cells (CCECs). MATERIALS AND METHODS: First, the rat model of T1DM was established. Then, the ratio of maximum penile intracavernous pressure (ICPmax) and mean arterial pressure (MAP) was detected to assess the erectile function in various groups, and the protein expression of HMGCS2, mTOR and p-mTOR was evaluated by western blot (WB) and immunohistochemistry (IHC). To explore the relationship between HMGCS2 and the mTOR signaling pathway in T1DM ED rats, we silenced the expression of HMGCS2 and activated the mTOR signaling pathway with MHY1485 in CCECs and then assessed the expression of beclin1, P62, LC3, autophagosome, endothelial nitric oxide synthase (eNOS), phosphorylation of eNOS (p-eNOS), and nitric oxide (NO) to evaluate autophagy and the erectile function by reverse transcription quantitative polymerase chain reaction and western blot. RESULTS: The study conducted on T1DM ED rats showed that the expression of HMGCS2 was significantly increased, while the autophagy was suppressed. Additionally, the mTOR signaling pathway was highly activated. In contrast, when HMGCS2 was silenced in vitro, p-mTOR/mTOR was reduced, and autophagy was improved. These effects were accompanied by the enhanced activity of eNOS. Furthermore, when HMGCS2 was silenced and the mTOR signaling pathway was simultaneously activated, the results revealed a decrease in autophagy as well as a reduction in activity of eNOS in comparison to just silencing HMGCS2 alone. DISCUSSION AND CONCLUSION: HMGCS2 upregulation in T1DM rats inhibited autophagy and eNOS activity by activating the mTOR pathway and led to a decrease in the erectile function.

Clinical characteristics and application value of risk prediction models of acute appendicitis in rural Tibet: a retrospective study.

INTRODUCTION: Acute appendicitis is the most common general surgical emergency worldwide; however, its diagnosis remains challenging, particularly in rural or remote areas such as Tibet. This study aimed to investigate the clinical characteristics and applicability of the routine risk prediction models of acute appendicitis for rural Tibetan populations. METHODS: Data of patients who underwent appendectomy at the Chaya People's Hospital between 1 April 2018 and 30 September 2021 were retrospectively collected. Multivariate logistic regression analysis was performed to identify risk factors associated with complicated appendicitis. The appendicitis risk prediction model scores for each patient were calculated by the binary logistic regression model based on the data. The index of union method was applied to identify the optimal cut-off value for the critical values of risk prediction models. RESULTS: We included 127 patients with suspected acute appendicitis in the study, consisting of 96 surgically and 31 non-surgically treated. The diagnoses of 93 patients who underwent appendectomy included 55 (59.1%) cases of uncomplicated appendicitis. Patients with complicated appendicitis had a significantly longer postoperative hospital stay (11.0 (interquartile range 8.8-13.3) days v 8.0 (interquartile range 6.0-11.0) days; p<0.001) and higher hospital costs (US$2147.2 (interquartile range US$1625.1-2516.6) v US$1487.9 (interquartile range US$1202.6-1809.2); p24 hours, age >30 years, and male sex were independent risk factors associated with complicated appendicitis. The appendicitis inflammatory response score showed the best performance among the prediction models. Incorporating imaging features in the prediction models may provide better diagnostic value for appendicitis. CONCLUSION: Acute appendicitis in the rural Tibetan population has unique clinical features. To reduce the incidence of complicated appendicitis, local health workers must balance religious beliefs and professional services for residents.

Intraoperative Pathological Evaluation of Suspicious Peritoneal Nodules for Surgical Decision-making in Gastric Cancer.

BACKGROUND: When frozen pathological results of suspicious peritoneal nodules found in gastric cancer (GC) patients are negative or indeterminant, whether to perform gastrectomy will always be a dilemma for surgeons. This study aimed to facilitate intraoperative surgical decision-making based on frozen section (FS) results and clinicopathological characteristics. METHODS: From January 2015 to July 2021, 318 GC patients were enrolled retrospectively. The correlations between frozen and paraffin pathology of peritoneal nodules were examined. Then, predictive factors of positive paraffin section (PS) results were identified, and a nomogram was constructed. The survival significance of gastrectomy was also explored. RESULTS: Of 70 FS-negative patients, 59 (84.3%) had concordant negative PS results, while the PS results of 11 (15.7%) were positive. Forty-six (93.9%) and 3 (6.1%) of 49 patients with indeterminant FS results had positive and negative PS results, respectively. The PS results of 95 FS-positive patients were all positive. A nomogram for predicting positive PS results was developed based on Lauren type, nodule distribution, and CA125. Gastrectomy for FS-negative patients improved survival compared to no gastrectomy (HR 0.26, 95% CI 0.11-0.62; P = 0.0012). Survival benefits for gastrectomy vs. no gastrectomy were not demonstrated in patients with indeterminant (HR 0.74, 95% CI 0.27-2.01; P = 0.53) and positive (HR 0.87, 95% CI 0.43-1.74; P = 0.69) FS results. CONCLUSIONS: Gastrectomy can be justified for the treatment of operable GC patients with negative frozen pathological results of peritoneal nodules. For patients with positive and indeterminant frozen pathological results, gastrectomy is not recommended unless it is performed as palliative surgery.

