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Abstract This review used traditional and network meta-analyses (NMA) to conduct a comprehensive study of antithrombotic therapies in children with thromboembolic disease. We searched the PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov databases from their inception to 26 February, 2023. And we finally included 16 randomized controlled trials. In the prevention of thromboembolic events (TEs), the use of anticoagulants had a low risk of TEs (relative risk (RR) 0.73, 95% CI 0.56 to 0.94) and a high risk of minor bleeding (RR 1.43, 95% CI 1.09 to 1.86) compared with no anticoagulants. In the treatment of TEs, direct oral anticoagulants (DOACs) were not inferior to standard anticoagulation in terms of efficacy and safety outcomes. In NMA, rivaroxaban and apixaban showed the lowest risk for TEs and major or clinically relevant nonmajor bleeding. According to the overall assessment of efficacy and safety, dabigatran may be the best choice for children with thromboembolic disease. The results of our study will provide references and suggestions for clinical drug selection.

Abstract Breast cancer bone metastasis is a terminal-stage disease and is typically treated with radiotherapy and chemotherapy, which causes severe side effects and limited effectiveness. To improve this, Sonodynamic therapy may be a more safe and effective approach in the future. Bacterial outer membrane vesicles (OMV) have excellent immune-regulating properties, including modulating macrophage polarization, promoting DC cell maturation, and enhancing anti-tumor effects. Combining OMV with Sonodynamic therapy can result in synergetic anti-tumor effects. Therefore, we constructed multifunctional nanoparticles for treating breast cancer bone metastasis. We fused breast cancer cell membranes and bacterial outer membrane vesicles to form a hybrid membrane (HM) and then encapsulated IR780-loaded PLGA with HM to produce the nanoparticles, IR780@PLGA@HM, which had tumor targeting, immune regulating, and Sonodynamic abilities. Experiments showed that the IR780@PLGA@HM nanoparticles had good biocompatibility, effectively targeted to 4T1 tumors, promoted macrophage type I polarization and DC cells activation, strengthened anti-tumor inflammatory factors expression, and presented the ability to effectively kill tumors both in vitro and in vivo, which showed a promising therapeutic effect on breast cancer bone metastasis. Therefore, the nanoparticles we constructed provided a new strategy for effectively treating breast cancer bone metastasis. Graphical Abstract

Abstract Regulatory T cells (Tregs) are essential to the negative regulation of the immune system, as they avoid excessive inflammation and mediate tumor development. The abundance of Tregs in tumor tissues suggests that Tregs may be eliminated or functionally inhibited to stimulate antitumor immunity. However, immunotherapy targeting Tregs has been severely hampered by autoimmune diseases due to the systemic elimination of Tregs. Recently, emerging studies have shown that metabolic regulation can specifically target tumor-infiltrating immune cells, and lipid accumulation in TME is associated with immunosuppression. Nevertheless, how Tregs actively regulate metabolic reprogramming to outcompete effector T cells (Teffs), and how lipid metabolic reprogramming contributes to the immunomodulatory capacity of Tregs have not been fully discussed. This review will discuss the physiological processes by which lipid accumulation confers a metabolic advantage to tumor-infiltrating Tregs (TI-Tregs) and amplifies their immunosuppressive functions. Furthermore, we will provide a summary of the driving effects of various metabolic regulators on the metabolic reprogramming of Tregs. Finally, we propose that targeting the lipid metabolism of TI-Tregs could be efficacious either alone or in conjunction with immune checkpoint therapy.

Abstract Objective It is currently unclear whether there is a relationship between the ratio of glycated albumin to hemoglobin A1c (GA/HbA1c) and mortality in individuals diagnosed with nonalcoholic fatty liver disease (NAFLD). The primary objective of the study was to investigate the relationship between the GA/HbA1c ratio and all-cause mortality in adults with NAFLD in the U.S. Methods The investigation included a total of 5,295 individuals aged ≥ 18 years who were diagnosed with NAFLD, these individuals were selected from the National Health and Nutrition Examination Survey conducted between 1999 and 2004. To evaluate the outcomes of death, the researchers relied on National Death Index (NDI) records up to December 31, 2019. To better understand the nonlinear relationship between the GA/HbA1c ratio and mortality among individuals with NAFLD, this study employed both subgroup and sensitivity analyses. Furthermore, Cox proportional hazards models and two-part Cox proportional hazards model were utilized. Results The study included a total of 5,295 adult patients with NAFLD in the U.S. During a median follow-up period of 16.9 years, there were 1,471 recorded deaths, including 419 cardiovascular deaths. After accounting for various factors, a higher GA/HbA1c ratio exhibited a positive and nonlinear association with an increased risk of all-cause mortality in patients with NAFLD. Furthermore, the study revealed an L-shaped relationship between the GA/HbA1c ratio and all-cause mortality, with the inflection point occurring at a GA/HbA1c ratio of 2.21. When the GA/HbA1c ratio exceeded 2.21, each 1-unit increase in the ratio was associated with a 33% increase in the adjusted hazard ratio (HR 1.33; 95% CI 1.14, 1.60) for all-cause mortality. Conclusions A nonlinear correlation between the ratio of GA to HbA1c and all-cause mortality was observed in U.S. adults with NAFLD. In addition, an elevated GA/HbA1c ratio was linked to an increased risk of all-cause mortality in these patients.

The satellite low-light imagers can detect changes in nighttime lights caused by ground military conflict. The Kyiv Offensive in Kyiv, Ukraine, which lasted less than 40 days during the Russia – Ukraine conflict, began on 24 February 2022. In addition to the monthly light product, we included a daily light product to analyse the number and average intensity of light pixels in the area around Kyiv over time. The changing trends of two parameters are similar. From February to March, the number of light pixels dropped by 65.2%, and average intensity by 24.5%. To account for daily fluctuations, the relative light ratio was introduced, comparing Kyiv to Moscow, Gomel, and Warsaw. This parameter showed a significant decrease in both the number and intensity of light pixels between days 411 and 423 since January 1, 2021, aligning with the conflict’s start. The relative light ratio revealed a 70.6%, 63.5%, and 57.3% drop in light pixel numbers, and a 9.5%, 24.2%, and 48.4% drop in their average intensity for the respective city pairs. However, unusual fluctuations in the reference cities, such as in Gomel during Christmas and in Moscow at the conflict’s onset, present some problems in using the relative light ratio.

Abstract On 15 January 2022, the largest eruption of the Hunga‐Tonga volcano in recorded history produced a plume registered by multi‐parametric instruments around the world. However, the far‐field hydrogeological responses to Lamb waves from this eruption remain underexplored. We studied the responses of groundwater to the volcanic eruption in the far‐field over 8,700 km, including 274 wells. Results show that the Lamb waves with a speed of 316 m/s affects the groundwater system, leading to similar fluctuations in well water level (WL) and opposite phase fluctuation in borehole strain. Different wells exhibit diverse responses in WL amplitudes, possibly for heterogeneities in local aquifer systems. Gain values of 5 wells that simultaneously measure atmospheric pressure, borehole air pressure, borehole strain and WL are consistent with results obtained through cross‐power spectrum estimation. This work demonstrates a novel response in far‐field groundwater systems induced by Lamb waves and expects application for aquifer parameter estimation.

