Glutamine addiction in tumor cell: oncogene regulation and clinical treatment.

After undergoing metabolic reprogramming, tumor cells consume additional glutamine to produce amino acids, nucleotides, fatty acids, and other substances to facilitate their unlimited proliferation. As such, the metabolism of glutamine is intricately linked to the survival and progression of cancer cells. Consequently, targeting the glutamine metabolism presents a promising strategy to inhibit growth of tumor cell and cancer development. This review describes glutamine uptake, metabolism, and transport in tumor cells and its pivotal role in biosynthesis of amino acids, fatty acids, nucleotides, and more. Furthermore, we have also summarized the impact of oncogenes like C-MYC, KRAS, HIF, and p53 on the regulation of glutamine metabolism and the mechanisms through which glutamine triggers mTORC1 activation. In addition, role of different anti-cancer agents in targeting glutamine metabolism has been described and their prospective applications are assessed.

Extracellular vesicle-cell adhesion molecules in tumours: biofunctions and clinical applications.

Cell adhesion molecule (CAM) is an umbrella term for several families of molecules, including the cadherin family, integrin family, selectin family, immunoglobulin superfamily, and some currently unclassified adhesion molecules. Extracellular vesicles (EVs) are important information mediators in cell-to-cell communication. Recent evidence has confirmed that CAMs transported by EVs interact with recipient cells to influence EV distribution in vivo and regulate multiple cellular processes. This review focuses on the loading of CAMs onto EVs, the roles of CAMs in regulating EV distribution, and the known and possible mechanisms of these actions. Moreover, herein, we summarize the impacts of CAMs transported by EVs to the tumour microenvironment (TME) on the malignant behaviour of tumour cells (proliferation, metastasis, immune escape, and so on). In addition, from the standpoint of clinical applications, the significance and challenges of using of EV-CAMs in the diagnosis and therapy of tumours are discussed. Finally, considering recent advances in the understanding of EV-CAMs, we outline significant challenges in this field that require urgent attention to advance research and promote the clinical applications of EV-CAMs. Video Abstract.

Specific imaging of intracellular hydrogen sulfide by a positively charged NIR fluorescent probe.

The poor water solubility of traditional activatable organic molecular probes usually limits their detection ability in physiological environment. In this work, a positively charged H2S probe was designed, which exhibited a significantly enhanced responsiveness to H2S in the aggregated state due to the increased positive charge density on the aggregate surface. Under physiological conditions, the probe could be activated by H2S with specificity and sensitivity to release near-infrared fluorescence signal. Moreover, endogenous H2S levels in living cells were successfully monitored by using this probe. We expect that this probe can provide a new strategy for the design of activatable probes to break the limitation of poor water solubility of conventional organic molecular probes.

Constructing a Resilient Hierarchical Conductive Network to Promote Cycling Stability of SiOx Anode via Binder Design.

Despite exhibiting high specific capacities, Si-based anode materials suffer from poor cycle life as their volume change leads to the collapse of conductive network within the electrode. For this reason, the challenge lies in retaining the conductive network during electrochemical processes. Herein, to address this prominent issue, a cross-linked conductive binder (CCB) is designed for commercially available silicon oxides (SiOx ) anode to construct a resilient hierarchical conductive network from two aspects: on the one hand, exhibiting high electronic conductivity, CCB serves as an adaptive secondary conductive network in addition to the stiff primary conductive network (e.g., conductive carbon), facilitating faster interfacial charge transfer processes for SiOx in molecular level; on the other hand, the cross-linked structure of CCB shows resilient mechanical properties, which maintains the integrity of the primary conductive network by preventing electrode deformation during prolonged cycling. With the aid of CCB, untreated micro-sized SiOx anode material delivers an areal capacity of 2.1 mAh cm-2 after 250 cycles at 0.8 A g-1 . The binder design strategy, as well as, the relevant concepts proposed herein, provide a new perspective toward promoting the cycling stability of high-capacity Si-based anodes.

Silk Fibroin-Laponite Porous Microspheres as Cell Microcarriers for Osteogenic Differentiation.

