Search

Abstract Background Urolithiasis has emerged as a global affliction, recognized as one of the most excruciating medical issues. The elemental composition of stones provides crucial information, aiding in understanding the causes, mechanisms, and individual variations in stone formation. By understanding the interactions between elements in various types of stones and exploring the key role of elements in stone formation, insights are provided for the prevention and treatment of urinary stone disease. Methods This study collected urinary stone samples from 80 patients in Beijing. The chemical compositions of urinary stones were identified using an infrared spectrometer. The concentrations of major and trace elements in the urinary stones were determined using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS), respectively. The data were processed using correlation analysis and Principal Component Analysis (PCA) methods. Results Urinary stones are categorized into five types: the calcium oxalate (CO) stone, carbonate apatite (CA) stone, uric acid (UA) stone, mixed CO and CA stone, and mixed CO and UA stone. Ca is the predominant element, with an average content ranging from 2.64 to 27.68% across the five stone groups. Based on geochemical analysis, the high-content elements follow this order: Ca > Mg > Na > K > Zn > Sr. Correlation analysis and PCA suggested significant variations in the interactions between elements for different types of urinary stones. Trace elements with charges and ionic structures similar to Ca may substitute for Ca during the process of stone formation, such as Sr and Pb affecting the Ca in most stone types except mixed stone types. Moreover, the Mg, Zn and Ba can substitute for Ca in the mixed stone types, showing element behavior dependents on the stone types. Conclusion This study primarily reveals distinct elemental features associated with five types of urinary stones. Additionally, the analysis of these elements indicates that substitutions of trace elements with charges and ion structures similar to Ca (such as Sr and Pb) impact most stone types. This suggests a dependence of stone composition on elemental behavior. The findings of this study will enhance our ability to address the challenges posed by urinary stones to global health and improve the precision of interventions for individuals with different stone compositions.

A special microenvironment called the “pre-metastatic niche” is thought to help primary tumor cells migrate to new tissues and invade them, in part because the normal barrier function of the vascular endothelium is compromised. While the primary tumor itself can promote the creation of such niches by secreting pro-metastatic factors, the underlying molecular mechanisms are still poorly understood. Here, we show that the injection of primary tumor-secreted pro-metastatic factors from B16F10 melanoma or 4T1 breast cancer cells into healthy mice can induce the destruction of the vascular endothelial glycocalyx, which is a polysaccharide coating on the vascular endothelial lumen that normally inhibits tumor cell passage into and out of the circulation. However, when human umbilical vein endothelial cultures were treated in vitro with these secreted pro-metastatic factors, no significant destruction of the glycocalyx was observed, implying that this destruction requires a complex in vivo microenvironment. The tissue section analysis revealed that secreted pro-metastatic factors could clearly upregulate macrophage-related molecules such as CD11b and tumor necrosis factor-α (TNF-α) in the heart, liver, spleen, lung, and kidney, which is associated with the upregulation and activation of heparanase. In addition, macrophage depletion significantly attenuated the degradation of the vascular endothelial glycocalyx induced by secreted pro-metastatic factors. This indicates that the secreted pro-metastatic factors that destroy the vascular endothelial glycocalyx rely primarily on macrophages. Our findings suggest that the formation of pre-metastatic niches involves degradation of the vascular endothelial glycocalyx, which may hence be a useful target for developing therapies to inhibit cancer metastasis.

Background: Preserving parathyroid glands in situ is crucial to avoid surgical hypoparathyroidism, but it is also one of the greatest challenges during thyroid surgery. Magnified endoscopic imaging has been proposed as a way to improve parathyroid preservation. Methods: 2,603 consecutive patients who underwent thyroid surgery at the First People’s Hospital of Zunyi from January 2018 to July 2022 were screened. 1,355 patients were eligible, including 965 endoscopic and 390 open cases. Parathyroid hormone (PTH) loss levels and severe parathyroid injury rates were compared between endoscopic and open cases. Meanwhile, factors that contribute to parathyroid injuries were assessed, including surgical extent, tumor size, carbon nanoparticle guidance, and surgical proficiency. Results: PTH loss levels were similar between endoscopic and open cases (P = 0.440). The incidence of severe parathyroid injuries was also comparable (7.8% for endoscopic vs. 6.9% for open, P = 0.592). The endoscopic group had higher rates of autologous parathyroid transplantation (39.5% vs. 24.4%, P = 0.000), while accidental parathyroidectomy rates were similar (11.4% vs. 10.8%, P = 0.739). Among patients who received the same extent of thyroid surgeries, no significant difference was found in PTH loss levels and severe parathyroid injury rates, except for a higher risk of severe parathyroid injuries in endoscopic bilateral thyroidectomy (18.52% vs. 11.52%, P = 0.033). Conclusions: Despite the magnified endoscopic imaging facilitating the identification of parathyroid tissues, endoscopic approaches are not superior to open ones for the in-situ preservation of parathyroid glands. For a bilateral thyroidectomy, open approaches are safer for parathyroid preservation.

Abstract Changing thermal regime is one of the key mechanisms driving seismogenic behaviors at cold megathrusts, but it is difficult to interpret warm subduction zones such as Vanuatu for the temperatures are higher than that accommodates shallow brittle failures. We construct a 3-D thermomechanical model to clarify the thermal structure that controls tectonic seismicity in Vanuatu and predict a warm circumstance associated with abundant seismicity. Results reveal a heterogeneous slab ranging from 300 °C to over 900 °C from the Moho to subvolcanic depth. The subduction seismicity corresponds well to the plate interface where dynamic thermal dehydration is focused. The transformation from hydrated basalts to eclogites along the slab facilitates the occurrence of intense earthquakes and slips. Multistage mineralogical metamorphism affects the dynamic stability of megathrusts and favors the generation of active interplate large events. Therefore, slab thermal dehydration plays a greater role than slab temperature condition in influencing the subduction earthquake distribution in warm subduction systems.