Abstract The wear particle-induced dissolution of bone around implants is a significant pathological factor in aseptic loosening, and controlling prosthetic aseptic loosening holds crucial social significance. While human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exos, Exos) have been found to effectively promote osteogenesis and angiogenesis, their role in periprosthetic osteolysis remains unexplored. To enhance their in vivo application, we engineered HucMSCs-Exos-encapsulated poly lactic-co-glycolic acid (PLGA) nanoparticles (PLGA-Exos). In our study, we demonstrate that PLGA-Exos stimulate osteogenic differentiation while inhibiting the generation of reactive oxygen species (ROS) and subsequent osteoclast differentiation in vitro. In vivo imaging revealed that PLGA-Exos released exosomes slowly and maintained a therapeutic concentration. Our in vivo experiments demonstrated that PLGA-Exos effectively suppressed osteolysis induced by polyethylene particles. These findings suggest that PLGA-Exos hold potential as a therapeutic approach for the prevention and treatment of periprosthetic osteolysis. Furthermore, they provide novel insights for the clinical management of osteolysis.

Vehicle routing problems (VRPs) are challenging problems. Many variants of the VRP have been proposed. However, few studies on VRP have combined robustness and just-in-time (JIT) requirements with uncertainty. To solve the problem, this paper proposes the just-in-time-based robust multiobjective vehicle routing problem with time windows (JIT-RMOVRPTW) for the assembly workshop. Based on the conflict between uncertain time and JIT requirements, a JIT strategy was proposed. To measure the robustness of the solution, a metric was designed as the objective. Afterwards, a two-stage nondominated sorting ant colony algorithm with deep reinforcement learning (NSACOWDRL) was proposed. In stage I, ACO combines with NSGA-III to obtain the Pareto frontier. Based on the model, a pheromone update strategy and a transfer probability formula were designed. DDQN was introduced as a local search algorithm which trains networks through Pareto solutions to participate in probabilistic selection and nondominated sorting. In stage II, the Pareto frontier was quantified in feasibility by Monte Carlo simulation, and tested by diversity-robust selection based on uniformly distributed weights in the solution space to select robust Pareto solutions that take diversity into account. The effectiveness of NSACOWDRL was demonstrated through comparative experiments with other algorithms on instances. The impact of JIT strategy is analyzed and the effect of networks on the NSACOWDRL is further discussed.

This study aims to start from the macroscale of the megacity, explore a top-down operational technical path from the identification of community regeneration units as the evaluation objects to the BID priority intervention evaluation, and then propose differentiated community regeneration strategies based on the BID model. In the post-epidemic era, it is necessary for global megacities to take new measures in urban regeneration to respond to worldwide changes and challenges. As an innovative tool to promote central city revitalization, the BID model has played an important role in community transformation. In the context of the continuous decentralization of population and industry in China’s megacities, it is urgent to explore the technical path to apply the BID model to local community regeneration. Given the shortcomings of existing studies in the method to identify the scope of BID implementation and evaluate intervention priorities, this study takes Tianjin, a megacity in China, as an example and uses DBSCAN (density-based spatial clustering of applications with noise) and service area analysis to define the community regeneration units with commercial agglomeration characteristics as the objects. Then, the BID priority intervention evaluation system is constructed from the two measurement aspects of the intervention potential and the necessity of community regeneration to classify the BID intervention priorities of community regeneration units. The main conclusions are as follows: 1. When the DBSCAN analysis parameters take the minimum number of elements as 30 and the search distance as 120 m, the result is most suitable for identifying community units with commercial agglomeration of the study area; 2. Population vitality, especially working and residential population density, is the key factor affecting BID intervention potential, while road network density is an important indicator for determining the necessity of community regeneration; 3. Community regeneration units with high BID priority levels need to develop differentiated regeneration strategies combining their BID intervention potential, regeneration necessity characteristics, and location attributes. These conclusions can provide references for the governments of megacities to screen and establish BIDs.

Abstract Aims To examine the effectiveness of Self-Help Plus (SH+) as an intervention for alleviating stress levels and mental health problems among healthcare workers. Methods This was a prospective, two-arm, unblinded, parallel-designed randomised controlled trial. Participants were recruited at all levels of medical facilities within all municipal districts of Guangzhou. Eligible participants were adult healthcare workers experiencing psychological stress (10-item Perceived Stress Scale scores of ≥15) but without serious mental health problems or active suicidal ideation. A self-help psychological intervention developed by the World Health Organization in alleviating psychological stress and preventing the development of mental health problems. The primary outcome was psychological stress, assessed at the 3-month follow-up. Secondary outcomes were depression symptoms, anxiety symptoms, insomnia, positive affect (PA) and self-kindness assessed at the 3-month follow-up. Results Between November 2021 and April 2022, 270 participants were enrolled and randomly assigned to either SH+ (n = 135) or the control group (n = 135). The SH+ group had significantly lower stress at the 3-month follow-up (b = −1.23, 95% CI = −2.36, −0.10, p = 0.033) compared to the control group. The interaction effect indicated that the intervention effect in reducing stress differed over time (b = −0.89, 95% CI = −1.50, −0.27, p = 0.005). Analysis of the secondary outcomes suggested that SH+ led to statistically significant improvements in most of the secondary outcomes, including depression, insomnia, PA and self-kindness. Conclusions This is the first known randomised controlled trial ever conducted to improve stress and mental health problems among healthcare workers experiencing psychological stress in a low-resource setting. SH+ was found to be an effective strategy for alleviating psychological stress and reducing symptoms of common mental problems. SH+ has the potential to be scaled-up as a public health strategy to reduce the burden of mental health problems in healthcare workers exposed to high levels of stress.

Abstract Phototherapy of deep tumors still suffers from many obstacles, such as limited near-infrared (NIR) tissue penetration depth and low accumulation efficiency within the target sites. Herein, stimuli-sensitive tumor-targeted photodynamic nanoparticles (STPNs) with persistent luminescence for the treatment of deep tumors are reported. Purpurin 18 (Pu18), a porphyrin derivative, is utilized as a photosensitizer to produce persistent luminescence in STPNs, while lanthanide-doped upconversion nanoparticles (UCNPs) exhibit bioimaging properties and possess high photostability that can enhance photosensitizer efficacy. STPNs are initially stimulated by NIR irradiation before intravenous administration and accumulate at the tumor site to enter the cells through the HER2 receptor. Due to Pu18 afterglow luminescence properties, STPNs can continuously generate ROS to inhibit NFκB nuclear translocation, leading to tumor cell apoptosis. Moreover, STPNs can be used for diagnostic purposes through MRI and intraoperative NIR navigation. STPNs exceptional antitumor properties combined the advantages of UCNPs and persistent luminescence, representing a promising phototherapeutic strategy for deep tumors.