Silk fibroin (SF) has garnered significant attention as a natural polymer for fabricating porous scaffolds in various engineering applications. However, the limited osteoinductive property of SF has hindered its efficacy in bone repair applications. In this study, we constructed an SF-based injectable porous microcarrier that is doped with laponite (LAP), containing magnesium ions (Mg2+). The influence of freezing temperatures and concentrations of SF and LAP on the structural parameters of SF-LAP microcarriers was investigated. The SF-LAP microcarrier exhibited a porosity of 76.7 ± 1.2% and a controlled pore size of 24.6 ± 4.0 µm. At the 6 weeks of in vitro degradation test, a mild alkaline level in culture medium containing SF-LAP microcarriers was detected. The release of Mg2+ from the SF-LAP microcarrier was maintained at a concentration within the range of 1.2-2.3 mM during the 6 weeks. The seeded human adipose-derived stem cells in the SF-LAP microcarrier demonstrated a significant enhancement in osteogenic differentiation compared with cells seeded in the pure SF microcarrier, as evidenced by quantitative alkaline phosphatase activity and the expression of osteogenic marker genes. These findings underscore the potential of the SF-LAP microcarrier as an ideal cell carrier in the treatment of bone defects.

Alleviating Structure Collapse of Polycrystalline LiNixCoyMn1-x-yO2 via Surface Co Enrichment.

The structure collapse issues have long restricted the application of polycrystalline LiNixCoyMn1-x-yO2 (NCM) at high voltages beyond 4.4 V vs Li/Li+. Herein, for LiNi0.55Co0.12Mn0.33O2 (P-NCM), rapid surface degradation is observed upon the first charge, along with serious particle fragmentation upon repeated cycles. To alleviate these issues, a surface Co enrichment strategy is proposed [i.e., Co-enriched NCM (C-NCM)], which promotes the in situ formation of a robust surface rock-salt (RS) layer upon charge, serving as a highly stable interface for effective Li+ migration. Benefiting from this stabilized surface RS layer, Li+ extraction occurs mainly through this surface RS layer, rather than along the grain boundaries (GBs), thus reducing the risk of GBs' cracking and even particle fragmentation upon cycles. Besides, O loss and TM (TM = Ni, Co, and Mn) dissolution are also effectively reduced with fewer side reactions. The C-NCM/graphite cell presents a highly reversible capacity of 205.1 mA h g-1 at 0.2 C and a high capacity retention of 86% after 500 cycles at 1 C (1 C = 200 mA g-1), which is among the best reported cell performances. This work provides a different path for alleviating particle fragmentation of NCM cathodes.

Constructing Matching Cathode-Anode Interphases with Improved Chemo-mechanical Stability for High-Energy Batteries.

Coupling Ni-rich layered oxide cathodes with Si-based anodes is one of the most promising strategies to realize high-energy-density Li-ion batteries. However, unstable interfaces on both cathode and anode sides cause continuous parasitic reactions, resulting in structural degradation and capacity fading of full cells. Herein, lithium tetrafluoro(oxalato) phosphate is synthesized and applied as a multifunctional electrolyte additive to mitigate irreversible volume swing of the SiOx anode and suppress undesirable interfacial evolution of the LiNi0.83Co0.12Mn0.05O2 (NCM) cathode simultaneously, resulting in improved cycle life. Benefiting from its desirable redox thermodynamics and kinetics, the molecularly tailored additive facilitates matching interphases consisting of LiF, Li3PO4, and P-containing macromolecular polymer on both the NCM cathode and SiOx anode, respectively, modulating interfacial chemo-mechanical stability as well as charge transfer kinetics. More encouragingly, the proposed strategy enables 4.4 V 21700 cylindrical batteries (5 Ah) with excellent cycling stability (92.9% capacity retention after 300 cycles) under practical conditions. The key finding points out a fresh perspective on interfacial optimization for high-energy-density battery systems.

Mechanochemically Robust LiCoO2 with Ultrahigh Capacity and Prolonged Cyclability.