Abstract Background Folates (Vitamin B9) are critical for normal neurodevelopment and function, with transport mediated by three major pathways: folate receptor alpha (FRα), proton-coupled folate transporter (PCFT), and reduced folate carrier (RFC). Cerebral folate uptake primarily occurs at the blood-cerebrospinal fluid barrier (BCSFB) through concerted actions of FRα and PCFT, with impaired folate transport resulting in the neurological disorder cerebral folate deficiency (CFD). Increasing evidence suggests that disorders associated with CFD also present with neuroinflammation, oxidative stress, and mitochondrial dysfunction, however the role of brain folate deficiency in inducing these abnormalities is not well-understood. Our laboratory has identified the upregulation of RFC by nuclear respiratory factor 1 (NRF-1) at the blood–brain barrier (BBB) once indirectly activated by the natural compound pyrroloquinoline quinone (PQQ). PQQ is also of interest due to its anti-inflammatory, antioxidant, and mitochondrial biogenesis effects. In this study, we examined the effects of folate deficiency and PQQ treatment on inflammatory and oxidative stress responses, and changes in mitochondrial function. Methods Primary cultures of mouse mixed glial cells exposed to folate-deficient (FD) conditions and treated with PQQ were analyzed for changes in gene expression of the folate transporters, inflammatory markers, oxidative stress markers, and mitochondrial DNA (mtDNA) content through qPCR analysis. Changes in cellular reactive oxygen species (ROS) levels were analyzed in vitro through a DCFDA assay. Wildtype (C57BL6/N) mice exposed to FD (0 mg/kg folate), or control (2 mg/kg folate) diets underwent a 10-day (20 mg/kg/day) PQQ treatment regimen and brain tissues were collected and analyzed. Results Folate deficiency resulted in increased expression of inflammatory and oxidative stress markers in vitro and in vivo, with increased cellular ROS levels observed in mixed glial cells as well as a reduction of mitochondrial DNA (mtDNA) content observed in FD mixed glial cells. PQQ treatment was able to reverse these changes, while increasing RFC expression through activation of the PGC-1α/NRF-1 signaling pathway. Conclusion These results demonstrate the effects of brain folate deficiency, which may contribute to the neurological deficits commonly seen in disorders of CFD. PQQ may represent a novel treatment strategy for disorders associated with CFD, as it can increase folate uptake, while in parallel reversing many abnormalities that arise with brain folate deficiency.

Abstract Background Recent studies have reported associations between body mass index (BMI) and various autoimmune disorders. However, it is still uncertain whether there exists a direct cause-and-effect relationship between BMI and autoimmune thyroiditis (AIT). The aim of our study is to investigate the causal association between BMI and AIT. Methods We conducted a two-sample summary data Mendelian randomization (MR) analysis using genome-wide association studies (GWAS) summary statistics data related to BMI as exposure, and GWAS summary statistic data sets for AIT as the outcome. Robustly associated single-nucleotide polymorphisms (SNPs) for BMI were selected as instrumental variables (IVs). We used the inverse variance weighted (IVW) method as the primary method and performed other MR methods such as MR-Egger regression, weighted median, simple mode, and weighted mode analyses for further validation. The slope of MR-Egger regression was used to correct for pleiotropy and provide estimates of causality. The p-value for the intercept in MR-Egger was utilized to detect any directional pleiotropic effects. Heterogeneity and sensitivity analyses were performed to assess the robustness of our findings. Results Seventy-eight SNPs were selected from GWAS on BMI as the IVs. Our MR analysis using the IVW method showed a potential causal association between BMI and AIT (OR = 3.071, 95% CI 1.324–7.118). Findings from other MR methods are non-significant, although the direction of effect is consistent. There was no evidence that the result was affected by genetic pleiotropy (MR-Egger regression intercept = 0.01, SE = 0.00025, p = 0.719). Heterogeneity and sensitivity analyses revealed no significant heterogeneity among SNPs, and no single SNP drove the observed associations. Conclusion Our findings suggest a potential causal association between BMI and AIT, which may provide a basis for further investigation into the relationship between BMI and AIT. Further studies are required as only the IVW method shows significant results, and the case sample size is small.

Targeting the dynamic image-motion problem of aerial cameras in the process of swing imaging, the image-motion compensation technology of aerial cameras based on the multi-dimensional motion of the secondary mirror was adopted. The secondary mirror was used as the image-motion compensation element, and the comprehensive image-motion compensation of the aerial camera was realized through the multi-dimensional motion of the secondary mirror. However, in the process of compensating for the image motion, the secondary mirror would be eccentric and inclined, which would cause the secondary mirror to be off-axis and affect the image quality. Therefore, a misalignment optical system model was established to study the relationship between the deviation vector and the misalignment of the secondary mirror, and the influence of the secondary mirror’s motion on the distribution of the aberration was analyzed. In order to verify the image-motion compensation ability of the multi-dimensional motion of the secondary mirror, an experimental platform was built to conduct a laboratory imaging experiment and flight experiment on the aerial camera. The experimental results showed that the dynamic resolution of the aerial camera using the image-motion compensation technology could reach 74 lp/mm, and the image-motion compensation accuracy was better than 0.5 pixels, which met the design expectation. In conclusion, the image-motion compensation technology is expected to be applied to various high-precision optical imaging as well as optical detection systems.

Compelling evidence has shown that geomagnetic disturbances in vertical intensity polarization before great earthquakes are promising precursors across diverse rupture conditions. However, the geomagnetic vertical intensity polarization method uses the spectrum of smooth signals, and the anomalous waveforms of seismic electromagnetic radiation, which are basically nonstationary, have not been adequately considered. By combining pulse amplitude analysis and an experimental study of the cumulative frequency of anomalies, we found that the pulse amplitudes before the 2022 Luding M6.8 earthquake show characteristics of multiple synchronous anomalies, with the highest (or higher) values occurring during the analyzed period. Similar synchronous anomalies were observed before the 2021 Yangbi M6.4 earthquake, the 2022 Lushan M6.1 earthquake and the 2022 Malcolm M6.0 earthquake, and these anomalies indicate migration from the periphery toward the epicenters over time. The synchronous changes are in line with the recognition of previous geomagnetic anomalies with characteristics of high values before an earthquake and gradual recovery after the earthquake. Our study suggests that the pulse amplitude is effective for extracting anomalies in geomagnetic vertical intensity polarization, especially in the presence of nonstationary signals when utilizing observations from multiple station arrays. Our findings highlight the importance of incorporating pulse amplitude analysis into earthquake prediction research on geomagnetic disturbances.

A novel functional polycarbonate (PAGC), characterized by the presence of double bonds within its side chain, was successfully synthesized through a ternary copolymerization of propylene oxide (PO), allyl glycidyl ether (AGE), and carbon dioxide (CO2). Polyhedral oligomeric silsesquioxanes octamercaptopropyl (POSS-SH) was employed as a crosslinking agent, contributing to the formation of organic–inorganic hybrid materials. This incorporation was facilitated through thiol-ene click reactions, enabling effective interactions between the POSS molecules and the double bonds in the side chains of the polycarbonate. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) confirmed a homogeneous distribution of silicon (Si) and sulfur (S) in the polycarbonate matrix. The thiol-ene click reaction between POSS-SH and the polycarbonate led to a micro-crosslinked structure. This enhancement significantly increased the tensile strength of the polycarbonate to 42 MPa, a notable improvement over traditional poly (propylene carbonate) (PPC). Moreover, the cross-linked structure exhibited enhanced solvent resistance, expanding the potential applications of these polycarbonates in various plastic materials.

