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Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Most HCC patients have the complication of chronic liver disease and need overall consideration and whole-course management, including diagnosis, treatment and follow-up. To develop a reasonable, long-term, and complete management plan, multiple factors need to be considered, including the patient's general condition, basic liver diseases, tumor stage, tumor biological characteristics, treatment requirements and economic cost. Summary: To better guide the whole-course management of HCC patients, the Chinese Association of Liver Cancer and the Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the “Chinese Expert Consensus on The Whole-Course Management of Hepatocellular Carcinoma (2023).” Key Messages: This expert consensus, based on the current clinical evidence and experience, proposes surgical and nonsurgical HCC management pathways and involves 18 recommendations, including perioperative treatment, systematic treatment combined with local treatment, conversion treatment, special population management, symptomatic support treatment, and follow-up management.

Abstract Cardiomyocyte hypertrophy is a major outcome of pathological cardiac hypertrophy. The m6A demethylase ALKBH5 is reported to be associated with cardiovascular diseases, whereas the functional role of ALKBH5 in cardiomyocyte hypertrophy remains confused. We engineered Alkbh5 siRNA (siAlkbh5) and Alkbh5 overexpressing plasmid (Alkbh5 OE) to transfect cardiomyocytes. Subsequently, RNA immunoprecipitation (RIP)-qPCR, MeRIP-qPCR analysis and the dual-luciferase reporter assays were applied to elucidate the regulatory mechanism of ALKBH5 on cardiomyocyte hypertrophy. Our study identified ALKBH5 as a new contributor of cardiomyocyte hypertrophy. ALKBH5 showed upregulation in both phenylephrine (PE)-induced cardiomyocyte hypertrophic responses in vitro and transverse aortic constriction (TAC)/high fat diet (HFD)-induced pathological cardiac hypertrophy in vivo. Knockdown or overexpression of ALKBH5 regulated the occurrence of hypertrophic responses, including the increased cardiomyocyte surface areas and elevation of the hypertrophic marker levels, such as brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP). Mechanically, we indicated that ALKBH5 activated JAK2/STAT3 signaling pathway and mediated m6A demethylation on Stat3 mRNA, but not Jak2 mRNA, resulting in the phosphorylation and nuclear translocation of STAT3, which enhances the transcription of hypertrophic genes (e.g., Nppa) and ultimately leads to the emergence of cardiomyocytes hypertrophic growth. Our work highlights the functional role of ALKBH5 in regulating the onset of cardiomyocyte hypertrophy and provides a potential target for hypertrophic heart diseases prevention and treatment. ALKBH5 activated JAK2/STAT3 signaling pathway and mediated m6A demethylation on Stat3 mRNA, but not Jak2 mRNA, resulting in the phosphorylation and nuclear translocation of STAT3, which enhances the transcription of hypertrophic genes (e.g., Nppa) and ultimately leads to the emergence of cardiomyocytes hypertrophic growth.

Abstract Recruitment of non-canonical BCOR-PRC1.1 to non-methylated CpG islands via KDM2B plays a fundamental role in transcription control during developmental processes and cancer progression. However, the mechanism is still largely unknown on how this recruitment is regulated. Here, we unveiled the importance of the Poly-D/E regions within the linker of BCOR for its binding to KDM2B. Interestingly, we also demonstrated that these negatively charged Poly-D/E regions on BCOR play autoinhibitory roles in liquid-liquid phase separation (LLPS) of BCORANK-linker-PUFD/PCGF1RAWUL. Through neutralizing negative charges of these Poly-D/E regions, Ca2+ not only weakens the interaction between BCOR/PCGF1 and KDM2B, but also promotes co-condensation of the enzymatic core of BCOR-PRC1.1 with KDM2B into liquid-like droplet. Accordingly, we propose that Ca2+ could modulate the compartmentation and recruitment of the enzymatic core of BCOR-PRC1.1 on KDM2B target loci. Thus, our finding advances the mechanistic understanding on how the tethering of BCOR-PRC1.1 enzymatic core to KDM2B is regulated.

Abstract Background Ischemia reperfusion (IR) causes impaired myocardial function, and autophagy activation ameliorates myocardial IR injury. Isoliquiritigenin (ISO) has been found to protect myocardial tissues via AMPK, with exerting anti-tumor property through autophagy activation. This study aims to investigate ISO capacity to attenuate myocardial IR through autophagy activation mediated by AMPK/mTOR/ULK1 signaling. Methods ISO effects were explored by SD rats and H9c2 cells. IR rats and IR-induced H9c2 cell models were established by ligating left anterior descending (LAD) coronary artery and hypoxia/re-oxygenation, respectively, followed by low, medium and high dosages of ISO intervention (Rats: 10, 20, and 40 mg/kg; H9c2 cells: 1, 10, and 100 μmol/L). Myocardial tissue injury in rats was assessed by myocardial function-related index, HE staining, Masson trichrome staining, TTC staining, and ELISA. Autophagy of H9c2 cells was detected by transmission electron microscopy (TEM) and immunofluorescence. Autophagy-related and AMPK/mTOR/ULK1 pathway-related protein expressions were detected with western blot. Results ISO treatment caused myocardial function improvement, and inhibition of myocardial inflammatory infiltration, fibrosis, infarct area, oxidative stress, CK-MB, cTnI, and cTnT expression in IR rats. In IR-modeled H9c2 cells, ISO treatment lowered apoptosis rate and activated autophagy and LC3 fluorescence expression. In vivo and in vitro, ISO intervention exhibited enhanced Beclin1, LC3II/LC3I, and p-AMPK/AMPK levels, whereas inhibited P62, p-mTOR/mTOR and p-ULK1(S757)/ULK1 protein expression, activating autophagy and protecting myocardial tissues from IR injury. Conclusion ISO treatment may induce autophagy by regulating AMPK/mTOR/ULK1 signaling, thereby improving myocardial IR injury, as a potential candidate for treatment of myocardial IR injury.

Abstract Purpose We aimed to develop and evaluate a new diagnostic method, the 'chicken-wing muscle up test', to improve the accuracy of diagnosis of glenolabral articular disruption (GLAD) lesions compared to currently used clinical tests for injuries to the labrum. Methods Preoperative evaluations were conducted on 85 patients undergoing arthroscopic surgery at a single center between July 2021 to July 2022. The diagnostic performance of the preoperative clinical examinations (chicken-wing muscle up test, O'Brien test, crank test, and O'Driscoll test) were validated against the findings of arthroscopic examinations. Results 12 of the 85 patients in this study had arthroscopically confirmed GLAD lesions. The chicken-wing muscle up test demonstrated significantly higher sensitivity (83.33%) for GLAD lesions than the O'Brien test (33.33%), but not the crank test (50.00%) or O'Driscoll test (25.00%), and significantly higher specificity (95.89%) than the O'Brien test (75.34%), crank test (82.19%), and O'Driscoll test (71.23%). The chicken-wing muscle up test had the largest area under the receiver operating characteristic curve (AUC = 0.896, P 0.05; crank test AUC = 0.661, P > 0.05; O'Brien test AUC = 0.481, P > 0.05), indicating significantly better diagnostic efficacy for GLAD lesions than the other three tests. Conclusions The chicken-wing muscle up test is a reliable diagnostic method that improves the accuracy of diagnosis of GLAD lesions.

Abstract Aims Portal venous pressure frequently increases after a major hepatectomy. We aimed to assess the outcomes of patients with hepatocellular carcinoma (HCC) with different post‐hepatectomy portal pressure statuses and the predictive factors correlated with prognosis and post‐hepatectomy portal hypertension (PHPH). Methods Data from consecutive patients who underwent curative‐intent hepatectomy for HCC at the Eastern Hepatobiliary Surgery Hospital and Mengchao Hepatobiliary Hospital of Fujian Medical University between January 2008 and December 2016 were retrospectively analyzed. Patients were followed up until March 1, 2022. PHPH was defined as new‐onset portal hypertension (PH) in patients without preoperative PH within 1 month of hepatectomy. Patients were classified into two groups according to the presence or absence of PHPH: non‐PH and PHPH. The clinicopathological characteristics were compared between the two groups. Univariate and multivariate analyses were used to identify independent risk factors for early and late recurrence of HCC, overall survival (OS), and PHPH. Results Disease‐free survival rates were significantly higher in the non‐PH group (n = 1068) than those in the PHPH group (n = 423) (62.0%, 39.0%, and 31.0% vs. 46.2%, 24.5%, and 19.3% at 1, 3, and 5 years, respectively; all p 40 U/L, and major hepatectomy were identified as independent risk factors for PHPH. Conclusions PHPH was associated with early recurrence of HCC and poor OS but not with late recurrence. Therefore, PHPH may be an attractive target for therapeutic interventions and follow‐up surveillance to improve prognosis.

