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Melatonin is reportedly associated with intervertebral disc degeneration (IDD). Endplate cartilage is vitally important to intervertebral discs in physiological and pathological conditions. However, the effects and mechanism of melatonin on endplate chondrocytes (EPCs) are still unclear. Herein, we studied the effects of melatonin on EPC apoptosis and calcification and elucidated the underlying mechanism. Our study revealed that melatonin treatment decreases the incidence of apoptosis and inhibits EPC calcification in a dose‐dependent manner. We also found that melatonin upregulates Sirt1 expression and activity and promotes autophagy in EPCs. Autophagy inhibition by 3‐methyladenine reversed the protective effect of melatonin on apoptosis and calcification, while the Sirt1 inhibitor EX‐527 suppressed melatonin‐induced autophagy and the protective effects of melatonin against apoptosis and calcification, indicating that the beneficial effects of melatonin in EPCs are mediated through the Sirt1‐autophagy pathway. Furthermore, melatonin may ameliorate IDD in vivo in rats. Collectively, this study revealed that melatonin reduces EPC apoptosis and calcification and that the underlying mechanism may be related to Sirt1‐autophagy pathway regulation, which may help us better understand the association between melatonin and IDD. [ABSTRACT FROM AUTHOR]

Mach–Zehnder (MZ) modulators are widely used in optical transmitters to generate high-speed optical signals. With electronic dispersion compensation (EDC), the driving signals to MZ modulators change from digital to analog, or continuous waveforms. Consequently, there is signal degradation from their sinusoidal transfer curves. In this paper, we theoretically and numerically investigate the signal degradation in optical transmitters using MZ modulators in the presence of EDC. We show that the temporal waveforms follow the Gaussian distribution when the EDC is large, and therefore, the modulation index needs to be optimized between the output SNR and the excess insertion loss of MZ modulators. With varying modulation index, we quantify the output SNR and excess insertion loss of optical IQ modulators that consist of two parallel MZ modulators. The calculations are also extended to the scenarios where the sinusoidal transfer curves are compensated for. All the analytical results are verified in a simulation of QPSK transmissions, and they are useful for finding an optimized modulation index for a tradeoff between the output SNR and excess insertion loss. [ABSTRACT FROM PUBLISHER]

An isotopic study was systemically carried out on the granitic complex, diorite-porphyrite, ores and ore minerals of the 103 Ma Xiaoxinancha gold-rich copper deposit in Jilin province to determine the geodynamic model of diagenesis and metallogenesis. Results show that the initial Nd and Sr isotopic compositions of the granitic complex are in the range of 0.70425-0.70505 for (87Sr/86Sr)i, 0.51243-0.51264 for INd, and -1.31 to + 2.64 for εNd( t); those of the diorite-porphyrite are in the range from 0.70438-0.70448 for (87Sr/86Sr)i, 0.51259-0.51261 for INd, and + 1.56 to + 2.09 for εNd( t). For ores and sulfides, the (87Sr/86Sr)i, INd, and εNd( t) values are in the range from 0.70440-0.70805, 0.51259-0.51279 and +1.72 to +5.56, respectively. The Pb isotopic ratios of the granitic complex range from 18.2992-18.6636 for 206Pb/204Pb, from 15.5343-15.5660 for 207Pb/204Pb, and from 38.1640-38.5657 for 208Pb/204pb For diorite-porphyrite, the isotopic ratios of 206Pb/204Pb, 207Pb/204Pb and 208Pb/204b are 18.3919, 15.5794 and 38.3566, respectively, whereas those of the ores and ore sulfides vary from 18.2275-18.3770 for 206Pb/204Pb, from 15.5555-15.5934 for 207Pb/204Pb and from 38.1318-38.3131 for 208Pb/204Pb. The results indicate that the mineralization was correlated to the formation and evolution of the granitic complex and the diorite-porphyrite. Combining with the reported data in petrologic characteristics, elemental geochemistry and chronology, conclusions can be drawn that the geodynamic settings of diagenesis and metallogenesis of this deposit were consistent with the subduction of the Izanagi oceanic plate during the Early Cretaceous. The diorite-porphyrite was formed by the emplacement of the adakitic magma triggered by partial melting of the enriched mantle, which originated from the derivative continental lithospheric mantle metasomatized by dehydration fluids from the subducting oceanic crust. The granitic complex was produced by fractional crystallization of the mixture between the adakitic magma and the high-K calc-alkaline acidic magma, which were generated by the remelting of the lower crust in the course of intraplate upwelling of the adakitic magma. The ore-bearing fluid reservoir convened in a late stage of the evolution of the mixed magma chamber. [ABSTRACT FROM AUTHOR]

The article reports that foreign psychologists like E. J. Smythe, S. Goldstone and others studied both the active and passive time estimate by seconds of children of the six-to-fourteen age bracket. They held that the estimate of short time Intervals by children of the eight-to-four teen age bracket is relatively correct; their time concepts gradually tend to stablize, and they can use related reference signals to help correct mistakes. In fact, they are not much different from young adults. In comparison, children of the six-to-seven age group cannot judge time accurately. Their judgement is varied and unstable, and their estimate of the 30" interval tends to be on the short side. Moreover, they are unable to correct their mistakes in estimation by means of time-related reference signals. The entire experiment consisted of two parts. In the first part researchers did not provide the testees with a standard measure of time. Pressing the stopwatch twice, researchers indicated to the testees by the clicks the beginning and end of a certain time interval. Then the testees were asked to reproduce the indicated time interval by using the same method.