PurposeTo evaluate the feasibility, safety, and oncologic outcomes associated with endoscopic thyroidectomy via the areolar approach (ETAA), compared with conventional open thyroidectomy (COT) for the treatment of stage T1 papillary thyroid carcinoma (PTC).MethodsBetween January 2021 and June 2022, a total of 1204 patients diagnosed with PTC underwent screening, out of which 138 patients were selected for inclusion in the study population after propensity score matching (92 patients in the ETAA group and 46 patients in the COT group). The study included the collection and analysis of clinicopathologic characteristics, intraoperative outcomes, postoperative outcomes, complications, and follow-up data using R software.ResultsThe operative time for the ETAA group was longer than that for the COT group (160.42 ± 32.21 min vs. 121.93 ± 29.78 min, p < 0.0001). However, there were no significant differences between the two groups in terms of intraoperative blood loss, the extent of surgical resection, the number of dissected lymph nodes, the number of metastatic lymph nodes, and the rate of parathyroid autotransplantation. Postoperative drainage and C-reactive protein levels were higher in the ETAA group than in the COT group, but there were no significant differences in 24-hour visual analogue scale scores, white blood cell counts, drainage duration, or postoperative hospital stay. Complication rates were similar between the two groups, and no permanent recurrent laryngeal nerve palsy or hypoparathyroidism was observed. Patients who underwent ETAA reported greater cosmetic satisfaction and quality of life than those who underwent COT. During the follow-up phase, only one patient in the COT group developed lateral cervical lymph node involvement requiring reoperation.ConclusionETAA is a safe and feasible surgical method for patients with stage T1 PTC, providing results similar to COT in terms of oncologic completeness, while avoiding neck scars, with excellent cosmetic effects.Clinical trial registrationChinese Clinical Trial Registry center, identifier ChiCTR2300077109

Oncolytic viral (OV) therapies are promising novel treatment modalities for cancers refractory to conventional treatment, such as glioblastoma, within the central nervous system (CNS). Although OVs have received regulatory approval for use in the CNS, efficacy is hampered by obstacles related to delivery, under-/over-active immune responses, and the “immune-cold” nature of most CNS malignancies. SUMO, the Small Ubiquitin-like Modifier, is a family of proteins that serve as a high-level regulator of a large variety of key physiologic processes including the host immune response. The SUMO pathway has also been implicated in the pathogenesis of both wild-type viruses and CNS malignancies. As such, the intersection of OV biology with the SUMO pathway makes SUMOtherapeutics particularly interesting as adjuvant therapies for the enhancement of OV efficacy alone and in concert with other immunotherapeutic agents. Accordingly, the authors herein provide: 1) an overview of the SUMO pathway and its role in CNS malignancies; 2) describe the current state of CNS-targeted OVs; and 3) describe the interplay between the SUMO pathway and the viral lifecycle and host immune response.

Summary: Slow earthquakes predominant in Costa Rica indicate unstable faulting of segmented Central American megathrusts, but the recurrence of episodic tremors and slips reported to precede a giant earthquake remains still enigmatic. The underlying mechanism is related to the variation in the coupling along the heterogeneous subduction interface which is poorly understood. In this study, we used up-to-date 3D thermal modeling to provide insights into the along-strike variation in the thermal state and hydraulic distribution beneath the Central American subduction zone. Our results show that the subducted Cocos Plate is much warmer than previously estimated, and the slab geometry exhibits remarkable perturbations along the trench. We found that the regions of large dehydration rate along the slab are consistent with the seismicity occurrence depth beneath the Moho. Below the Nicoya Peninsula and the Guatemala-Nicaragua segment of megathrusts, fluids derived from subducted slab result in increased pore fluid pressures and subsequent recurrence of slow slip events and regular earthquakes.

Abstract Because of the steep subduction of a highly concave slab, researchers have characterized megathrusts under the Marianas as among the coldest and curviest plate coupling interfaces in various circum-Pacific subduction zones. Seismic tomography indicates that the heterogeneous underlying plate varies markedly in its subduction angle, velocity, and flexure along the strike and dip, while their effects on the thermal structure and intraslab earthquake occurrence remain enigmatic. By incorporating the 3-D MORVEL velocity and state-of-the-art slab geometry into thermomechanical modeling, we estimated the 3-D subduction thermal state and hydrothermal regime below the Marianas. We find that (1) the concave slab geometry and the complexity of the intraslab velocity variation in the Marianas are associated with a heterogeneous along-strike thermal regime and a cold mantle wedge beneath the central Marianas; (2) amphibolitization and eclogitization of subducted oceanic crust cause variations in fluid pressure and fluid release from the subduction interface, which may influence the distribution of interface seismicity in the Mariana system; (3) the concentration of active hydrothermal vents in the trench > 8 km deep is accompanied by a large temperature gradient and subsequent remarkable slab dehydration in the southern Marianas; and (4) slab dehydration (> 0.02 wt%/km) from 30 to 80 km indicates notable fluid release and potential fluid migration in subduction channels, which may correspond to the large water flux at depth beneath the Marianas.

Rheumatoid arthritis is a systemic inflammatory disease that can lead to articular cartilage destruction and periarticular bone erosion, thus ultimately compromising joint integrity and function. Anti-inflammatory drugs and biological agents are commonly used to treat rheumatoid arthritis, but they cannot selectively target inflamed joints, because of their systemic mechanisms, short half-lives and low bioavailability. Consequently, these agents must be used at high doses and delivered frequently, thereby increasing costs and the risk of adverse effects. Drug delivery systems, such as nanoparticles, liposomes and micelles, can significantly prolong drug half-life in the body and enable targeted delivery into the joints. In this review, we comprehensively describe the pathogenesis and clinical diagnosis of rheumatoid arthritis, and summarize recent advances in targeted therapeutic strategies, particularly nano-targeting systems for rheumatoid arthritis.