It is essential to efficiently perform collision detection for robotic manipulators obstacle-avoidance planning. Existing methods are excellent when manipulator links are simple and obstacles are convex. But they cannot keep the accuracy and the efficiency at the same time when manipulator links or obstacles are nonconvex. To decrease the computing time and keep a high accuracy, this article presents a collision detection method based on point clouds and stretched primitives (PCSP). In traditional methods, obstacles are often represented either by a convex body or enormous amounts of points. But this needs a trade-off between the accuracy and the computing time when obstacles are concave. In the proposed method, we represent obstacles and complex manipulator links as stretched geometric bodies while simple manipulator links are enclosed by capsules with different sizes. The stretched body is constructed by the original point cloud from sensors but it only requires a small number of points to approximate the original object. We conducted the simulation experiment in our specific scenarios, and the results indicated that PCSP required less computing time while maintaining a high level of accuracy compared to existing methods. We also conducted standard benchmark tests in general scenarios, which showed that PCSP had advantages over libraries based on bounding volume hierarchies when concave objects are close together. Finally, we implemented PCSP for a manipulator obstacle-avoidance motion planning in a real-world environment, which demonstrated that PCSP was effective.

Purpose: To assess the value of the driving pressure variation rate (ΔP%) in predicting the outcome of weaning from invasive mechanical ventilation in patients with acute respiratory distress syndrome. Methods: In this case-control study, a total of 35 patients with moderate-severe acute respiratory distress syndrome were admitted to the intensive care unit between January 2022 and December 2022 and received invasive mechanical ventilation for at least 48 h were enrolled. Patients were divided into successful weaning group and failed weaning group depending on whether they could be removed from ventilator support within 14 days. Outcome measures including driving pressure, PaO2:FiO2, and positive end-expiratory pressure, etc. were assessed every 24 h from day 0 to day 14 until successful weaning was achieved. The measurement data of non-normal distribution were presented as median (Q1, Q3), and the differences between groups were compared by Wilcoxon rank sum test. And categorical data use the Chi-square test or Fisher's exact test to compare. The predictive value of ΔP% in predicting the outcome of weaning from the ventilator was analyzed using receiver operating characteristic curves. Results: Of the total 35 patients included in the study, 17 were successful vs. 18 failed in weaning from a ventilator after 14 days of mechanical ventilation. The cut-off values of the median ΔP% measured by Operator 1 vs. Operator 2 in the first 4 days were ≥ 4.17% and 4.55%, respectively (p

Background: Glyphosate is a widely used herbicide. Clinical presentations of glyphosate intoxication show variation, but hepatic portal venous gas(HPVG) caused by glyphosate poisoning is rarely reported. Herein, we report a rare case of ominous HPVG after ingesting glyphosate. HPVG, which used to be an ominous abdominal radiologic sign, is associated with numerous underlying abdominal pathologies, ranging from benign conditions that require no invasive treatment to potentially lethal diseases that necessitate prompt surgical intervention. Case summary: A young woman who ingested 100 mL glyphosate 6-h prior was admitted to the emergency intensive care unit. Before admission to our hospital, the patient was administered gastric lavage treatment with 10000 mL of normal saline in the local hospital. After 14 h, her laboratory examinations showed systemic inflammatory response syndrome and multiple organ dysfunction syndrome, while the condition deteriorated. Computed tomography of the abdomen showed multilinear air densities in the portal vein, hepatic branches, and mesenteric vessels, intestinal obstruction, and intestinal necrosis. Septic shock and a severe abdominal infection were diagnosed. The patient was treated conservatively as they could not tolerate surgery and, after 20 h died of septic shock. Conclusion: We reviewed 289 cases of ''hepatic portal venous gas'' in PUBMED and analyzed the etiology and treatment of HPVG accompanied by the underlying pathology. We concluded that HPVG is a radiological sign associated with various diseases, and the prognosis mainly depends on the underlying cause and clinical condition. As glyphosate may erode the digestive tract, attention should be paid to the volume, pressure, and speed of gastric lavage in treating glyphosate poisoning to avoid fatal complications such as HPVG. Abdominal symptoms need to be closely observed, and changes in the early onset of the condition in clinical practice need to be responded to promptly.

ObjectivesPortal hypertension (PH) frequently gives rise to severe and life-threatening complications, including hemorrhage accompanied by the rupture of esophageal and gastric varices. In contrast to the guidelines for the management of PH in adults, the optimal endoscopic management of variceal bleeding for secondary prophylaxis in children remains unclear. The present study evaluated the efficacy and safety of endoscopic variceal ligation (EVL) and endoscopic sclerotherapy (EST) to control gastroesophageal variceal bleeding in children.MethodsThis retrospective study included children with gastroesophageal variceal bleeding who underwent EST or EVL at Xinhua Hospital, Shanghai Jiaotong University School of Medicine, between February 2013 and March 2020. Short-term hemostasis rate and long-term rebleeding rate were evaluated. Adverse events related to the procedures, such as esophageal ulcer, esophageal stricture, abnormal embolization, pneumonia and perforation, were also recorded.ResultsEVL (n = 8) and EST (n = 13) were performed successfully in all pediatric patients diagnosed with moderate to severe esophageal varices concurrent with gastric varices. Hemostasis was achieved during episodes of upper gastrointestinal bleeding. The mean volume of each single aliquot of cyanoacrylate injected was 0.3 ± 0.1 ml (range: 0.1–0.5 ml). Varices were eradicated in six (75%) of the eight patients who underwent EVL after a median 2 (range: 1–4) procedures and a median time of 3.40 months (range: 1.10–13.33 months). Eleven (52.4%) of the 21 patients developed rebleeding events, with the mean duration of hemostasis being 11.1 ± 11.6 months (range 1.0–39.2 months). No treatment-related complications, for example, distal embolism, occurred except for abdominal pain in one patient (4.8%).ConclusionsEST, alone or in combination with EVL, is an effective and safe method of managing gastroesophageal variceal hemorrhage in children undergoing secondary prophylaxis.

Recently, there has been increasing attention on the impact of acupuncture on the dysregulated neural circuits in different disease. This has led to new understandings of how acupuncture works. This review presents a comprehensive analysis of research that have examined the impact of acupuncture on abnormal neural circuits associated with pain, anxiety, Parkinson’s disease, addiction disorders, cognitive problems, and gastrointestinal disorders. These studies have shown that acupuncture’s therapeutic effects are mediated by specific brain areas and neurons involved in neural circuit mechanisms, emphasising its wide-ranging influence. The positive impacts of acupuncture can be ascribed to its ability to modify the functioning of neurocircuits in various physiological conditions. Nevertheless, contemporary studies on acupuncture neural circuits frequently overlook the comprehensive circuit mechanism including the periphery, central nervous system, and target organ. Additionally, the scope of diseases studied is restricted. Future study should focus on broadening the range of diseases studied and exploring the neural circuit mechanisms of these diseases in depth in order to enhance our understanding of acupuncture’s neurobiological impacts.