Abstract Background The influencing factors, especially time to treatment (TTT), for T1b/T2 gallbladder cancer (GBC) patients remain unknown. We aimed to identify the influencing factors on survival and surgical approaches selection for T1b/T2 GBC. Methods We retrospectively screened GBC patients between January 2011 and August 2018 from our hospital. Clinical variables, including patient characteristics, TTT, overall survival (OS), disease‐free survival (DFS), surgery‐related outcomes, and surgical approaches were collected. Results A total of 114 T1b/T2 GBC patients who underwent radical resection were included. Based on the median TTT of 7.5 days, the study cohort was divided into short TTT group (TTT ≤7 days, n = 57) and long TTT group (TTT >7 days, n = 57). Referrals were identified as the primary factor prolonging TTT (p 0.05) between both groups. Decreased referrals (p = 0.005), fewer positive lymph nodes (LNs; p = 0.004), and well tumor differentiation (p = 0.004) were all associated with better OS, while fewer positive LNs (p = 0.049) were associated with better DFS. Subgroup analyses revealed no significant difference in survival between patients undergoing laparoscopic or open approach in different TTT groups (all p > 0.05). And secondary subgroup analyses found no significance in survival and surgery‐related outcomes between different TTT groups of incidental GBC patients (all p > 0.05). Conclusions Positive LNs and tumor differentiation were prognostic factors for T1b/T2 GBC survival. Referrals associating with poor OS would delay TTT, while the prolonged TTT would not impact survival, surgery‐related outcomes, and surgical approaches decisions in T1b/T2 GBC patients.

The implementation of the Grain for Green Project has increased vegetation coverage and provided suitable habitats and food resources for soil fauna, thereby promoting the development of soil faunal communities. Studying seasonal variations in soil fauna communities in different vegetation areas can improve our understanding of the mechanisms that drive soil fauna recovery. We selected five typical artificially restored vegetation habitats, including Populus simonii (POS), Pinus tabulaeformis (PIT), Caragana korshinskii (CAK), Stipa bungeana (STB), and Medicago sativa (MES), and one farmland (Zea mays, FAL) habitat on the Loess Plateau. In this study, soil fauna communities and environmental factors were investigated during spring (May), summer (August), and autumn (November). Among the habitats, the STB habitat had the largest seasonal variation in soil faunal density (from 1173 ind·m−2 in May to 10,743 ind·m−2 in August), and the FAL habitat had the smallest (from 2827 ind·m−2 in August to 5550 ind·m−2 in November). Among the restored vegetation habitats, Acarina (44.89–88.56%) had the highest relative abundance of all taxa. The redundancy analysis (RDA) results showed that among the factors driving seasonal variation in soil animal communities, temperature (47.41%) was the most important, followed by precipitation (22.60%). In addition, the dominant groups, Acarina and Collembola, played an influential role in seasonal variations in soil faunal density. Temperature mainly determined the seasonal variations in soil faunal communities. Seasonal factors should be considered when conducting soil fauna research, as they contribute to biodiversity conservation and regional ecological management in the Loess Plateau.

Abstract This study aims to give a new perspective to the biomarkers in the lung adenocarcinoma (LUAD) brain metastasis, pathways involved and potential therapeutics. We performed a comprehensive single-cell level transcriptomic analysis on one LUAD patient with circulating tumor cells (CTCs), primary tumor tissue and metastatic tumor tissue using scRNA-seq approach to identify metastasis related biomarkers. Further scRNA-seq were performed on 7 patients to validate the cancer metastatic hallmark. with single cells collected from either metastatic or primary LUAD tissues. Pathological and functional studies were also performed to evidence the critical role of RAC1 in the LUAD metastasis. Hallmark gene was verified based on immunohistochemistry staining, cytological experiment, survival information from The Cancer Genome Atlas (TCGA), and staining results from Human Protein Atlas (HPA) databases. PCA analysis revealed that CTCs were in the intermediate place between the metastatic group and primary group. In the unsupervised clustering analysis CTCs were closer to one of the metastatic tumor cells, implying heterogeneity of the metastatic tumor and origin of the CTCs were from metastatic site. Transitional phase related gene analysis identified RAC1 was enriched in metastatic tumor tissue (MTT) preferred gene set functioning as regulated cell death and apoptosis as well as promoted macromolecule organization. Compared with normal tissue, expression levels of RAC1 increased significantly in LUAD tissue based on HPA database. High expression of RAC1 predicts worse prognosis and higher-risk. EMT analysis identified the propensity of mesenchymal state in primary cells while epithelial signals were higher in the metastatic site. Functional clustering and pathway analyses suggested genes in RAC1 highly expressed cells played critical roles in adhesion, ECM and VEGF signaling pathways. Inhibition of RAC1 attenuates the proliferation, invasiveness and migration ability of lung cancer cells. Besides, through MRI T2WI results, we proved that RAC1 can promote brain metastasis in the RAC1-overexpressed H1975 cell burden nude mouse model. RAC1 and its mechanisms might promote drug design against LUAD brain metastasis.

ObjectivesAlthough guidelines recommend extended cholecystectomy for T2 gallbladder cancer (GBC), the optimal hepatectomy strategy remains controversial. The study aims to compare the prognosis of T2 GBC patients who underwent wedge resection (WR) versus segment IVb and V resection (SR) of the liver.MethodsA specific search of online databases was performed from May 2001 to February 2023. The postoperative efficacy outcomes were synthesized and meta-analyses were conducted.ResultsA total of 9 studies involving 2,086 (SR = 627, WR = 1,459) patients were included in the study. The primary outcomes included disease-free survival (DFS) and overall survival (OS). For DFS, the 1-year DFS was statistically higher in patients undergoing SR than WR [risk ratio (RR) = 1.07, 95% confidence interval (CI) = 1.02-1.13, P = 0.007]. The 3-year DFS (P = 0.95), 5-year DFS (P = 0.77), and hazard ratio (HR) of DFS (P = 0.72) were similar between the two groups. However, the 3-year OS was significantly lower in patients who underwent SR than WR [RR = 0.90, 95% CI = 0.82-0.99, P = 0.03]. Moreover, SR had a higher hazard HR of OS [HR = 1.33, 95% CI = 1.01-1.75, P = 0.04]. No significant difference was found in 1-year (P = 0.32) and 5-year (P = 0.9) OS. For secondary outcomes, patients who received SR tended to develop postoperative complications (POC) [RR = 1.90, 95% CI = 1.00-3.60, P = 0.05]. In addition, no significant differences in intrahepatic recurrence (P = 0.12) were observed.ConclusionsIn conclusion, SR can improve the prognosis of T2 GBC patients in DFS. In contrast to WR, the high HR and complications associated with SR cannot be neglected. Therefore, surgeons should evaluate the condition of the patients and take their surgical skills into account when selecting SR.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier, CRD42022362974.

