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ObjectivesThe short-term effects of microwave ablation (MWA) for the treatment of benign thyroid nodules (BTNs) were satisfactory in previous studies. However, as a slowly progressing disease, the long-term efficacy of MWA for BTNs at present is not clear. Our study aim was to assess the long-term results of MWA for BTNs after a 48-month follow-up.MethodsFrom June 2015 to September 2017, 148 patients had 148 BTNs. All patients were from the China-Japan Union Hospital of Jilin University. Careful ultrasound examinations were performed 1 day, 1 month, 3 months, 6 months, 12 months, and every 6 months after MWA. The volume, volume reduction rate (VRR), recurrence rate of the ablated area and thyroid function were recorded.ResultsThe mean volumes of the 148 nodules were 15.6 ± 9.4 cm3 (range: 1.3-48.9 cm3) and 0.6 ± 0.6 cm3 (range: 0-3.5 cm3) before and 48 months after MWA, respectively, with a nodule VRR of 96.9 ± 2.5% (range: 90.4-100%). Two patients (1.35%) had recurrence after MWA. Compared with thyroid function before MWA, no significant variation was observed after MWA. Five patients experienced complications (3.38%): two patients (1.35%) had bleeding, two patients (1.35%) had ear pain and toothache during MWA, and one patient (0.68%) had hoarseness after MWA. No cases of oesophageal injury, tracheal injury, infection, skin burns, etc., were reported during or after MWA.ConclusionsBased on a long-term follow-up, MWA is an effective method for treating BTNs and is expected to be a potential first-line treatment.

BACKGROUND A geological database is an important part of earth information science, which will provide reliable data support for geological research and application. Re-Os dating technology is widely applied in the study of ore deposit, mantle evolution, and marine environment. OBJECTIVES To construct a journal publication-based Re-Os dating database to integrate related research achievements, and improve the management and application of the technology. METHODS The technical route of GIS spatial database construction was adopted, and systematically studied database construction methods from multiple dimensions such as database construction ideas, data integration methods, and data database construction. RESULTS The database used publicly published Re-Os isotope dating documents as the data source and gathered more than 100 publicly published Re-Os dating documents from the last ten years. More than 35 journals were involved. The data sources were authoritative, extensive and representative. Through the structural transformation and spatial processing of unstructured fragmented document data, the database had the characteristics of authoritative data source, structured data content, and attributed spatial location. CONCLUSIONS The Re-Os dating database has a reliable data source, which can provide data support for the geological survey and research of mineral deposits.

Chain damage is a new phenomenon that occurs when a reactive jet impacts and penetrates multi-spaced plates. The reactive jet produces mechanical perforations on the spaced plates by its kinetic energy (KE), and then results in unusual chain rupturing effects and excessive structural damage on the spaced plates by its deflagration reaction. In the present study, the chain damage behavior is initially demonstrated by experiments. The reactive liners, composed of 26 wt%Al and 74 wt% PTFE, are fabricated through a pressing and sintering process. Three reactive liner thicknesses of 0.08 CD, 0.10 CD and 0.12 CD (charge diameter) are chosen to carry out the chain damage experiments. The results show a chain rupturing phenomenon caused by reactive jet. The constant reaction delay time and the different penetration velocities of reactive jets from liners with different thicknesses result in the variation of the deflagration position, which consequently determines the number of ruptured plates behind the armor. Then, the finite-element code AUTODYN-3D has been used to simulate the kinetic energy only-induced rupturing effects on plates, based on the mechanism of behind armor debris (BAD). The significant discrepancies between simulations and experiments indicate that one enhanced damage mechanism, the behind armor blast (BAB), has acted on the ruptured plates. Finally, a theoretical model is used to consider the BAB-induced enhancement, and the analysis shows that the rupturing area on aluminum plates depends strongly upon the KE only-induced pre-perforations, the mass of reactive materials, and the thickness of plates.