Abstract Background Alveolar hypercoagulation and fibrinolytic inhibition are mainly responsible for massive alveolar fibrin deposition, which are closely related with refractory hypoxemia in acute respiratory distress syndrome (ARDS). Our previous study testified runt-related transcription factor (RUNX1) participated in the regulation of this pathophysiology in this syndrome, but the mechanism is unknown. We speculate that screening the downstream genes associated with RUNX1 will presumably help uncover the mechanism of RUNX1. Methods Genes associated with RUNX1 were screened by CHIP-seq, among which the target gene was verified by Dual Luciferase experiment. Then the efficacy of the target gene on alveolar hypercoagulation and fibrinolytic inhibition in LPS-induced ARDS was explored in vivo as well as in vitro. Finally, whether the regulatory effects of RUNX1 on alveolar hypercoagulation and fibrinolytic in ARDS would be related with the screened target gene was also sufficiently explored. Results Among these screened genes, AKT3 was verified to be the direct target gene of RUNX1. Results showed that AKT3 was highly expressed either in lung tissues of LPS-induced rat ARDS or in LPS-treated alveolar epithelia cell type II (AECII). Tissue factor (TF) and plasminogen activator inhibitor 1 (PAI-1) were increasingly expressed both in lung tissues of ARDS and in LPS-induced AECII, which were all significantly attenuated by down-regulation of AKT3. Inhibition of AKT3 gene obviously ameliorated the LPS-induced lung injury as well as the collagen I expression in ARDS. RUNX1 overexpression not only promoted the expressions of TF, PAI-1, but also boosted AKT3 expression in vitro. More importantly, the efficacy of RUNX1 on TF, PAI-1 were all effectively reversed by down-regulation of AKT3 gene. Conclusion AKT3 is an important target gene of RUNX1, through which RUNX1 exerted its regulatory role on alveolar hypercoagulation and fibrinolytic inhibition in LPS-induced ARDS. RUNX1/ATK3 signaling axis is expected to be a new target for the exploration of ARDS genesis and treatment.

Abstract Retention time (RT) alignment is a crucial step in liquid chromatography-mass spectrometry (LC-MS)-based proteomic and metabolomic experiments, especially for large cohort studies. The most popular alignment tools are based on warping function method and direct matching method. However, existing tools can hardly handle monotonic and non-monotonic RT shifts simultaneously. Here, we develop a deep learning-based RT alignment tool, DeepRTAlign, for large cohort LC-MS data analysis. DeepRTAlign has been demonstrated to have improved performances by benchmarking it against current state-of-the-art approaches on multiple real-world and simulated proteomic and metabolomic datasets. The results also show that DeepRTAlign can improve identification sensitivity without compromising quantitative accuracy. Furthermore, using the MS features aligned by DeepRTAlign, we trained and validated a robust classifier to predict the early recurrence of hepatocellular carcinoma. DeepRTAlign provides an advanced solution to RT alignment in large cohort LC-MS studies, which is currently a major bottleneck in proteomics and metabolomics research.

Purpose: Atrophic nonunion is one of the most difficult complications of fracture. The cellular factors that contribute to atrophic nonunion are poorly understood, and mesenchymal stem cells (MSCs) are recognized as the key contributor to bone formation. This study aimed to characterize the MSCs isolated from the fibrotic tissue of atrophic nonunion (AN-MSCs) from the perspective of proliferation, differentiation potential, senescence, and paracrine function. Methods: Human atrophic fibrotic tissue was obtained from four donors aged 29–37 for isolating AN-MSCs, and donor-matched bone marrow acquired from the iliac crest for isolating MSCs (IC-MSCs) as control. The AN-MSCs or IC-MSCs in passage 3 were applied for the following evaluations. The surface markers expressed on the two cells were evaluated using flow cytometry. The proliferation of the two cells for up to 11 days was comparatively investigated. After osteogenic, chondrogenic, or adipogenic induction, multi-lineage differentiation of AN-MSCs or IC-MSCs was comparatively evaluated using lineage-specific stains and lineage-specific gene expression. Enzyme-linked immunosorbent assay (ELISA) assessment was applied to evaluate the paracrine function of AN-MSCs or IC-MSCs. Cellular senescence of AN-MSCs or IC-MSCs was evaluated using senescence-associated β-galactosidase (SA-β-gal) staining. Results: AN-MSCs or IC-MSCs from the four donors showed morphologic and immunophenotypic characteristics of MSCs, with the expression of MSCs markers and negative expression of hematopoietic markers. In general, AN-MSCs showed similar proliferation and adipogenic capacity with IC-MSCs. In contrast, IC-MSCs showed significantly higher osteogenic and chondrogenic capacity compared to AN-MSCs. Moreover, the culture medium of IC-MSCs contains significantly higher levels of VEGF, TGF-β1, PDGF-BB, and IGF-1 than the culture medium of AN-MSCs. Lastly, the AN-MSCs are more prone to cellular senescence than the IC-MSCs. Conclusions: In-vitro, AN-MSCs were similar to IC-MSCs in proliferation and adipogenic capacity, but inferior to IC-MSCs in osteogenic and chondrogenic capacity, paracrine function, and anti-senescence.

The inverse kinematics problem plays a crucial role in robotic manipulator planning, autonomous control, and object grasping. This problem can be solved in simple environments based on existing studies. However, it is still challenging to quickly find a feasible inverse kinematic solution when obstacle avoidance is required. In this paper, we present a nonconvex composite programming method to solve the inverse kinematics problem with overhead obstacle-avoidance requirements. Our method enables efficient obstacle avoidance by directly calculating the minimum distance between the manipulator and the overhead environment. We construct end-effector error functions based on the Product of Exponentials model and explicitly provide their gradient formula. We derive the minimum distance based on the geometry parametric equation and directly utilize it to construct the obstacle avoidance function. We propose an enhanced version of adaptive moment estimation based on short-time gradient information to improve optimization performance. Finally, we conduct simulations and experiments in overhead line environments. Comparative results with other optimization methods demonstrate that our proposed method achieves a high success rate with a low solution time.

Aim: To compare the survival outcomes between male and female patients with intrahepatic cholangiocarcinoma who underwent liver resection. Methods: Data from 976 consecutive intrahepatic cholangiocarcinoma patients undergoing liver resection between January 2005 and May 2013 at the Eastern Hepatobiliary Surgery Hospital were prospectively collected and retrospectively reviewed. Patient clinicopathological characteristics, overall survival, and cumulative recurrence rates were compared between male and female patients using propensity score matching. Results: Propensity score matching generated 313 matched pairs of patients. Among the entire cohort, the 1-, 3-, and 5-year overall survival and recurrence rates of the male and female patients were 60.2 %, 37.3 %, and 27.7 % vs. 65.8 %, 40.4 %, and 31.0 % (P = 0.380) and 50.6 %, 67.4 %, and 74.2 % vs. 44.4 %, 63.5 %, and 69.6 % (P = 0.123), respectively. In the matched cohort, the 1-, 3-, and 5-year overall survival and recurrence rates of the male and female patients were 60.6 %, 35.9 % and 22.4 % vs. 66.4 %, 40.6 % and 31.1 % (P = 0.041) and 51.5 %, 69.3 % and 83.9 % vs. 44.3 %, 63.6 %, and 69.9 % (P = 0.041), respectively. After adjustment for other confounding variables by multivariate Cox regression analysis, male sex was independently associated with worse overall survival (hazard ratio = 1.322, 95 % confidence interval: 1.079–1.621, P = 0.007) and tumor recurrence (hazard ratio = 1.337, 95 % confidence interval: 1.088–1.645, P = 0.006). A subgroup analysis of patients younger than 55 years old after propensity score matching showed that male patients had significantly worse overall survival and higher recurrence rates than female patients after surgery, while no significant difference in long-term overall survival and recurrence was observed between male and female patients older than 55 years old after propensity score matching. Conclusion: Male sex was an independent risk factor for overall survival and tumor recurrence in patients after liver resection for intrahepatic cholangiocarcinoma.

Abstract Hepatocellular carcinoma (HCC) is acknowledged as an immunosuppressive neoplasm, whereby the inactive microenvironment facilitates immune tolerance and evasion of HCC. Post‐surgical resected liver cancer exhibits a proclivity for relapse, rendering prevention of recurrence challenging as it may transpire at any point subsequent to surgery. Among the various anti‐recurrence interventions, the primary clinical approach involving the administration of regimens atezolizumab and bevacizumab (A+T) is deemed the most efficacious in reversing the tumor microenvironment, albeit still lacking in complete satisfaction. Therefore, the objective is to utilize a recently developed block copolymer as a protective carrier for two specific monoclonal antibody drugs. Subsequently, a modified hemostatic hydrogel will be synthesized for application during hepatic surgery. The immunotherapy impact of this approach is significantly prolonged and intensified due to the combined hemostasis properties and controlled release of the constituents within the synthesized nanocomposite hydrogel. Furthermore, these nanocomposite hydrogels exhibit remarkable efficacy in preventing postoperative wound bleeding and substantially enhancing the safety of liver cancer resection. This research on the anti‐recurrence hydrogel system presents a novel therapeutic approach for addressing local recurrence of liver cancer, potentially offering a substantial contribution to the field of surgical treatment for liver cancer in the future.