A self-sacrifice template strategy to synthesize Co-LDH/MXene for lithium-ion batteries.

To overcome the limitations of both LDHs and MXenes, we develop a self-sacrifice template strategy using a zeolite imidazolate framework-67 (ZIF-67) to derive Co-LDH anchored on an MXene conductive substrate (Co-LDH/MXene). In this process, ZIF-67 grows on the MXene nanosheets, then spontaneously transforms into Co-LDH/MXene in aqueous solution at room temperature. As the LIB anode, it shows a reversible capacity of 854.9 and 398.0 mAh g-1 at 0.1 and 1 A g-1, respectively. This work proposes a feasible synthesis method for the in situ construction of a Co-LDH/MXene hybrid, which may be suitable for other MXenes.

Anti-cholinergics mecamylamine and scopolamine alleviate motion sickness-induced gastrointestinal symptoms through both peripheral and central actions.

Enhanced cholinergic activity contributes to the production of complex autonomic manifestations of motion sickness (MS). However, whether anti-cholinergics exert their anti-MS effects through central or peripheral actions remained unclarified. In the present study, we investigated the effects of mecamylamine (MEC) and scopolamine (SCOP) on rotation-induced gastrointestinal symptoms (conditioned gaping and defecation), locomotion disturbances (hypoactivity and impaired balance performance), hypothermia as well as Fos expression in vestibulo-autonomic regions in rats. We also observed the effects of hexamethonium (HEX) and methyl scopolamine (MSCP) on those MS behavioral responses. The efficacy of all these drugs on rotation-induced emesis and other MS symptoms in cats was also examined. We found that intragastric administration of MEC and SCOP inhibited rotation-induced gaping and defecation in rats, but only MEC showed a dose-dependent manner. MEC aggravated rotation-induced balance disorder and failed to attenuate rotation-induced hypothermia as the SCOP did. MEC was more effective for inhibiting Fos expression in the caudal vestibular nucleus and nucleus of solitary tract than SCOP. Intraperitoneal injection of HEX and MSCP also significantly alleviated rotation-induced gastrointestinal symptoms, and showed benefit to balance performance in rats. In cats, MEC, SCOP and HEX had prophylactic effects against rotation-induced emesis and salivation, and deceased non-retching/vomiting symptoms, but MSCP only attenuated emesis. It suggested that MEC and SCOP might alleviate gastrointestinal symptoms of MS via inhibiting peripheral autonomic nervous system and central vestibulo-autonomic pathways. The nicotinic acetylcholine receptor inhibitors like MEC might be new candidates against gastrointestinal symptoms induced by MS or other vestibular disorders.

Intimate contacted two-dimensional/zero-dimensional composite of bismuth titanate nanosheets supported ultrafine bismuth oxychloride nanoparticles for enhanced antibiotic residue degradation.

Constructing a two-dimensional/zero-dimensional (2D/0D) composite with matched crystal structure, suitable energy band structure as well as intimate contact interface is an effective way to improve carriers separation for achieving highly photocatalytic performance. In this work, a novel bismuth titanate/bismuth oxychloride (Bi4Ti3O12/BiOCl) composite consisting of 2D Bi4Ti3O12 nanosheets and 0D BiOCl nanoparticles was constructed for the first time. Germinating ultrafine BiOCl nanoparticles on Bi4Ti3O12 nanosheets can provide abundant contact interface and shorten migration distance of photoinduced carriers via two-step synthesis contained molten salt process and facile chemical transformation process. The obtained Bi4Ti3O12/BiOCl 2D/0D composites exhibited enhanced photocatalytic performance for antibiotic tetracycline hydrochloride degradation. The rate constant of optimal Bi4Ti3O12/BiOCl composite was about 4.4 times higher than that of bare Bi4Ti3O12 although Bi4Ti3O12/BiOCl composite appeared lesser photoabsorption. The enhanced photocatalytic performance can be mainly ascribed to matched crystal structure, suitable energy band structure and intimate contact interface between Bi4Ti3O12 nanosheets and ultrafine BiOCl nanoparticles as well as unique 2D/0D composite structure. Besides, a probable degradation mechanism on the basis of active species trapping experiments, electrochemical impedance spectroscopy, photocurrent responses and energy band structures was proposed. This work may be stretched to other 2D/0D composite photocatalysts construction, which is inspiring for antibiotic residue treatment.

Improved Short-Term Clock Prediction Method for Real-Time Positioning.

