Over the last two or three decades, the pace of development of treatments for osteosarcoma tends has been slow. Novel effective therapies for osteosarcoma are still lacking. Previously, we reported ...that tumor-suppressing STF cDNA 3 (TSSC3) functions as an imprinted tumor suppressor gene in osteosarcoma; however, the underlying mechanism by which TSSC3 suppresses the tumorigenesis and metastasis remain unclear.
We investigated the dynamic expression patterns of TSSC3 and autophagy-related proteins (autophagy related 5 (ATG5) and P62) in 33 human benign bone tumors and 58 osteosarcoma tissues using immunohistochemistry. We further investigated the correlations between TSSC3 and autophagy in osteosarcoma using western blotting and transmission electronic microscopy. CCK-8, Edu, and clone formation assays; wound healing and Transwell assays; PCR; immunohistochemistry; immunofluorescence; and western blotting were used to investigated the responses in TSSC3-overexpressing osteosarcoma cell lines, and in xenografts and metastasis in vivo models, with or without autophagy deficiency caused by chloroquine or ATG5 silencing.
We found that ATG5 expression correlated positively with TSSC3 expression in human osteosarcoma tissues. We demonstrated that TSSC3 was an independent prognostic marker for overall survival in osteosarcoma, and positive ATG5 expression associated with positive TSSC3 expression suggested a favorable prognosis for patients. Then, we showed that TSSC3 overexpression enhanced autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway in osteosarcoma. Further results suggested autophagy contributed to TSSC3-induced suppression of tumorigenesis and metastasis in osteosarcoma in vitro and in vivo models.
Our findings highlighted, for the first time, the importance of autophagy as an underlying mechanism in TSSC3-induced antitumor effects in osteosarcoma. We also revealed that TSSC3-associated positive ATG5 expression might be a potential predictor of favorable prognosis in patients with osteosarcoma.
Enteric bacteria use up to 15% of their cellular energy for ammonium assimilation via glutamine synthetase (GS)/glutamate synthase (GOGAT) and glutamate dehydrogenase (GDH) in response to varying ...ammonium availability. However, the sensory mechanisms for effective and appropriate coordination between carbon metabolism and ammonium assimilation have not been fully elucidated. Here, we report that in Salmonella enterica, carbon metabolism coordinates the activities of GS/GDH via functionally reversible protein lysine acetylation. Glucose promotes Pat acetyltransferase‐mediated acetylation and activation of adenylylated GS. Simultaneously, glucose induces GDH acetylation to inactivate the enzyme by impeding its catalytic centre, which is reversed upon GDH deacetylation by deacetylase CobB. Molecular dynamics (MD) simulations indicate that adenylylation is required for acetylation‐dependent activation of GS. We show that acetylation and deacetylation occur within minutes of “glucose shock” to promptly adapt to ammonium/carbon variation and finely balance glutamine/glutamate synthesis. Finally, in a mouse infection model, reduced S. enterica growth caused by the expression of adenylylation‐mimetic GS is rescued by acetylation‐mimicking mutations. Thus, glucose‐driven acetylation integrates signals from ammonium assimilation and carbon metabolism to fine‐tune bacterial growth control.
Synopsis
In Salmonella enterica, metabolic enzyme acetylation regulates carbon metabolism. Here, glucose availability is shown to regulate ammonium assimilation and virulence in Salmonella.
Acetylation of glutamine synthetase (GS) and glutamate dehydrogenase (GDH) is regulated by acetyltransferase Pat and deacetylase CobB.
Glucose promotes acetylation to activate adenylylated GS and inactivate GDH by impeding its catalytic centre.
Acetylation of GS and GDH occurs within minutes to adapt to the ammonium/carbon variation and balance glutamate/glutamine synthesis.
GS acetylation‐mimicking mutations enhance Salmonella survival in infected mice.
Glucose regulates acetylation of glutamate and glutamine biosynthesis enzymes to enhance bacterial survival in infected mice.
Background
Robotic distal pancreatectomy (RDP) is considered a safe and feasible alternative to laparoscopic distal pancreatectomy (LDP). However, previous studies have some limitations including ...small sample size and selection bias. This study aimed to evaluate whether the robotic approach has advantages over laparoscopic surgery in distal pancreatectomy.