In the increasingly complex electromagnetic spectrum environment, accurately obtaining comprehensive spectrum situation is a crucial prerequisite for making precise spectrum decisions.First, the spectrum mapping was introduced and compared with spectrum sensing.Then, an in-depth review of existing spectrum situation generation methods was conducted.Next, multidimensional spectrum situation compressed mapping in the face of challenges such as heterogeneity, large scale missing data, time variability and environmental complexity was proposed.It effectively compensated for the incompleteness of the spectrum mapping framework caused by ignoring the spectrum situation sensing process in traditional spectrum situation generation methods.This could further provide more accurate guidance for enhancing spectrum utilization efficiency, strengthening spectrum security maintenance, and intensifying electromagnetic warfare decision-making.Lastly, the future development trends of spectrum compressed mapping were discussed.

Abstract Background Previous studies have traditionally attributed the initiation of cancer cells to genetic mutations, considering them as the fundamental drivers of carcinogenesis. However, recent research has shed light on the crucial role of epigenomic alterations in various cell types present within the tumor microenvironment, suggesting their potential contribution to tumor formation and progression. Despite these significant findings, the progress in understanding the epigenetic mechanisms regulating tumor heterogeneity has been impeded over the past few years due to the lack of appropriate technical tools and methodologies. Results The emergence of single-cell sequencing has enhanced our understanding of the epigenetic mechanisms governing tumor heterogeneity by revealing the distinct epigenetic layers of individual cells (chromatin accessibility, DNA/RNA methylation, histone modifications, nucleosome localization) and the diverse omics (transcriptomics, genomics, multi-omics) at the single-cell level. These technologies provide us with new insights into the molecular basis of intratumoral heterogeneity and help uncover key molecular events and driving mechanisms in tumor development. Conclusion This paper provides a comprehensive review of the emerging analytical and experimental approaches of single-cell sequencing in various omics, focusing specifically on epigenomics. These approaches have the potential to capture and integrate multiple dimensions of individual cancer cells, thereby revealing tumor heterogeneity and epigenetic features. Additionally, this paper outlines the future trends of these technologies and their current technical limitations.

Radish is an important root vegetable that is widely grown in Asia. The root-knot nematode (RKN) Meloidogyne incognita seriously affects the growth and development of radish root and causes poor appearance quality. However, the molecular mechanism of radish response to RKNs remains poorly understood. In this study, a total of 220 lncRNAs, 1144 mRNAs, 20 miRNAs and 153 proteins were differential expressed between the RKN-infected and WT samples. Correlation analysis of all DEPs compared with all DGEs showed that 8 mRNAs-DEPs showed a changed abundance. The results showed that 18 DEmiRNAs have 167 target DEGs in 220 miRNA-target modules and 29 DElncRNAs were predicted as putative targets of 16 DEmiRNAs in 37 miRNA-target modules. In all, 6 DGEs in the ABA pathway and 2 DGEs in the JA pathway were identified under RKN infection, respectively. The four regulatory networks of lncRNA-miRNA-mRNA were constructed in response to RKN infection. qRT-PCR analysis found that the expression pattern of 6 DElncRNAs, 6 DEmRNAs, 6 DEmiRNAs and 6 DEPs were consistent with sequencing results. These results provide a theoretical basis for studying the molecular mechanism of radish in response to M. incognita and breeding resistant varieties to this nematode.

Microbial community composition, function, and viability are important for biofilm-based sewage treatment technologies. Most studies of microbial communities mainly rely on the total deoxyribonucleic acid (DNA) extracted from the biofilm. However, nucleotide materials released from dead microorganisms may interfere with the analysis of viable microorganisms and their metabolic potential. In this study, we developed a protocol to assess viability as well as viable community composition and function in biofilm in a sewage treatment system using propidium monoazide (PMA) coupled with real-time quantitative polymerase chain reaction (qPCR) and metagenomic technology. The optimal removal of PMA from non-viable cells was achieved by a PMA concentration of 4 μM, incubation in darkness for 5 min, and exposure for 5 min. Simultaneously, the detection limit can reach a viable bacteria proportion of 1%, within the detection concentration range of 102–108 CFU/mL (colony forming unit/mL), showing its effectiveness in removing interference from dead cells. Under the optimal conditions, the result of PMA–metagenomic sequencing revealed that 6.72% to 8.18% of non-viable microorganisms were influenced and the composition and relative abundance of the dominant genera were changed. Overall, this study established a fast, sensitive, and highly specific biofilm viability detection method, which could provide technical support for accurately deciphering the structural composition and function of viable microbial communities in sewage treatment biofilms.

ZnS-based mechanoluminescent film has been widely used in the fields of stress visualization and stress sensing, due to its high brightness and repeatable stable luminescent characteristics. To evaluate the flexibleelastic deformation performance of ZnS-based mechanoluminescent film, both visual inspection and digital image correlation (DIC) are, respectively, employed for measuring the ZnS-based mechanoluminescent film. ZnS:Cu 2+ mechanoluminescent powders are first mixed with polydimethylsiloxane (PDMS) matrix to produce ZnS:Cu 2+–PDMS mechanoluminescent film. Then, two measurement experiments are, respectively, conducted to investigate the mechanical response and the flexible-elastic deformation performance of the prepared ZnS:Cu2+–PDMS mechanoluminescent film. On one hand, the mechanical response performance of the ZnS:Cu 2+–PDMS mechanoluminescent film is validated by visual monitoring of composite concrete fracture processes. On the other hand, the prepared ZnS:Cu 2+–PDMS mechanoluminescent film is also measured by DIC to obtain its full-field deformations and strains information. The flexible-elastic deformation performance of the ZnS:Cu 2+–PDMS mechanoluminescent film is well demonstrated by the DIC measured results.

In-situ MgO-doped ordered mesoporous carbon (OMC@MgO) was fabricated by formaldehyde-free self-assembly method, in which biomass-derived tannin was used as carbon precursor replacing fossil-based phenolics, Mg2+ as both cross-linker and precursor of catalytic sites. Up to ∼20 wt% MgO could be doped in the carbon skeleton with good dispersion retaining well-ordered mesoporous structures, while more MgO content (35 wt%) led to the failing in the formation of ordered mesoporous structure. The OMC@MgO possessed a high specific surface area (298.8 m2 g−1), uniform pore size distribution (4.8 nm) and small crystallite size of MgO (1.73 nm) due to the confinement effect of ordered mesoporous structure. Using OMC@MgO as the heterogeneous catalyst, a maximum fructose yield of 32.4% with a selectivity up to 81.1% was achieved from glucose in water (90 °C, 60 min), which is much higher than that obtained using the MgO doped active carbon via conventional post-impregnation method (26.5% yield with 58.3% selectivity). Higher reaction temperature (>90 °C) resulted in decrease of selectivity due to the formation of humins. The designed OMC@MgO displayed tolerant to high initial glucose concentrations (10 wt%) and could remain good recyclability without significant loss of activity for three cycles.