Scouring around the fixed foundations of offshore wind turbines (OWTs) remains a pressing concern within the offshore wind industry, significantly jeopardizing OWT safety. Despite previous efforts, the current understanding of this phenomenon remains incomplete, as various factors related to offshore wind farms and OWT operations can exert intricate influences. To further explore this matter, this paper undertakes a new study to further understand the interplay between monopile vibrations, tidal currents, and sea waves, elucidating their combined impact on scour surrounding an OWT’s foundation. It was found that, besides pile vibration amplitude and frequency, the pile vibration direction can also notably influence the scour around the monopile. Specifically, the most pronounced scour mostly transpires when the monopile undergoes vibrations along the 135° direction relative to the inflow direction. The mildest scour mostly occurs when the pile vibrates along the 90° direction. Additionally, this study reveals that different types of waves, indicated by the ratio of water depth, H, to wavelength, L, also engender varying scour around the monopile. The influence of waves on scour increases with the decrease in the H/L ratio, implying that OWT foundations are more threatened by shallow water waves than by deep water waves.

Summary: Previous subduction thermal models are inconsistent with the values of forearc heat flow (50–140 mW/m2) and global P‒T conditions of exhumed rocks, both suggesting a shallow environment 200–300°C warmer than model predictions. Here, we revaluate these problems in Kuril-Kamchatka using 3D thermomechanical modeling that satisfies the observed subduction history and slab geometry, while our refined 3D slab thermal state is warmer than that predicted by previous 2D models and better matches observational constraints. We show that warmer slabs create hierarchical slab dehydration fronts at various forearc depths, causing fast and slow subduction earthquakes. We conclude that fast-to-slow subduction earthquakes all play a key role in balancing plate coupling energy release on megathrusts trenchward of high P-T volcanism.

Summary: Tissue-resident macrophages (TRMs) and dendritic cells (DCs) are highly heterogeneous and essential for immunity, tissue regeneration, and homeostasis maintenance. Here, we comprehensively profile the heterogeneity of TRMs and DCs across adult zebrafish organs via single-cell RNA sequencing. We identify two macrophage subsets: pro-inflammatory macrophages with potent phagocytosis signatures and pro-remodeling macrophages with tissue regeneration signatures in barrier tissues, liver, and heart. In parallel, one conventional dendritic cell (cDC) population with prominent antigen presentation capacity and plasmacytoid dendritic cells (pDCs) featured by anti-virus properties are also observed in these organs. Remarkably, in addition to a single macrophage/microglia population with potent phagocytosis capacity, a pDC population and two distinct cDC populations are identified in the brain. Finally, we generate specific reporter lines for in vivo tracking of macrophage and DC subsets. Our study depicts the landscape of TRMs and DCs and creates valuable tools for in-depth study of these cells in zebrafish.

The production of biodegradable polycarbonate by copolymerizing CO2 with epoxides has emerged as an effective method to utilize CO2 in response to growing concerns about CO2 emissions and plastic pollution. Previous studies have mainly focused on the preparation of CO2-based polycarbonates from petrochemical-derived propylene oxide (PO) or cyclohexene oxide (CHO). However, to reduce dependence on fossil fuels, the development of 100% bio-based polymers has gained attention in polymer synthesis. Herein, we reported the synthesis of glycidyl 4-pentenoate (GPA) from lignocellulose based 4-pentenoic acid (4-PA), which was further copolymerized with CO2 using a binary catalyst SalenCoCl/PPNCl to produce bio-based polycarbonates with vinyl side chains and molecular weights up to 17.1 kg/mol. Introducing a third monomer, PO, allows for the synthesis of the GPA/PO/CO2 terpolymer, and the glass transition temperature (Tg) of the terpolymer can be adjusted from 2°C to 19°C by controlling the molar feeding ratio of GPA to PO from 7:3 to 3:7. Additionally, post-modification of the vinyl side chains enables the production of functional polycarbonates, providing a novel approach to the preparation of bio-based materials with diverse side chains and functions.

Landslide disasters with dense vegetation and steep terrain, and high concealment frequently occur in Southwest China. Current field surveys, unmanned aerial vehicle (UAV) photogrammetry, and Interferometric Synthetic Aperture Radar (InSAR) technologies all have limitations in complex environments with high vegetation coverage. In this study, the landslide in Xinmo Village, Mao County, Aba Prefecture, Sichuan Province, was used as the research object. The slope types were divided according to the regional stratum occurrence and slope direction, and the dip slope was identified as the pre-selected area for the landslide. Nine vegetation indexes were constructed based on Landsat 8 Operational Land Imager (OLI) data, and Modified Soil Adjusted Vegetation Index (MSAVI) with high correlation was selected as the indicator of landslide change to estimate the vegetation coverage. The relationship between vegetation anomalies and landslide creep was analyzed by superimposing slope structure and vegetation spatial variation characteristics. The results showed that from May 2015 to May 2017, the vegetation coverage in the landslide main source area, above the deformation body, local collapse area, and around the washouts showed a significant decrease; i.e., as the time of landslide was approaching, some vegetation in the study area was affected by the landslide deformation and the growth condition became worse. Between April and May 2017, the vegetation coverage in the area not affected by the landslide was less than 0.6 (i.e., bare ground area) decreased abruptly, with change rates of 78.4, 87.7, and 89.7%, respectively, which is consistent with the development pattern of vegetation in the growing period; while the reduction rate of image elements in the vegetation abnormal area was only 20.5%, which judged that the vegetation might be affected by landslide creep and the growth and development were hindered. The study shows that there is an obvious spatial–temporal correlation between vegetation anomalies and landslide deformation during the landslide creep phase, which indirectly reflects the evolution process of landslide gradual destabilization and provides a theoretical basis for the early identification of landslides in high vegetation coverage areas.

The infrared search and track system (IRST) is a type of special electrical optical (EO) system that can be used in various scenarios to fulfill situation awareness, reconnaissance, and tracking of targets. We proposed a homogeneous coordinate transformation method to analyze the residual image wandering induced by the rotation of the scanning platform and the compensation fast steering mirror and help with the commonly trivial selection of the telescope magnification and the objective focal length. The analysis and simulation are carried out with specified IRST optics, which adopt a 640 × 512 array and 15 μm pitch detector, in a focal range of 60 mm~360 mm, and a scan speed of 360°/s to 60 °/s at 50 fps, and optical specifications are determined further. The presented optical system, with only three kinds of common infrared materials, works at 3.7 μm~4.8 μm, demonstrates good image performance and tolerance characteristics, and shows potential in manufacturing. Also, the resulting image wandering of 8 μm, less than a 0.6-pixel size, at an integral time of 16 ms, proves the correctness of the method and makes the scheme of considerable interest for electrical optical systems.

