Cancer-associated fibroblasts promote enzalutamide resistance and PD-L1 expression in prostate cancer through CCL5-CCR5 paracrine axis.

Cancer-associated fibroblasts (CAFs) have been shown to play a key role in prostate cancer treatment resistance, but the role of CAFs in the initial course of enzalutamide therapy for prostate cancer remains unclear. Our research revealed that CAFs secrete CCL5, which promotes the upregulation of androgen receptor (AR) expression in prostate cancer cells, leading to resistance to enzalutamide therapy. Furthermore, CCL5 also enhances the expression of tumor programmed death-ligand 1 (PD-L1), resulting in immune escape. Mechanistically, CCL5 binds to the receptor CCR5 on prostate cancer cells and activates the AKT signaling pathway, leading to the upregulation of AR and PD-L1. The CCR5 antagonist maraviroc to inhibit the CAFs mediated CCL5 signaling pathway can effectively reduce the expression of AR and PD-L1, and improve the efficacy of enzalutamide. This study highlights a promising therapeutic approach targeting the CCL5-CCR5 signaling pathway to improve the effectiveness of enzalutamide.

Delivery of gefitinib loaded nanoparticles for effectively inhibiting prostate cancer progression.

Androgen deprivation therapy is administered to suppress the growth of prostate cancer (PCa). However, some cells continue to proliferate independent of hormones, leading to the development of castration-resistant prostate cancer (CRPC). Overexpression of the epidermal growth factor receptor (EGFR) has been observed in CRPC and is associated with an unfavorable prognosis. Gefitinib (GEF) is an EGFR inhibitor used to treat patients with CRPC. Nevertheless, some clinical studies have reported that gefitinib does not result in prostate-specific antigen (PSA) or objectively measurable CRPC reactions. This lack of response may be attributed to the limited solubility in water, high side effects, low tumor aggregation, and insufficient tumor-specific reactions of GEF. In order to tackle these obstacles, we present a practical and efficient approach to administer GEF, encompassing the utilization of biocompatible nanostructures as a vehicle for drug delivery to augment its bioaccessibility and curative potency. Despite their small particle size, poly(D,L-lactide-co-glycolide) acid nanoparticles (PLGA NPs) exhibit a high drug-loading capacity, low toxicity, biocompatibility, biodegradability, and minimal immunogenicity. The drug delivery efficiency can be improved by employing GEF@PLGA NPs, which could also enhance drug cytotoxicity and impede the advancement of prostate cancer. Moreover, through experiments in vivo, it has been verified that GEF@PLGA NPs exhibit selective accumulation in the tumor and effectively restrain tumor growth. Therefore, the GEF@PLGA NPs hold great promise for the treatment of PCa.

Direct observation of topological magnon polarons in a multiferroic material.

Magnon polarons are novel elementary excitations possessing hybrid magnonic and phononic signatures, and are responsible for many exotic spintronic and magnonic phenomena. Despite long-term sustained experimental efforts in chasing for magnon polarons, direct spectroscopic evidence of their existence is hardly observed. Here, we report the direct observation of magnon polarons using neutron spectroscopy on a multiferroic Fe2Mo3O8 possessing strong magnon-phonon coupling. Specifically, below the magnetic ordering temperature, a gap opens at the nominal intersection of the original magnon and phonon bands, leading to two separated magnon-polaron bands. Each of the bands undergoes mixing, interconverting and reversing between its magnonic and phononic components. We attribute the formation of magnon polarons to the strong magnon-phonon coupling induced by Dzyaloshinskii-Moriya interaction. Intriguingly, we find that the band-inverted magnon polarons are topologically nontrivial. These results uncover exotic elementary excitations arising from the magnon-phonon coupling, and offer a new route to topological states by considering hybridizations between different types of fundamental excitations.

Superconductivity and density-wave fluctuations in an extended triangular Hubbard model: an application to SnSe2.

We employ the fluctuation-exchange approximation to study the relation of superconducting pairing symmetries and density-wave fluctuations based on the extended triangular Hubbard model upon electron doping and interactions, with an possible application to the layered metal dichalcogenide SnSe2. For the case where the interactions between electrons contain only the on-site Hubbard term, the superconducting pairings are mainly mediated by spin fluctuations, and the spin-singlet pairing with thed-wave symmetry robustly dominates in the low and moderate doping levels, and ad-wave to extendeds-wave transition is observed as the electron doping reachesn = 1. When the near-neighbor site Coulomb interactions are also included, the charge fluctuations are enhanced, and the spin-triplet pairings with thep-wave andf-wave symmetries can be realized in the high and low doping levels, respectively.