Community detection is a significant research topic in network science, which has been revisited with graph neural networks. As a powerful graph representation learning model, graph autoencoder (GAE) is commonly used for unsupervised community detection. However, most GAE-based methods ignore multi-scale features of encoding layers, which inherently provide useful information for community detection. Moreover, these methods fail to simultaneously improve the representation learning process and clustering performance through a unified objective function. To address these issues, we propose a self-supervised graph autoencoder model with redundancy reduction for community detection. Firstly, we introduce a multi-scale module based on GAE to obtain discriminative node representations from different encoding layers. In particular, a redundancy reduction strategy is employed to eliminate redundancy information in the latent embedding space. Then, a node clustering module is used to obtain initial community labels. To fully utilize the multi-scale features to further refine clustering performance, a self-supervised module is designed to utilize current clustering labels to supervise the node representation learning process, thus constructing an end-to-end model for community detection. Finally, we validate the effectiveness of the proposed method on real-world networks. Experimental results demonstrate that our method outperforms several state-of-the-art methods in community detection. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective Cohort Study.Objectives: This study compared the function and radiographical outcomes of the patients who underwent C2 dome-like expansive laminoplasty to those C2 expansive open-door laminoplasty for the treatment of OPLL with C2 involved.Summary Of Background Data: There are few comparative studies of these two surgical methods. C2 dome-like and C2 expansive open-door laminoplasty are posterior approaches for posterior longitudinal ligament ossification with C2 level and above.Methods: This study performed a retrospective cohort analysis of 59 patients with OPLL up to C2 which cause compression symptoms. 31 patients underwent C2 dome-like expansive laminoplasty with C3-7 expansive open-door laminoplasty (Group Dom) and 28 underwent C2-7 expansive open-door laminoplasty (Group Exp). The preoperative and postoperative space available for cord (SAC) of C2 segment, cervical curvature index of C2-7, C2-7 range of motion, Japanese orthopedic association (JOA) score, visual analog scale (VAS) score, and neck disability index (NDI) were used to assess clinical out-comes and statistically analyzed.Results: The cervical curvature index, JOA score, and NDI significantly changed at the final follow-up in two groups with no significant intergroup differences. There were no significant differences in preoperative SAC and VAS between the two groups. At the final follow-up, the SAC of C2/3 in Group Exp was significantly larger than Group Dom, while the VAS and range of motion of Group Dom became significantly better than Group Exp.Conclusion: The C2 dome-like expansive laminoplasty can reduce postoperative neck pain more obviously and achieve better cervical curvature. C2 expansive open-door laminoplasty can get more adequate decompression in the spinal canal, which may be recommend to the patients with OPLL occupying more than 50% of the vertebral canal at C2/3, or with developmental spinal stenosis.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

The Yangtze River is the largest river in Asia, and its evolution has been a subject of debate for more than a century. The formation of the First Bend is widely recognized as a key drainage reorganization event that led to the birth of the modern Yangtze River. In this study, we use new detrital rutile U Pb ages to constrain the sedimentary provenance of the Cenozoic deposits in the Jianchuan Basin. Our results show that detrital rutile U Pb ages of the Eocene sandstones from the Jianchuan Basin are similar to those of the Yalong River and Jinsha River, indicating that the upper Yangtze is likely to have flowed through the Jianchuan Basin in the late Eocene. Moreover, the characteristic zircon age signature of the Yalong and Jinsha Rivers also appear in the Jianchuan Basin, which is consistent with the rutile data. Our new rutile data and previous detrital zircon data suggest that the upper Yangtze River is likely to connect the Red River via the Jianchuan Basin since the late Eocene. [Display omitted] • New detrital rutile results indicate Cenozoic sediment in the Jianchuan Basin source from upper Yangtze (Yalong and Jinsha rivers). • The characteristic zircon age signature of the Yalong and Jinsha rivers are also appearance in the Jianchuan Basin, which is consistent with the rutile data. • The upper Yangtze is likely to flow southwards into the Red River through the Jianchuan Basin prior to ∼36 Ma. [ABSTRACT FROM AUTHOR]

Engineering approaches for growth factor delivery have been considerably advanced for tissue regeneration, yet most of them fail to provide a complex combination of signals emulating a natural healing cascade, which substantially limits their clinical successes. Herein, we aimed to emulate the natural bone healing cascades by coupling the processes of angiogenesis and osteogenesis with a hybrid dual growth factor delivery system to achieve vascularized bone formation. Basic fibroblast growth factor (bFGF) was loaded into methacrylate gelatin (GelMA) to mimic angiogenic signalling during the inflammation and soft callus phases of the bone healing process, while bone morphogenetic protein-2 (BMP-2) was bound onto mineral coated microparticles (MCM) to mimics osteogenic signalling in the hard callus and bone remodelling phases. An Initial high concentration of bFGF accompanied by a sustainable release of BMP-2 and inorganic ions was realized to orchestrate well-coupled osteogenic and angiogenic effects for bone regeneration. In vitro experiments indicated that the hybrid hydrogel markedly enhanced the formation of vasculature in human umbilical vein endothelial cells (HUVECs), as well as the osteogenic differentiation of mesenchymal stem cells (BMSCs). In vivo results confirmed the optimal osteogenic performance of our F/G-B/M hydrogel, which was primarily attributed to the FGF-induced vascularization. This research presents a facile and potent alternative for treating bone defects by emulating natural cascades of bone healing. [ABSTRACT FROM AUTHOR]