We report APW+lo (augmented plane wave plus local orbital) density functional theory (DFT) calculations of large molecular systems using the domain specific SIRIUS multi-functional DFT package. The APW and FLAPW (full potential linearized APW) task and data parallelism options and the advanced eigen-system solver provided by SIRIUS can be exploited for performance gains in ground state Kohn–Sham calculations on large systems. This approach is distinct from our prior use of SIRIUS as a library backend to another APW+lo or FLAPW code. We benchmark the code and demonstrate performance on several magnetic molecule and metal organic framework systems. We show that the SIRIUS package in itself is capable of handling systems as large as a several hundred atoms in the unit cell without having to make technical choices that result in the loss of accuracy with respect to that needed for the study of magnetic systems. [ABSTRACT FROM AUTHOR]

Signaling circuits crucial to systemic physiology are widespread, yet uncovering their molecular underpinnings remains a barrier to understanding the etiology of many metabolic disorders. Here, we identified a copper-linked signaling circuit activated by disruption of mitochondrial function in the murine liver or heart that resulted in atrophy of the spleen and thymus and caused a peripheral white blood cell deficiency. We demonstrated that the leukopenia was caused by a-fetoprotein, which required copper and the cell surface receptor CCR5 to promote white blood cell death. We further showed that a-fetoprotein expression was upregulated in several cell types upon inhibition of oxidative phosphorylation. Collectively, our data argue that a-fetoprotein may be secreted by bioenergetically stressed tissue to suppress the immune system, an effect that may explain the recurrent or chronic infections that are observed in a subset of mitochondrial diseases or in other disorders with secondary mitochondrial dysfunction., Introduction To maintain homeostasis, tissue and organ systems must adapt in unison to varying metabolic challenges (1). These responses involve a cell autonomous component that acts locally at the affected [...]

Precipitation δ18O has offered valuable insights into the evolution of the Asian monsoon. Recent researches focusing on precipitation Δ′17O has enhanced our understanding by offering new perspectives beyond those of δ18O, revealing insights into vapor sources and continental recycling. Nevertheless, there remains a lack of interannual triple oxygen isotope data, particularly in the Asian monsoon region. In this study, we analyzed the triple oxygen isotopes and hydrogen isotopes in monthly precipitation samples collected from Chongqing in Southwest China between 2019 and 2022 A.D. Seasonal variations in δD, δ18O, δ17O, and d‐excess values were observed, with lower values during the rainy season and higher values during the dry season, highlighting the impact of changes in moisture sources and local meteorological conditions on seasonal shifts in δD, δ18O, and δ17O. While, mean Δ′17O values were higher in rainy season and lower in dry season. Notably, during rainy season, there is a negative correlation between monthly Δ′17O values and the RH of the vapor source area, as well as a positive correlation with d‐excess. Recalculated Δ′17O values based on RH of oceanic moisture source, are higher than the measured values for this period, indicating the contribution of terrigenous moisture to precipitation in SW China. Precipitation Δ′17O values provide a more precise reflection of changes in moisture source, continental recycling, and evapotranspiration processes that drive water cycling compared Integrating modeling works in future will facilitate the use of precipitation Δ′17O values to quantify the impact of different moisture source on precipitation. Plain Language Summary: In the context of climatic warming, changes in water vapor source areas have substantial implications for the stability of regional water resources. Despite the importance of these changes, few studies have analyzed them using precipitation data from SW China. We conducted monthly measurements of isotopic compositions in precipitation samples collected in monsoonal SW China between 2019 and 2022 A.D. Seasonal variations in δD, δ18O, δ17O, and d‐excess revealed low values during the rainy season (May–October) and significantly higher values during the dry season (November–April). These variations are primarily attributed to different water vapor sources in distinct seasons. Moreover, we observed a negative correlation between precipitation Δ′17O and relative humidity in the source area of the water vapor during the rainy season, suggesting that Δ′17O contains valuable information about the water vapor's source area. Additionally, the relatively higher Δ′17O values observed in the rainy season imply the influence of continental recycling and evapotranspiration processes. Key Points: Characteristics of triple oxygen and hydrogen isotopes in precipitation were analyzed based on a 4‐year monitoring period in Southwest ChinaTriple oxygen isotopes in precipitation serve as indicators of the extent of isotopic fractionation in water vapor between different seasonsChanges in precipitation Δ′17O show a negative correlation with relative humidity from the moisture source area during the rainy season [ABSTRACT FROM AUTHOR]