Abstract Background Penfluridol (PF) is an FDA-approved antipsychotic drug that has recently been shown to have anticancer activity. However, the anticancer effects and underlying mechanisms of PF are not well-established in gallbladder cancer (GBC). Methods The anticancer efficacy of PF on GBC was investigated via a series of cell functions experiments, including cell viability, colony formation, apoptosis assays, and so on. The corresponding signaling changes after PF treatment were explored by western blotting. Then, nude mice were utilized to study and test the anticancer activity of PF in vivo. Besides, glucose consumption and lactic production assays were used to detect the glycolysis alteration. Results In this study, we discovered that PF greatly inhibited the proliferation and invasion ability of GBC cells (GBCs). The glucose consumption and lactic generation ability of GBCs were dramatically elevated following PF treatment. Additionally, we discovered that inhibiting glycolysis could improve PF's anticancer efficacy. Further studies established that the activation of the AMPK/PFKFB3 signaling pathway medicated glycolysis after PF treatment. We proved mechanistically that inhibition of AMPK/PFKFB3 singling pathway mediated glycolysis was a potential synergetic strategy to improve the anticancer efficacy of PF on GBC. Conclusions By inhibiting AMPK, the anticancer effects of PF on GBCs were amplified. As a result, our investigations shed new light on the possibility of repurposing PF as an anticancer drug for GBC, and AMPK inhibition in combination with PF may represent a novel therapeutic strategy for GBC. Graphical abstract Video abstract

Background: Limited literature is available on new-onset diabetes mellitus (NODM) after distal pancreatectomy. This study aimed to investigate the correlation between surgery-related factors and the incidence of NODM after distal pancreatectomy. Methods: Patients were divided into the NODM-positive or NODM-negative group according to the diagnosis of NODM. After propensity score matching, the correlation between operation-related factors and the incidence of NODM was analyzed. The diagnostic threshold for predicting NODM was determined using the receiver operating characteristic (ROC) curve and the Youden index. Results: No significant correlation was observed between the NODM incidence after distal pancreatectomy and operative blood loss, spleen preservation, surgical method (open or laparoscopy), postoperative ALB and HB (first day after surgery), and postoperative pathology. However, a significant correlation was found between the NODM incidence and the postoperative pancreatic volume or the resected pancreatic volume ratio. Resected pancreatic volume ratio was identified as a predictive risk factor for NODM. Youden index of the ROC curve was 0.548, with a cut off value of 32.05% for resected pancreatic volume ratio. The sensitivity and specificity of the cut off values were 0.952 and 0.595, respectively. Conclusions: This study demonstrated that the volume ratio of pancreatic resection is a risk factor for the incidence of NODM after distal pancreatectomy. This can be used to predict the incidence of NODM and may have further clinical applications.

Abstract Background Recent studies exploring the roles of invasion-metastasis associated miRNAs in gallbladder cancer (GBC) are limited. In the study, we aimed to identify the invasion-metastasis associated miRNAs in GBC by bioinformatics and experimental validation. Methods MiRNAs of different expression were identified by comparing GBC tumor samples with different survival from Gene Expression Omnibus database. MiRTarBase was used for identifying the potential target genes of miRNAs. Then, we performed Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. And miRNA-gene and protein–protein interaction (PPI) network were constructed for hub genes evaluation. We further explored and compared miR-642a-3p and miR-145-5p expression in both The Cancer Genome Atlas database and our hospital data. Finally, quantitative real-time PCR, wound healing assay, and Transwell assay were conducted to validate the invasion-metastasis associated miRNAs in GBC. Results In GSE104165 database, 25 up-regulated and 97 down-regulated miRNAs were detected with significantly different expression in GBC tumor samples. Then, 477 potential target genes were identified from the 2 most up-regulated miRNAs (miR-4430 and miR-642a-3p) and 268 genes from the 2 most down-regulated miRNAs (miR-451a and miR-145-5p). After GO and KEGG analysis, mTOR and PI3K-Akt signaling pathways were found associated with the potential target genes. Based on PPI network, the top 10 highest degree hub nodes were selected for hub genes. Furthermore, the miRNA-hub gene network showed significant miR-642a-3p up-regulation and miR-145-5p down-regulation in both GBC tissues and cell lines. In the experimental validation, miR-145-5p up-regulation and miR-642a-3p down-regulation were confirmed to suppress GBC invasion and metastasis. Conclusions MiR-642a-3p and miR-145-5p were identified as invasion-metastasis associated miRNAs via bioinformatics and experimental validation, and both up-regulation of miR-642a-3p and down-regulation of miR-145-5p would be served as novel treatment options for GBC in the future.

Abstract DNA molecules are subject to various lesions that can be detrimental to the cells. DNA damage response (DDR) pathways encompass a variety of mechanisms that cells employ in response to DNA damage. While DDR promotes genomic stability in normal cells, it also protects cancer cells from DNA lesions, particularly against exogenous DNA‐damaging agents. Therefore, DDR pathways can be exploited to account for resistance to chemotherapy and radiotherapy and have the potential to be targeted in cancer treatment. Apart from the poly (ADP‐ribose) polymerase (PARP) inhibitors used in BRCA‐mutant cancers, other DDR inhibitors are being developed and tested in clinical trials. Based on the synthetic lethality theory, combination therapies utilizing DDR inhibitors have been explored and are currently undergoing clinical trials, with promising results in cancer treatment. Combination therapies typically employ a DDR inhibitor to sensitize cancer cells to traditional chemotherapeutic agents, radiotherapy, immunotherapy, and even PARP inhibitors. Herein, we focus on recent advances in DDR inhibitor‐based combination therapies other than PARP inhibitors, explore the advantages and disadvantages of the strategies, and discuss the current challenges and future perspectives.

Background: Although recent studies have reported potential benefits of laparoscopic approach in distal pancreatectomy, reports of conversion during minimally invasive distal pancreatectomy (MIDP) were limited. Methods: This was a retrospective study using data from Sir Run Run Shaw Hospital around May 2013 to December 2018. Outcomes of patients who had conversions during MIDP were compared with patients with successful MIDP and with patients undergoing open distal pancreatectomy (ODP). Results: Two-hundred and eighty-three cases were included in this study: 225 (79.5%) had MIDP, 30 (10.6%) had conversions and 28 (9.9%) had outpatient department. The risk factors for conversion included large lesion size (heart rates [HR]: 5.632, 95% confidencevinterval [CI]: 1.036–1.450, P = 0.018) and pancreatic cancer (HR: 6.957, 95% CI: 1.359–8.022, P = 0.009). Compared with MIDP, those who required conversion were associated with longer operations (P = 0.003), higher blood loss (P < 0.001) and more severe of the complications (P < 0.001). However, no statistically significant differences were found between the conversion group and ODP. Conclusions: Large lesion size and pancreatic cancer were reported to be independent risk factors for conversion during MIDP. As for post-operative outcomes, the outcomes of successfully MIDP were better than those for conversion. However, conversion did not lead to worsening outcomes when compared with ODP.