Sedimentary basins in the southeastern margin of the Tibetan Plateau yield valuable geophysical and fossil records, documenting the paleoenvironmental and biodiversity changes in the Tibetan Plateau and the Hengduan Mountains. Constraining the age of sediment deposition is fundamental in understanding the evolutionary history of biodiversity, climate (e.g. development of the monsoon), and regional landscape changes. Many basins in this area were originally considered as Miocene basins based on regional lithostratigraphic comparison and biostratigraphy, although this has been challenged recently for several basins (e.g. Lühe, Markma, Jianchuan, Wenshan and Relu basins). Here we report a new age for the Mouding Basin, Central Yunnan, China. We arrive at an early Oligocene (33 ± 1 Ma) instead of a Miocene age for the fossil-bearing strata of this basin. U Pb and 40Ar/39Ar dating of a volcanic ash layer from the Mouding Basin and one from the Lühe Basin in combination with zircon Hf isotope data suggest that the early Oligocene Laojiezi eruption is a likely source for ash layers in both basins. Fossilized dicot leaves were used to reconstruct the paleoclimate and the paleo-elevation of the Mouding Basin. This paleoclimate reconstruction indicates that the paleoclimate in the Mouding Basin closely resembles that of the Lühe Basin. The paleoclimate between the two floras is in fact more similar than their respective modern climates. During the early Oligocene, the Mouding Basin experienced colder and more humid winters with a milder monsoonal climate compared to today. Despite this, the Mouding flora exhibits high floristic similarities with its contemporary Lühe and Markam floras, as well as with the modern vegetation in southwestern China, supporting that the modernization of the biodiversity in the SE margin of the Tibetan Plateau has initiated since the Paleogene. • New zircon U Pb and K-feldspar 40Ar/39Ar ages of volcanic ash revise the 'Miocene' Mouding Basin, Yunnan, to early Oligocene. • Volcanic ash layers in the Mouding and Lühe basins are likely to originate from the Laojiezi eruption in the early Oligocene. • Time of modernization of the flora in SE Tibet began before the early Oligocene, most likely in the late Eocene. [ABSTRACT FROM AUTHOR]

The ore-forming fluids were ultimately derived from low-δ18O meteoric waters. The ore-forming fluids leached 34S-rich gypsum, 11B-borate, sodium chloride and other salts in the evaporites of the Liaohe Group, which made the ore-forming hydrothermal fluids slightly alkaline and weakly oxidized. Some of this silica reacted with metamorphosed clay minerals in the wall rocks to form chlorite, garnet, tremolite, and biotite. Some of silica migrated and, as the temperature decreased, precipitated in veins or as aggregates around the high-grade iron ores. Most iron was enriched (semi-) in situ and this formed the high-grade iron ores. A small amount of "iron activation–reprecipitation" developed high-grade iron veins. [Display omitted] • The Gongchangling high-grade magnetite ores were formed by Paleoproterozoic hydrothermal replacement of BIFs. • The ore-forming hydrothermal fluids leached soluble salts from evaporites of the Liaohe Group. • Desilicification and Fe enrichment was the primary mineralization mechanism of the Gongchangling high-grade iron ores. The Gongchangling iron deposit in North China hosts abundant high-grade (>50 wt% total Fe) magnetite ores and represents one of the largest BIF-hosted magnetite deposits worldwide. These high-grade magnetite ores are generally accepted to be formed by replacement of banded iron formation (BIF) (∼30 wt% total Fe), but the mechanism of iron enrichment remains controversial. Here we report new O–S–B isotope data of BIFs, high-grade iron ores, and related altered wall rocks, from the Gongchangling iron deposit, together with the geological and geochronological data to constrain the formation of the high-grade iron ores, and proposed new genetic model. The high-grade iron ores have positive δ56Fe and negative δ30Si values, similar to the BIFs, whereas the δ18O values of the high-grade iron ores and altered wall rocks are significantly lower than those of the BIFs. The δ34S values of pyrite from the high-grade iron ores are much higher than those of the BIFs. The δ11B values of tourmaline in the altered wall rocks of the high-grade iron ores are anomalously high, which is distinct from those of the BIFs and wall rocks, but similar to those of the evaporites from the Liaohe Group. At ca. 1.85 Ga, intense hydrothermal activity was initiated by post-orogenic extension and uplift with 18O-poor meteoric water circulated along crustal structures. Compositions of Na+, K+, Mg2+, Cl–, CO 3 2–, 34S-rich SO 4 2–, 11B-rich borate, and other soluble salts minerals were leached from the evaporitic rocks of the Liaohe Group, which driving the ore-forming hydrothermal fluids toward slightly alkaline and weakly oxidized as system matures. As the alkaline fluids migrated along the structures and fractures in the BIFs and reacted with the wall rocks, SiO 2 was mobilized from the low-grade iron ores and consequently formed chlorite, garnet, and tremolite in the wall rocks due to reactions with clay minerals. These Si-rich hydrothermal fluids was also related to vein type quartz and massive quartz-bearing rocks. Most Fe was retained in situ and resulted in the formation of magnetite-rich iron ores. The SO 4 2– in the hydrothermal fluids was reduced to form pyrite while B in the hydrothermal fluids reacted with the wall rocks to form 11B-rich tourmaline. [ABSTRACT FROM AUTHOR]

Bromine (Br) is one of the trace elements in halite. Br content and the Br/chlorine (Cl) molar ratio can be used to reveal dry climates, the degree of evaporation, and/or brine concentration. The Br content of basal halite is more useful than that the Br content of halite from later stages when being used to distinguishing marine from nonmarine origins. Evaporite deposits on the Khorat Plateau (KP) have been a primary source of evaporites in southeastern Asia. The origin (i.e., marine, nonmarine, or a combination of the two) of these deposits is still disputed. In this study, we used the Br concentration of basal halite and the Br/Cl molar ratio to explore the origin of these deposits and the environmental changes that took place in the Late Cretaceous. We analyzed a total of 330 halite samples from borehole ZK2893 for cations (K+, Ca2+, Na+, and Mg2+) and anions (Br−, Cl−, and SO42−). The Br content ranged from 24.04 to 277.87 ppm, and the Br/Cl molar ratio ranged from 0.02 to 0.27 ppm. The low Br content (24.04 ppm) and Br × 103/Cl molar ratio (0.02) of the basal halite suggested that no marine water was in the basin when the halite precipitation began. The temporal variations in the Br content and the Br × 103/Cl molar ratio of halite implied that: (1) the climate in this area during the Late Cretaceous was dry, with two dry stages occurring from 92 to 85 Ma and from 80 to 72 Ma; and (2) the drying trend increased from 92 to 85 Ma and from 80 to 72 Ma, with two extremely dry events occurring during the periods 89–85 Ma and 76–73 Ma. [ABSTRACT FROM AUTHOR]

