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Next Point-of-Interest (POI) recommendation has shown great value for both users and providers in location-based services. Existing methods mainly rely on partial information in users' check-in sequences, and are brittle to users with few interactions. Moreover, they ignore the impact of multi-dimensional auxiliary information such as user check-in frequency, POI category on user preferences modeling and the impact of dynamic changes in user preferences over different time periods on recommendation performance. To address the above limitations, we propose a novel method for next POI recommendation by modeling long and short term user preferences with multi-dimensional auxiliary information. In particular, the proposed model includes a static LSTM module to capture users' multi-dimensional long term static preferences and a dynamic meta-learning module to capture users' multi-dimensional dynamic preferences. Furthermore, we incorporate a POI category filter into our model to comprehensively simulate users' preferences. Experimental results on two real-world datasets demonstrate that our model outperforms the state-of-the-art baseline methods in two commonly used evaluation metrics. [ABSTRACT FROM AUTHOR]

Polygonati Rhizoma is a widely used traditional Chinese medicine (TCM) with complex pre-processing steps. Fermentation is a common method for processing TCM to reduce herb toxicity and enhance their properties and/or produce new effects. Here, in this study, using Bacillus subtilis and Saccharomyces cerevisiae, we aimed to evaluate the potential application of solid fermentation in isolating different functional polysaccharides from Polygonatum cyrtonema Hua. With hot water extraction, ethanol precipitation, DEAE anion exchange chromatography and gel filtration, multiple neutral and acidic polysaccharides were obtained, showing different yields, content, compositions and functional groups after fermentation. Combining in vitro experiments and in vivo aging and immunosuppressed mouse models, we further compared the antioxidant and immunomodulating bioactivities of these polysaccharides and found a prominent role of a natural polysaccharide (BNP) from fermented P. cyrtonema via Bacillus subtilis in regulating intestinal antioxidant defense and immune function, which may be a consequence of the ability of BNP to modulate the homeostasis of gut microbiota. Thus, this work provides evidence for the further development and utilization of P. cyrtonema with fermentation, and reveals the potential values of BNP in the treatment of intestinal disorders. [ABSTRACT FROM AUTHOR]

Pancreatic adenocarcinoma (PAAD) is a common, highly malignant, and aggressive gastrointestinal tumor. The conventional treatment of PAAD shows poor results, and patients have poor prognosis. The synthesis and degradation of proteins are essential for the occurrence and development of tumors. Aggrephagy is a type of autophagy that selectively degrades aggregated proteins. It decreases the formation of aggregates by degrading proteins, thus reducing the harm to cells. By breaking down proteins, it decreases the formation of aggregates; thus, minimizing damage to cells. For evaluating the response to immunotherapy and prognosis in PAAD patients, in this study, we developed a reliable signature based on aggrephagy-related genes (ARGs). We obtained 298 AGGLncRNAs. Based on the results of one-way Cox and LASSO analyses, the lncRNA signature was constructed. In the risk model, the prognosis of patients in the low-risk group was noticeably better than that of the patients in the high-risk group. Additionally, the ROC curves and nomograms validated the capacity of the risk model to predict the prognosis of PAAD. The patients in the low-risk and high-risk groups showed considerable variations in functional enrichment and immunological analysis. Regarding drug sensitivity, the low-risk and high-risk groups had different half-maximal inhibitory concentrations (IC50). [ABSTRACT FROM AUTHOR]

Seismic tomography is one of the main tools to explore the interior of the earth. In this study, the quasi-waveform seismic tomographic method is used for the first time to reveal the crustal structures in the capital region of China. 3-D high-resolution VP, VS and the Poisson's ratio models are generated by inverting 29839 direct P- and 29972 direct S-wave traveltimes selected from 3231 local earthquakes. The results reveal strong crustal heterogeneities. The velocity anomalies at shallow depths are well consistent with surface geologic structures. The relatively low-velocity anomaly layer in the middle crust may be the result of multiple phases of tectonic activity. Earthquakes generally occurred on the boundaries of high- and low-velocity and Poisson's ratio anomalies. There are obvious low-velocity anomalies below the hypocenters of the Tangshan earthquake and the historical Sanhe-Pinggu earthquake, implying the existence of fluids. The similar velocity structures around the hypocenters of the two earthquakes indicate that the occurrences of the two earthquakes may be related to the same mechanism. The highresolution velocity models provide important observational constraints on the small-scale heterogeneities and dynamic mechanism of the crust in the capital region of China. [ABSTRACT FROM AUTHOR]