Zinc (Zn) is an essential trace element widely present in rivers and plays a crucial role in ecosystems. Human activities have led to the extensive migration and dissemination of Zn in the environment. When the accumulation of Zn in rivers reaches excessive levels, it transforms into a potentially harmful contaminant. Consequently, tracing Zn’s origin by its isotope ratios (δ66Zn) from natural and anthropogenic sources is essential for the management of and safeguarding against river pollution and comprehending Zn behavior in rivers as well. This review presents the advancements in Zn isotope research in river environments, including a summary of Zn isotope measurement, the distribution and controlling factors (mineral adsorption, precipitation, and biological effects) of Zn isotopes, and the applications of Zn isotopes in rivers. The median δ66Zn values for uncontaminated river water and suspended particulate matter (SPM) were 0.37‰ and 0.22‰, respectively, close to the bulk silicate Earth (BSE) value of 0.28 ± 0.05‰. With respect to the contaminated river, δ66Zn falls within −0.73‰ to 1.77‰, with it being heavily influenced by anthropogenic sources, such as the electroplating and metal processing industries. Apart from contamination identification, this review summarizes the river material exchange process and the δ66Zn values of rainwater (−0.2‰~0.38‰), groundwater (−0.13‰~1.4‰), lake water (−0.66‰~0.21‰), and seawater (−1.1‰~0.9‰), which facilitates a holistic understanding of the Zn cycle and isotope fractionation in the river system. In conclusion, Zn isotopes are an effective tool for tracing pollution sources and Zn migration processes, with enormous unexplored potential. Therefore, this review finally summarizes some challenges and future directions in current research on Zn isotopes.

Abstract Quantum incompatibility is a fundamental property in quantum physics and is considered as a resource in quantum information processing tasks. Here, we construct a framework based on the incompatibility witness originated from quantum state discrimination. In this framework, we discuss the geometrical properties of the witnesses with noisy mutually unbiased bases and construct a quantifier of quantum incompatibility associated with geometrical information. Furthermore, we explore the incompatibility of a pair of positive operator valued measurements, which only depends on the information of measurements, and discuss the incompatibility of measurements which can be discriminated by mutually unbiased bases. Finally, if we take a resource-theory perspective, the new-defined quantifier can characterize the resource of incompatibility. This geometrical framework gives the evidence that vectors can be utilized to describe resourceful incompatibility and make a step to explore geometrical features of quantum resources.

Abstract B cells secreting IL-10 functionally are recognized as functional regulatory B (Breg) cells; however, direct evidence concerning the phenotype, regulation, and functional and clinical relevance of IL-10-secreting Breg cells in humans is still lacking. Here, we demonstrate that, although IL-10 itself is anti-inflammatory, IL-10+ functional Breg cells in patients with systemic lupus erythematosus (SLE) display aggressive inflammatory features; these features shift their functions away from inducing CD8+ T cell tolerance and cause them to induce a pathogenic CD4+ T cell response. Functional Breg cells polarized by environmental factors (e.g., CPG-DNA) or directly isolated from patients with SLE mainly exhibit a CD24intCD27−CD38−CD69+/hi phenotype that is different from that of their precursors. Mechanistically, MAPK/ERK/P38-elicited sequential oncogenic c-Myc upregulation and enhanced glycolysis are necessary for the generation and functional maintenance of functional Breg cells. Consistently, strategies that abrogate the activity of ERK, P38, c-Myc, and/or cell glycolysis can efficiently eliminate the pathogenic effects triggered by functional Breg cells.

The main purpose of this article is to investigate the bursting oscillations of the medical shaking tables resulted from friction in practical application. Using the theoretical method of linear loading, the analytic expression of friction acting on an eccentric turntable is derived in detail. Besides, through numerical simulation, the decisive role of friction in bursting oscillations is verified. On this basis, several practical operation plans are proposed to eliminate harmful vibrations. Last but not least, the effectiveness of theoretical methods is validated through example calculations in cases with special parameters.

Seismic quiescence or enhanced phenomena are anomalous changes against the background of normal seismic activity. Preliminary studies have found that earthquakes with a magnitude of ML≥4 often occur at a low occurrence frequency before giant earthquakes in Tibet. This study analyzed the catalog of ML≥4 earthquakes from 2008 to 2022 and examined the anomalous occurrence of ML≥4 earthquakes preceding most ML≥6 earthquakes. When the monthly occurrence frequency of ML≥4 earthquakes was lower than 4 times over six consecutive months, the subsequent occurrence of ML≥6 earthquakes was highly likely as evidenced by observations. The anomalous characteristics of low-intensity activities were analyzed as a medium- and short-term forecasting index for large earthquakes in the Tibetan area.

Abstract Objective To compare the radiographic parameters and clinical outcomes of isthmic L5–S1 spondylolisthesis with single segment or two-segment pedicle screw fixation. Methods Between January 2018 and January 2019, a total of 76 patients with isthmic L5–S1 spondylolisthesis were included in this study. All patients were treated with varying numbers of pedicle screw fixation with single-segment fusion during posterior lumbar interbody fusion (PLIF). Patients were divided into two groups, based on the number of pedicle screws placed during fixation, namely, 4 screws (4S) group and 6 screws (6S) group. Subsequently, the sagittal balance parameters were measured, which included slippage degree (SD), lumbar lordosis (LL), segmental lordosis (SL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and sagittal vertical axis (SVA). Clinical functional outcomes were assessed using the visual analog scale (VAS) for back pain and the oswestry disability index (ODI) scores. Results The 4S group comprised of 10 males and 27 females, with a median age of 55.2 ± 10.8 years old and a mean follow-up of 16.95 ± 4.16 months. The 6S group comprised of 14 males and 25 females, with a median age of 58.1 ± 7.5 years old and a median follow-up of 17.33 ± 3.81 months. No significant differences were evident in all preoperative parameters between both groups. In contrast, the postoperative LL, SL, PT, SS, and SD values increased significantly, compared to the preoperative values in both groups (all P

Tectonic extrusion bypassing the eastern Himalayan syntaxis results in a significant increase in regional stress instability and the associated frequent occurrence of earthquakes in southern Yunnan, China. However, the stress field, and the relationship between the focal mechanism of earthquakes and stress evolution in southern Yunnan, remain enigmatic. In this paper, using a modified grid point test method, we calculated the focal mechanism of ML ≥ 2.5 earthquakes in southern Yunnan (22–25° N, 100–104° E) from January 2009 to June 2023. Utilizing the solutions of historical earthquake focal mechanisms, we obtained the present-day regional tectonic stress field in southern Yunnan via inversion. The results indicate complex and diverse seismic focal mechanisms, and the main types of earthquakes are strike-slip events, followed by normal fault and reverse fault events. The orientations of the maximum and minimum principal stress axes rotate in a clockwise direction from northeast to southwest. The internal stress orientation distribution of the rhombic Sichuan–Yunnan block in the study area is consistent, and the block boundary zone is the site where stress deflection occurs, and the regional tectonic stress field is influenced by the interaction among different blocks. The distribution of R-value in the Lamping–Simao block gradually increases from north to south, indicating that the compressive stress required for material transport becomes relatively small. Combined with the geological and tectonic background of the study area, our results suggest that the speed of block movement gradually decreases from north to south; the distribution of R-value in the South China block is significantly smaller than that of the interior of the Sichuan–Yunnan rhombus, and the proportion of compressive stresses is larger, indicating a stronger extrusion in this region, which may be related to the fact that the Sichuan–Yunnan rhombus is strongly resisted by the South China block in the east.