Summary: Background: Liver cirrhosis (LC) is the highest risk factor for hepatocellular carcinoma (HCC) development worldwide. The efficacy of the guideline-recommended surveillance methods for patients with LC remains unpromising. Methods: A total of 4367 LCs not previously known to have HCC and 510 HCCs from 16 hospitals across 11 provinces of China were recruited in this multi-center, large-scale, cross-sectional study. Participants were divided into Stage Ⅰ cohort (510 HCCs and 2074 LCs) and Stage Ⅱ cohort (2293 LCs) according to their enrollment time and underwent Tri-phasic CT/enhanced MRI, US, AFP, and cell-free DNA (cfDNA). A screening model called PreCar Score was established based on five features of cfDNA using Stage Ⅰ cohort. Surveillance performance of PreCar Score alone or in combination with US/AFP was evaluated in Stage Ⅱ cohort. Findings: PreCar Score showed a significantly higher sensitivity for the detection of early/very early HCC (Barcelona stage A/0) in contrast to US (sensitivity of 51.32% [95% CI: 39.66%–62.84%] at 95.53% [95% CI: 94.62%–96.38%] specificity for PreCar Score; sensitivity of 23.68% [95% CI: 14.99%–35.07%] at 99.37% [95% CI: 98.91%–99.64%] specificity for US) (P

Background & aimsThe effectiveness of adjuvant immunotherapy to diminish recurrence and improve long-term prognosis following curative-intent surgical resection for hepatocellular carcinoma (HCC) is of increased interest, especially among individuals at high risk of recurrence. The objective of the current study was to investigate the impact of adjuvant immunotherapy on long-term recurrence and survival after curative resection among patients with intermediate/advanced HCC.MethodsUsing a prospectively-collected multicenter database, patients who underwent curative-intent resection for Barcelona Clinic Liver Cancer (BCLC) stage B/C HCC were identified. Propensity score matching (PSM) analysis was used to compare recurrence-free survival (RFS) and overall survival (OS) between patients treated with and without adjuvant immune checkpoint inhibitors (ICIs). Multivariate Cox-regression analysis further identified independent factors of RFS and OS.ResultsAmong the 627 enrolled patients, 109 patients (23.3%) received adjuvant immunotherapy. Most ICI-related adverse reactions were grading I-II. PSM analysis created 99 matched pairs of patients with comparable baseline characteristics between patients treated with and without adjuvant immunotherapy. In the PSM cohort, the median RFS (29.6 vs. 19.3 months, P=0.031) and OS (35.1 vs. 27.8 months, P=0.036) were better among patients who received adjuvant immunotherapy versus patients who did not. After adjustment for other confounding factors on multivariable analyzes, adjuvant immunotherapy remained independently associated with favorable RFS (HR: 0.630; 95% CI: 0.435-0.914; P=0.015) and OS (HR: 0.601; 95% CI: 0.401-0.898; P=0.013). Subgroup analyzes identified potentially prognostic benefits of adjuvant immunotherapy among patients with intermediate-stage and advanced-stage HCC.ConclusionThis real-world observational study demonstrated that adjuvant immunotherapy was associated with improved RFS and OS following curative-intent resection of intermediate/advanced HCC. Future randomized controlled trials are warranted to establish definitive evidence for this specific population at high risks of recurrence.

Introduction: Acute respiratory distress syndrome (ARDS) remains a challenging disease with limited prevention and treatment options. The usage of beta-blockers may have potential benefits in different critical illnesses. This study aimed to investigate the correlation between beta-blocker therapy and mortality in patients with ARDS.Materials and methods: This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care (MIMIC) IV database and focused on patients diagnosed with ARDS. The primary outcome of the study was 30-day mortality. To account for confounding factors, a multivariable analysis was performed. Propensity score matching (PSM) was carried out on a 1:1 ratio. Robust assessments were conducted using inverse probability weighting (IPTW), standardized mortality ratio weighting (SMRW), pairwise algorithms (PA), and overlap weights (OW).Results: A total of 1,104 patients with ARDS were included in the study. Univariate and multivariate Cox regression analyses found that the 30-day mortality for 489 patients (23.7%) who received beta-blockers was significantly lower than the mortality rate of 615 patients (35.9%) who did not receive beta-blockers. After adjusting for potential confounders through PSM and propensity score, as well as utilizing IPTW, SMRW, PA, and OW, the results remained robust, with the hazard ratios (HR) ranging from 0.42 to 0.58 and all p-values < 0.001. Evaluation of the E-values indicated the robustness of the results even in the presence of unmeasured confounding.Conclusion: The findings suggest a potential association between beta-blocker usage and reduced mortality in critically ill patients with ARDS. However, further validation of this observation is needed through randomized controlled trials.

Abstract Objective Lung is often implicated in sepsis, resulting in acute respiratory distress syndrome (ARDS). The alveolar–arterial oxygen gradient [D(A‐a)O2] reflects lung diffusing capacity, which is usually compromised in ARDS. But whether D(A‐a)O2 impacts the prognosis of patients with sepsis remains to be explored. Our study aims to investigate the association between D(A‐a)O2 and 28‐day mortality in patients with sepsis using a large sample, multicenter Medical Information Mart for Intensive Care (MIMIC)‐IV database. Methods We extracted a data of 35 010 patients with sepsis from the retrospective cohort MIMIC‐IV database, by which the independent effects of D(A‐a)O2 on 28‐day death risk was investigated, with D(A‐a)O2 as being the exposure variable and 28‐day fatality being the outcome variable. Binary logistic regression and a two‐piecewise linear model were employed to explore the relationship between D(A‐a)O2 and the 28‐day death risk after confounding factors were optimized including demographic indicators, Charlson comorbidity index (CCI), Sequential Organ Failure Assessment (SOFA) score, drug administration, and vital signs. Results A total of 18 933 patients were finally included in our analysis. The patients' average age was 66.67 ± 16.01 years, and the mortality at 28 days was 19.23% (3640/18933). Multivariate analysis demonstrated that each 10‐mmHg rise of D(A‐a)O2 was linked with a 3% increase in the probability of death at 28 days either in the unadjusted model or in adjustment for demographic variables (Odds ratio [OR]: 1.03, 95% CI: 1.02 to 1.03). But, each 10 mmHg increase in D(A‐a)O2 was associated with a 3% increase of death (OR: 1.03, 95% CI: 1.023 to 1.033) in the case of adjustment for all covariants. Through smoothed curve fitting and generalized summation models, we found that non‐linear relationship existed between D(A‐a)O2 and the death at 28‐day, which demonstrated that D(A‐a)O2 had no any impacts on the prognosis of patients with sepsis when D(A‐a)O2 was less than or equal to 300 mmHg, but once D(A‐a)O2 exceeded 300 mmHg, however, every 10 mmHg elevation of D(A‐a)O2 is accompanied by a 5% increase of the 28‐day death (OR: 1.05; 95% CI:1.04 to 1.05, p

Under irrigation with saline wastewater, SO42−, Cl−, and Ca2+ aggregated in the topsoil, and Mg2+ was significantly higher in the deeper soil than in the topsoil and 40 cm soil layers. The abundance of Zoopagomycota, Ascomycota, Mortierellomycota, Basidiomycota, Chytridiomycota, Rozellomycota, Blastocladiomycota, Monoblepharomycota, Mucoromycota and Olpidiomycota in the surface soil was influenced by Mg2+, whereas Ca2+ affected the abundance of Zoopagomycota and Chytridiomycota. In the 40 cm soil layer, Mg2+ and Cl− promoted Actinobacteria, Proteobacteria, Nitrospirae, Firmicutes, Entotheonellaeota, Myxococcota, Gemmatimonadota and Methylomirabilota, whereas they inhibited Planctomycetota, Acidobacteria, Chloroflexi, Patescibacteria and Bacteroidota. In the 80 cm soil layer, SO42− and Cl− promoted Rozellomycota, Mortierellomycota, Chytridiomycota, Ascomycota, and Mucoromycota, but had a negative effect on Glomeromycota, Blastocladiomycota, Olpidiomycota and Monoblepharomycota. The increase in salinity significantly reduced the abundance of the Actinomycetes phylum and the Amoebozoa phylum. Both saprophytic and symbiotic fungi decreased with increasing salinity.

In the blood sample management pipeline environment, we have innovatively improved the traditional A-star algorithm to enhance the efficiency of mobile robots. This study employs a grid environmental modeling approach to accurately simulate medical testing laboratories. On the grid map, we utilize an 8-neighbor search method for path planning to accommodate the complex structure within the laboratory. By introducing an improved evaluation function and a bidirectional search strategy, we have successfully reduced the number of search nodes and significantly improved path search efficiency. Additionally, we eliminate redundant nodes in the path, smooth the path using cubic uniform B-spline curves, remove unnecessary inflection points, and further optimize the motion trajectory of the robot. The experimental results of the path planning simulation under different scenarios and specifications show that the improved A-star algorithm has higher search efficiency and traverses fewer nodes compared to the traditional A-star algorithm and the bidirectional A-star algorithm. Overall, the simulation experiments verify the feasibility of the improved A-star algorithm, which can better meet the needs of actual mobile robots in real medical testing laboratories.