Conventional anti-tumour chemotherapy is facing the challenges of poor specificity, high toxicity and drug resistance. Tumour microenvironment (TME) plays a critical role in tumour development and drug resistance. To address this problem, we constructed a novel anti-tumour nanoparticle platform RBC@BPQDs-DOX/KIR, black phosphorus nanoparticle quantum dots (BPQDs) with one of the chemotherapeutics (doxorubicin, DOX) and an anti-inflammatory traditional Chinese medicine active component (Kirenol, KIR). Red blood cell membrane (RBCm) vesicles were used as the shell to envelop several nanocores. The combination of DOX and KIR may promote therapeutic efficacy, at which the anti-apoptotic effect of the tumour cells was inhibited (by downregulating Bcl-2 and upregulating Bax) and the tumour progression-related inflammatory factors, such as tumour necrosis factor α (TNF-α) and interleukin-6 (IL-6) were downregulated. Furthermore, TME was remodelled and the anti-tumour effect of DOX was magnified. RBCm imparts high biocompatibility and enhanced permeability and retention (EPR) effects to RBC@BPQDs-DOX/KIR, thus enhancing its tumour passively targetability. Overall, the RBCm-camouflaged drug delivery system RBC@BPQDs-DOX/KIR as a promising therapy for targeted chemotherapeutics and anti-inflammatory therapeutics may provide a specific and highly efficient anti-tumour treatment choice. [ABSTRACT FROM AUTHOR]

Nanodrug carrier-based cancer therapy has been actively developed in the past decades. The main challenges faced by nanodrug carriers include poor drug loading capacity, rapid clearance from blood circulation, and low antitumor efficiency. In this work, a new type of antineoplastic agents, F-RGID, were developed using a two-dimensional graphene oxide (GO) with an incorporated photosensitizer (Indocyanine Green, ICG) and a chemotherapeutic drug (Doxorubicin, DOX) as the internally wrapped nanoparticles, and the RBC membrane (RM) inserted with the targeting molecule (folic acid, F) as a shell. The endogenous nature of RM confers F-RGID excellent biocompatibility and the ability to evade from clearance by the reticuloendothelial system (RES). In addition, F-RGID is decorated with folic acid for selective recognition of tumor cells via a lipid-insertion approach. Another salient feature of the antineoplastic platform is the combination of photothermal-chemotherapy with ICG and DOX. In vitro and in vivo experiments revealed that F-RGID could provide a bionic nanoplatform for tumor-targeted photothermal-chemotherapy in clinic. A new type of antineoplastic agents, F-RGID, were developed using a two-dimensional graphene oxide (GO) with an incorporated photosensitizer (Indocyanine Green, ICG) and a chemotherapeutic drug (Doxorubicin, DOX) as the internally wrapped nanoparticles, and the RBC membrane (RM) inserted with the targeting molecule (folic acid, F) as a shell. Image 1 [ABSTRACT FROM AUTHOR]