Aim: Bladder outlet obstruction (BOO) leads to bladder wall remodeling accompanying the progression from inflammation to fibrosis where pathological hydrostatic pressure (HP)-induced alteration of bladder smooth muscle cells (BSMCs) hypertrophic and excessive extracellular matrix (ECM) deposition play a pivotal role. Recently, we have predicted survivin (BIRC5) as a potential hub gene that might be critical during bladder fibrosis by bioinformatics analyses from rat BOO bladder, but its function during BOO progression remains unknown. Here, we investigated the role of survivin protein on bladder dysfunction of BOO both in vitro and in vivo.Methods: Sprague-Dawley female rats were divided into three groups: control group, BOO group, and BOO followed by the treatment with YM155 group. Bladder morphology and function were evaluated by Masson staining and urodynamic testing. To elucidate the underlying mechanism, hBSMCs were subjected to pathological HP of 200 cm H2O and co-cultured with the presence or absence of survivin siRNA and/or autophagy inhibitor 3-MA. Autophagy was evaluated by the detection of Beclin1 and LC3B-II expression, proliferation was conducted by the EdU analysis and PCNA expression, and fibrosis was assessed by the examination of Col 1 and Fn expression.Results: BOO led to a gradual alteration of hypertrophy and fibrosis of the bladder, and subsequently induced bladder dysfunction accompanied by increased survivin expression, while these histological and function changes were attenuated by the treatment with YM155. HP significantly increased survivin expression, upregulated Col1 and Fn expression, enhanced proliferation, and downregulated autophagy markers, but these changes were partially abolished by survivin siRNA treatment, which was consistent with the results of the BOO rat experiment. In addition, the anti-fibrotic and anti-proliferative effects of the survivin siRNA treatment on hBSMCs were diminished after the inhibition of autophagy by the treatment with 3-MA.Conclusion: In summary, the upregulation of survivin increased cell proliferation and fibrotic protein expression of hBSMC and drove the onset of bladder remodeling through autophagy during BOO. Targeting survivin in pathological hBSMCs could be a promising way to anti-fibrotic therapeutic approach in bladder remodeling secondary to BOO.

Background Karst ecosystems are widely distributed in the world, with one of the largest continuous Karst landforms in Southwest China. Karst regions are characterized by water shortage, high soil calcium (Ca) and magnesium (Mg) content, and soil nutrient leaching, resulting in drought stress and growth limitation of plants. Methods This study compared nitrogen (N), phosphorus (P), potassium (K), Ca, and Mg of herbaceous and woody plants in a small Karst ecosystem in Southwest China. The indexes of water use efficiency (WUE) were calculated to identify the drought stress of plants in this Karst ecosystem. Meanwhile, the relationship between Ca and Mg accumulation and WUE was evaluated in herbaceous and woody plants. Results Herbaceous plants showed a higher content of leaf N (13.4 to 40.1 g·kg−1), leaf P (2.2 to 4.8 g·kg−1) and leaf K (14.6 to 35.5 g·kg−1) than woody plants (N: 10.4 g to 22.4 g·kg−1; P: 0.4 to 2.3 g·kg−1; K: 5.7 to 15.5 g·kg−1). Herbaceous plants showed a significantly positive correlation between WUE and K:Ca ratio (R = 0.79), while WUE has a strongly positive correlation with K:Mg ratio in woody plants (R = 0.63). Conclusion Herbaceous plants suffered from nitrogen (N) limitation, and woody plants were constrained by P or N+P content. Herbaceous plants had higher leaf N, P, and K than woody plants, while Ca and Mg showed no significant differences, probably resulting from the Karst environment of high Ca and Mg contents. Under high Karst Ca and Mg stress, herbaceous and woody plants responded differently to Ca and Mg stress, respectively. WUE of herbaceous plants is more sensitive to Ca stress, while that of woody plants is more sensitive to Mg stress. These findings establish a link between plant nutrients and hydraulic processes in a unique Karst ecosystem, further facilitating studies of the nutrient-water cycling system in the ecosystem.

Abstract Background Compared with conventional open surgery, endoscopic thyroidectomy via the oral vestibular approach (ETVOA) and endoscopic thyroidectomy via the areola approach (ETAA) avoided scarring of the skin, which may help patients achieve a better quality of life (QOL). However, the benefit of the QOL from this technique has not been adequately investigated, therefore this study compared the QOL outcomes between ETVOA and ETAA. Methods 131 patients were enrolled in this study. ETAA surgery and ETVOA surgery were performed in 74 patients and 57 patients, respectively. These patients were followed up at 2 weeks, 4 weeks, and 8 weeks, and their QOL was evaluated using a thyroid surgery-specific questionnaire and a short-form health survey (SF-36). Results There were no differences in clinical characteristics such as gender, age, body mass index (BMI), and tumor size between the two groups. The volume of intraoperative blood loss, cost of hospitalization, and complications between the two procedures showed no differences. Compared with ETAA, ETVOA has a longer operation time, no drainage, and shorter hospital stay. In the QOL questionnaire, several parameters in ETVOA were better. The satisfaction scores of patients undergoing ETVOA were higher. In addition, the cosmetic satisfaction in patients who received ETOVA was significantly better than that of patients who underwent ETAA. The degree of neck movement disorder in patients with ETVOA was milder. Patients who received ETVOA had higher score on the SF-36. Conclusions The trans-oral endoscopic approach can acquire better cosmetic results and achieved high-level QOL.