Active water management brings possibility restoration to degraded lakes in dryland regions: a case study of Lop Nur, China.

Protecting and restoring the degraded arid lakes are globally urgent issues. We document a potential recovery of the dried salt-lake, Lop Nur called "the Sea of Death" which is located at the terminus of the largest inland basin in China, the Tarim River Basin. The changes and relationship of surface water with climate parameters and groundwater in the basin over the last 30 years are analyzed, by using satellite remote sensing and land data assimilation products. We find that with increased surface water in the basin, the groundwater level in Lop Nur began to show an obvious positive response in 2015; and the rate of decline of the groundwater level is slowing down. We argue that after a balance is achieved between regional groundwater recharge and evapotranspiration, the Lop Nur ecosystem will gradually recover. This study shows an encouraging case for the protection and restoration of degraded lakes in dryland regions around the world.

Propagule size and seed development duration: high photosynthate allocation and growth allometry.

MAIN CONCLUSION: The divergences in propagule mass have been more consistently associated with divergences in seed development duration or fruit pedicel cross-sectional area than with divergences in any other biotic factors. Allometry and Corner's rule became an important theme in evolutionary biology of plant trait structure and function. Being one of the most widely noticed plant traits, propagule (seed and fruit) mass variation mechanism across species is still controversial. Here we examined correlations between propagule mass and seed development duration as well as other traits, such as cross-sectional area of fruit pedicel, life form, fruit type and leaf area over four census years, to test an important life history strategy for propagule biomass allocation. We investigated 491 species, belonging to 91 families and 320 genera, representing 95% of native wild species in Beijing Botanical Garden. The scaling correlations between propagule mass and seed development duration and the other traits were determined using phylogenetic generalized linear models. Results show a significant positive relationship among propagule mass and seed development duration, leaf area and pedicel cross-sectional area for all species and for each life form (except vines) regardless of phylogeny. The variation in seed mass has been more consistently associated with variation in seed development duration than with divergences in any other variable, such as growth form, fruit type, pedicel cross-sectional area and leaf area, whereas variation in fruit weight was found to be more associated with variation in pedicel cross-sectional area than the other. Biotic factors, such as seed development duration, pedicel cross-sectional area, growth form and leaf area, mediate propagule size variation, of which seed development duration or pedicel cross-sectional area is the most important. The results further supported a hypothesis that large-seeded species evolved owing to high photosynthate availability and growth allometry in plant body. A mechanistic mathematical model involving seed development duration was provided to expound propagule mass variations across species.

Quantum interference and domain-wall-like magnetic correlations in hexagonal graphene nanodisks.

Quantum interference and traditional domain wall effects are two common ways to manipulate the magnetism in magnetic materials. Here, we report both effects emerge in the designed graphene nanodisks simultaneously, and thus providing an accessible way to engineer the magnetism in graphene nanostructures. By adjusting the length of the armchair edges at the corners of hexagonal disk, connecting the adjacent zigzag edges, we show that the quantum interference among the zigzag edges remains robust and consequently determines the magnetic structure in the small-size systems, in analogy with the nanoribbons. More importantly, a domain-wall-like magnetic mechanism is numerically identified to dominate the larger-size disks. In particular, a magnetic state with fully spin-polarized edges achieved in a wide parameter region promises the future applications for spintronics.

Immune Signatures Combined With BRCA1-Associated Protein 1 Mutations Predict Prognosis and Immunotherapy Efficacy in Clear Cell Renal Cell Carcinoma.

Immunotherapy is gradually emerging in the field of tumor treatment. However, because of the complexity of the tumor microenvironment (TME), some patients cannot benefit from immunotherapy. Therefore, we comprehensively analyzed the TME and gene mutations of ccRCC to identify a comprehensive index that could more accurately guide the immunotherapy of patients with ccRCC. We divided ccRCC patients into two groups based on immune infiltration activity. Next, we investigated the differentially expressed genes (DEGs) and constructed a prognostic immune score using univariate Cox regression analysis, unsupervised cluster analysis, and principal component analysis (PCA) and validated its predictive power in both internal and total sets. Subsequently, the gene mutations in the groups were investigated, and patients suitable for immunotherapy were selected in combination with the immune score. The prognosis of the immune score-low group was significantly worse than that of the immune score-high group. The patients with BRCA1-associated protein 1 (BAP1) mutation had a poor prognosis. Thus, this study indicated that establishing an immune score model combined with BAP1 mutation can better predict the prognosis of patients, screen suitable ccRCC patients for immunotherapy, and select more appropriate drug combinations.