Objective: To analyze the use of packed red blood cells (PRBCs) for patients with pelvic fracture and evaluate factors associated with PRBC transfusion for patients with pelvic fracture. Methods: This retrospective cohort study collected 551 patients with pelvic fractures from six hospitals between September 1, 2012, and June 31, 2019. The age span of patients varied from 10 to 95 years old, and they were classified into two groups based on high‐energy pelvic fractures (HE‐PFs) or low‐energy pelvic fractures (LE‐PFs). The study's outcome was the use of PRBCs, fresh frozen plasma (FFP), and albumin. Demographic data, characteristics, laboratory tests, clinical treatment details, and clinical outcomes were compared between the two groups. Factors that were statistically associated with perioperative PRBCs in univariate analyses were included to conduct an optimal scale regression to determine the independent factors for perioperative PRBCs. Results: A total of 551 patients were screened from six hospitals, and after inclusion and exclusion, 319 were finally included and finished the follow‐up from admission to discharge, while four patients died during hospitalization. Three hundred and nineteen patients were classified into two groups by their injury mechanisms. A total of 230/319 (72.1%) patients were classified into the HE‐PF group, and 89/319 (27.8%) patients were classified into the LE‐PF group. Patients in the HE‐PF group were transfused with 4.5 (3–8) units of PRBCs, 300 (0–600) ml of FFP, and 0 (0–30) g of albumin, while patients in the LE‐PF group were transfused with 3.5 (2–4.5) units of PRBCs, 0 (0–295) ml of FFP, and 0 (0–0) g of albumin (all P < 0.001). There were higher proportions of male patients and patients under 65 in the HE‐PF group (all P < 0.001). HE‐PF group patients were more severely injured and likely to take external fixation. The optimal scale regression revealed four significant factors associated with perioperative transfused PRBCs, which were patients on admission with hemorrhagic shock (importance = 0.283, P = 0.004), followed by fracture types identified by Tile classification (importance = 0.156, P < 0.001), hemoglobin levels below 70 g/L on admission (importance = 0.283, P = 0.004), followed by fracture types identified by Tile classification (importance = 0.156, P < 0.001), hemoglobin levels below 70 g/L on admission (importance = 0.148, P = 0.039), and methods of pelvic fixation (importance = 0.008, P = 0.026), ranked by the importance. Conclusion: Patients with HE‐PFs had increased transfusions of PRBCs, FFP, and albumin, and hemorrhagic shock on admission, Tile classification, Hb levels, and stabilization methods were found to be associated with perioperative PRBCs. [ABSTRACT FROM AUTHOR]

Impaired angiogenesis and excessive inflammation are major factors contributing to delayed wound healing in diabetic patients. This study presents the development of a novel multifunctional hydrogel, Pltm@CNPs/Gel, which incorporates platelet membrane camouflaged cerium nanoparticles into a gelatin methacryloyl matrix. The Pltm@CNPs/Gel nanocomposite hydrogel was characterized and tested for its effects on platelet activation, coagulation, cell viability, anti-oxidation, and anti-inflammation in vitro. Moreover, we evaluated the wound healing potential of the hydrogel in a diabetic rat model. Our findings demonstrate that the Pltm@CNPs/Gel hydrogel possesses anti-oxidative and anti-inflammatory properties. Furthermore, it accelerates diabetic wound healing by promoting neovascularization, cell proliferation, and collagen fiber organization. This study highlights the potential of the Pltm@CNPs/Gel hydrogel as a therapeutic option for diabetic wound healing and its promising applications as a diabetic wound dressing candidate. [ABSTRACT FROM AUTHOR]