Intervertebral disc degeneration (IDD) is widely considered one of the main causes of low back pain, which is a chronic progressive disease closely related to inflammation and degeneration of nucleus pulposus (NP) cells. Baicalein is a natural bioactive compound with anti-inflammatory effects in different diseases, including inhibition of the inflammatory response in chondrocytes, whose morphology and avascular supply are similar to those of NP cells. Therefore, we hypothesized that baicalein may have a therapeutic effect on IDD by suppressing the inflammatory response. In vitro, NP cells were pretreated with baicalein for 2 h and then incubated with IL-1β for 24 h. We found that baicalein not only inhibited the overexpression of inflammatory cytokine production, including NO, PGE2, TNF-α, and IL-6, but also suppressed the expression of COX-2 and iNOS. The IL-1β-induced overexpression of MMP13 and ADAMTS5 and degradation of aggrecan and type II collagen were reversed by baicalein in a dose-dependent manner. Mechanistically, we found that baicalein suppressed the IL-1β-induced activation of the NF-κB and MAPK pathways. Moreover, an in vivo study demonstrated that baicalein treatment could ameliorate IDD in a puncture-induced rat model. Thus, baicalein has great value as a potential therapeutic agent for IDD. [ABSTRACT FROM AUTHOR]

The origins of the evaporite deposits of the Khorat Plateau remain disputed. Based purely on the known evolution of the Khorat Plateau, materials of marine origin and/or remnant seawater should be present, but instead the salt layers of the deposits found there present typically continental lithological features. New data suggest that the Laotian evaporite deposits can be dated to the Middle to Late Cretaceous. In this paper we present the sulfate δ 34 S (5.2‰ to 15.6‰) and δ 18 O- SO4 (10.3‰ to 14.1‰) records, Sr isotopic compositions (0.707443 to 0.708587), δ 18 O -inclusion (− 7.1‰ to 13.9‰) and δD -inclusion (− 72‰ to − 150‰) records and the trace metal elements for halite deposits extracted from Core ZK2893 in the Sakhon Nakhon Basin, Laos. These values suggest that the deposits are of continental and hydrothermal origins with trace marine remnants. Evaporites in the basins are very likely to have been formed originally by the evaporation of seawater, prior to being dissolved in meteoric water and hydrothermal fluid, and subsequently precipitated. [ABSTRACT FROM AUTHOR]

The Yanghuidongzi Cu deposit is located in the southeastern part of Heilongjiang Province in NE China and represents one of the few known Early Jurassic porphyry Cu deposits within the eastern edge of the Xing’an–Mongolia Orogenic Belt. Here we present new whole-rock major and trace element and Sr–Nd isotopic data, zircon U–Pb and Hf isotopic data, and molybdenite Re–Os data for units associated with the deposit. Laser ablation inductively coupled plasma mass spectrometry (LA–ICP–MS) dating of zircons from the granodiorite porphyry in the study area yielded ages of 191.0 ± 1.1 and 191.2 ± 1.0 Ma that are interpreted to be the emplacement age of this intrusion. The molybdenite Re–Os dating undertaken during this study yielded model ages of 192.7–187.0 Ma, an isochron age of 188.2 ± 3.8 Ma, and a weighted mean model age of 190.2 ± 2.6 Ma, representing the timing of formation of the Cu mineralization in this area. The Yanghuidongzi granodiorite porphyry contains relatively high concentrations of SiO 2 (68.88–72.49 wt%), Al 2 O 3 (15.37–16.31 wt%), and Sr (230–479 ppm), but relatively low concentrations of Y (7.97–9.87 ppm) and Yb (0.72–0.85 ppm), suggesting that this intrusion has an adakitic affinity. Combining this with the positive εNd (t) (0.7–1.1) and εHf(t) values (4.0–6.9), low Mg # values (41–50), and the low concentrations of MgO (0.86–1.22 wt%), Cr (3.17–4.37 ppm), and Ni (2.11–4.20 ppm) within this intrusion suggests it formed from a magma generated by the partial melting of juvenile lower crustal material during the Early Jurassic subduction of the Paleo-Pacific Plate. [ABSTRACT FROM AUTHOR]