The application of real-time precise point positioning (PPP) requires real-time precise orbit and clock products that should be predicted within a short time to compensate for the communication delay or data gap. Unlike orbit correction, clock correction is difficult to model and predict. The widely used linear model hardly fits long periodic trends with a small data set and exhibits significant accuracy degradation in real-time prediction when a large data set is used. This study proposes a new prediction model for maintaining short-term satellite clocks to meet the high-precision requirements of real-time clocks and provide clock extrapolation without interrupting the real-time data stream. Fast Fourier transform (FFT) is used to analyze the linear prediction residuals of real-time clocks. The periodic terms obtained through FFT are adopted in the sliding window prediction to achieve a significant improvement in short-term prediction accuracy. This study also analyzes and compares the accuracy of short-term forecasts (less than 3 h) by using different length observations. Experimental results obtained from International GNSS Service (IGS) final products and our own real-time clocks show that the 3-h prediction accuracy is better than 0.85 ns. The new model can replace IGS ultra-rapid products in the application of real-time PPP. It is also found that there is a positive correlation between the prediction accuracy and the short-term stability of on-board clocks. Compared with the accuracy of the traditional linear model, the accuracy of the static PPP using the new model of the 2-h prediction clock in N, E, and U directions is improved by about 50%. Furthermore, the static PPP accuracy of 2-h clock products is better than 0.1 m. When an interruption occurs in the real-time model, the accuracy of the kinematic PPP solution using 1-h clock prediction product is better than 0.2 m, without significant accuracy degradation. This model is of practical significance because it solves the problems of interruption and delay in data broadcast in real-time clock estimation and can meet the requirements of real-time PPP.

P2X7 Receptor Suppression Preserves Blood-Brain Barrier through Inhibiting RhoA Activation after Experimental Intracerebral Hemorrhage in Rats.

Blockading P2X7 receptor(P2X7R) provides neuroprotection toward various neurological disorders, including stroke, traumatic brain injury, and subarachnoid hemorrhage. However, whether and how P2X7 receptor suppression protects blood-brain barrier(BBB) after intracerebral hemorrhage(ICH) remains unexplored. In present study, intrastriatal autologous-blood injection was used to mimic ICH in rats. Selective P2X7R inhibitor A438079, P2X7R agonist BzATP, and P2X7R siRNA were administrated to evaluate the effects of P2X7R suppression. Selective RhoA inhibitor C3 transferase was administered to clarify the involvement of RhoA. Post-assessments, including neurological deficits, Fluoro-Jade C staining, brain edema, Evans blue extravasation and fluorescence, western blot, RhoA activity assay and immunohistochemistry were performed. Then the key results were verified in collagenase induced ICH model. We found that endogenous P2X7R increased at 3 hrs after ICH with peak at 24 hrs, then returned to normal at 72 hrs after ICH. Enhanced immunoreactivity was observed on the neurovascular structure around hematoma at 24 hrs after ICH, along with perivascular astrocytes and endothelial cells. Both A438079 and P2X7R siRNA alleviated neurological deficits, brain edema, and BBB disruption after ICH, in association with RhoA activation and down-regulated endothelial junction proteins. However, BzATP abolished those effects. In addition, C3 transferase reduced brain injury and increased endothelial junction proteins' expression after ICH. These data indicated P2X7R suppression could preserve BBB integrity after ICH through inhibiting RhoA activation.

Analysis of BeiDou Satellite Measurements with Code Multipath and Geometry-Free Ionosphere-Free Combinations.

Using GNSS observable from some stations in the Asia-Pacific area, the carrier-to-noise ratio (CNR) and multipath combinations of BeiDou Navigation Satellite System (BDS), as well as their variations with time and/or elevation were investigated and compared with those of GPS and Galileo. Provided the same elevation, the CNR of B1 observables is the lowest among the three BDS frequencies, while B3 is the highest. The code multipath combinations of BDS inclined geosynchronous orbit (IGSO) and medium Earth orbit (MEO) satellites are remarkably correlated with elevation, and the systematic "V" shape trends could be eliminated through between-station-differencing or modeling correction. Daily periodicity was found in the geometry-free ionosphere-free (GFIF) combinations of both BDS geostationary Earth orbit (GEO) and IGSO satellites. The variation range of carrier phase GFIF combinations of GEO satellites is -2.0 to 2.0 cm. The periodicity of carrier phase GFIF combination could be significantly mitigated through between-station differencing. Carrier phase GFIF combinations of BDS GEO and IGSO satellites might also contain delays related to satellites. Cross-correlation suggests that the GFIF combinations' time series of some GEO satellites might vary according to their relative geometries with the sun.

First Results of Field Absolute Calibration of the GPS Receiver Antenna at Wuhan University.

GNSS receiver antenna phase center variations (PCVs), which arise from the non-spherical phase response of GNSS signals have to be well corrected for high-precision GNSS applications. Without using a precise antenna phase center correction (PCC) model, the estimated position of a station monument will lead to a bias of up to several centimeters. The Chinese large-scale research project "Crustal Movement Observation Network of China" (CMONOC), which requires high-precision positions in a comprehensive GPS observational network motived establishment of a set of absolute field calibrations of the GPS receiver antenna located at Wuhan University. In this paper the calibration facilities are firstly introduced and then the multipath elimination and PCV estimation strategies currently used are elaborated. The validation of estimated PCV values of test antenna are finally conducted, compared with the International GNSS Service (IGS) type values. Examples of TRM57971.00 NONE antenna calibrations from our calibration facility demonstrate that the derived PCVs and IGS type mean values agree at the 1 mm level.