We discuss the performance of the multiple-grid model parametrization in seismic tomographic inversion. Rather than mapping the velocity perturbation Δ c (x) = c (x) − c 0(x) on only one regular/collocated grid as many previous studies did, we obtain individual Δ c (x) models on multiple grids and generate several updated velocity models during one iteration. The average of all the updated velocity models is considered to be the input model of the next iteration. Different grids should partially/fully shift from each other and/or have different grid spacings to form the multiple-grid model parametrization. The efficacy of the multiple-grid model parametrization is demonstrated through the practical example of imaging the P -wave velocity structure along the San Jacinto fault, which is one of the most seismically active faults in California. A series of synthetic recovery examples shows that the multiple-grid model parametrization generally has a better or comparable performance in capturing the heterogeneous subsurface structures than a collocated grid. The root mean square values of the traveltime residuals in the final tomographic models obtained with the multiple-grid model parametrization are smaller than those with collocated grids. Tomographic results reveal strong heterogeneities in the crust along the San Jacinto fault. Significant velocity contrasts are observable across the fault at shallow depths. A low-velocity anomaly dominates the trifurcation area of the San Jacinto fault from the middle crust to the lower crust. Relatively large earthquakes occurred at the boundaries of low-velocity structures but with high-velocity anomalies nearby. All the results suggest that the multiple-grid model parametrization can be a reliable approach in future seismic tomography studies. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in the elderly population. Despite significant advances in studies of the pathobiology on AD, there is still no effective treatment. Here, an erythrocyte membrane‐camouflaged nanodrug delivery system (TR‐ZRA) modified with transferrin receptor aptamers that can be targeted across the blood–brain barrier to ameliorate AD immune environment is established. Based on metal‐organic framework (Zn‐CA), TR‐ZRA is loaded with CD22shRNA plasmid to silence the abnormally high expression molecule CD22 in aging microglia. Most importantly, TR‐ZRA can enhance the ability of microglia to phagocytose Aβ and alleviate complement activation, which can promote neuronal activity and decrease inflammation level in the AD brain. Moreover, TR‐ZRA is also loaded with Aβ aptamers, which allow rapid and low‐cost monitoring of Aβ plaques in vitro. After treatment with TR‐ZRA, learning, and memory abilities are enhanced in AD mice. In conclusion, the biomimetic delivery nanosystem TR‐ZRA in this study provides a promising strategy and novel immune targets for AD therapy. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a syndrome of physiological, pathological and biochemical abnormalities caused by infection. Although the mortality rate is lower than before, many survivors have persistent infection, which means sepsis calls for new treatment. After infection, inflammatory mediators were largely released into the blood, leading to multiple organ dysfunction. Therefore, anti-infection and anti-inflammation are critical issues in sepsis management. Results: Here, we successfully constructed a novel nanometer drug loading system for sepsis management, FZ/MER-AgMOF@Bm. The nanoparticles were modified with LPS-treated bone marrow mesenchymal stem cell (BMSC) membrane, and silver metal organic framework (AgMOF) was used as the nanocore for loading FPS-ZM1 and meropenem which was delivery to the infectious microenvironments (IMEs) to exert dual anti-inflammatory and antibacterial effects. FZ/MER-AgMOF@Bm effectively alleviated excessive inflammatory response and eliminated bacteria. FZ/MER-AgMOF@Bm also played an anti-inflammatory role by promoting the polarization of macrophages to M2. When sepsis induced by cecal ligation and puncture (CLP) challenged mice was treated, FZ/MER-AgMOF@Bm could not only reduce the levels of pro-inflammatory factors and lung injury, but also help to improve hypothermia caused by septic shock and prolong survival time. Conclusions: Together, the nanoparticles played a role in combined anti-inflammatory and antimicrobial properties, alleviating cytokine storm and protecting vital organ functions, could be a potential new strategy for sepsis management. [ABSTRACT FROM AUTHOR]

Seismic exploration of complex geological structure model has been paid much attention as the increasing complexity of geological structure in seismic exploration, and especially, the research on saturated porous medium saturated with fluid has become a hot topic. In our study, we propose a new Padé approximation (PAM) method of solving the elastic wave equation in the porous medium of low-frequency case. This method uses an implicit scheme derived from the rational function of time difference operator for the time discretization, which has the characters of low-dispersion and high-efficiency for time advancing. An explicit iteration for this implicit algorithm is obtained for avoiding solving a large linear system with a block tridiagonal coefficient matrix at each time step. Then, we employ the stereo-modelling method with the eighth-order accuracy for space discretization, which uses linear combination of wave field displacements and their gradients to discretize spatial derivatives and obtains a high-order approximation. Compared with the traditional method, this discretization operator has shorter operator radius and better compactness, which is beneficial for increasing the precision and imaging quality of seismic inversion and seismic migration. Theoretical analysis and numerical experiments verify that the PAM method is an accurate forwarding modelling tool. Waveforms obtained by the PAM method can well match the analytical solutions. Moreover, the seismic wave fields including fast P wave, S wave, and slow P wave for the saturated fluid porous medium can be observed clearly on coarser grids. This is in contrast with the FD method, which suffers from serious numerical dispersion. [ABSTRACT FROM AUTHOR]

