Search

Metastatic castration-resistant prostate cancer (CRPC) is a currently incurable disease associated with high mortality. Novel therapeutic approaches for CRPC are urgently needed to improve prognosis. In this study, we developed cross-linked, PSMA-targeted lipoic acid nanoparticles (cPLANPs), which can interact with transmembrane glycoprotein to accumulate inside prostate cancer cells, where they upregulate caspase-3, downregulate anti-apoptotic B-cell lymphoma-2 (BCL-2), and thereby induce apoptosis. The trans-cyclooctene (TCO) decoration on cPLANPs acts as a bioorthogonal handle allowing pretargeted single-photon emission computed tomography and radiotherapy, which revealed significantly enhanced tumor accumulation and minimal off-target toxicity in our experiments. The developed strategy showed a strong synergistic anti-cancer effect in vivo, with a tumor inhibition rate of up to 95.6% after 14 days of treatment. Our results suggest the potential of combining bioorthogonal pretargeted radiotherapy with suitable PSMA-targeted nanoparticles for the treatment of metastatic CRPC. [ABSTRACT FROM AUTHOR]

Here we describe a cost-effective and simplified cell sorting method using tetrazine bioorthogonal chemistry. We successfully isolated SKOV3 cells from complex mixtures, demonstrating efficacy in separating mouse lymphocytes expressing interferon and HeLa cells expressing virally transduced green fluorescent protein post-infection. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) is a promising therapy for refractory cancer based on the cytotoxic reaction of 10B (n, α) 7Li. Although two BNCT agents are clinically available, they are quickly metabolized and show modest enrichment in tumor sites, partially limiting BNCT widespread application. Consequently, novel agents that perform active targeting and show good biocompatibility have to be developed. Herein, boronophenylalanine‐containing polydopamine (B‐PDA) nanoparticles are easily fabricated by encapsulating boronophenylalanine (BPA) in polydopamine via nitrogen‐boronate coordination. In this study, B‐PDA achieves increased tumor accumulation and prolonged retention effects in the tumor site and superior antitumor activity post neutron irradiation in the orthotopic xenograft glioma model. In brief, this study offers a novel strategy for BPA delivery and may broaden the perspective on nanomedicine design for BNCT. [ABSTRACT FROM AUTHOR]

Synergistic photothermal immunotherapy has emerged as a favorable therapeutic approach to fight cancer. However, design of an effective photothermal immunotherapy system to suppress tumor growth and simultaneously inhibit tumor metastases continues to be a challenge. Here a dual toll‐like receptor agonists delivery system CPG@Au NRs/m‐R848 for combined photothermal immunotherapy of melanoma is developed. CPG@Au NRs/m‐R848 displays strong antitumor effects by promoting maturation of dendritic cells (DCs) and reprogramming of M2 macrophages into M1 phenotype. Moreover, immunogenic cell death (ICD) induced by photothermal ablation of Au NRs could synergistically produce in situ vaccination effect with CPG ODN and R848, generating systemic and lasting antitumor immunity. It is further proved that CPG@Au NRs/m‐R848 treatment inhibits tumor growth in bilateral B16F10 tumors model by eliciting CD8+ T cell response. Overall, this work suggests that this strategy hold great potential in tumor immunotherapy by regulating tumor‐associated macrophage polarization, triggering DCs maturation and inducing ICD. [ABSTRACT FROM AUTHOR]