Methods
Demographics and perioperative outcomes among patients undergoing RDP (n = 102) and LDP (n = 102) between January 2011 and December 2015 were reviewed. A 1:1 propensity score matched analysis was performed between both groups.
Results
Both groups displayed no significant differences in perioperative outcomes including operative time, blood loss, transfusion rate, and rates of overall morbidities and pancreatic fistula. Robotic approach reduced the rate of conversion to laparotomy (2.9% vs 9.8%, P = 0.045), especially in patients with large tumors (0% vs 22.2%, P = 0.042). RDP improved spleen (SP) and splenic vessels preservation (SVP) rates in patients with moderate tumors (60.0% vs 35.5%, P = 0.047; 37.1% vs 12.9%, P = 0.025), especially in patients without malignancy (95.5% vs 52.4%, P = 0.001; 59.1% vs 19.0%, P = 0.007). RDP also reduced postoperative hospital stay (PHS) significantly (7.67% vs 8.58, P = 0.032).
Conclusions
RDP is associated with less rate of conversion to laparotomy, shorter PHS, and improved SP and SVP rates in selected patients than LDP.
Understanding ecological niches of major tick species and prevalent tick-borne pathogens is crucial for efficient surveillance and control of tick-borne diseases. Here we provide an up-to-date review ...on the spatial distributions of ticks and tick-borne pathogens in China. We map at the county level 124 tick species, 103 tick-borne agents, and human cases infected with 29 species (subspecies) of tick-borne pathogens that were reported in China during 1950-2018. Haemaphysalis longicornis is found to harbor the highest variety of tick-borne agents, followed by Ixodes persulcatus, Dermacentor nutalli and Rhipicephalus microplus. Using a machine learning algorithm, we assess ecoclimatic and socioenvironmental drivers for the distributions of 19 predominant vector ticks and two tick-borne pathogens associated with the highest disease burden. The model-predicted suitable habitats for the 19 tick species are 14‒476% larger in size than the geographic areas where these species were detected, indicating severe under-detection. Tick species harboring pathogens of imminent threats to public health should be prioritized for more active field surveillance.
The Tian Shan of Central Asia is located in the southwestern part of the Central Asian Orogenic Belt (CAOB, also known as the Central Asian Orogenic System or CAOS). Formation of the South Tian Shan ...Orogen is a diachronous, scissors-like process during the Paleozoic and its western segment in China–Kyrgyzstan contiguous regions is accepted as the site of the final collision zone between the Tarim craton to the south and the Kazakhstan–Yili terrane to the north in the Late Paleozoic. However, when the final collision occurred is still in hot debate. Particularly, an end-Permian to Triassic collisional model is recently proposed for the western segment of the South Tian Shan Orogen. This even leads to the speculation that the complicated accretion–collision processes in the Northern Xinjiang of western China, which involved the terrane amalgamation in the East and West Junggar and the collision between the Altai and Kazakhstan terranes and between the Yili–Central Tian Shan and Junggar terranes, were finally terminated during the end-Permian to mid-Triassic, rather than the Late Paleozoic as usually accepted. Obviously, the western segment of the South Tian Shan Orogen also presents the key issue associated with the termination time of accretion–collision processes in the Northern Xinjiang. A collisional model that is derived from the knowledge of the Himalayan Orogen is helpful for establishing a sequence of major tectonothermal events in the western segment of the South Tian Shan Orogen and constraining the time of collision between the Tarim craton and the Kazakhstan–Yili terrane.
For the western segment of the South Tian Shan Orogen, the end-Permian to Triassic collisional model is mainly based on Triassic zircon U–Pb ages of 234 to 226
Ma from the West Tian Shan eclogite and two suspected Late Permian radiolarian specimens
Albaillella excelsa Ishiga, Kito and Imoto (?) from the Baleigong ophiolitic mélange. Actually, the poor preservation of the two radiolarian specimens and the lack of a ventral wing make their identifications difficult. Furthermore, the Baleigong ophiolitic mélange was intruded by one granite pluton with a zircon age of 273
Ma, and this provides geological evidence against the reliability of the Late Permian radiolarian specimens. Because the Triassic zircons contain no index mineral inclusions such as omphacite and coesite grown under high to ultrahigh pressure conditions, it is difficult to link their ages to high to ultrahigh pressure peak metamorphism. In addition, this model is not compatible with extensive Permian plutonism and molasse sedimentation and Triassic to Jurassic tectonomagmatic quiescence and continental deposits in the collisional zone and adjacent tectonic units.