In carbonate coastlines, karst studies have traditionally focused on reconstructing Quaternary coastal uplift and sea level oscillations. However, their potential for investigating coastal subsidence remains unexplored in regions with limited sedimentary records and scientific monitoring. In line with this, our study delved into the utility of karst research for deciphering the Quaternary evolution of the Granada coast in southern Spain—a shoreline marked by a conspicuous scarcity of records and information regarding recent tectonic movements. The current labelling data and the absence of evidence for uplift led to the hypothesis that the Granada coast may be susceptible to subsidence, though this conjecture remained unconfirmed. While submerged marine terraces were clearly identified, they were previously interpreted as consequences of sea‐level oscillations. Our multidisciplinary approach integrated karst vadose features, biostratigraphy, and the dating of 22 speleothems to address the potential uplifting or subsiding dynamics of the Granada coast. The findings indicated that the Granada coast experienced emersion between 3.5/2.4 Ma and 650 ka ago. Notably, this uplift predated similar occurrences in neighbouring coastal regions to the W and E, which occurred within the last 200–180 ka. These disparities in timing cannot be solely attributed to sea‐level fluctuations, suggesting the involvement of the tectonic activity during the Quaternary. The tectonic likely led to the emergence of the Granada coast and its karstification, followed by subsidence. Furthermore, we identified the extensional faults that caused the coastal subsidence, previously documented in studies conducted in nearby regions. However, until now, their specific impact on the Granada coast had not been comprehensively stated. In summary, our research introduces a novel application of classical karst investigations in the understanding coastal subsidence and the extensional active tectonic. By comparing vadose cave ages with established chronologies in adjacent coastal areas, this approach sheds light on the complex tectonic evolution of coastal regions. [ABSTRACT FROM AUTHOR]

The influence of chimeric antigen receptor T (CAR-T) cell therapy on platelet function in relapsed/refractory (R/R) multiple myeloma (MM) has not been thoroughly investigated. Our cohort comprised fifty MM patients treated with CAR-T cells. The mean platelet closure time (PCT) induced by collagen/adenosine diphosphate (CADP) in peripheral blood was significantly prolonged before lymphodepletion (195.24 ± 11.740 s) and notably reduced post-CAR-T cell therapy (128.02 ± 5.60 s), with a statistically significant improvement (67.22, 95% CI 46.91–87.53, P < 0.001). This post-treatment PCT was not significantly different from that of healthy controls (10.64, 95% CI 1.11–22.40, P > 0.05). Furthermore, a pronounced enhancement in PCT was observed in patients with a response greater than partial remission (PR) following CAR-T cell infusion compared to pre-treatment values (P < 0.001). An extended PCT was also associated with a less favorable remission status. In patients with cytokine release syndrome (CRS) grades 0–2, those with a PCT over 240.5 s exhibited a shorter progression-free survival (PFS), with median PFS times of 10.2 months for the PCT > 240.5 s group versus 22.0 months for the PCT ≤ 240.5 s group. Multivariate analysis revealed that a PCT value exceeding 240.5 s is an independent prognostic factor for overall survival (OS) in R/R MM patients after CAR-T cell therapy. The study demonstrates that CAR-T cell therapy enhances platelet function in R/R MM patients, and PCT emerges as a potential prognostic biomarker for the efficacy of CAR-T cell therapy. [ABSTRACT FROM AUTHOR]