In this study new isotropic P- and S-wave velocity models as well as the P-wave azimuthally anisotropic model of the crust and uppermost mantle beneath southern Sumatra are derived from regional earthquake data by using the eikonal equation-based seismic tomography method. All the tomographic results reveal a clear high-velocity (high-V) belt in the uppermost mantle that represents the subducting Indo-Australian slab. In the mantle wedge, relatively low velocity (low-V) anomalies are clearly imaged, which may be related to the ascending fluids and partial melts caused by slab dehydration. The P-wave azimuthally anisotropic model shows complex patterns in the upper crust, which may be due to the effects of the maximum horizontal compressive stress and/or geological structure. Trench-normal fast velocity directions (FVDs) prevail in the lower crust, which may be associated with the plastic flow induced by the oblique plate convergence. Predominant trench-parallel FVDs in the fore-arc and volcanic-arc mantle wedge and trench-normal FVDs in the back-arc mantle wedge are observable, which are possibly related to 2-D slab-driven corner flow and/or 3-D complex mantle flow. The subducting slab generally displays trench-parallel FVDs, suggesting that the slab may keep the original fossil anisotropy. [Display omitted] • Velocity heterogeneity and seismic anisotropy in southern Sumatra are revealed by using the eikonal equation-based seismic tomography method. • Seismic anisotropy reflects the complex mantle flow around the subduction zone beneath southern Sumatra. • Different mechanisms of seismic anisotropy in the upper and lower crust are revealed. [ABSTRACT FROM AUTHOR]

Background: Non-Hodgkin's lymphoma (NHL) possesses great heterogeneity in cytogenetics, immunophenotype and clinical features, and chemotherapy currently serves as the main treatment modality. Although employing monoclonal antibody targeted drugs has significantly improved its overall efficacy, various patients continue to suffer from drug resistance or recurrence. Chinese medicine has long been used in the treatment of malignant tumors. Therefore, we constructed a low pH value sensitivity drug delivery system based on the cancer cell membrane modified mesoporous silica nanoparticles loaded with traditional Chinese medicine, which can reduce systemic toxicity and improve the therapeutic effect for the targeted drug delivery of tumor cells. Results: Accordingly, this study put forward the construction of a nano-platform based on mesoporous silica nanoparticles (MSNs) loaded with the traditional Chinese medicine isoimperatorin (ISOIM), which was camouflaged by the cancer cell membrane (CCM) called CCM@MSNs-ISOIM. The proposed nano-platform has characteristics of immune escape, anti-phagocytosis, high drug loading rate, low pH value sensitivity, good biocompatibility and active targeting of the tumor site, blocking the lymphoma cell cycle and promoting mitochondrial-mediated apoptosis. Conclusions: Furthermore, this study provides a theoretical basis in finding novel clinical treatments for lymphoma. [ABSTRACT FROM AUTHOR]

The trace interval in the common shot and receiver gathers is always inconsistent. The inconsistency affects the final performance of seismic data processing, and the reconstruction methods can enhance the consistency. Unfortunately, most interpolation algorithms are suitable in randomly missing cases, and the difficulty increases sharply in regularly missing cases, especially with big gaps. As deep learning (DL) has a strong self-learning ability in nonlinear characterizations to avoid linear events, sparsity, and low rank assumptions, we introduce DL into missing shots’ reconstruction. The spatial reciprocity of Green’s function is used to provide reasonable training data sets. First, the residual learning networks (ResNets) and the interpolation issue are briefly illustrated. Then, the spatial reciprocity is reviewed and illustrated qualitatively using the common shot and receiver gathers. The similar features in the common shot and receiver gathers guarantee the reasonability to regard the common shot gathers as the training sets and to regard the common receiver gathers as the test sets. The common shot gathers are divided into the training sets to train ResNets and the validation sets to verify the performance of the trained ResNets. Finally, the trained ResNets are used to reconstruct missing shots intelligently in the common receiver gather. Three different data sets are used to prove the validity of the proposed strategy. After reconstruction, the events are more continuous with less serrations and serious frequency wavenumber (FK) aliasing is attenuated effectively. The reconstructed data with a better consistency can improve the accuracy of migration and the final reservoir characterization. [ABSTRACT FROM AUTHOR]