In contrast, new U–Pb ages of the zircon domains containing omphacite and phengite inclusions and Sm–Nd and rutile U–Pb ages of eclogite samples from the western segment of the South Tian Shan Orogen consistently indicate that high pressure peak metamorphism of subducted oceanic material occurred at ~
319
Ma (the end of the Early Carboniferous). This and the youngest Early Carboniferous radiolarian and conodonts fossils from ophiolitic mélanges show that the collision must have taken place after the Early Carboniferous, whereas the oldest stitching granitic plutons in the collisional zone place an upper-age bound of ~
300
Ma (the end of the Late Carboniferous) for the collision. These specify that the final collision in the western segment of the South Tian Shan took place in the Late Carboniferous rather than the end-Permian to Triassic. Noticeably, syn-collisional granitoids are rare, but Permian post-collisional plutonism and molasse sedimentation are widespread in the western segment of the South Tian Shan and adjacent tectonic units, and the oldest post-collisional plutons were nearly concurrent with low pressure, high temperature metamorphism in the south edge of the Kazakhstan–Yili terrane. All these suggest a significant geodynamic change at ~
300
Ma, which may be caused by delamination of the thickened lithospheric root and asthenospheric upwelling. Such a process might have provided heat for low pressure, high temperature metamorphism and triggered partial melting of the lower crust and underlying lithosphere in the western segment of the South Tian Shan Orogen and adjacent tectonic units. The Late Carboniferous collisional model is also compatible with the Triassic to Jurassic tectonomagmatic quiescence and continental deposits in the western segment of the South Tian Shan Orogen and adjacent tectonic units.
For the South Tian Shan Orogen, the final collision in the western segment occurred in the Late Carboniferous, significantly younger than that in the eastern segment. In the Northern Xinjiang, the Late Carboniferous collision in the western segment of the South Tian Shan Orogen was nearly simultaneous with the final collision in the North Tian Shan collisional zone between the Yili–Central Tian Shan and Junggar terranes and in the Irtysh–Zaysan collisional zone between the Altai and Kazakhstan terranes, and these collisional events postdated the terrane amalgamation in the East and West Junggar. Therefore, the accretion–collision processes in the Northern Xinjiang were finally terminated during the Late Carboniferous rather than the end-Permian to mid-Triassic.
Paleogeographic reconstruction of Precambrian terranes reworked by Phanerozoic orogens (e.g., the Tibetan Plateau) results in complex lithotectonic relations due to intracrustal reworking by ...tectonothermal events. Detrital zircon rare earth element (REE) databases at global (global major river sands) and regional (the Gangdese Mountains, southern Tibet) scales reveal trends in LREEN‾/HREEN‾ $\overline{{\mathrm{L}\mathrm{R}\mathrm{E}\mathrm{E}}_{\mathrm{N}}}/\overline{{\mathrm{H}\mathrm{R}\mathrm{E}\mathrm{E}}_{\mathrm{N}}}$ and Eu/Eu* that effectively record the crustal evolution of the source, including crustal thickness and redox state of the magma that generated the zircons. Regional comparisons of these chemical markers provide a new approach for paleogeographic reconstructions that we apply to study the origin of the Lhasa terrane, southern Tibet. Using Precambrian to early Paleozoic sedimentary and igneous rocks in the Lhasa terrane and compiling detrital zircon analyses from the northern margin of Gondwana, we show that the Lhasa terrane had an African affinity in the Rodinia–Gondwana supercontinent cycles (ca. 1.4–0.4 Ga).
Plain Language Summary
Constraining the paleogeographic positions and affinities of continental fragments plays a crucial role in validating the concept of the supercontinent cycle. However, tracking the evolving paleogeographic position of these fragments, especially for those of Precambrian age, has proven difficult. We explore the potential for solving this problem by using detrital zircon rare earth element (REE) abundances, which are controlled by the magma source depth, protolith type, oxygen fugacity, and magmatic water content of parental melts. We reveal correlations between detrital zircon REE abundances and crustal evolution in different tectonic settings based on global and regional detrital zircon databases. We subsequently demonstrate how detrital zircon REE abundances show that the Lhasa terrane in the southern Tibet is a fragment derived from Africa. Our study provides a new perspective on the paleogeographic reconstruction of continental fragments through Earth's history and thus has important implications for supercontinent research.