A pair of atropisomers secofumitremorgins C (1a) and D (1b), together with fifteen known alkaloids (2-16), were isolated from a saltern-derived fungus Aspergillus fumigatus GXIMD00544. The structures of atropisomers 1a and 1b were elucidated by the detailed spectroscopic data, chemical reaction and quantum chemical calculations. Compounds 1 and 8 displayed antifungal spore germination effects against plant pathogenic fungus associated with sugarcane Fusarium sp. with inhibitory rates of 53% and 77% at the concentration of 100 µM, repectively. Atropisomers 1 also exhibited antifouling potential against Balanus amphitrite larval settlement with an inhibitory rate of 96% at the concentration of 100 µM. [ABSTRACT FROM AUTHOR]

The full understanding of climate feedbacks responsible for the amplification of deglaciations requires robust chronologies for these climate transitions, but, in the case of marine records, radiocarbon chronologies are possible only for the last glacial termination. Although the assumed relationships between the marine isotopic record and the orbital parameters provide a first order chronology for the previous terminations, an independent chronological control allows the relationships between orbital forcing and the climate response to be assessed over multiple previous terminations. Here we present new geochemical records of Marine Isotope Stages 11 to 7 from a western Mediterranean speleothem, establishing a new long terrestrial climate record for this region. Its absolute U/Th dates provide an exceptional chronology for the glacial terminations IV, III, and III.a. The onset of these three glacial terminations was marked by rapid δ18O depletions, reflecting ocean freshening by ice melting, thus providing an excellent tie point for regional marine records also sensitive to such freshening. These new chronologies reveal an earlier onset of the deglacial melting for the TIV and TIII.a in contrast to the generally accepted marine chronologies and indicate that the duration of these deglaciations was variable, with TIV particularly longer (~20 kyr). This study also supports that the onset of deglacial melting always occurred during declining precession index while a nonunique relation occurred with the obliquity parameter. [ABSTRACT FROM AUTHOR]

The Forkhead box transcription factors FOXC1 and FOXC2 are expressed in condensing mesenchyme cells at the onset of endochondral ossification. We used the Prx1-cre mouse to ablate Foxc1 and Foxc2 in limb skeletal progenitor cells. Prx1-cre;Foxc1Δ/Δ; Foxc2Δ/Δ limbs were shorter than controls, with worsening phenotypes in distal structures. Cartilage formation andmineralization was severely disrupted in the paws. The radius and tibia were malformed, whereas the fibula and ulna remained unmineralized. Chondrocyte maturation was delayed, with fewer Indian hedgehog-expressing, prehypertrophic chondrocytes forming and a smaller hypertrophic chondrocyte zone. Later, progression out of chondrocyte hypertrophy was slowed, leading to an accumulation of COLX-expressing hypertrophic chondrocytes and formation of a smaller primary ossification center with fewer osteoblast progenitor cells populating this region. Targeting Foxc1 and Foxc2 in hypertrophic chondrocytes with Col10a1-cre also resulted in an expanded hypertrophic chondrocyte zone and smaller primary ossification center.Our findings suggest that FOXC1 and FOXC2 direct chondrocyte maturation towards hypertrophic chondrocyte formation. At later stages, FOXC1 and FOXC2 regulate function in hypertrophic chondrocyte remodeling to allow primary ossification center formation and osteoblast recruitment. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor-T (CAR-T) cells have exhibited remarkable efficacy in treating refractory or relapsed multiple myeloma (R/R MM). Although obesity has a favorable value in enhancing the response to immunotherapy, less is known about its predictive value regarding the efficacy and prognosis of CAR-T cell immunotherapy. We conducted a retrospective study of 111 patients with R/R MM who underwent CAR-T cell treatment. Using the body mass index (BMI) classification, the patients were divided into a normal-weight group (73/111) and an overweight group (38/111). We investigated the effect of BMI on CAR-T cell therapy outcomes in patients with R/R MM. The objective remission rates after CAR-T cell infusion were 94.7% and 89.0% in the overweight and normal-weight groups, respectively. The duration of response and overall survival were not significant difference between BMI groups. Compared to normal-weight patients, overweight patients had an improved median progression-free survival. There was no significant difference in cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome between the subgroups. In terms of hematological toxicity, the erythrocyte, hemoglobin, platelet, leukocyte and neutrophil recovery was accelerated in the overweight group. Fewer patients in the overweight group displayed moderate percent CD4 and CD4/CD8 ratios compared to the normal-weight group. Furthermore, the percent CD4 ratios were positively correlated with the levels of cytokines [interleukin-2 (IL-2) (day 14), interferon gamma (IFN-γ) (day 7) and tumor necrosis factor alpha (TNF-α) (days 14 and 21)] after cells infusion. On the other hand, BMI was positively associated with the levels of IFN-γ (day 7) and TNF-α (days 14 and 21) after CAR-T cells infusion. Overall, this study highlights the potential beneficial effect of a higher BMI on CAR-T cell therapy outcomes. [ABSTRACT FROM AUTHOR]