Sonodynamic therapy (SDT) is a promising new anti-tumor therapy that inhibits tumor growth by ultrasound activation of sonosensitizers to produce reactive oxygen species (ROS). However, the problems of hypoxia in the microenvironment within solid tumors and the effectiveness of SDT will decrease due to the little accumulation of sonosensitizers at the tumor site, as well as tumor cell tolerance, have limited the development of SDT. To overcome these problems, a core-shell structured nanoparticle (IR780/PLGA@MnO2 NPs) loaded with IR780 and manganese dioxide (MnO2) was developed as a nanocarrier to transport the sonosensitizer IR780 and the generated oxygen into the tumor tissue. The MnO2 shell layer of IR780/PLGA@MnO2 NPs can prevent the premature release of IR780 in the blood and also it can react with acidic and high H2O2, the generated oxygen can relieve tumor tissue hypoxia, and the generated Mn can enhance magnetic resonance imaging (MRI) signal intensity by acting as a contrast agent for MRI. More importantly, the released IR780 can produce ROS to kill tumor cells under ultrasound excitation. This PH-responsive and H2O2-triggered SDT based on the IR780/PLGA@MnO2NPs is an effective platform to inhibit tumor growth with negligible systemic toxicity. This work develops a multifunctional therapeutic integrated nanoplatform for breast cancer treatment, which is expected to be used in the clinic.

Abstract TP53 is a critical tumor-suppressor gene that is mutated in more than half of all human cancers. Mutations in TP53 not only impair its antitumor activity, but also confer mutant p53 protein oncogenic properties. The p53-targeted therapy approach began with the identification of compounds capable of restoring/reactivating wild-type p53 functions or eliminating mutant p53. Treatments that directly target mutant p53 are extremely structure and drug-species-dependent. Due to the mutation of wild-type p53, multiple survival pathways that are normally maintained by wild-type p53 are disrupted, necessitating the activation of compensatory genes or pathways to promote cancer cell survival. Additionally, because the oncogenic functions of mutant p53 contribute to cancer proliferation and metastasis, targeting the signaling pathways altered by p53 mutation appears to be an attractive strategy. Synthetic lethality implies that while disruption of either gene alone is permissible among two genes with synthetic lethal interactions, complete disruption of both genes results in cell death. Thus, rather than directly targeting p53, exploiting mutant p53 synthetic lethal genes may provide additional therapeutic benefits. Additionally, research progress on the functions of noncoding RNAs has made it clear that disrupting noncoding RNA networks has a favorable antitumor effect, supporting the hypothesis that targeting noncoding RNAs may have potential synthetic lethal effects in cancers with p53 mutations. The purpose of this review is to discuss treatments for cancers with mutant p53 that focus on directly targeting mutant p53, restoring wild-type functions, and exploiting synthetic lethal interactions with mutant p53. Additionally, the possibility of noncoding RNAs acting as synthetic lethal targets for mutant p53 will be discussed.

Emerging and future applications rely heavily upon systems consisting of Internet of Things (IoT), edges, data centers, and humans-in-the-loop. Significantly different from warehouse-scale computers that serve independent concurrent user requests, this new class of computer systems directly interacts with the physical world, considering humans an essential part and performing safety-critical and mission-critical operations; their computations have intertwined dependencies between not only adjacent execution loops but also actions or decisions triggered by IoTs, edge, datacenters, or humans-in-the-loop; the systems must first satisfy the accuracy metric in predicting, interpreting, or taking action before meeting the performance goal under different cases.This article argues we need a paradigm shift to reconstruct the IoTs, edges, data centers, and humans-in-the-loop as a computer rather than a distributed system. We coin a new term, high fusion computers (HFCs), to describe this class of systems. The fusion in the term has two implications: fusing IoTs, edges, data centers, and humans-in-the-loop as a computer, fusing the physical and digital worlds through HFC systems. HFC is a pivotal case of the open-source computer systems initiative. We laid out the challenges, plan, and call for uniting our community’s wisdom and actions to address the HFC challenges. Everything, including the source code, will be publicly available from the project homepage: https://www.computercouncil.org/HFC/.

Glioma is one of the most fatal primary brain tumors, and it is well-known for its difficulty in diagnosis and management. Medical imaging techniques such as magnetic resonance imaging (MRI), positron emission tomography (PET), and spectral imaging can efficiently aid physicians in diagnosing, treating, and evaluating patients with gliomas. With the increasing clinical records and digital images, the application of artificial intelligence (AI) based on medical imaging has reduced the burden on physicians treating gliomas even further. This review will classify AI technologies and procedures used in medical imaging analysis. Additionally, we will discuss the applications of AI in glioma, including tumor segmentation and classification, prediction of genetic markers, and prediction of treatment response and prognosis, using MRI, PET, and spectral imaging. Despite the benefits of AI in clinical applications, several issues such as data management, incomprehension, safety, clinical efficacy evaluation, and ethical or legal considerations, remain to be solved. In the future, doctors and researchers should collaborate to solve these issues, with a particular emphasis on interdisciplinary teamwork.

The development of automatic chest X-ray (CXR) disease classification algorithms is significant for diagnosing thoracic diseases. Owing to the characteristics of lesions in CXR images, including high similarity in appearance of the disease, varied sizes, and different occurrence locations, most existing convolutional neural network-based methods have insufficient feature extraction for thoracic lesions and struggle to adapt to changes in lesion size and location. To address these issues, this study proposes a high-resolution classification network with dynamic convolution and coordinate attention (HRCC-Net). In the method, this study suggests a parallel multi-resolution network in which a high-resolution branch acquires essential detailed features of the lesion and multi-resolution feature swapping and fusion to obtain multiple receptive fields to extract complicated disease features adequately. Furthermore, this study proposes dynamic convolution to enhance the network’s ability to represent multi-scale information to accommodate lesions of diverse scales. In addition, this study introduces a coordinate attention mechanism, which enables automatic focus on pathologically relevant regions and capturing the variations in lesion location. The proposed method is evaluated on ChestX-ray14 and CheXpert datasets. The average AUC (area under ROC curve) values reach 0.845 and 0.913, respectively, indicating this method’s advantages compared with the currently available methods. Meanwhile, with its specificity and sensitivity to measure the performance of medical diagnostic systems, the network can improve diagnostic efficiency while reducing the rate of misdiagnosis. The proposed algorithm has great potential for thoracic disease diagnosis and treatment.

In future data centers, applications will make heavy use of far memory (including disaggregated memory pools and NVM). The access latency of far memory is more widely distributed than that of local memory accesses. This makes the efficiency of traditional out-of-order load/store mechanism in most general-purpose processors decrease in this scenario. Therefore, this work proposes an in-core asynchronous memory access unit to fully utilize the far memory resources.

Abstract The recent realisations of hydrogen doped LnFeAsO (Ln = Nd and Sm) superconducting epitaxial thin films call for further investigation of their structural and electrical transport properties. Here, we report on the microstructure of a NdFeAs(O,H) epitaxial thin film and its temperature, field, and orientation dependencies of the resistivity and the critical current density J c. The superconducting transition temperature T c is comparable to NdFeAs(O,F). Transmission electron microscopy investigation supported that hydrogen is homogenously substituted for oxygen. A high self-field J c of over 10 MA/cm2 was recorded at 5 K, which is likely to be caused by a short London penetration depth. The anisotropic Ginzburg–Landau scaling for the angle dependence of J c yielded temperature-dependent scaling parameters γJ that decreased from 1.6 at 30 K to 1.3 at 5 K. This is opposite to the behaviour of NdFeAs(O,F). Additionally, γJ of NdFeAs(O,H) is smaller than that of NdFeAs(O,F). Our results indicate that heavily electron doping by means of hydrogen substitution for oxygen in LnFeAsO is highly beneficial for achieving high J c with low anisotropy without compromising T c, which is favourable for high-field magnet applications.