Understanding the spatio-temporal distribution of strain during Cenozoic growth of the Tibetan Plateau is important for constraining the geodynamic processes underpinning plateau formation. Offset Quaternary landforms and historic earthquake data suggest an along-strike change in deformation style for the eastern margin of the Tibetan Plateau, characterized by a transition from ESE-verging shortening to right-lateral shear from the southern to northern segment of the Long-Men Shan fault zone within a distance of ca. 500 km. When and how this along-strike deformation pattern formed is central to understanding the uplift history and spatio-temporal distribution of strain in the eastern margin of the Tibetan Plateau, and the underpinning geodynamics. To address this, we report a suite of low-temperature thermochronology data from the northern segment of Long-Men Shan fault zone that show a contrast in post late Cretaceous cooling and exhumation histories between the hinterland (west of the marginal Yingxiu-Beichuan fault) and foreland sides (east of the fault). Prior to the Eocene (ca. 40 Ma), the hinterland experienced significant exhumation in contrast to minor exhumation on the foreland side, but, post Eocene exhumation accelerated on the foreland side. This change reflects a switch in the deformation regime from shortening to strike-slip-dominated. This switch reduced hinterland rock uplift and tectonic and topographic loading over the foreland basin, leading to accelerated foreland exhumation through isostatic adjustments. A compilation of fault deformation history for the eastern Tibetan Plateau shows a second tectonic transition in the late Miocene, characterized by formation of the south-striking Huya and Minjiang faults. Our results highlight the importance of progressive late Eocene and late Miocene tectonic transitions in shaping the eastern margin of the Tibetan Plateau. • The hinterland and foreland sides of the eastern Tibetan Plateau margin experienced differential Eocene exhumation. • The differential evolution indicates a coeval tectonic transition from shortening-dominated to strike-slip-dominated. • A second tectonic transition is characterized by the late Miocene formation of the Huya and Minjiang faults. • The eastern margin of the Tibetan Plateau is shaped by progressive late Eocene and late Miocene tectonic transitions. [ABSTRACT FROM AUTHOR]

The development of modern drainage patterns in eastern Tibet is closely related to uplift of the Tibetan Plateau. The Yangtze River is the longest river in Asia. When and how this river formed is still vigorously debated. Here we compile published detrital zircon U Pb ages from the Chuxiong, Sichuan, Jianghan, Jianchuan, Simao, Vientiane, Song Hong-Yinggehai basins, marginal sea basins in East China and Taiwan to reconstruct the evolution of the Yangtze River. Reassessment of published detrital zircon data from the broader region sheds new light on the development of the Yangtze. Detrital zircon data from the Jianghan Basin, marginal sea basins in East China and Taiwan suggest that the pre-Miocene Yangtze River did not include the present upper reaches. The detrital zircon ages from the Song Hong-Yinggehai Basin suggest that the upper Yangtze River did not flow southward into the Red River since the Oligocene. Instead, similarities in detrital zircon U Pb ages between the Sichuan, Chuxiong and Simao basins imply that the paleo-upper Yangtze flowed southwestward into the Vientiane Basin via the Chuxiong and Simao basins before the Miocene. The appearance of Cenozoic zircons in the Miocene sediment in the Jianghan Basin suggests that the southwestward-flowing paleo-upper Yangtze River was captured by the mid-lower Yangtze between the late Oligocene and the early Miocene. • Compiled detrital zircon U Pb ages were used to reconstruct paleo-drainage patterns. • The upper Yangtze did not flow southward into the South China Sea in the Cenozoic. • The upper Yangtze flowed southwestward into the Vientiane Basin before the Miocene. [ABSTRACT FROM AUTHOR]

Detrital muscovite and biotite 40Ar/39Ar analyses are useful tools for studying regional tectonic histories, sediment provenances and paleo-drainage reconstructions. During transport and recycling of detrital micas physical and chemical weathering occurs. This process effects the grain size and age populations ultimately found in river sediments, but is often ignored in provenance studies. Here, we present detrital muscovite and biotite 40Ar/39Ar results of 15 modern sediments from the Yangtze River to address the impact of grainsize on provenance age populations. The beam intensities of 39Ar, formed from 39K by neutron capture reaction during sample irradiation, have been used as an index for grain size. We found that relatively older detrital mica ages of the Yangtze River are often characterized by small 39Ar signals (i.e., grain sizes), and large grain sizes correspond to younger grains. This observation is also revealed by reanalysis of previously reported detrital mica studies in other major river systems (Red and Brahmaputra rivers) and sediments (Scotian Basin, Canada and Antarctic) and probably results from physical and chemical weathering during transport and recycling. Our Yangtze results indicate that detrital muscovite and biotite ages of grainsize ranging from 100 to 1000 μm cover all age components as identified in all dated grains (with a size of >100 μm), and thus indicate that detrital mica 40Ar/39Ar analyses should include also small grains from >100 μm to reduce the effects of hydraulic sorting and weathering. Grainsizes smaller than 100 μm have not been tested in this study, but will be more difficult to date due to both smaller beam intensities and possible recoil effects. [ABSTRACT FROM AUTHOR]

Background: Erastin has been found to induce ferroptosis; however, whether erastin may have roles other than ferroptosis inducer in cells is unknown. Nutrient deficiency is one of the major causes of many diseases including intervertebral disc (IVD) degeneration., Purpose: The current study investigates the effect of erastin in nucleus pulposus cells under nutrient deprivation condition., Study Design: Experiment in vitro and ex vivo., Methods: The effect of erastin on the cell survival of nucleus pulposus cells was evaluated in fetal bovine serum (FBS) and glucose deprivation condition. RSL3 and ferrostatin-1 were applied to illustrate whether the effect of erastin is ferroptosis dependent. The involvement of solute carrier family 7, membrane 11(SLC7A11), autophagy as well as mechanistic target of rapamycin kinase complex 1(mTORC1) and transcription factor EB (TFEB) were assessed to demonstrate the working mechanism of erastin., Results: Erastin may induce cell death at the concentration of ≥ 5μM; however, it may protect nucleus pulposus cells against nutrient deprivation induced cell death at lower concentration (0.25-1μM) and the effect of erastin is ferroptosis independent. The mechanism study showed that the effect of erastin may relate to its SCL7A11 regulation, as SCL7A11 knock-down may have the similar effect as erastin. Furthermore, it was also demonstrated that mTORC1-TFEB mediated autophagy was involved in protective effect of erastin., Conclusions: Low dose erastin may promote cell survival under nutrient deprivation condition, and its effect is ferroptosis independent; erastin may exert its protective effect through mTORC1-TFEB mediated autophagy regulation., Clinical Significance: Nutrient deprivation is a major contributor to intervertebral disc degeneration. Our in vitro and ex vivo study showed that low dose of erastin may suppress nutrient deprivation induced cell death in IVD degeneration. Although it was not validated in vivo model due to lack of in vivo nutrient deprivation induced IVD degeneration model currently, this study may still provide a potential therapeutic option for IVD degeneration, which of cause need further validation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Many microRNAs (miRNAs) have been identified as being involved in diabetes; however, the question of which ones may be the most promising therapeutical targets still needs more investigation. This study aims to understand the overall development tendency and identify a specific miRNA molecule to attenuate diabetes. We developed a combined analysis method based on bibliometrics and bioinformatics to visualize research institutions, authors, cited references, and keywords to identify a promising target for diabetes. Our data showed that diabetes-related miRNA is receiving continuously increasing attention, with a large number of publications, indicating that this is still a hot topic in diabetes research. Scientists from different institutions are collaborating closely in this field. miR-21, miR-146a, miR-155, and miR-34a are frequently mentioned as high-frequency keywords in the related references. Moreover, among all the above miRNAs, bioinformatics analysis further strengthens the argument that miR-21 is the top significantly upregulated molecule in diabetes patients and plays an important role in the pathogenesis of diabetes. Our study may provide a way to identify targets and promote the clinical translation of miRNA-related therapeutical strategies for diabetes, which could also indicate present and future directions for research in this area.