The Hendy Test is widely used for assessing whether isotopic equilibrium was reached in speleothems by examining the δ18O and δ13C correlation along a single growth layer. However, stalagmite micro-layers are typically only a few micrometers thick and taper off from the center towards the sides, making it challenging to sample within the same growth layer in practice. To address this, we selected three caves in the monsoon region of China (Shihua Cave in the north, Heshang Cave in the central, and Baojinggong Cave in the south) to verify whether the modern cave calcite has reached equilibrium fractionation with drip water. We examined the spatial variations in the δ18O and δ13C values of farmed calcite on glass plates, which are analogous to a single growth layer. The δ18O and δ13C correlations of farmed calcite from different cave sites are consistently strong, suggesting that kinetic fractionation effects are prevalent, especially at the drip sites with lower drip rates due to longer CO2 degassing. The δ18O–δ13C covariations can also occur along speleothem growth axes on short time scales, while isotopic variations over longer time scales are still in response to climate change. We propose that the Hendy Test criteria might not be prerequisites to isotopic equilibrium, and a Replication Test provides a more reliable indication of the integrity of isotopic proxies in paleoclimate research. [ABSTRACT FROM AUTHOR]

Identifying tropical cyclone (TC) signatures in paleoclimate records enhances our understanding of long-term TC activity trends and the climatic factors influencing TC evolution. Stalagmites are considered promising archives for recording TC activity. However, despite the western North Pacific being the most TC-active ocean basin globally, it lacks stalagmite-based TC reconstructions. Here, we present a seasonally resolved stalagmite δ18O record from XRY cave in Southeast China, covering the period from 1951 to 2018 CE, to identify annual signals of strong TC activity. We propose that the minimum seasonal XRY δ18O value of each year can reconstruct regional TC activity, achieving an identification rate of 86% for strong TC years in study area. This demonstrates the feasibility of using stalagmites for TC reconstruction in Southeast China. Moreover, our research shows that inland stalagmites can still capture TC activity signals, which will promote the use of stalagmites in obtaining long-term records of post-landfall TC activity and inland impacts. [ABSTRACT FROM AUTHOR]