Abstract Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer (BrC) subtype lacking effective therapeutic targets currently. The development of multi-omics databases facilities the identification of core genes for TNBC. Using TCGA-BRCA and METABRIC datasets, we identified CT83 as the most TNBC-specific gene. By further integrating FUSCC-TNBC, CCLE, TCGA pan-cancer, Expression Atlas, and Human Protein Atlas datasets, we found CT83 is frequently activated in TNBC and many other cancers, while it is always silenced in non-TNBC, 120 types of normal non-testis tissues, and 18 types of blood cells. Notably, according to the TCGA-BRCA methylation data, hypomethylation on chromosome X 116,463,019 to 116,463,039 is significantly correlated with the abnormal activation of CT83 in BrC. Using Kaplan–Meier Plotter, we demonstrated that activated CT83 is significantly associated with unfavorably overall survival in BrC and worse outcomes in some other cancers. Furthermore, GSEA suggested that the abnormal activation of CT83 in BrC is probably oncogenic by triggering the activation of cell cycle signaling. Meanwhile, we also noticed copy number variations and mutations of CT83 are quite rare in any cancer type, and its role in immune infiltration is not significant. In summary, we highlighted the significance of CT83 for TNBC and presented a comprehensive bioinformatics strategy for single-gene analysis in cancer.

ObjectiveIn order to analyze the clinical characteristics of epileptic seizures in children with acute lymphoblastic leukemia (ALL) during treatment.MethodsThe clinical and imaging data of children diagnosed as ALL with epilepsy seizures from January 2013 to December 2020 were retrospectively analyzed.ResultsA total of 2217 children with ALL were admitted during the study, of whom 229 (10.33%) had epileptic seizures after ALL treatment. Among them, 45 (19.65%) were in the high-risk group and 184 (80.35%) were in the low-risk group. Epileptic seizures mainly occurred in the induction remission period (24.02%), maintenance treatment period (25.33%) and after bone marrow transplantation (21.40%). The common causes were MTX-related demyelinating encephalopathy (34.06%) and reversible posterior encephalopathy syndrome (PRES) (25.3%). The first symptom was mainly convulsion (34.50%). The first attack had a comprehensive attack and partial attack. Most patients stop themselves. 30 cases (13.10%) had acute recurrence of epilepsy (recurrence within 3 months after the first attack), and 49 cases (25.76%) had neurological dysfunction after follow-up. 36 cases developed symptomatic epilepsy. Among the 130 children who completed the follow-up, 78 (60.00%) had no obvious neurological sequelae, and 52 (40.0%) had neurological sequelae. Among the 52 cases, there were 34 cases of mild sequelae and 18 cases of severe sequelae, including 8 cases of epilepsy combined with cognitive impairment.ConclusionEpileptic seizure is a common neurological complication during ALL treatment. The etiology and associated manifestations of the first epileptic seizure are diverse. Early neuroimaging and EEG examination are helpful for early diagnosis and treatment.

Summary: Small cell lung cancers (SCLCs) have high mutational burden but are relatively unresponsive to immune checkpoint blockade (ICB). Using SCLC models, we demonstrate that inhibition of WEE1, a G2/M checkpoint regulator induced by DNA damage, activates the STING-TBK1-IRF3 pathway, which increases type I interferons (IFN-α and IFN-β) and pro-inflammatory chemokines (CXCL10 and CCL5), facilitating an immune response via CD8+ cytotoxic T cell infiltration. We further show that WEE1 inhibition concomitantly activates the STAT1 pathway, increasing IFN-γ and PD-L1 expression. Consistent with these findings, combined WEE1 inhibition (AZD1775) and PD-L1 blockade causes remarkable tumor regression, activation of type I and II interferon pathways, and infiltration of cytotoxic T cells in multiple immunocompetent SCLC genetically engineered mouse models, including an aggressive model with stabilized MYC. Our study demonstrates cell-autonomous and immune-stimulating activity of WEE1 inhibition in SCLC models. Combined inhibition of WEE1 plus PD-L1 blockade represents a promising immunotherapeutic approach in SCLC.

The data include the 3-D temperature field (degrees Celsius), water content (wt%), dehydration rate (wt%/km), and subduction velocity field (cm/yr) of the subducting plate, as well as the coastline and volcano distribution in Alaska. The data of the model region have dimensions of 800 × 1600 × 400 km (length × width × depth). The geometry of the subducted plate is well constrained by Slab2.0, and the plate ages are provided by EarthByte. The subduction velocities inside a prescribed 3-D constrained volume of the oceanic lithosphere are given based on the kinematic plate subduction modeling method and the MORVEL plate motion data. The observation of surface heat flow and Curie point depths are used to constrain the model thermal regime. The geophysical calculation is ensured after the subduction thermal regime reaches a steady state. Data are deposited in the TPDC repository, which has granted a persistent identifier https://data.tpdc.ac.cn/en/disallow/8b266d22-fea7-4259-9a5f-8ac0bd9e7869/. Data include (1) paraview_eq_USGS.vtk (earthquake catalog by IRIS, 2000-2010, Trabant et al., 2012), (2) paraview_slab.vtk (3-D thermal regime, slab water content and slab dehydration), (3) paraview_volcano.vtk (global volcanoes at NCEI, Siebert et al., 2010), and (4) paraview_map.vtk (coastline, GMT).

Peripheral nerve injury (PNI) is common and, unlike damage to the central nervous system injured nerves can effectively regenerate depending on the location and severity of injury. Peripheral myelinating glia, Schwann cells (SCs), interact with various cells in and around the injury site and are important for debris elimination, repair, and nerve regeneration. Following PNI, Wallerian degeneration of the distal stump is rapidly initiated by degeneration of damaged axons followed by morphologic changes in SCs and the recruitment of circulating macrophages. Interaction with fibroblasts from the injured nerve microenvironment also plays a role in nerve repair. The replication and migration of injury-induced dedifferentiated SCs are also important in repairing the nerve. In particular, SC migration stimulates axonal regeneration and subsequent myelination of regenerated nerve fibers. This mobility increases SC interactions with other cells in the nerve and the exogenous environment, which influence SC behavior post-injury. Following PNI, SCs directly and indirectly interact with other SCs, fibroblasts, and macrophages. In addition, the inter- and intracellular mechanisms that underlie morphological and functional changes in SCs following PNI still require further research to explain known phenomena and less understood cell-specific roles in the repair of the injured peripheral nerve. This review provides a basic assessment of SC function post-PNI, as well as a more comprehensive evaluation of the literature concerning the SC interactions with macrophages and fibroblasts that can influence SC behavior and, ultimately, repair of the injured nerve.