Introduction Prompt detection of hepatocellular carcinoma (HCC) in patients with chronic liver diseases is critical for enhancing prognosis. Existing imaging techniques and serum markers fall short of clinical needs. This study aims to establish a non-invasive diagnostic model for early HCC detection in the Chinese population.Methods and analysis This prospective, multicentre, observational study will enrol 2000 participants, including HCC patients, those with chronic liver diseases (hepatitis, cirrhosis and benign liver space-occupying lesions), and healthy individuals. The study will collect demographic data and blood samples, which will be used to test α-fetoprotein (AFP), des-γ-carboxy-prothrombin (DCP) and circulating tumour DNA (ctDNA) methylation. The GAMAD (Gender+Age+Methylation+AFP+DCP) model involving gender, age, ctDNA methylation signature, AFP and DCP will be developed and blindly validated in training and validation sets (1400 and 600 cases, respectively). Primary endpoints include sensitivity, specificity and accuracy (receiver operating characteristic curves; area under the curve value) of GAMAD for HCC and/or high-risk HCC groups. Secondary endpoints involve comparing GAMAD with the established GALAD (Gender+Age+AFP-L3+AFP+DCP) model and each blood index (AFP, DCP and methylation signature) to evaluate: (1) GAMAD’s clinical utility for HCC patients in all stages according to different staging systems; (2) GAMAD’s discrimination ability for patients in various subgroups, including liver cirrhosis (LC) related HCC and LC, hepatitis B virus (HBV) related HCC and HBV, hepatitis C virus (HCV) related HCC and HCV, and non-alcoholic fatty liver disease (NAFLD) related HCC and NAFLD.Ethics and dissemination This trial has been approved by the Medical Ethics Committees of the First Hospital of Jilin University (#22K073-001), the Eastern Hepatobiliary Surgery Hospital, Naval Medical University (#EHBHKY2023-H0003-P001) and Tianjin Third Central Hospital (#IRB2023-007-01). All participants in the trial will provide written informed consent. Results of this study will be disseminated in peer-reviewed scientific journals and at conferences nationally and internationally.Trial registration number NCT05626985.

Objective: Alveolar type II (ATII) cells produce pulmonary surfactant (PS) essential for maintaining lung function. The aberration or depletion of PS can cause alveolar collapse, a hallmark of acute respiratory distress syndrome (ARDS). However, the intricacies underlying these changes remain unclear. This study aimed to elucidate the mechanisms underlying PS perturbations in ATII cells using transcriptional RNA-seq, offering insights into the pathogenesis of ARDS. Methods: ATII cells were identified using immunofluorescence targeting surface-active protein C. We used 24-h lipopolysaccharide (LPS)-induced ATII cells as an ARDS cell model. The efficacy of the injury model was gauged by detecting the presence of tumour necrosis factor-α and interleukin-6. RNA-seq analysis was performed to investigate the dynamics of PS deviation in unaltered and LPS-exposed ATII cells. Results: Whole-transcriptome sequencing revealed that LPS-stimulated ATII cells showed significantly increased transcription of genes, including Lss, Nsdhl, Hmgcs1, Mvd, Cyp51, Idi1, Acss2, Insig1, and Hsd17b7, which play key roles in regulating cholesterol biosynthesis. We further verified gene levels using real-time quantitative PCR, and the results showed that the mRNA expression of these genes increased, which was consistent with the RNA-seq results. Conclusion: Our study revealed pivotal transcriptional shifts in ATII cells after LPS exposure, particularly in nine key lipid and cholesterol metabolism genes. This altered expression might disrupt the lipid balance, ultimately affecting PS function. This finding deepens our understanding of the aetiology of ARDS and may lead to new therapeutic directions.

Utilizing Unmanned Aerial Vehicles (UAV) and instance segmentation for construction site monitoring(such as construction machinery and operation surfaces) offers a significant leap in management efficiency over traditional manual supervision methods. However, in UAV-based remote sensing images, the subtle presence of construction machinery and the image features resemblances among various operational surfaces make it difficult to segment instances. To address these challenges, this study proposed a novel instance segmentation model based on the YOLOv8-seg model. Given the unique challenges, the proposed model makes three improvements to the original YOLOv8-seg model. First, the paper incorporates the FocalNext module, which extends the sense field of the convolutional kernel to capture contextual data and integrates multilevel features, enhancing the perception of local details. Second, the paper incorporates the Efficient Multiscale Attention (EMA) module, which refines image features by emphasizing spatial-channel interactions and adeptly contrasts patterns across scales to detect nuances overlooked by conventional models, aiding in distinguishing similar construction operation surfaces. Last, given the intricate nature of construction site images, this paper incorporates the Context Aggregation module, which enhances pixel analysis by intelligently modulating feature weights to highlight essential global contexts. The ablation experiment demonstrates that the enhancements perform well on the YOLOv8-seg two variants model. Comparative experimental results show that the improved model significantly outperforms existing instance segmentation models regarding model performance, complexity, and inference speed. Overall, the improved YOLOv8-seg model balances model performance and computational complexity to meet the needs of edge device deployment in field monitoring.

Convolutional neural networks are a popular method in hyperspectral image classification. However, the accuracy of the models is closely related to the number and spatial size of training samples. Which relieve the performance decline by the number and spatial size of training samples, we designed a 3-D multihead self-attention spectral–spatial feature fusion network (3DMHSA-SSFFN) that contains step-by-step feature extracted blocks (SBSFE) and 3-D multihead-self-attention-module (3DMHSA). The proposed step-by-step feature extracted blocks relieved the declining-accuracy phenomenon for the limited number of training samples. Multiscale convolution kernels extract more spatial–spectral features in the step-by-step feature-extracted blocks. In hyperspectral image classification, the 3DMHSA module enhances the stability of classification by correlating disparate features. Experimental results show that 3DMHSA-SSFFN possesses a better classification performance than other advanced models through the limited number of balance and imbalance training data in three data.

Abstract Background Hepatocellular carcinoma (HCC) generally arises from a background of liver cirrhosis (LC). Patients with cirrhosis and suspected HCC are recommended to undergo serum biomarker tests and imaging diagnostic evaluation. However, the performance of routine diagnostic methods in detecting early HCC remains unpromising. Methods Here, we conducted a large-scale, multicenter study of 1675 participants including 490 healthy controls, 577 LC patients, and 608 HCC patients from nine clinical centers across nine provinces of China, profiled gene mutation signatures of cell-free DNA (cfDNA) using Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) through detecting 931 mutation sites across 21 genes. Results An integrated diagnostic model called “Combined method” was developed by combining three mutation sites and three serum biomarkers. Combined method outperformed AFP in the diagnosis of HCC, especially early HCC, with sensitivities of 81.25% for all stages and 66.67% for early HCC, respectively. Importantly, the integrated model exhibited high accuracy in differentiating AFP-negative, AFP-L3-negative, and PIVKA-II-negative HCCs from LCs.

The combined application of manure and chemical fertilizers has been recognized as a critical factor driving significant changes in crop yield and nutrient use efficiency, holding the potential to optimize agricultural management to achieve high yields. In this 40-year study, we investigated the effect of manure amendment on soybean and maize yields, water and nitrogen use efficiencies (WUE and NUE), and water and mineral N storage at 0–100 cm soil depths from 2017 to 2018 to explore the optimization of fertilization management strategies for soybean and maize production in Northeast China. To elucidate the impact of chemical fertilizers and manure, twelve treatments—control (CK); single N fertilizer at a low rate (N1) and that at a high rate (N2); N1, phosphorus (P), and potassium (K) fertilizer (N1PK); manure alone at 13.5 and 27 t ha−1 (M1 and M2); and those combined with N, P, or K fertilizer (M1N1, M1N2, and M1N1PK and M2N1, M2N2, and M2N1PK)—were selected and studied. The results showed that long-term amendment with manure significantly increased crop biomass and yield in the soybean–maize–maize rotation system. Combining with manure increased the WUE, the partial factor productivity of N fertilizer (PFPN), and N physiological efficiency (PEN) in both the soybean and maize seasons; conserved soil water (mainly at 40–60 cm); and increased soil N retention (in the upper 60 cm layer), which reduced the risk of N leaching, with a better effect being observed after the application of 13.5 t ha−1 manure. These results provide insight into the potential of using fertilization management strategies that include amendment with 13.5 t ha−1 manure in combination with N, P, and K fertilizer in the maize season and only chemical fertilizer in the soybean season, as these results indicate that such strategies can achieve high yields and be used to implement agricultural sustainable development in brown soil regions in Northeast China.