Oceanic lithosphere is generated at divergent plate boundaries and disappears at convergent plate boundaries. Seafloor spreading and plate subduction together constitute the physical coupling and mass conservation relationships to the movement of lithospheres on Earth. Subduction zones are a key site for the transfer of both matter and energy at converging plate boundaries, and their study has been the hot spot and frontier of Earth system science since the development of plate tectonics theory. As far as the dynamic regime and geothermal gradient of convergent plate margins are concerned, they have different properties in different stages of the subduction zone evolution. In general, the early low-angle subduction leads to compressional tectonism dominated by low geothermal gradients at the plate interface, and the late high-angle subduction results in extensional tectonism dominated by high geothermal gradients at the plate interface and its hanging wall. Active rifts are produced along suture zones through not only slab rollback or slab breakoff in the terminal stage of oceanic subduction but also foundering and thinning of the lithosphere in the post-subduction stage. Due to the differences and changes in the geometric and thermobaric structures of convergent plate margins, a series of changes in the type of metamorphism and magmatism can occur in active and fossil subduction zones. Dehydration and melting of the subducting oceanic crust are prominent at subarc depths, giving rise to fluids that dissolve different concentrations of fluid-mobile incompatible elements. The subduction zone fluids at subarc depths would chemically react with the overlying mantle wedge peridotite, generating metasomatites as the mantle sources of mafic magmas in oceanic and continental arcs. However, these metasomatites did not partially melt immediately upon the fluid metasomatism to trigger arc magmatism, and they did not melt until they were heated by asthenospheric convection due to rollback of the subducting slab. Therefore, recognition of the changes in the dynamic regime and geothermal gradient of subduction zones in different stages of plate convergence not only provides insights into geodynamic mechanisms of the tectonic evolution from subduction zones to orogenic belts, but also places constraints on the formation and evolution of different types of metamorphic and magmatic rocks within the advanced framework of plate tectonics. [ABSTRACT FROM AUTHOR]

Macrophages have been reported to exert a crucial role in hepatocellular carcinoma (HCC). This study aimed to explore the macrophage-related genes and establish a macrophage-related signature (MRS) model to predict the overall survival (OS) of patients with HCC based on these genes' expression. We screened the macrophage-related gene module by weighted gene coexpression network analysis (WGCNA), the least absolute shrinkage and selection operator (LASSO) Cox regression analysis was utilized for further selection, and the selected genes were entered into stepwise regression to develop the MRS model, which was further validated in the Gene Expression Omnibus (GEO) and International Cancer Genome Consortium (ICGC) datasets. We analyzed the biological phenotypes associated with macrophages in terms of functional enrichment, tumor immune signature, and tumor mutational signature. The patient's response to immunotherapy was inferred by the tumor immune dysfunction and exclusion (TIDE) score, the immunophenotype score (IPS), and the IMvigor210 dataset. A novel MRS model was established based on the LASSO regression coefficients of the genes PON1 , IL15RA , NEIL3 , HILPDA , PFN2 , HAVCR1 , ANXA10 , CDCA8 , EPO , S100A9 , TTK , KLRB1 , SPP1 , STC2 , CYP26B1 , GPC1 , G6PD , and CBX2. In either dataset, MRS was identified as an independent risk factor for OS in HCC patients. Additionally, our research indicated that a high-risk score in the MRS model was significantly correlated with tumor staging, pathological grade, tumor–node–metastasis (TNM) stage, and survival. Several genes of the human leukocyte antigen (HLA) family and immune checkpoints were highly expressed in the high-risk group. In addition, the frequency of tumor mutations was also higher in the high-risk group. According to our analyses, a higher risk score in the MRS model may predict a better response to immunotherapy. [ABSTRACT FROM AUTHOR]

Objective. To study the effect of preoperative rehabilitation training on the rehabilitation of patients after total knee arthroplasty. Methods. A total of 120 patients diagnosed with knee osteoarthritis and undergoing total knee arthroplasty were selected and divided into experimental group and control group according to a random number table, with 60 cases in each group. The control group only carried out routine clinical nursing before the operation, and the experimental group used the formulated preoperative rehabilitation training method based on the control group for training. By comparing the visual analogue score (VAS), keen society score (KSS), postoperative time to get out of bed for the first time, patient satisfaction, and other related indicators between the two groups of patients, the recovery of keen joint function of patients after surgery was evaluated. Results. The visual analogue scale (VAS) of the experimental group was significantly lower than that of the experimental group at three days after operation. The keen society score (KSS) of the experimental group was significantly better than that of the control group at three days after surgery and one month after surgery. The time to get out of bed for the first time after operation in the experimental group (44.93 ± 13.63) was significantly less than that in the control group (78.33 ± 13.52). The patient satisfaction of the experimental group was significantly higher than that of the control group (88.30 ± 3.61). The above statistical results were all p < 0.05 of the two groups, and the differences were statistically significant. Conclusion. Preoperative rehabilitation training can significantly reduce the pain of patients after knee replacement, improve the functional state of knee joints, shorten the time to get out of bed for the first time after surgery, and win the best recovery opportunity, which can better improve patient satisfaction in hospitalization and improve medical care services level. [ABSTRACT FROM AUTHOR]