UBAC2 promotes bladder cancer proliferation through BCRC-3/miRNA-182-5p/p27 axis.

Emerging evidences have demonstrated that ubiquitin-associated domain-containing protein 2 (UBAC2) is closely related to the occurrence and development of malignant tumors. However, the functions and underlying molecular mechanisms of UBAC2 in bladder cancer (BC) development have not been defined. In this study, we found that both UBAC2 mRNA and protein levels were upregulated in BC tissues and cell lines, and knockdown of UBAC2 inhibited BC cells proliferation both in vitro and in vivo. Meanwhile, Kaplan-Meier survival plots of 406 BC cases from TCGA database showed that higher expression of UBAC2 in BC patients was associated with lower survival rate. Mechanistic studies revealed that knockdown of UBAC2 increased the expression of p27 by posttranscriptional regulation. Our previous study indicated that circular RNA BCRC-3 (BCRC-3) promoted the expression of p27 through interacting with miR-182-5p, and reversed miR-182-5p-induced inhibition of p27 3'UTR activity. In the present study, we found that UBAC2 could bind to BCRC-3, and subsequently affected the interaction of BCRC-3 with miR-182-5p to inhibit the expression of p27. Furthermore, knockdown of BCRC-3 partly reversed the upregulation of p27 expression induced by knockdown of UBAC2. Our findings highlight a novel mechanism of UBAC2 in regulating p27 through affecting the function of BCRC-3, and provide a research basis for the diagnostic and therapeutic application of BC.

Erratum: Realization of a Metallic State in 1T-TaS_{2} with Persisting Long-Range Order of a Charge Density Wave [Phys. Rev. Lett. 123, 206405 (2019)].

This corrects the article DOI: 10.1103/PhysRevLett.123.206405.

Discovery of twin orbital-order phases in ferromagnetic semiconducting VI3 monolayer.

Spontaneous orbital symmetry breaking in crystals gives rise to abundant novel and interesting physical properties, which sometimes are concealed by the absence of geometrical distortions. We show that a recently discovered 3d2 system, namely the layered VI3 ferromagnetic semiconductor, is a strongly correlated and orbital ordering system. Our analysis reveals that in a VI3-like system, there could be two types of orbital splitting, which are stabilized respectively by strong electronic correlation and inter-atomic exchange interactions. Consequently, on the basis of first-principles calculations, two competing low-energy phases of VI3 monolayer (denoted as twin orbital-order phases) are discovered, in which the metal-insulator transition is driven by strong electronic correlation, and the orbital symmetry breaking is robust against geometrical distortions. In addition, similar phenomena are also observed in other VI3-like systems. These findings shed light on the unusual electronic behavior of a strongly correlated 2D system and will be interesting for nanoscale multi-functional spintronic applications.

Realization of a Metallic State in 1T-TaS_{2} with Persisting Long-Range Order of a Charge Density Wave.

Metallization of 1T-TaS_{2} is generally initiated at the domain boundary of a charge density wave (CDW), at the expense of its long-range order. However, we demonstrate in this study that the metallization of 1T-TaS_{2} can be also realized without breaking the long-range CDW order upon surface alkali doping. By using scanning tunneling microscopy, we find the long-range CDW order is always persisting, and the metallization is instead associated with additional in-gap excitations. Interestingly, the in-gap excitation is near the top of the lower Hubbard band, in contrast to a conventional electron-doped Mott insulator where it is beneath the upper Hubbard band. In combination with the numerical calculations, we suggest that the appearance of the in-gap excitations near the lower Hubbard band is mainly due to the effectively reduced on-site Coulomb energy by the adsorbed alkali ions.

Clinical analysis of 547 patients with neuroendocrine tumors in a Chinese population: A single-center study.