The fatigue crack initiation direction of wind turbine gearbox bearings is investigated. Through theoretical research，it is believed that the direction of crack initiation depends on the direction of the maximum shear stress amplitude plane at the local initiation position. After calculation，it is found that the orthogonal shear stress amplitude of the shallow layer inside the bearing raceway is greater than the principal shear stress amplitude，and the principal shear stress amplitude at the deeper layer is greater than the orthogonal shear stress amplitude. Therefore，the crack initiation angle varies with the initiation depth. Aiming at the problem of crack propagation，the method of stress superposition in the polar coordinate of the crack tip in fracture mechanics is used to clarify the influence of Hertz contact stress，residual stress，assembly interference pressure，etc. on the direction of crack propagation. The applicability of the theory is verified by analyzing the failure cases of bearings with different thermal treatment microstructure.

Abstract Background Andrographolide (Andro) has been confirmed to ameliorate alveolar hypercoagulation and fibrinolysis inhibition via NF-κB pathway in acute respiratory distress syndrome (ARDS), but the specific target of Andro is unknown. Purpose Our aim is to explore the specific target of Andro through which the drug exerted its effects on alveolar hypercoagulation and fibrinolytic inhibition in LPS-induced ARDS. Methods AECII was treated with different doses of Andro for 1 h, and then stimulated with LPS for 24 h. Expressions of tissue factor (TF), plasminogen activator inhibitor (PAI)-1 and tissue factor pathway inhibitor (TFPI) were detected. Concentrations of thrombin-antithrombin complex (TAT), pro-collagen type III peptide (PIIIP), antithrombin III (ATIII) and activated protein C (APC) in cell supernatant were measured by enzyme linked immunosorbent assay (ELISA). NF-κB signaling pathways activation was simultaneously determined. AECII with p65 down-/over-expression were used as control. Results Andro effectively inhibited TF and PAI-1 and promoted TFPI expressions on AECII induced by LPS stimulation. Andro also significantly suppressed the productions of TAT and PIIIP but promoted ATIII and APC secretions from the LPS-treated cell. Furthermore, Andro application obviously inhibited NF-κB signaling pathway activation provoked by LPS, as shown by decreased level of phosphorylation (p‑)-IKKβ/IKKβ, p-p65/p65 and p65 DNA binding activity. The effects of Andro on those factors were obviously strengthened by down- but were weakened by up-regulation of p65 gene in AECII cell. Conclusions Our data demonstrates that targeting AECII is the mechanism by which Andro ameliorates alveolar hypercoagulaiton and fibrinolytic inhibition via NF-κB pathway in ARDS. Andro is worth to be clinically further studied in ARDS treatment.

Article highlights Carbonization (1 h, 400 °C, N2) of mix ball-milled (10 min) waste leaves and humic acid affords weak-acid biochars. As-prepared weak-acid biochars (–COOH, OH, amino groups) were activated solids with adsorptive and catalytic properties. Weak-acid biochar catalyst is reusable and promotes fructose dehydration to 5-HMF in yields of 77.5% (140 °C, 60 min).

Objective: The relationship between base excess (BE) and 28-day death in sepsis patients remains to be elucidated. The aim of our clinical study is to explore the association of BE with 28-day mortality in patients with sepsis by using a large sample, multicenter Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Methods: We extracted the data of 35,010 patients with sepsis from the MIMIC-IV database, in which we used BE as an exposure variable and the 28-day mortality as an outcome variable, respectively, so as to explore the impact of BE on the 28-day mortality of patients with sepsis after adjusting for covariates. Results: BE and the 28-day mortality of patients with sepsis appeared to have a U-shaped relationship. The calculated inflection points were −2.5 mEq/L and 1.9 mEq/L, respectively. Our data demonstrated that BE was negatively associated with 28-day mortality in the range of −41.0 mEq/L to −2.5 mEq/L (odds ratio: 0.95; 95% confidence intervals (95%CI): 0.93 to 0.96), p

Background and AimThe prediction models of postoperative survival for hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) with microvascular invasion (MVI) have not been well established. The study objective was the development of nomograms to predict disease recurrence and overall survival (OS) in these patients.MethodsData were obtained from 1046 HBV-related MVI-positive HCC patients who had undergone curative resection from January 2014 to December 2017. The study was approved by the Eastern Hepatobiliary Surgery Hospital and Jinling Hospital ethics committee, and patients provided informed consent for the use of their data. Nomograms for recurrence and OS were created by Cox regression model in the training cohort (n=530). The modes were verified in an internal validation cohort (n= 265) and an external validation cohort (n= 251).ResultsThe nomograms of recurrence and OS based on preoperative serological indicators (HBV-DNA, neutrophil-lymphocyte ratio, a-fetoprotein), tumor clinicopathologic features (diameter, number), surgical margin and postoperative adjuvant TACE achieved high C-indexes of 0.722 (95% confidence interval [CI], 0.711-0.732) and 0.759 (95% CI, 0.747-0.771) in the training cohort, respectively, which were significantly higher than conventional HCC staging systems (BCLC, CNLC, HKLC).The nomograms were validated in the internal validation cohort (0.747 for recurrence, 0.758 for OS) and external validation cohort(0.719 for recurrence, 0.714 for OS) had well-fitted calibration curves. Our nomograms accurately stratified patients with HBV-HCC with MVI into low-, intermediate- and high-risk groups of postsurgical recurrence and mortality. Prediction models for recurrence-free survival (https://baishileiehbh.shinyapps.io/HBV-MVI-HCC-RFS/) and OS (https://baishileiehbh.shinyapps.io/HBV-MVI-HCC-OS/) were constructed.ConclusionsThe two nomograms showed good predictive performance and accurately distinguished different recurrence and OS by the nomograms scores for HBV-HCC patients with MVI after resection.

Background: Primary liver cancer, around 75%–85% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China, but also may re-shape the nationwide diagnosis and treatment of liver cancer. Key Messages: The new guideline aims to encourage the implementation of evidence-based practice, and improve the national average five-year survival rate for patients with liver cancer, as proposed in the "Health China 2030 Blueprint."

Portal vein tumor thrombus (PVTT) is very common and it plays a major role in the prognosis and clinical staging of hepatocellular carcinoma (HCC). We have published the first version of the guideline in 2016 and revised in 2018. Over the past several years, many new evidences for the treatment of PVTT become available, especially for the advent of new targeted drugs and immune checkpoint inhibitors which have further improved the prognosis of PVTT. So, the Chinese Association of Liver Cancer and Chinese Medical Doctor Association revised the 2018 version of the guideline to adapt to the development of PVTT treatment. Future treatment strategies for HCC with PVTT in China would depend on new evidences from more future clinical trials.

Transmission line fault detection using drones provides real-time assessment of the operational status of transmission equipment, and therefore it has immense importance in ensuring stable functioning of the transmission lines. Currently, identification of transmission line equipment relies predominantly on manual inspections that are susceptible to the influence of natural surroundings, resulting in sluggishness and a high rate of false detections. In view of this, in this study, we propose an insulator defect recognition algorithm based on a YOLOv5 model with a new lightweight network as the backbone network, combining noise reduction and target detection. First, we propose a new noise reduction algorithm, i.e., the adaptive neighborhood-weighted median filtering (NW-AMF) algorithm. This algorithm employs a weighted summation technique to determine the median value of the pixel point’s neighborhood, effectively filtering out noise from the captured aerial images. Consequently, this approach significantly mitigates the adverse effects of varying noise levels on target detection. Subsequently, the RepVGG lightweight network structure is improved to the newly proposed lightweight structure called RcpVGG-YOLOv5. This structure facilitates single-branch inference, multi-branch training, and branch normalization, thereby improving the quantization performance while simultaneously striking a balance between target detection accuracy and speed. Furthermore, we propose a new loss function, i.e., Focal EIOU, to replace the original CIOU loss function. This optimization incorporates a penalty on the edge length of the target frame, which improves the contribution of the high-quality target gradient. This modification effectively addresses the issue of imbalanced positive and negative samples for small targets, suppresses background positive samples, and ultimately enhances the accuracy of detection. Finally, to align more closely with real-world engineering applications, the dataset utilized in this study consists of machine patrol images captured by the Unmanned Aerial Systems (UAS) of the Yunnan Power Supply Bureau Company. The experimental findings demonstrate that the proposed algorithm yields notable improvements in accuracy and inference speed compared to YOLOv5s, YOLOv7, and YOLOv8. Specifically, the improved algorithm achieves a 3.7% increase in accuracy and a 48.2% enhancement in inference speed compared to those of YOLOv5s. Similarly, it achieves a 2.7% accuracy improvement and a 33.5% increase in inference speed compared to those of YOLOv7, as well as a 1.5% accuracy enhancement and a 13.1% improvement in inference speed compared to those of YOLOv8. These results validate the effectiveness of the proposed algorithm through ablation experiments. Consequently, the method presented in this paper exhibits practical applicability in the detection of aerial images of transmission lines within complex environments. In future research endeavors, it is recommended to continue collecting aerial images for continuous iterative training, to optimize the model further, and to conduct in-depth investigations into the challenges associated with detecting small targets. Such endeavors hold significant importance for the advancement of transmission line detection.