Background: The preoperative selection of patients with intermediate-stage hepatocellular carcinoma (HCC) who are likely to have an objective response to first transarterial chemoembolization (TACE) remains challenging. Objective: To develop and validate a clinical-radiomic model (CR model) for preoperatively predicting treatment response to first TACE in patients with intermediate-stage HCC. Methods: A total of 595 patients with intermediate-stage HCC were included in this retrospective study. A tumoral and peritumoral (10 mm) radiomic signature (TPR-signature) was constructed based on 3,404 radiomic features from 4 regions of interest. A predictive CR model based on TPR-signature and clinical factors was developed using multivariate logistic regression. Calibration curves and area under the receiver operating characteristic curves (AUCs) were used to evaluate the model’s performance. Results: The final CR model consisted of 5 independent predictors, including TPR-signature (p < 0.001), AFP (p = 0.004), Barcelona Clinic Liver Cancer System Stage B (BCLC B) subclassification (p = 0.01), tumor location (p = 0.039), and arterial hyperenhancement (p = 0.050). The internal and external validation results demonstrated the high-performance level of this model, with internal and external AUCs of 0.94 and 0.90, respectively. In addition, the predicted objective response via the CR model was associated with improved survival in the external validation cohort (hazard ratio: 2.43; 95% confidence interval: 1.60–3.69; p < 0.001). The predicted treatment response also allowed for significant discrimination between the Kaplan-Meier curves of each BCLC B subclassification. Conclusions: The CR model had an excellent performance in predicting the first TACE response in patients with intermediate-stage HCC and could provide a robust predictive tool to assist with the selection of patients for TACE.

Steel–concrete composite box beams are widely used in bridge engineering, which might bear transverse and longitudinal bending moments simultaneously under vehicle loads. To investigate the fatigue performance of joints between the steel girders and the top reinforced concrete (RC) slabs under transverse bending moments, a reduced scale joint between the weathering steel girder with the corrugated steel web (CSW) and the top RC slab was designed and tested under constant amplitude fatigue loads. Test results show that the joint initially cracked in the weld metal connecting the CSW with the bottom girder flange during the fatigue loading process. The initial crack propagated from the longitudinal fold to the adjacent inclined folds after the specimen was subjected to 7.63 × 105 loading cycles and caused the final fatigue failure. Compared with the calculated fatigue lives in the methods recommended by EC3 and AASHTO, the fatigue performance of the details involved in the joint satisfied the demands of fatigue design. Meanwhile, finite element (FE) models of joints with different parameters were established to determine their effect on the stress ranges at the hot spot regions of the joints. Numerical results show that improving the bending radius or the thickness of the CSW helps to reduce the stress ranges in the hot spot regions, which is beneficial to enhance the fatigue resistance of the investigated fatigue details accordingly.

Abstract Gallbladder cancer (GBC) is a rare but the most malignant type of biliary tract tumor. It is usually diagnosed at an advanced stage and conventional treatments are unsatisfactory. As a proteasome inhibitor, bortezomib (BTZ) exhibits excellent antitumor ability in GBC. However, the long‐term treatment efficacy is limited by its resistance, poor stability, and high toxicity. Herein, BTZ‐encapsulated pH‐responsive copolymeric nanoparticles with estrone (ES‐NP(BTZ; Ce6)) for GBC‐specific targeted therapy is reported. Due to the high estrogen receptor expression in GBC, ES‐NP(BTZ; Ce6) can rapidly enter the cells and accumulate near the nucleus via ES‐mediated endocytosis. Under acidic tumor microenvironment (TME) and 808 nm laser irradiation, BTZ is released and ROS is generated by Ce6 to destroy the “bounce‐back” response pathway proteins, such as DDI2 and p97, which can effectively inhibit proteasomes and increase apoptosis. Compared to the traditional treatment using BTZ monotherapy, ES‐NP(BTZ; Ce6) can significantly impede disease progression at lower BTZ concentrations and improve its resistance. Moreover, ES‐NP(BTZ; Ce6) demonstrates similar antitumor abilities in patient‐derived xenograft animal models and five other types of solid tumor cells, revealing its potential as a broad‐spectrum antitumor formulation.

BackgroundEnhanced recovery care could alleviate surgical stress and accelerate the recovery rates of patients. Previous studies showed the benefits of enhanced recovery after surgery program in liver surgery, but the exact role in laparoscopic hepatectomy is still unclear.AimWe aimed to perform a meta-analysis to evaluate the safety and efficacy of enhanced recovery after a surgery program in laparoscopic hepatectomy.MethodsThe relative studies from a specific search of PUBMED, EMBASE, OVID, and Cochrane database from June 2008 to February 2022 were selected and included in this meta-analysis. The primary outcomes included length of hospital stay, duration to functional recovery, and overall postoperative complication rate. The secondary outcomes included operative time, intraoperative blood loss, cost of hospitalization, readmission rate, Grade I complication rate, and Grade II–V complication rate.ResultsA total of six studies with 643 patients [enhanced recovery care (n = 274) vs. traditional care (n = 369)] were eligible for analysis. These comprised three randomized controlled trials and three retrospective studies. Enhanced recovery care group was associated with decreased hospital stay [standard mean difference (SMD) = −0.56, 95% confidence interval (CI) = −0.83~−0.28, p < 0.0001], shorter duration to functional recovery (SMD = −1.14, 95% CI = −1.92~−0.37, p = 0.004), and lower cost of hospitalization Mean Difference (MD) = −1,539.62, 95% CI = −1992.85~−1086.39, p < 0.00001). Moreover, a lower overall postoperative complication rate was observed in enhanced recovery care group [Risk ratio (RR) = 0.64, 95% CI = 0.51~0.80, p < 0.0001] as well as lower Grade II–V complication rate (RR = 0.55, 95% CI = 0.38~0.80, p = 0.002), while there was no significant difference in intraoperative blood loss (MD = −65.75, 95% CI = −158.47~26.97, p = 0.16), operative time (MD = −5.44, 95% CI = −43.46~32.58, p = 0.78), intraoperative blood transfusion rate [Odds ratio (OR) = 0.71, 95% CI = 0.41~1.22, p = 0.22], and Grade I complication rate (RR = 0.73, 95% CI = 0.53~1.03, p = 0.07).ConclusionEnhanced recovery care in laparoscopic hepatectomy should be recommended, because it is not only safe and effective, but also can accelerate the postoperative recovery and lighten the financial burden of patients.