Deep tissue infection is a common clinical issue and therapeutic difficulty caused by the disruption of the host antibacterial immune function, resulting in treatment failure and infection relapse. Intracellular pathogens are refractory to elimination and can manipulate host cell biology even after appropriate treatment, resulting in a locoregional immunosuppressive state that leads to an inadequate response to conventional anti-infective therapies. Here, a novel antibacterial strategy involving autogenous immunity using a biomimetic nanoparticle (NP)-based regulating system is reported to induce in situ collaborative innate-adaptive immune responses. It is observed that a macrophage membrane coating facilitates NP enrichment at the infection site, followed by active NP accumulation in macrophages in a mannose-dependent manner. These NP-armed macrophages exhibit considerably improved innate capabilities, including more efficient intracellular ROS generation and pro-inflammatory factor secretion, M1 phenotype promotion, and effective eradication of invasive bacteria. Furthermore, the reprogrammed macrophages direct T cell activation at infectious sites, resulting in a robust adaptive antimicrobial immune response to ultimately achieve bacterial clearance and prevent infection relapse. Overall, these results provide a conceptual framework for a novel macrophage-based strategy for infection treatment via the regulation of autogenous immunity., (© 2024 Wiley‐VCH GmbH.)

Bone is a common organ for solid tumor metastasis. Malignant bone tumor becomes insensitive to systemic therapy after colonization, followed by poor prognosis and high relapse rate. Immune and bone cells in situ constitute a unique immune microenvironment, which plays a crucial role in the context of bone metastasis. This review firstly focuses on lymphatic cells in bone metastatic cancer, including their function in tumor dissemination, invasion, growth and possible cytotoxicity-induced eradication. Subsequently, we examine myeloid cells, namely macrophages, myeloid-derived suppressor cells, dendritic cells, and megakaryocytes, evaluating their interaction with cytotoxic T lymphocytes and contribution to bone metastasis. As important components of skeletal tissue, osteoclasts and osteoblasts derived from bone marrow stromal cells, engaging in 'vicious cycle' accelerate osteolytic bone metastasis. We also explain the concept tumor dormancy and investigate underlying role of immune microenvironment on it. Additionally, a thorough review of emerging treatments for bone metastatic malignancy in clinical research, especially immunotherapy, is presented, indicating current challenges and opportunities in research and development of bone metastasis therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Lei, Mou, Zhang, Jin, Lu, Yinwang, Xue, Shao, Chen, Wang, Zhao, Chai, Wang, Zhang, Zhang, Ye and Li.)

Tumor-associated macrophage (TAM) reprogramming is a promising therapeutic approach for cancer immunotherapy; however, its efficacy remains modest due to the low bioactivity of the recombinant cytokines used for TAM reprogramming. mRNA therapeutics are capable of generating fully functional proteins for various therapeutic purposes but accused for its poor sustainability. Inspired by kinetic energy recovery systems (KERS) in hybrid vehicles, a cytokine efficacy recovery system (CERS) is designed to substantially augment the therapeutic index of mRNA-based tumor immunotherapy via a "capture and stabilize" mechanism exerted by a nanostructured mineral coating carrying therapeutic cytokine mRNA. CERS remarkably recycles nearly 40% expressed cytokines by capturing them onto the mineral coating to extend its therapeutic timeframe, further polarizing the macrophages to strengthen their tumoricidal activity and activate adaptive immunity against tumors. Notably, interferon-γ (IFN-γ) produced by CERS exhibits ≈42-fold higher biological activity than recombinant IFN-γ, remarkably decreasing the required IFN-γ dosage for TAM reprogramming. In tumor-bearing mice, IFN-γ cmRNA@CERS effectively polarizes TAMs to inhibit osteosarcoma progression. When combined with the PD-L1 monoclonal antibody, IFN-γ cmRNA@CERS significantly boosts antitumor immune responses, and substantially prevents malignant lung metastases. Thus, CERS-mediated mRNA delivery represents a promising strategy to boost antitumor immunity for tumor treatment., (© 2023 Wiley-VCH GmbH.)