Highly fluorogenic tetrazine bioorthogonal probes emitting at near‐infrared wavelengths are in strong demand for biomedical imaging applications. Herein, we have developed a strategy for forming a palette of novel Huaxi‐Fluor probes in situ, whose fluorescence increases hundreds of times upon forming the bioorthogonal reaction product, pyridazine. The resulting probes show large Stokes shifts and high quantum yields. Manipulating the conjugate length and pull–push strength in the fluorophore skeleton allows the emission wavelength to be fine‐tuned from 556 to 728 nm. The highly photo‐stable and biocompatible probes are suitable for visualizing organelles in live cells without a washing step and for imaging of tumors in live small animals to depths of 500 μm by two‐photon excitation. [ABSTRACT FROM AUTHOR]

Highly fluorogenic tetrazine bioorthogonal probes emitting at near‐infrared wavelengths are in strong demand for biomedical imaging applications. Herein, we have developed a strategy for forming a palette of novel Huaxi‐Fluor probes in situ, whose fluorescence increases hundreds of times upon forming the bioorthogonal reaction product, pyridazine. The resulting probes show large Stokes shifts and high quantum yields. Manipulating the conjugate length and pull–push strength in the fluorophore skeleton allows the emission wavelength to be fine‐tuned from 556 to 728 nm. The highly photo‐stable and biocompatible probes are suitable for visualizing organelles in live cells without a washing step and for imaging of tumors in live small animals to depths of 500 μm by two‐photon excitation. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA) is highly expressed on the surface of most prostate tumor cells and is considered a promising target for prostate cancer imaging and treatment. It is possible to establish a PSMA-targeted theranostic probe to achieve early diagnosis and treatment of this cancer type. In this contribution, we prepared a multifunctional melanin-like polydopamine (PDA) nanocarrier decorated with a small-molecule PSMA inhibitor, N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-l-lysine (DCL). PDA-DCL was then functionalized with perfluoropentane (PFP) and loaded with the photosensitizer chlorin e6 (Ce6) to give Ce6@PDA-DCL-PFP, which was successfully used for ultrasound-guided combined photodynamic/photothermal therapy (PDT/PTT) of prostate cancer. Compared with the corresponding non-targeted probe (Ce6@PDA-PEG-PFP), our targeted probe induced higher cellular uptake in vitro (6.5-fold) and more tumor accumulation in vivo (4.6-fold), suggesting strong active targeting capacity. Meanwhile, this new nanoplatform significantly enhanced the ultrasound contrast signal at the tumor site in vivo, thus facilitating precise and real-time detection of the tumor. In addition, this Ce6-loaded PDA nanoplatform produced a synergistic effect of PDT and PTT under 660 nm and 808 nm irradiation, inducing a more efficient killing effect compared with the individual therapy in vitro and in vivo. Furthermore, the tumor in the targeted group was more effectively suppressed than that in the non-targeted group under the same irradiation condition. This multifunctional probe may hold great potential for precise and early theranostics of prostate cancer. [ABSTRACT FROM AUTHOR]

In order to better understand the role of post-collisional mafic magmatism at convergent plate boundaries in revealing the earth's evolution, this paper has systematically summarized the research history of post-collisional mafic magmatism, different types of collision and their influence on the nature of orogenic mantle, the concept and implication of post-collisional magmatism, and the relationship between post-collisional mafic magmatism and orogenic mantle evolution and mineralization. Post-collisional mafic igneous rocks are not only the direct records for studying the nature and evolution of orogenic mantle, but also the important carriers for regional mineralization. However, the type and quantity of the crustal materials involved in modifying the overlying lithospheric mantle during collisional orogeny, the process and mechanism of such modification, and the major control factors and mechanism of mafic magmatism-related mineralization during the post-collisional period are the main contents and direction of future researches in this field. Therefore, the study of post-collisional mafic magmatism is of significant implications for developing the theory of plate tectonics. [ABSTRACT FROM AUTHOR]