Theoretical modeling is a popular method for quantitative analysis and performance prediction of computer systems, including cloud systems. Low entropy cloud (i.e., low interference among workloads and low system jitter) is becoming a new trend, where the Labeled Network Stack (LNS) based server is a good case to gain orders of magnitude performance improvement compared to servers based on traditional network stacks. However, it is desirable to figure out 1) where the low tail latency and the low entropy of LNS mainly come from, compared with mTCP, a typical user-space network stack in academia, and Linux network stack, the mainstream network stack in industry, and 2) how much LNS can be further optimized. Therefore, we propose a queueing theory-based analytical method defining a bottleneck stage to simplify the quantitative analysis of tail latency. Facilitated by the analytical method, we establish models characterizing the change of processing speed in different stages for an LNS-based server, an mTCP-based server, and a Linux-based server, with bursty traffic as an example. Under such traffic, each network service stage's processing speed is obtained by non-intrusive basic tests to identify the slowest stage as the bottleneck according to traffic and system characteristics. Our models reveal that the full-datapath prioritized processing and the full-path zero-copy are primary sources of the low tail latency and the low entropy of the LNS-based server, with 0.8%-24.4% error for the [Formula: see text] percentile latency. In addition, the model of the LNS-based server can give the best number of worker threads querying a database, improving 2.1[Formula: see text]-3.5[Formula: see text] in concurrency.

Abstract Synthetic lethality is a lethal phenomenon in which the occurrence of a single genetic event is tolerable for cell survival, whereas the co-occurrence of multiple genetic events results in cell death. The main obstacle for synthetic lethality lies in the tumor biology heterogeneity and complexity, the inadequate understanding of synthetic lethal interactions, drug resistance, and the challenges regarding screening and clinical translation. Recently, DNA damage response inhibitors are being tested in various trials with promising results. This review will describe the current challenges, development, and opportunities for synthetic lethality in cancer therapy. The characterization of potential synthetic lethal interactions and novel technologies to develop a more effective targeted drug for cancer patients will be explored. Furthermore, this review will discuss the clinical development and drug resistance mechanisms of synthetic lethality in cancer therapy. The ultimate goal of this review is to guide clinicians at selecting patients that will receive the maximum benefits of DNA damage response inhibitors for cancer therapy.

Abstract For decades, cancer metastasis has been a heated topic for its high mortality. Previous research has shown that pre-metastatic niche and metastatic niche are the 2 crucial steps in cancer metastasis, assisting cancerous cells’ infiltration, survival, and colonization at target sites. More recent studies have unraveled details about the specific mechanisms related to the modification of pro-invasion environments. Here, we will review literatures on extracellular matrix (ECM) alterations, general cancer metastasis, organ specificity, pre-metastatic niche, metastatic niche, colony formation and impact on the course of metastasis. Respectively, the metastatic mechanisms like effect of hypoxia or inflammation on pre-metastatic niche construction, as well as the interaction between cancer cells and local milieu will be discussed. Based on the evidences of metastatic niches, we revisit and discussed the “Seed and Soil” hypothesis by Paget. This review will seek to provide insight into the mechanism of metastatic organ specificity which pre-metastatic niche and metastatic niche might suggest from an evolutionary aspect.

Abstract Background Pancreatic adenocarcinoma is a highly lethal malignancy. Neoadjuvant chemo(radio)therapy [NAC(R)T] is recommended to use for borderline resectable pancreatic cancer (BRPC) and high-risk resectable pancreatic cancer (RPC), but no high-level evidence exists. Methods We searched PubMed, EMBASE, Web of Science, and Cochrane library to identify trials comparing survival data of NAC(R)T with SF for RPC or BRPC. Overall survival (OS) was synthesized in analysis of all the patients (intention-to-treat [ITT] analysis) and resected patients respectively. Results The meta-analysis included 17 trials with 2286 participants. For BRPC, NAC(R)T improved OS both in ITT analysis (HR, 0.49; 95% CI, 0.37–0.65; P

ObjectivesThe primary laparoscopic approach (PLA) for T1b/T2 gallbladder cancer (GBC) remains contradicted. We aimed to compare the perioperative and long-term outcomes after PLA versus open approach (OA) for T1b/T2 GBC.MethodsPatients with resected T1b/T2 GBC were selected from our hospital between January 2011 and August 2018. Overall survival (OS), disease-free survival (DFS), and several secondary outcomes were used to evaluate safety and effectiveness. Subgroup analyses were performed to identify significant risk factors for OS/DFS in GBC patients undergoing PLA/OA.ResultsA total of 114 patients who underwent OA (n = 61) or PLA (n = 53) were included in the study. The percent of PLA cases was increased over time from 40.0% in 2011 to 70.0% in 2018 (p < 0.05). There was no significant difference in OS [hazard ratio (HR), 1.572; 95% confidence interval (CI), 0.866–2.855; p = 0.13] and DFS (HR, 1.225; 95% CI, 0.677–2.218; p = 0.49). No significance was found for intraoperative drainage placement (p = 0.253), intraoperative blood loss (p = 0.497), operation time (p = 0.105), postoperative hospitalization (p = 0.797), positive LNs (p = 0.494), total harvested LNs (p = 0.067), and recurrence rates (P = 0.334). Subgroup analyses demonstrated no significance of conversion rates after PLA (all p > 0.05). Patients undergoing PLA with good/poor OS would have similar recurrence rates (p = 0.402). Positive LNs (p = 0.032) and tumor differentiation (p = 0.048) were identified as risk factors for OS after PLA, while positive LNs (p = 0.005) was identified for OS after OA. Moreover, age (p = 0.013), gallbladder stone (p = 0.008), tumor size (p = 0.028), and positive LNs (p = 0.044) were potential risk factors for DFS after OA.ConclusionsPLA for T1b/T2 GBC was comparable to OA in terms of perioperative and long-term outcomes. Less positive LNs and well-differentiated tumors were independent predictors for better OS after PLA, and less positive LNs were also identified for better OS after OA. Additionally, younger age, without gallbladder stone, smaller tumor size, and less positive LNs were potential risk factors for better DFS after OA.

BackgroundThe physiological regulatory functions of circRNAs have become a topic of intensive research in recent years. Increasing evidence supports a significant role of circRNAs during cancer initiation and progression, including hepatocellular carcinoma (HCC).Materials and MethodsA bioinformatics analysis from three independent Gene Expression Omnibus (GEO) databases was performed to profile and screen the dysregulated circRNAs in HCC. RT-qPCR was used to examine the expression level of circUBAP2 in HCC and adjacent non-tumor tissues. Then, proliferation assays (CCK8 and colony formation) and migration assays (transwell and wound healing) were performed to examine effect of circUBAP2 in vitro. Immunoprecipitation, RNA pulldown, FISH, and dual-luciferase reporter assay was conducted to explore the circUBAP2-related mechanism for regulating HCC progression. Moreover, a mouse xenograft model and a mouse lung metastasis model confirmed the effect of circUBAP2 in vivo.ResultsIn this study, we found a novel circRNA: circUBAP2, which was identified by bioinformatics analysis. Among 91 HCC patients, circUBAP2 was significantly upregulated in HCC tissues, and negatively correlated with aggressive clinical characteristics and prognosis. Functional assays demonstrated that circUBAP2 promoted cell proliferation, colony formation, migration, and invasion in vitro. Moreover, circUBAP2 enhanced tumor growth and pulmonary metastasis in vivo. Mechanistically, circUBAP2 acts as a competing endogenous RNA (ceRNA) for miR-194-3p, a tumor suppressor in HCC. We confirmed that MMP9 was direct target for miR-194-3p, which was regulated by circUBAP2.ConclusionCircUBAP2 plays a significant role in promoting HCC via the miR-194-3p/MMP9 pathway and could serve as a promising prognostic biomarker and novel therapeutic target for HCC patients.