Purpose: We retrospectively study twenty-nine surgical cases of aggressive vertebral hemangiomas (AVHs) with neurological deficits and extradural compression to determine the optimal surgical treatment strategy for AVHs at a single institution., Methods: Patients with AVHs with neurological deficits who underwent partial tumor resection plus decompression with or without vertebroplasty (VP), and radiotherapy between 2010 and 2021 were included in this study. Clinical characteristics, surgical outcomes, and follow-up data of the patients were reviewed retrospectively., Results: Twenty-nine AVH cases with neurological deficits and spinal instability were included in this study and treated surgically. The mean operation time of patients with decompression surgery plus VP (Groupe A) was 215.9 (120-265 min), shorter than that of decompression surgery without VP (Group B) 240.2 (120-320 min). Intraoperative blood loss was 273.3 (100-550 mL) in group A and 635.3 (200-1600 mL) in group B. In addition, a significant reduction in blood loss was observed in group A compared to the group B ( p= 0.0001). All patients experienced immediate pain relief and improvement in their neurological symptoms. Neurological function was assessed by the Frankel score, ASIA score, and the visual analogue scale (VAS) pain score decreased from 7.4 (4-9) to 1.3 (0-3). Of twenty-nine patients in this study,  only 7% (2/29 patients) showed signs of recurrence., Conclusion: Decompression plus VP achieve good tumor control and decrease surgical complication. Preoperative vascular embolization and VP can reduce intraoperative bleeding in the treatment of AVH surgery. Moreover, postoperative radiotherapy seems to be a good technique to prevent tumor recurrence., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zhan Wang reports financial support was provided by The Second Affiliated Hospital Zhejiang University School of Medicine., (© 2023 The Authors. Published by Elsevier GmbH.)

Background: Evident adolescent idiopathic scoliosis (AIS) incurs high treatment costs, low quality of life, and many complications. Early screening of AIS is essential to avoid progressing to an evident stage. However, there is no valid serum biomarker for AIS for early screening., Methods: Antibody-based array is a large-scale study of proteins, which is expected to reveal a serum protein signature as biomarker for AIS. There are two segments of the research, including biomarkers screening and validation. In the biomarkers screening group, a total of 16 volunteers participated in this study, and we carried out differentially expressed proteins screening via protein array assay between No-AIS group and the AIS group, through which GeneSet enrichment analysis was performed. In the validation group with a total of 62 volunteers, the differentially expressed proteins from screening group were verified by Enzyme-Linked immunosorbent assay (ELISA), and then multiple regression analysis., Results: In our study, there were twenty-nine differentially expressed proteins in AIS, through Protein array assay and GeneSet enrichment analysis in the biomarkers screening group. Then the expression of FAP, CD23 and B2M decreased as the degree of AIS increased via ELISA in validation group (FAP, p < 0.0001; CD23, p = 0.0002; B2M, p < 0.0001). Further, the results of multiple regression analysis showed that FAP, CD23 are linked to Cobb angle, whereas B2M were excluded because of multicollinearity., Conclusions: Altogether, we found that serum protein FAP and CD23 are intimately related to AIS, suggesting FAP and CD23 are expected to serve as the serum biomarkers, which significantly facilitate frequent longitudinal monitoring as to keep track of disease progression and tailor treatment accordingly., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Tumor resection and prosthetic replacement have become the treatments of choice for malignant bone tumors. Infections are the leading cause of failure of limb salvage surgeries. Therefore, treating infections around prostheses after limb salvage is essential and challenging. Our research team designed a "domino" sequential treatment plan to treat postoperative infections around tumor prostheses and evaluated its efficacy., Purpose: To introduce the new domino sequential treatment plan for postoperative infections of tumor prostheses, and evaluate the technical points of the plan and prognosis in medium- and long-term follow-ups., Methods: Between January 2015 and August 2021, 14 patients were treated with prosthesis-preserving domino sequential therapy for peripheral prosthesis infections after bone-tumor limb salvage. The sample included eight cases of distal femur tumor, two of proximal tibia tumor, three of pelvic tumor, and one of middle femur tumor. We evaluated routine blood test results, C-reactive protein level, the erythrocyte sedimentation rate, and other indicators. X-rays and CT scans of the surgical site were obtained and the Musculoskeletal Tumor Society (MSTS) score was calculated. Treatment involved debridement and lavage of the prosthesis, and systemic and local antibiotics., Results: The positivity rate of microbial culture was 78.6%. There were three cases of Staphylococcus aureus, one of Staphylococcus epidermidis, two of methicillin-resistant Staphylococcus epidermidis, one of methicillin-resistant Staphylococcus aureus, two of Acinetobacter baumannii, one of Streptococcus lactis (group C), one of Streptococcus mitis, and three with negative cultures. In three cases, sequential treatment failed to control the infection. The operation success rate was 78.6% (11/14). One case eventually required amputation, and another required long-term wound dressings. To control the infection, a third had to be treated using antibiotic bone cement combined with the "intramedullary nail reverse double insertion" technique. The MSTS scores of patients before infection debridement and at the last follow-up showed statistically significant differences (t = 5.312, p = 0.02)., Conclusions: The prosthesis-preserving domino sequential method has certain advantages for treating bone-tumor limb salvage infections around the prosthesis., Level of Evidence: Level IV, therapeutic., (Copyright © 2022. Published by Elsevier Ltd.)

Exosome therapy is a promising therapeutic approach for intervertebral disc degeneration (IVDD) and achieves its therapeutic effects by regulating metabolic disorders, the microenvironment and cell homeostasis with the sustained release of microRNAs, proteins, and transcription factors. However, the rapid clearance and disruption of exosomes are the two major challenges for the application of exosome therapy in IVDD. Herein, a thermosensitive acellular extracellular matrix (ECM) hydrogel coupled with adipose-derived mesenchymal stem cell (ADSC) exosomes (dECM@exo) that inherits the superior properties of nucleus pulposus tissue and ADSCs was fabricated to ameliorate IVDD. This thermosensitive dECM@exo hydrogel system can provide not only in situ gelation to replenish ECM leakage in nucleus pulposus cells (NPCs) but also an environment for the growth of NPCs. In addition, sustained release of ADSC-derived exosomes from this system regulates matrix synthesis and degradation by regulating matrix metalloproteinases (MMPs) and inhibits pyroptosis by mitigating the inflammatory response in vitro. Animal results demonstrated that the dECM@exo hydrogel system maintained early IVD microenvironment homeostasis and ameliorated IVDD. This functional system can serve as a powerful platform for IVD drug delivery and biotherapy and an alternative therapy for IVDD., (© 2021. The Author(s).)