As a powerful protocol for the preparation of common polymers, such as polyolefins, polyesters, and polycarbonates, late-transition-metal-catalyzed polymerization can be carried out by controlling the reaction conditions or developing dynamic catalytic systems that use external stimuli to influence the performance of the active sites, resulting in well-defined polymeric materials. In particularly, under the latter conditions, ‘one catalyst’ can provide more than one kind of polymer with a controlled sequence from the monomer mixture, making full use of the prepared catalyst. In this review, tunable modes, including reaction conditions, redox, light or electrochemical properties, Lewis acids, and alkali metal cations, of late-transition-metal-complex (especially iron, cobalt, and nickel)-catalyzed polymerization were collected and thoroughly discussed.

The copolymerization of carbon dioxide (CO2) with epoxides demonstrates promise as a new synthetic method for low-carbon polymer materials, such as aliphatic polycarbonate materials. In this study, a binary Schiff base cobalt system was successfully used to catalyze the copolymerization of 1,2-butylene oxide (BO) and CO2 and its terpolymerization with other epoxides such as propylene oxide (PO) and cyclohexene oxide (CHO). 1H nuclear magnetic resonance (1H NMR), diffusion-ordered spectroscopy (DOSY), gel permeation chromatography (GPC), and differential scanning calorimetry (DSC) confirmed the successful synthesis of the alternating terpolymer. In addition, the effects of the polymerization reaction conditions and copolymerization monomer composition on the polymer structure and properties were examined systematically. By regulating the epoxide feed ratio, polycarbonates with an adjustable glass transition temperature (Tg) (11.2–67.8 °C) and hydrophilicity (water contact angle: 85.2–95.2°) were prepared. Thus, this ternary polymerization method provides an effective method of modulating the surface hydrophobicity of CO2-based polymers and their biodegradation properties.

Halimodendron halodendron (Pall.) Voss. is a deciduous shrub belonging to the genus Halimodendron, Leguminosae, and is mainly distributed in dry areas. This species can be used for saline-alkali soil improvement and sand fixation. The complete plastid genome of H. halodendron first reported here is 129,342 bp in length, and contains 110 genes, including 76 protein coding genes, 30 tRNA genes, and 4 rRNA genes. A total of 105 simple sequence repeats (SSRs) were identified in the chloroplast genome. This information will be useful for study on the evolution and genetic diversity of Halimodendron halodendron in the future.

Abstract Background The influence of pedicle screw number and insertion depth on outcomes of lumbar fixation remains uncertain. The purpose of this study was to compare the imaging balance stability and clinical functional improvement of lumbar fracture patients with different pedicle screw numbers and insertion depths. Methods Sixty-five patients undergoing lumbar pedicle screw fixation from January 2016 to January 2018 were enrolled. They were included in long screw (LS) group and short screw (SS) group or 6 screw (6S) group and 4 screw (4S) group. The radiographic outcomes were assessed with lumbar lordosis (LL), segmental lordosis (SL), fractured vertebral lordosis (FL), sacral slope (SS), pelvic incidence (PL), and pelvic tilt (PT). The visual analog scale (VAS) and the Oswestry Disability Index (ODI) score were used for functional assessment. Multiple linear regression was performed to identify the risk factors of FL, SL, and LL correction at the final follow-up. Results FL, SL, and LL were significantly different in all matching subgroups to compare long and short screws and in most matching subgroups to compare 6 and 4 screws. The SS, PT, and PI seem to be similar in all subgroups in different periods. Significant differences of VAS and ODI were found between LS and SS in the 4S group and between 4S and 6S in the SS group. Insertion depth, screw number, BMD, age, and preoperative imaging data were significant factors for imaging balance stability correction at the final follow-up. Conclusions Long screws and 6 screws showed better fracture vertebral restoration and lumbar spinal sagittal stabilities. The surgery type, age, and BMD are important focus points for the treatment of lumbar vertebral fractures.

Peganum harmala L. is a perennial herbaceous plant belonging to the family of Zygophyllaceae, and is grows in semi-arid climates, such as Xinjiang, Gansu, Ningxia, Qinghai, and Inner Mongolia in China, and also Middle East and North Africa. This species is of high medicinal value. The complete chloroplast genome was reported in this study. The chloroplast genome with a total size of 159,957 bp consists of two inverted repeats (IR, 26,550 bp) separated by a large single-copy region (LSC, 88,098 bp) and a small single-copy region (SSC, 18,759 bp). Further annotation revealed the chloroplast genome contains 113 genes, including 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. A total of 90 simple sequence repeats (SSRs) were identified in the chloroplast genome. This information will be useful for study on the evolution and genetic diversity of Peganum harmala in the future.

Summary: FBXO31 is the substrate receptor of one of many CUL1-RING ubiquitin ligase (CRL1) complexes. Here, we show that low FBXO31 mRNA levels are associated with high pre-operative prostate-specific antigen (PSA) levels and Gleason grade in human prostate cancer. Mechanistically, the ubiquitin ligase CRL1FBXO31 promotes the ubiquitylation-mediated degradation of DUSP6, a dual specificity phosphatase that dephosphorylates and inactivates the extracellular-signal-regulated kinase-1 and -2 (ERK1/2). Depletion of FBXO31 stabilizes DUSP6, suppresses ERK signaling, and activates the PI3K-AKT signaling cascade. Moreover, deletion of FBXO31 promotes tumor development in a mouse orthotopic model of prostate cancer. Treatment with BCI, a small molecule inhibitor of DUSP6, suppresses AKT activation and prevents tumor formation, suggesting that the FBXO31 tumor suppressor activity is dependent on DUSP6. Taken together, our studies highlight the relevance of the FBXO31-DUSP6 axis in the regulation of ERK- and PI3K-AKT-mediated signaling pathways, as well as its therapeutic potential in prostate cancer.

Well water levels can reflect the stress placed on a confined subsurface aquifer system in a similar manner to a strain meter. Based on observations of the geophysical field in Lhasa combined with digital data recorded at an underground fluid well at the Lhasa geomagnetic station in recent years, we comprehensively analyzed the characteristics of co-seismic changes caused by 14 different-magnitude M ≥ 5 earthquakes recorded in the well. The results show that (1) the co-seismic changes in water temperature and water level are different; the water level exhibits oscillation-type changes, while the water temperature variations indicate first heating and subsequent recovery. (2) The co-seismic changes are related to the epicentral distance, magnitude and focal depth of the earthquake. The closer the epicenter is to the well, the earlier the co-seismic responses occur, but the time interval between the co-seismic changes in the water level and temperature differs. (3) The co-seismic ratio of the water temperature is higher than that of the water level; this may be related to faulty water level instrumentation or segmented records.