BACKGROUND: Neuroendocrine tumors (NETs) are rare, which has resulted in a lack of published data on their epidemiology and clinical features. We therefore aimed to investigate the epidemiology, clinical features, treatments, and prognosis of patients with NETs. METHODS: The clinicopathologic characteristics of 547 patients who were pathologically diagnosed with NETs were retrospectively analyzed, including age, sex, primary and metastatic sites, symptoms, pathology, treatment, and prognosis. RESULTS: The 547 patients had a wide age range (9-87 years), with a male to female ratio of 1:1.1. The primary tumor sites included 413 in the digestive system, 74 in the lung, 15 in the mediastinum, 8 in unknown sites, and 37 in other sites. Of the 413 patients with digestive system NETs, the pancreas, rectum, and stomach were the most common primary sites. Blood metastases were found in 84 patients at initial diagnosis, and the liver, bone, and lung were the most frequent sites of metastasis. Lymph node metastases were found in 82 patients at initial diagnosis. Surgery and chemotherapy were the most widely applied treatments. Statistical analysis showed that age <50 years, female sex, lower-grade tumor, no distant metastasis, intestinal NET and surgery indicated a favorable prognosis. CONCLUSIONS: A difference between China and other countries is that small intestinal NETs are quite common in other countries but are rare in China. In China, the most common primary sites are the pancreas, rectum, and stomach. Furthermore, no unified treatments exist, though prognoses could be improved by using methods such as surgery, targeted therapies, and somatostatin analogs. CLINICAL TRIAL REGISTRATION: This study was not a clinical trial.

Quasiparticle Properties under Interactions in Weyl and Nodal Line Semimetals.

The quasiparticle spectra of interacting Weyl and nodal-line semimetals on a cubic lattice are studied using the cluster perturbation theory. By tracking the spectral functions under interaction, we find that the Weyl points will move to and meet at a specific point in one Weyl semimetal model, while in the other Weyl semimetal model they are immobile. In the nodal-line semimetals, we find that the nodal line shrinks to a point and then disappears under interaction in one-nodal-line system. When we add another nodal line to this system, we find that the two nodal lines both shrink to specific points, but the disappearing processes of the two nodal lines are not synchronized. We argue that the nontrivial evolution of Weyl points and nodal lines under interaction is due to the presence of symmetry breaking order, e.g., a ferromagnetic moment, in the framework of mean field theory, whereas the stability of Weyl points under interaction is protected by symmetry. Among all these models, the spectral gap is finally opened when the interaction is strong enough.

Increasing water availability and facilitation weaken biodiversity-biomass relationships in shrublands.

Positive biodiversity-ecosystem-functioning (BEF) relationships are commonly found in experimental and observational studies, but how they vary in different environmental contexts and under the influence of coexisting life forms is still controversial. Investigating these variations is important for making predictions regarding the dynamics of plant communities and carbon pools under global change. We conducted this study across 433 shrubland sites in northern China. We fitted structural equation models (SEMs) to analyze the variation in the species-richness-biomass relationships of shrubs and herbs along a wetness gradient and general liner models (GLMs) to analyze how shrub or herb biomass affected the species-richness-biomass relationship of the other life form. We found that the positive species-richness-biomass relationships for both shrubs and herbs became weaker or even negative with higher water availability, likely indicating stronger interspecific competition within life forms under more benign conditions. After accounting for variation in environmental contexts using residual regression, we found that the benign effect of greater facilitation by a larger shrub biomass reduced the positive species-richness-biomass relationships of herbs, causing them to become nonsignificant. Different levels of herb biomass, however, did not change the species-richness-biomass relationship of shrubs, possibly because greater herb biomass did not alter the stress level for shrubs. We conclude that biodiversity in the studied plant communities is particularly important for plant biomass production under arid conditions and that it might be possible to use shrubs as nurse plants to facilitate understory herb establishment in ecological restoration.

[Clinical characterization of testicular yolk sac tumor in children and adults].