BACKGROUND: The use of cold therapy to promote rehabilitation after total knee arthroplasty has a certain theoretical basis, but whether cold therapy can reduce bleeding, reduce pain, and promote early recovery of activity is still controversial. OBJECTIVE: To evaluate the effectiveness of cold therapy in total knee arthroplasty in reducing postoperative bleeding, reducing pain, and promoting recovery of motion range using meta-analysis. METHODS: Medline, EMBASE, Cochrane, China Biomedical Literature Database, CNKI, Wanfang and other databases were searched to find randomized controlled trials of cold therapy and other rehabilitation therapies after total knee arthroplasty. Data ware extracted. Statistical analysis was performed using Revman 5.3. Effect values were combined. RESULTS AND CONCLUSION: (1) A total of 10 randomized controlled trials were included, including 1 070 patients. The experimental group received cold therapy after total knee arthroplasty, and the control group received other rehabilitation therapies. (2) Meta-analysis showed that compared with other rehabilitation therapies, cold therapy after replacement alleviated postoperative pain [MD=-0. 75, 95%C/ (-1.29, -0.21 ), P=0.006], reduced hemoglobin drop [MlP-12.11, 95%C/ (-17.66, -6.56), P < 0.000 1]. However, cold therapy could not reduce the amount of opioids usage [MD=0.01, 95%C/ (-0.15, -0.16), P=0.92], or improve joint motion range [MD=6.58, 95%C/ (-0.54, 13. 70), P=0.07]. (3) The results show that the application of cold therapy after total knee arthroplasty can effectively relieve pain and reduce the drop of postoperative hemoglobin, but has no significant effect on reducing the application of opioid analgesics or improving motion range. [ABSTRACT FROM AUTHOR]

The North China Craton (NCC) has been thinned from >200 km to <100 km in its eastern part. The ancient subcontinental lithospheric mantle (SCLM) has been replaced by the juvenile SCLM in the Meoszoic. During this period, the NCC was destructed as indicated by extensive magmatism in the Early Cretaceous. While there is a consensus on the thinning and destruction of cratonic lithosphere in North China, it has been hotly debated about the mechanism of cartonic destruction. This study attempts to provide a resolution to current debates in the view of Mesozoic mafic magmatism in North China. We made a compilation of geochemical data available for Mesozoic mafic igneous rocks in the NCC. The results indicate that these mafic igneous rocks can be categorized into two series, manifesting a dramatic change in the nature of mantle sources at ~121 Ma. Mafic igneous rocks emplaced at this age start to show both oceanic island basalts (OIB)-like trace element distribution patterns and depleted to weakly enriched Sr-Nd isotope compositions. In contrast, mafic igneous rocks emplaced before and after this age exhibit both island arc basalts (IAB)-like trace element distribution patterns and enriched Sr-Nd isotope compositions. This difference indicates a geochemical mutation in the SCLM of North China at ~121 Ma. Although mafic magmatism also took place in the Late Triassic, it was related to exhumation of the deeply subducted South China continental crust because the subduction of Paleo-Pacific slab was not operated at that time. Paleo-Pacific slab started to subduct beneath the eastern margin of Eruasian continent since the Jurrasic. The subducting slab and its overlying SCLM wedge were coupled in the Jurassic, and slab dehydration resulted in hydration and weakening of the cratonic mantle. The mantle sources of ancient IAB-like mafic igneous rocks are a kind of ultramafic metasomatites that were generated by reaction of the cratonic mantle wedge peridotite not only with aqueous solutions derived from dehydration of the subducting Paleo-Pacific oceanic crust in the Jurassic but also with hydrous melts derived from partial melting of the subducting South China continental crust in the Triassic. On the other hand, the mantle sources of juvenile OIB-like mafic igneous rocks are also a kind of ultramafic metasomatites that were generated by reaction of the asthenospheric mantle underneath the North China lithosphere with hydrous felsic melts derived from partial melting of the subducting Paleo-Pacific oceanic crust. The subducting Paleo-Pacific slab became rollback at ~144 Ma. Afterwards the SCLM base was heated by laterally filled asthenospheric mantle, leading to thinning of the hydrated and weakened cratonic mantle. There was extensive bimodal magmatism at 130 to 120 Ma, marking intensive destruction of the cratonic lithosphere. Not only the ultramafic metasomatites in the lower part of the cratonic mantle wedge underwent partial melting to produce mafic igneous rocks showing negative εNd(t) values, depletion in Nb and Ta but enrichment in Pb, but also the lower continent crust overlying the cratonic mantle wedge was heated for extensive felsic magmatism. At the same time, the rollback slab surface was heated by the laterally filled asthenospheric mantle, resulting in partial melting of the previously dehydrated rocks beyond rutile stability on the slab surface. This produce still hydrous felsic melts, which metasomatized the overlying asthenospheric mantle peridotite to generate the ultramafic metasomatites that show positive εNd(t) values, no depletion or even enrichment in Nb and Ta but depletion in Pb. Partial melting of such metasomatites started at ~121 Ma, giving rise to the mafic igneous rocks with juvenile OIB-like geochemical signatures. In this context, the age of ~121 Ma may terminate replacement of the ancient SCLM by the juvenile SCLM in North China. Paleo-Pacific slab was not subducted to the mantle transition zone in the Mesozoic as revealed by modern seismic tomography, and it was subducted at a low angle since the Jurassic, like the subduction of Nazca Plate beneath American continent. This flat subduction would not only chemically metasomatize the cratonic mantle but also physically erode the cratonic mantle. Therefore, the interaction between Paleo-Pacific slab and the cratonic mantle is the first-order geodynamic mechanism for the thinning and destruction of cratonic lithosphere in North China. [ABSTRACT FROM AUTHOR]