Background and aim: Huashi Baidu Decoction (HSBD) is a novel complex prescription which has positive effects on severe COVID-19. This study was aimed to discover key Chinese materia medica, main active compounds, hub therapeutic target proteins and core signal pathways in the potential therapeutic mechanism of HSBD on severe COVID-19 through integrating network pharmacological methods. Experimental procedure: TCMSP, TCMID and STITCH databases were used to screen out active compounds and target proteins of HSBD. GeneCards database was used to screen out disease genes of severe COVID-19. The potential therapeutic targets of HSBD on severe COVID-19 were used to construct protein-protein interaction network through STRING database and the hub target proteins were discovered. Next, GO and KEGG enrichment analysis were carried out to discover core signal pathways. Finally, the network diagram of “Chinese materia medica-active compounds-therapeutic target proteins” was built, then key Chinese materia medica and main active compounds were selected. Results and conclusion: HSBD might treat severe COVID-19 through 45 potential target genes, among them, there were 13 hub target genes: RELA, TNF, IL6, IL1B, MAPK14, TP53, CXCL8, MAPK3, MAPK1, IL4, MAPK8, CASP8, STAT1. Meanswhile, GO_BiologicalProcess and KEGG signaling pathways analysis results showed that the core signal pathways were inflammation and immune regulation pathways. Finally, 4 key Chinese materia medica and 11 main active compounds were discovered in the HSBD. In conclusion, the therapeutic mechanism of HSBD on severe COVID-19 might involve its pharmacological effects of anti-inflammation and immune regulation via acting on 45 disease-related proteins of severe COVID-19. Taxonomy (classification by evise): Viral Pneumonia, COVID-19, Acute Respiratory Distress Syndrome, Septic Shock, Chinese Herbal Medicine.

Abstract Background Natural model systems are indispensable for exploring adaptations in response to environmental pressures. Sinocyclocheilus of China, the most diverse cavefish clade in the world (75 species), provide unique opportunities to understand recurrent evolution of stereotypic traits (such as eye loss and sensory expansion) in the context of a deep and diverse phylogenetic group. However, they remain poorly understood in terms of their morphological evolution. Therefore, we explore key patterns of morphological evolution, habitat utilization and geographic distribution in these fishes. Results We constructed phylogenies and categorized 49 species based on eye-related condition (Blind, Micro-eyed, and Normal-eyed), habitat types (Troglobitic—cave-restricted; Troglophilic—cave-associated; Surface—outside caves) and existence of horns. Geometric-morphometric analyses show Normal-eyed morphs with fusiform shapes segregating from Blind/Micro-eyed deeper bodied morphs along the first principal-component axis; second axis accounts for shape complexity related to horns. The body shapes showed a significant association with eye-related condition and horn, but not habitat types. Ancestral reconstructions suggest at least three independent origins of Blind morphs, each with different levels of modification in relation to their ancestral Normal-eyed morphs; Sinocyclocheilus are also pre-adapted for cave dwelling. Our geophylogeny shows an east-to-west diversification spanning Pliocene and Pleistocene, with early-diversifying Troglobitic species dominating subterranean habitats of karstic plains whereas predominantly Surface forms inhabit hills to the west. Evolutionary rates analyses suggest that lineages leading to Blind morphs were characterized by significant rate shifts, such as a slowdown in body size evolution and a 5–20 fold increase in rate of eye regression, possibly explained by limited resource availability. Body size and eye size have undergone reversals, but not horns, a trait entailing considerable time to form. Conclusions Sinocyclocheilus occupied cave habitats in response to drying associated with aridification of China during late Miocene and the Pliocene. The prominent cave-adaptations (eye-regression, horn-evolution) occur in clades associated with the extensive subterranean cave system in Guangxi and Guizhou provinces. Integration of morphology, phylogeny, rate analyses, molecular-dating and distribution show not only several remarkable patterns of evolution, but also interesting exceptions to these patterns signifying the diversification of Sinocyclocheilus as an invaluable model system to explore evolutionary novelty.

Zhang et al. identify Creb5 as a transcription factor that is required for induction of Prg4 expression by TGFβ and EGFR ligands. They show that Creb5 directly binds to two Prg4 promoter-proximal regulatory elements, working together with a more distal regulatory element to drive induction of Prg4 by TGFβ. These findings provide new insight into the molecular regulation of Prg4 expression in superficial zone articular chondrocytes.