OBJECTIVE: To compare the clinical characteristics of simple testicular yolk sac tumor (YST) in children with those in adults so as to improve the diagnosis and treatment of the malignance. METHODS: This study included 75 cases of simple testicular YST pathologically confirmed between May 2008 and July 2018, which were divided into groups A (aged <18 years, n = 64) and B (aged ≥18 years, n = 11). We analyzed the clinical data on all the cases and compared the clinical manifestations, laboratory results, pathological findings, clinical stages, treatment methods and prognostic outcomes between the two groups of patients. RESULTS: The patients of group A ranged in age from 6 months to 5 years (ï¼»1.38 ± 0.89ï¼½ yr), with the tumor diameter of 0.9－6.0 (2.48 ± 1.12) cm, while those of group B from 25 to 49 years (median 34 years), with the tumor diameter of 3.5－6.3 (5.16 ± 1.32) cm, most presenting with a painless scrotal mass, 4 (6.2%) in group A and 5 (45.5%) in group B with testis pain. There were statistically significant differences between the two groups in the tumor diameter and initial manifestations (P < 0.05). All the patients were treated by radical high-level spermatectomy and orchiectomy and, in addition, 1 in group A and 3 in group B by retroperitoneal lymph node dissection (RPLND), 24 in the former and 5 in the latter group followed by chemotherapy. Elevated levels of serum alpha-fetoprotein (AFP) were observed in all the cases. Sixty-five of the patients were followed up for 10－78 (52.00 ± 23.78) months, during which 2 cases of simple metastasis, 3 cases of simple relapse, 3 cases of relapse with metastasis and 5 cases of death were found in group A, and 5 cases of simple metastasis, 1 case of simple relapse, 1 case of relapse with metastasis and 4 cases of death in group B. CONCLUSIONS: There are significant differences in the clinical manifestation, biological behavior, treatment and prognosis of testicular YST between children and adults. In children, most of the testicular YST cases are at clinical stage I and preferably treated by radical high-level spermatectomy and orchiectomy with favorable prognosis. In adults, however, the tumor is highly malignant, with high incidences of recurrence and metastasis and poor prognosis, for the treatment of which the first choice is radical high-level spermatectomy and orchiectomy combined with RPLND and chemotherapy.

circGprc5a Promoted Bladder Oncogenesis and Metastasis through Gprc5a-Targeting Peptide.

Bladder cancer is a serious cancer in the world, especially in advanced countries. Bladder cancer stem cells (CSCs) drive bladder tumorigenesis and metastasis. Circular RNAs (circRNAs) are involved in many biological processes, but their roles in bladder oncogenesis and bladder CSCs are unclear. Here, we identified that circGprc5a is upregulated in bladder tumors and CSCs. circGpr5a knockdown impairs the self-renewal and metastasis of bladder CSCs, and its overexpression exerts an opposite role. circGpr5a has peptide-coding potential and functions through a peptide-dependent manner. circGprc5a-peptide binds to Gprc5a, a surface protein highly expressed in bladder CSCs. Gprc5a knockout inhibits the bladder CSC self-renewal and metastasis. circGprc5a-peptide-Gprc5a can be utilized to target bladder cancer and bladder CSCs.

Dynamics of a single hole in the Heisenberg-Kitaev model: a self-consistent Born approximation study.

The magnetic properties of 4d and 5d transition-metal insulating compounds with the honeycomb structure are believed to be described by the Heisenberg-Kitaev model, which contains both the isotropic Heisenberg interaction J and anisotropic Kitaev interaction K. In this paper, we study the single-hole propagation of the t-J-K model in various magnetically ordered phases by the self-consistent Born approximation. We find that there are low-energy coherent quasiparticle (QP) excitations in all of these phases which appear firstly around the K point in the first Brillouin zone (BZ), but the bandwidths of these QPs are very small due to the hole-magnon coupling. Interestingly, in the zigzag phase relevant to recent experiments, though the QP weights are largely suppressed in the physical spectra in the first BZ, we find that they recover in the extended BZs. Moreover, our results reveal that the low-energy QP spectra are reduced with the increase of K.

Discovery of coexisting Dirac and triply degenerate magnons in a three-dimensional antiferromagnet.

Topological magnons are emergent quantum spin excitations featured by magnon bands crossing linearly at the points dubbed nodes, analogous to fermions in topological electronic systems. Experimental realisation of topological magnons in three dimensions has not been reported so far. Here, by measuring spin excitations (magnons) of a three-dimensional antiferromagnet Cu3TeO6 with inelastic neutron scattering, we provide direct spectroscopic evidence for the coexistence of symmetry-protected Dirac and triply degenerate nodes, the latter involving three-component magnons beyond the Dirac-Weyl framework. Our theoretical calculations show that the observed topological magnon band structure can be well described by the linear-spin-wave theory based on a Hamiltonian dominated by the nearest-neighbour exchange interaction J1. As such, we showcase Cu3TeO6 as an example system where Dirac and triply degenerate magnonic nodal excitations coexist, demonstrate an exotic topological state of matter, and provide a fresh ground to explore the topological properties in quantum materials.