Plate subduction is an important mechanism for exchanging the mass and energy between the mantle and the crust, and the igneous rocks in subduction zones are the important carriers for studying the recycling of crustal materials and the crust-mantle interaction. This study presents a review of geochronology and geochemistry for postcollisional mafic igneous rocks from the Hong'an-Dabie-Sulu orogens and the southeastern edge of the North China Block. The available results indicate two types of the crust-mantle interaction in the continental subduction zone, which are represented by two types of mafic igneous rocks with distinct geochemical compositions. The first type of rocks exhibit arc-like trace element distribution patterns (i.e. enrichment of LILE, LREE and Pb, but depletion of HFSE) and enriched radiogenic Sr-Nd isotope compositions, whereas the second type of rocks show OIB-like trace element distribution patterns (i.e. enrichment of LILE and LREE, but no depletion of HFSE) and depleted radiogenic Sr-Nd isotope compositions. Both of them have variable zircon O isotope compositions, which are different from those of the normal mantle zircon, and contain residual crustal zircons. These geochemical features indicate that the two types of mafic igneous rocks were originated from the different natures of mantle sources. The mantle source for the second type of rocks would be generated by reaction of the overlying juvenile lithospheric mantle with felsic melts originated from previously subducted oceanic crust, whereas the mantle source for the first type of rocks would be generated by reaction of the overlying ancient lithospheric mantle of the North China Block with felsic melts from subsequently subducted continental crust of the South China Block. Therefore, there exist two types of the crust-mantle interaction in the continental subduction zone, and the postcollisional mafic igneous rocks provide petrological and geochemical records of the slab-mantle interactions in continental collision orogens. [ABSTRACT FROM AUTHOR]

Crustal subduction and continental collision is the core of plate tectonics theory. Understanding the formation and evolution of continental collision orogens is a key to develop the theory of plate tectonics. Different types of subduction zones have been categorized based on the nature of subducted crust. Two types of collisional orogens, i.e. arc-continent and continent-continent collisional orogens, have been recognized based on the nature of collisional blocks and the composition of derivative rocks. Arc-continent collisional orogens contain both ancient and juvenile crustal rocks, and reworking of those rocks at the post-collisional stage generates magmatic rocks with different geochemical compositions. If an orogen is built by collision between two relatively old continental blocks, post-collisional magmatic rocks are only derived from reworking of the old crustal rocks. Collisional orogens undergo reactivation and reworking at action of lithosphere extension, with inheritance not only in the tectonic regime but also in the geochemical compositions of reworked products (i.e., magmatic rocks). In order to unravel basic principles for the evolution of continental tectonics at the post-collisional stages, it is necessary to investigate the reworking of orogenic belts in the post-collisional regime, to recognize physicochemical differences in deep continental collision zones, and to understand petrogenetic links between the nature of subducted crust and post-collisional magmatic rocks. Afterwards we are in a position to build the systematics of continental tectonics and thus to develop the plate tectonics theory. [ABSTRACT FROM AUTHOR]