Background: Isatin derivatives have extensive biological activities, such as antitumor. IF203, a novel isatin derivative, has not previously been reported to have antitumor activity. Methods: Acid phosphatase assays (APAs) and Ki-67 immunohistochemistry were used to detect the proliferation of HepG2 cells. Transmission electron microscope (TEM) was applied to detect ultrastructural changes. Flow cytometry (FCM) was used to detect cell cycle, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) of HepG2 cells in vitro. TUNEL, MMP and ROS immunofluorescence assays were applied to assess apoptosis, MMP, and ROS of HepG2 cells in vivo. Western Blotting was applied to assess the levels of apoptosis- and autophagy-related proteins. Results: In this study, in vivo and in vitro experiments showed that IF203 possesses antitumor activity. The results of APAs and Ki-67 immunohistochemistry demonstrated that IF203 could inhibit the proliferation of HepG2 cells. Cell cycle assays, downregulation of Cyclin B1 and Cdc2, and upregulation of P53 suggested that IF203 could lead to G2/M cell cycle arrest. In addition, ultrastructural changes, apoptosis assays, TUNEL immunofluorescence results, upregulated expression of Bax, and downregulated expression of Bcl-2 suggest that IF203 can induce apoptosis in HepG2 cells. After IF203 treatment, intracellular ROS levels increased, MMP decreased, JC-1 green fluorescence was enhanced, and the levels of Caspase-9, Caspase-3 and Cytochrome C expression were upregulated, suggesting that IF203 could induce apoptosis of HepG2 cells through the mitochondrial apoptosis pathway. Moreover, characteristic apoptotic ultrastructural changes were accompanied by the appearance of many autophagy bubbles and upregulation of Atg5, Atg12, ULK1, Beclin-1 and LC3-II proteins, suggesting that IF203 could induce autophagy in HepG2 cells. Conclusion: This study showed that IF203 leads to the death of HepG2 cells through cell cycle arrest, apoptotic induction, and autophagy promotion. [ABSTRACT FROM AUTHOR]

An eikonal equation‐based tomography method is used to invert the high‐quality regional and teleseismic traveltime data recorded by 26 broadband seismic stations in northern Sumatra, following which we obtain the P and S wave velocity structures of the crust and mantle down to a depth of 800 km. The results of both P and S wave tomography clearly show that the Indo‐Australian oceanic plate continuously penetrates downward beneath northern Sumatra and the maximum penetration depth varies approximately from 400 km at the northern tip of Sumatra to about 800 km around the southern boundary of our study area. Significant slab folding or bending reported in the literature as the main feature of the subducted slab beneath northern Sumatra is not found in our results. Instead, our tomographic images demonstrate only a less curved slab that mimics the shape of the Sunda Trench and volcanic arc and generally extends over depths from 120 to 450 km. P wave tomography shows broad and pronounced low‐velocity anomalies beneath the island of Sumatra in the lower crust and uppermost mantle. Our model also reveals a slab tear approximately at 120‐km depth, which has been documented in previous studies and considered to be related to the eruption of the Toba supervolcano. Key Points: New seismic data recorded by 26 broadband seismic stations are used to image the crust and mantle structure beneath northern SumatraResults show that slab morphology beneath northern Sumatra is characterized by slab curving, tearing, deflection and dip angle variationsA slab tear is revealed at a depth of about 120 km, which is one of the main factors for the strong low anomalies in the uppermost mantle [ABSTRACT FROM AUTHOR]

Lymphoma is a well-known malignant tumor in the human body. Although many anticancer drugs have been developed to improve the survival rate of patients, about 40% of patients continue to be recurrent or refractory, a key issue needing remedy. Therefore, it is necessary to identify alternative treatments to reduce the disease's mortality. To this effect, a new type of anti-lymphoma nanocomplex FA@RBCm-AgNPs was prepared using AgNPs as the core of nanoparticles along with the targeting molecule folic acid inserted erythrocyte membrane as the shell. The biomimetic properties of red blood cell membrane (RBCm) endow F-RAN with good biocompatibility as well as the ability to evade clearance of the reticuloendothelial system. In addition, F-RAN was modified with folic acid to actively and selectively identify tumor cells. In vivo and in vitro experiments demonstrate that F-RAN can inhibit lymphoma cells and induce apoptosis of stem cells while promoting apoptosis of lymphoma with no obvious side effects. Hence, F-RAN may serve as a new treatment for lymphoma. • A new type of anti-lymphoma nanocomposite were fabricated FA, RBCm and AgNPs (FA@RBCm-AgNPs, F-RAN). • F-RAN has remarkable stability, and the RBCm coating on F-RAN effectively camouflages the nanomaterials and reduces phagocytosis. • F-RAN could inhibit lymphoma cells and induce apoptosis of stem cells in-vitro and in-vivo. [ABSTRACT FROM AUTHOR]