Tissue damage caused by hyperthermia during photothermal therapy (PTT) has largely limited its clinical applications for implant infection. However, rescue of tissue regeneration by conjugating orthobiologics with PTT has been problematic as they can easily deactivate biologics while eradicating bacteria. Herein, we report an orthobiologics-free strategy to synergistically couple photocatalytic antibacterial with pro-osteogenic capacity via self-assembly of copper sulphide nanoparticle (CuS NP) and reduced graphene oxide (rGO) on implant surface. This strategy not only offers enhanced photothermal effects for bacterial eradiation via near-infrared light (NIR), but also promotes vascularized osseointegration via cooperation of copper ion with rGO. In vitro and in vivo data showed that coupling CuS and rGO synergistically increased antibacterial efficacy of implants by 40 times and successfully destroyed bacterial biofilm upon NIR. Moreover, CuS/rGO decorated surface substantially improved bone marrow stromal cell adhesion, proliferation, as well as subsequent differentiation toward osteoblast. We also revealed that enhanced peri-implant vascularization may be attributed to the sustained release of copper ion from CuS NPs, which further collaborated with rGO to promote vascularized osseointegration. Altogether, this novel orthobiologics-free approach offers a practical alternative to circumvent the intrinsic drawbacks of PTT and endows powerful antibacterial and pro-osteogenic capacities for implant associated infections., (Copyright © 2021. Published by Elsevier Ltd.)

Objective: To elucidate the role of LRRK2 in intervertebral disc degeneration (IDD) as well as its mitophagy regulation mechanism., Methods: The expression of LRRK2 in human degenerative nucleus pulposus tissues as well as in oxidative stress-induced rat nucleus pulposus cells (NPCs) was detected by western blot. LRRK2 was knocked down in NPCs by lentivirus (LV)-shLRRK2 transfection; apoptosis and mitophagy were assessed by western blot, TUNEL assay, immunofluorescence staining and mitophagy detection assay in LRRK2-deficient NPCs under oxidative stress. After knockdown of Parkin in NPCs with siRNA transfection, apoptosis and mitophagy were further assessed. In puncture-induced rat IDD model, X-ray, MRI, hematoxylin-eosin (HE) and Safranin O-Fast green (SO) staining were performed to evaluate the therapeutic effects of LV-shLRRK2 on IDD., Results: We found that the expression of LRRK2 was increased in degenerative NPCs both in vivo and in vitro. LRRK2 deficiency significantly suppressed oxidative stress-induced mitochondria-dependent apoptosis in NPCs; meanwhile, mitophagy was promoted. However, these effects were abolished by the mitophagy inhibitor, suggesting the effect of LRRK2 on apoptosis in NPCs is mitophagy-dependent. Furthermore, Parkin knockdown study showed that LRRK2 deficiency activated mitophagy by recruiting Parkin. In vivo study demonstrated that LRRK2 inhibition ameliorated IDD in rats., Conclusions: The results revealed that LRRK2 is involved in the pathogenesis of IDD, while knockdown of LRRK2 inhibits oxidative stress-induced apoptosis through mitophagy. Thus, inhibition of LRRK2 may be a promising therapeutic strategy for IDD., (Copyright © 2021 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Bacteria-associated infection represents one of the major threats for orthopedic implants failure during their life cycles. However, ordinary antimicrobial treatments usually failed to combat multiple waves of infections during arthroplasty and prosthesis revisions etc. As these incidents could easily introduce new microbial pathogens in/onto the implants. Herein, we demonstrate that an antimicrobial trilogy strategy incorporating a sophisticated multilayered coating system leveraging multiple ion exchange mechanisms and fine nanotopography tuning, could effectively eradicate bacterial infection at various stages of implantation. Early stage bacteriostatic effect was realized via nano-topological structure of top mineral coating. Antibacterial effect at intermediate stage was mediated by sustained release of zinc ions from doped CaP coating. Strong antibacterial potency was validated at 4 weeks post implantation via an implanted model in vivo . Finally, the underlying zinc titanate fiber network enabled a long-term contact and release effect of residual zinc, which maintained a strong antibacterial ability against both Staphylococcus aureus and Escherichia coli even after the removal of top layer coating. Moreover, sustained release of Sr 2+ and Zn 2+ during CaP coating degradation substantially promoted implant osseointegration even under an infectious environment by showing more peri-implant new bone formation and substantially improved bone-implant bonding strength., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Based on field investigation and experimental data analysis, ecological economic principles were applied to study the structure and function, the characteristics of material and energy flows, and the economic and ecological benefits of a rice-crab model. The results show that rice-crab model had a higher integral benefit than rice model, and its net income, cost-benefit ratio, and labor productivity were increased by 382%, 67.7% and 295%, respectively. In view of the ecological benefits produced, the total nitrogen, alkaline-hydrolyzal nitrogen, total phosphorus, rapidly available phosphorus, rapidly available potassium, and organic matter in the soil after 1-year carb breeding were increased by 10.6%, 3.3%, 5.8%, 11.7%, 3.5% and 10.5%, respectively. Moreover, 6.375 kg N.hm-2 of non-point source pollution load could be cut down annually.