The relationship between soil fauna and vegetation diversity has been of continuous concern. The effects of the “Grain-for-Green” program on the Loess Plateau in maintaining the abundance and diversity of soil fauna are poorly understood. This study assessed the spatial influence of five common artificial restoration habitats, Populus simonii, Pinus tabulaeformis, Caragana korshinskii, Medicago sativa, and Stipa bungeana, and one farmland habitat on the characteristics of soil fauna communities. Results showed that six soil fauna groups (Araneae, Acarina, Collembola, Isoptera, Coleoptera larvae, and Coleoptera adults) were shared among these habitats, accounting for 37.5% of the total number of groups. Acarina was the dominant group in each habitat. The soil fauna abundance in the P. tabulaeformis habitat was the highest among the habitats, reaching 7656 ind m−2. S. bungeana had the highest diversity, richness, and evenness indices of soil fauna among the habitats. Furthermore, a remarkable correlation among main soil properties (water content, organic carbon, and available potassium), litter properties (vegetation coverage, vegetation density, and litter thickness), and soil fauna were observed. The differences in microenvironment among the six habitats had a strong influence on the composition of soil fauna communities. Compared with other habitats, the S. bungeana habitat is more conducive to the protection of biodiversity. Vegetation restoration increases the diversity of soil fauna by improving their living environment, and soil fauna communities can be used as assessment indicators for “vegetation restoration benefits.” These findings help reveal the developmental tendencies of soil fauna during vegetation restoration in the Loess Plateau, and provide important support for evaluating environmental quality by soil fauna.

BackgroundThe management of gallbladder cancer (GBC) patients with recurrence who need additional therapy or intensive follow-up remains controversial. Therefore, we aim to develop a nomogram to predict survival in GBC patients with recurrence after surgery.MethodsA total of 313 GBC patients with recurrence from our center was identified as a primary cohort, which were randomly divided into a training cohort (N = 209) and an internal validation cohort (N = 104). In addition, 105 patients from other centers were selected as an external validation cohort. Independent prognostic factors, identified by univariate and multivariable analysis, were used to construct a nomogram. The performance of this nomogram was measured using Harrell’s concordance index (C-index) and calibration curves.ResultsOur nomogram was established by four factors, including time-to-recurrence, site of recurrence, CA19-9 at recurrence, and treatment of recurrence. The C-index of this nomogram in the training, internal and external validation cohort was 0.871, 0.812, and 0.754, respectively. The calibration curves showed an optimal agreement between nomogram prediction and actual observation. Notably, this nomogram could accurately stratify patients into different risk subgroups, which allowed more significant distinction of Kaplan-Meier curves than that of using T category. The 3-year post-recurrence survival (PRS) rates in the low-, medium-, and high-risk subgroups from the external validation cohort were 53.3, 26.2, and 4.1%, respectively.ConclusionThis nomogram provides a tool to predict 1- and 3-year PRS rates in GBC patients with recurrence after surgery.

Lung cancer, renowned for its fast progression and metastatic potency, is rising to become a leading cause of death globally. It has been long observed that lung cancer is particularly ept in spawning distant metastasis at its early stages, and it can readily colonize virtually any human organ. In recent years, cancer research has shed light on why lung cancer is endowed with its exceptional ability to metastasize. In this review, we will take a comprehensive look at the current research on lung cancer metastasis, including molecular pathways, anatomical features and genetic traits that make lung cancer intrinsically metastatic, as we go from lung cancer’s general metastatic potential to the particular metastasis mechanisms in multiple organs. We highly concerned about the advanced discovery and development of lung cancer metastasis, indicating the importance of lung cancer specific gene mutations, heterogeneity or biomarker discovery, and discussing potential opportunities and challenges. We will also introduce some current treatments that targets certain metastatic strategies of non-small cell lung cancer (NSCLC). Advances made in these regards could be critical to our current knowledge base of lung cancer metastasis.

Vestibular schwannoma (VS) is a common disease in the region of the cerebellopontine angle in the posterior cranial fossa. Large VS and its surgical management usually lead to severe cranial nerve dysfunction and affect the patient’s quality of life. We aimed to find some possible progression markers of VS. Here, we sought to characterize the cerebrospinal fluid (CSF) proteome of patients with different VS grades and recurrence to identify biomarkers predictive of VS growth or recurrence. CSF was collected intraoperatively prior to removal of untreated VS, including grade I–V and recurrence. Isobaric tags for relative and absolute quantitation–based proteomic analysis of CSF from 43 VS patients and 3 control patients was used to identify candidate proteins. Ninety-three overlapping proteins were found to display differential expression in grade I, II, III, IV, and V VS patients compared with the control group. Nine proteins were chosen for validation with enzyme-linked immunosorbent assay. VS was distinguished from control patients based on the expression patterns of six proteins (ATP-binding cassette subfamily A member 3 [ABCA3], secretogranin-1 [SCG1], Krueppel-like factor 11 [KLF11], voltage-dependent calcium channel subunit alpha-2/delta-1 [CA2D1], brain acid soluble protein 1 [BASP1], and peroxiredoxin-2 [PRDX2]. ABCA3 and KLF11 were positively correlated with the size of early-phase of VS, while BASP1 and PRDX2 showed a negative correlation. ABCA3, CA2D1, and KLF11 were upregulated, while BASP1 and PRDX2 were downregulated in the CSF from VS recurrence. But SCG1 was increased only at early-phase. These data suggest that increased ABCA3 and KLF11 and decreased BASP1 and PRDX2 in CSF are associated with VS growth at the early phase or recurrence.

With the development of the technologies such as computer vision, natural language interaction, process control technology, and sensor technology, the discussion of automatic sorting system of robot hits a hotspot in the robot community. This paper presents an automatic sorting system for industrial robot with the technologies of 3D visual perception, natural language interaction and automatic programming. Therein, a ‘rule-scene’ matching and interaction algorithm is proposed to combine all these modules together. By utilising our algorithm, robot can interact with human beings according to the real-time actual three-dimensional scene information and can guide users to give correct rules through speech when the rule is invalid. After getting the correct rules, robot can sort the object automatically using the automatic programming and execution algorithm designed in this study. In the experimental section, the designed system is applied to a fruit-sorting scene, which proves the effectiveness and practicability of the system.