Background & Aims: Gut microbiota and microbial factors regulate the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in patients with obesity and metabolic abnormalities, but little is known about their roles in nonobese NAFLD. Expansion of Escherichia is associated with NAFLD pathogenesis. We aimed to investigate the pathogenic role of Escherichia fergusonii and its products in the development of nonobese NAFLD. Methods: We characterized the intestinal microbiome signature in a cohort of NAFLD patients and healthy controls by 16S ribosomal RNA sequencing. The role of E fergusonii was estimated in rats after 16 weeks of administration, and features of NAFLD were assessed. E fergusonii–derived microRNA-sized, small RNAs (msRNAs) were analyzed by deep sequencing. Results: We detected an expansion of Escherichia_Shigella in NAFLD patients compared with healthy controls, and its increase was associated with disease severity independent of obesity. E fergusonii, a member of the genus Escherichia, induced the development of nonobese NAFLD characterized by hepatic steatosis and hepatocyte ballooning in rats without obesity. It disturbed host lipid metabolism by inhibiting hepatic lipid β-oxidation and promoting de novo lipogenesis. We also showed that E fergusonii caused the development of hepatic inflammation and fibrosis in a sizable fraction of animals at an advanced stage of NAFLD. Mechanistically, E fergusonii–derived msRNA 23487 down-regulated host hepatic peroxisome proliferator-activated receptor α expression, which could contribute to lipid accumulation in the liver. Conclusions: These results suggest that E fergusonii promotes the pathogenesis of steatohepatitis and fibrosis in nonobese rats by secreting msRNA 23487, and it might be a potential biomarker for predicting steatohepatitis in nonobese NAFLD.

The Laguerre-Gaussian (LG) and Hermite-Gaussian (HG) modes can be interconverted with an astigmatism phase. In this paper, based on the single beam, the interconversion of LG and HG beams array with the astigmatism phase is analyzed theoretically and the spatial mapping relationship is derived. In the experiment, 1 × 3, 2 × 2, 3 × 3 LG beams arrays are generated and converted into HG beams array via employing a spatial light modulator loaded with 0°, 90°, 45°, −45° astigmatism phases. The experimental results are in great agreement with the theoretical analyses. Moreover, from the number and direction of the dark fringe of converted HG beams array, the orbital angular momentum information of LG beams array can be obtained. This work theoretically perfects the theoretical model of the interconversion between LG and HG beams based on an astigmatism phase, and also provides a theoretical support for measuring the LG beams array.

Global awareness of the need to enhance crop production and reduce environmental issues associated with nitrogen (N) fertilizer has increased. However, studies on how the N fate changed with manure addition are still limited. To explore efficient fertilization management for an improved grain yield, N recovery efficiency, and reduced N residual in the soil or that unaccounted for, a field 15N micro-plot trial in a soybean–maize–maize rotation was conducted to evaluate the effect of fertilization regimes on soybean and maize yields and the fertilizer N fate in the plant–soil system during 2017–2019 within a 41-year experiment in Northeast China. Treatments included chemical N alone (N), N and phosphorus (NP), N, P, and potassium (NPK), and those combined with manure (MN, MNP, and MNPK). Application of manure increased grain yield, on average, by 153% for soybean (2017) and 105% and 222% for maize (2018 and 2019) compared to no manure, with the highest at MNPK. Crop N uptake and that from labeled 15N-urea also benefited from manure addition, mainly partitioned to grain, and the average 15N-urea recovery was 28.8% in the soybean season with a reduction in the subsequent maize seasons (12.6%, and 4.1%). Across the three years, the fertilizer 15N recovery ranged from 31.2–63.1% (crop) and 21.9–40.5% (0–40 cm soil), with 14.6–29.9% unaccounted for, including N losses. In the two maize seasons, manure addition significantly increased the residual 15N recovery in crop attributed to the enhancing 15N remineralization, and reduced that in soil and unaccounted for compared to single chemical fertilizer, with MNPK performing the best. Therefore, applying N, P, and K fertilizers in the soybean season and NPK combined with manure (13.5 t ha–1) in the maize seasons is a promising fertilization management strategy in Northeast China and similar regions.

Hepatocellular carcinoma (HCC) is one of the most malignant cancers worldwide, with high mortality. However, the molecular regulatory mechanisms of liver cancer, especially transcriptional and post-transcriptional mechanisms, should be further studied. Here we used chromatin and cross-linking immunoprecipitation with high throughput sequencing methods (ChIP-seq and CLIP-seq) to capture the global binding profiles on RNAs and DNAs of Enhancer of zeste homolog 2 (EZH2) and its partner Jumonji And AT-Rich Interaction Domain Containing 2 (JARID2) in liver carcinoma cell lines (HepG2) and normal liver cell line (THLE-2), respectively. We also integrated HCC transcriptome data from the TCGA to analyze the expression pattern of bound genes. We found that EZH2 and JARID2 both showed distinct binding profiles between HepG2 and THLE-2 cells. By binding to the primary RNAs, bound transcripts of EZH2 and JARID2 in HepG2 showed significantly increased transcriptional levels in HCC patients. By performing gene set enrichment analysis (GSEA), the bound transcripts were also highly related to HCC development. We also found EZH2 and JARID2 could specifically bind to several long noncoding RNAs (lncRNAs), including H19. By exploring the DNA binding profile, we detected a dramatically repressed DNA binding ability of EZH2 in HepG2 cells. We also found that the EZH2-bound genes showed slightly increased transcriptional levels in HepG2 cells. Integrating analysis of the RNA and DNA binding profiles suggests EZH2 and JARID2 shift their binding ability from DNA to RNA in HepG2 cells to promote cancer development in HCC. Our study provided a comprehensive and distinct binding profile on RNAs and DNAs of EZH2 and JARID2 in liver cancer cell lines, suggesting their potential novel functional manners to promote HCC development.

Abstract Background and aims Although adjuvant transcatheter arterial chemoembolization (TACE) for resected hepatocellular carcinoma (HCC) may improve survival for some patients, identifying which patients can benefit remains challenging. The present study aimed to construct a survival prediction calculator for individualized estimating the net survival benefit of adjuvant TACE for patients with resected HCC. Methods From a multicenter database, consecutive patients undergoing curative resection for HCC were enrolled and divided into the developing and validation cohorts. Using the independent survival predictors in the developing cohort, two nomogram models were constructed for patients with and without adjuvant TACE, respectively, which predictive performance was validated internally and externally by measuring concordance index (C-index) and calibration. The difference between two estimates of the prediction models was the expected survival benefit of adjuvant TACE. Results A total of 2514 patients met the inclusion criteria for the study. The nomogram prediction models for patients with and without adjuvant TACE were, respectively, built by incorporating the same eight independent survival predictors, including portal hypertension, Child–Pugh score, alpha-fetoprotein level, tumor size and number, macrovascular and microvascular invasion, and resection margin. These two prediction models demonstrated good calibration and discrimination, with all the C-indexes of greater than 0.75 in the developing and validation cohorts. A browser-based calculator was generated for individualized estimating the net survival benefit of adjuvant TACE. Conclusions Based on large-scale real-world data, an easy-to-use online calculator can be adopted as a decision aid to predict which patients with resected HCC can benefit from adjuvant TACE.