Key Points
Zircon rare earth element (REE) abundances reflect the composition of, and the conditions that generated, the parental melts
Trends in detrital zircon REE effectively preserve a crustal evolution history and provide a new approach for paleogeographic reconstruction
The Lhasa terrane in the southern Tibet had an African affinity in the Rodinia‐Gondwana supercontinent cycles
Chronic wound infections resulting from severe bacterial invasion have become a major medical threat worldwide. Herein, we report a large‐area, homogeneous, and self‐standing porphyrin‐covalent ...organic framework (COF)‐based membrane with encapsulated ibuprofen (IBU) via an in situ interfacial polymerization and impregnation approach. The obtained IBU@DhaTph‐membrane exhibits highly effective antibacterial and anti‐inflammatory effects via synergistic light‐induced singlet oxygen (1O2) generation and controllable IBU release, which is well supported by in vitro experiments. In addition, the IBU@DhaTph‐membrane‐based biocompatible “band‐aid” type dressing is fabricated, and its excellent anti‐infection and tissue remodeling activities are fully evidenced by in vivo chronic wound‐healing experiments. This study may inspire and promote the fabrication of many more new types of COF‐based multifunctional biomaterials for various skin injuries in clinical medicine.
An ibuprofen‐loaded porphyrin‐COF‐based biocompatible and non‐toxic “band‐aid” type dressing is fabricated, and its excellent synergistic photodynamic antibacterial and controllable drug anti‐inflammatory effects are fully evidenced by in vitro and in vivo bacteria‐infected chronic wound‐healing experiments.
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•Recent development of g-C3N4-based materials for environmental remediation were comprehensively summarized.•The different synthesis approaches of g-C3N4 and g-C3N4-based materials ...were reviewed.•A variety of pollutant removal methods based on g-C3N4 materials were systematically summarized.•Future insights to give overview on g-C3N4-based materials for remediation of environmental pollutants.
Environmental contaminants have become one kind of the most rigorous environmental issues, and the removal of various environmental contaminant (dyes, pesticides, pharmaceuticals, phenols, metal ions, VOCs, etc.) is of particular concern because they are poisonous and recalcitrant in the environment. In recent years, graphitic carbon nitride obtained more and more attention due to its abundance of raw material, chemical stability, metal-free nature, environmental friendliness, as well as adjustable structure. Hence, this design and application of high efficiency g-C3N4-based functional materials for remediation of representative environmental pollutants is a promising area of research. In view of this, the critical review summarizes the recent advances in the design and preparation of novel g-C3N4-based composites via various methods and the removal efficiencies and related mechanisms via different techniques (adsorption, photocatalysis, electrocatalysis, photoelectrocatalysis, and membrane separation) are also summarized. Furthermore, some perspectives and research direction are briefly discussed. All in all, the g-C3N4-based composites have great advantages environmental remediation in the future.
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•The basic principle of rational design of electrochemical chiral sensor for sensing is summarized.•Preparation of doped electrodes and their recognition performance for chiral ...enantiomers are summarized.•Construction of modified electrodes and their recognition performances are discussed.•The challenges and scientific prospects of new generation of modifiers in electrochemical chiral sensing are proposed.
Chiral recognition, especially rendering specificity in biomolecular recognition, is a basic property of many biomolecules. Being closely related to the chirality of biomolecules, it has been regarded as one of the most important areas in biological and medical sciences due to the different effects in biological systems. Based on the possible interactions between chiral selectors and the enantiomers, various methods including chromatographic techniques such as gas or liquid chromatography, electromigration techniques such as capillary electrophoresis and so on were developed for the chiral separation and recognition of different optical isomers. Recently, chemical sensors and biosensors have been gradually designed and developed for the analysis of chiral compounds. Based on the difference in electrical response to different isomers, chiral identifications can be successfully implemented. Major successes in enantiomer recognition based on electrochemical analysis are reviewed. The research data available for highly enantio-selective recognition are categorized into several subgroups according to specific topics and critically discussed for the period since 1994, and the latest techniques for electrochemical chiral recognition of enantiomers were also reviewed. Simultaneously, a brief conclusive summary and future perspectives are presented, and the challenges and scientific prospects of the newest generation of electrode modifiers in electrochemical sensing are also proposed.
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