Pushing intercalation-type cathode materials to their theoretical capacity often suffers from fragile Li-deficient frameworks and severe lattice strain, leading to mechanical failure issues within the crystal structure and fast capacity fading. This is particularly pronounced in layered oxide cathodes because the intrinsic nature of their structures is susceptible to structural degradation with excessive Li extraction, which remains unsolved yet despite attempts involving elemental doping and surface coating strategies. Herein, a mechanochemical strengthening strategy is developed through a gradient disordering structure to address these challenges and push the LiCoO2 (LCO) layered cathode approaching the capacity limit (256 mAh g-1, up to 93% of Li utilization). This innovative approach also demonstrates exceptional cyclability and rate capability, as validated in practical Ah-level pouch full cells, surpassing the current performance benchmarks. Comprehensive characterizations with multiscale X-ray, electron diffraction, and imaging techniques unveil that the gradient disordering structure notably diminishes the anisotropic lattice strain and exhibits high fatigue resistance, even under extreme delithiation states and harsh operating voltages. Consequently, this designed LCO cathode impedes the growth and propagation of particle cracks, and mitigates irreversible phase transitions. This work sheds light on promising directions toward next-generation high-energy-density battery materials through structural chemistry design.

Revealing the Grain-Boundary-Cracking Induced Capacity Decay of a High-Voltage LiCoO2 at 4.6 V.

During a practical battery manufacture process, the LiCoO2 (LCO) electrodes are usually rolled with high pressure to achieve better performance, including reducing electrode polarization, increasing compact density, enhancing mechanical toughness, etc. In this work, a high-voltage LCO (HV-LCO) is achieved via modulating a commercialized LCO with an Al/F enriched and spinel reinforced surface structure. We reveal that the rolling can more or less introduce risk of grain-boundary-cracking (GBC) inside the HV-LCO and accelerate the capacity decay when cycled at 3-4.6 V vs Li/Li+. In particular, the concept of interface structure is proposed to explain the reason for the deteriorated cycle stability. As the GBC is generated, the interface structure of HV-LCO alters from a surface spinel phase to a hybrid of surface spinel plus boundary layer phases, leading to the exposure of some the nonprotective layer phase against the electrolyte. This alternation causes serious bulk structure damage upon cycles, including expanding GBC among the primary crystals, forming intragranular cracks and inactive spinel phases inside the bulk regions, etc., eventually leading to the deteriorated cycle stability. Above all, we realize that it is far from enough to achieve a eligible high-voltage LCO via only applying surface modification. This work provides a new insight for developing more advanced LCO cathodes.

Crosstalk between autophagy and CSCs: molecular mechanisms and translational implications.

Cancer stem cells(CSCs) play a key role in regulating tumorigenesis, progression, as well as recurrence, and possess typical metabolic characteristics. Autophagy is a catabolic process that can aid cells to survive under stressful conditions such as nutrient deficiency and hypoxia. Although the role of autophagy in cancer cells has been extensively studied, CSCs possess unique stemness, and their potential relationship with autophagy has not been fully analyzed. This study summarizes the possible role of autophagy in the renewal, proliferation, differentiation, survival, metastasis, invasion, and treatment resistance of CSCs. It has been found that autophagy can contribute to the maintenance of CSC stemness, facilitate the tumor cells adapt to changes in the microenvironment, and promote tumor survival, whereas in some other cases autophagy acts as an important process involved in the deprivation of CSC stemness thus leading to tumor death. Mitophagy, which has emerged as another popular research area in recent years, has a great scope when explored together with stem cells. In this study, we have aimed to elaborate on the mechanism of action of autophagy in regulating the functions of CSCs to provide deeper insights for future cancer treatment.

Metal-organic framework (MOF)-incorporated polymeric electrolyte realizing fast lithium-ion transportation with high Li+ transference number for solid-state batteries.

Composite polymer electrolytes (CPEs) show significant advantages in developing solid-state batteries due to their high flexibility and easy processability. In CPEs, solid fillers play a considerable effect on electrochemical performances. Recently, metal-organic frameworks (MOFs) are emerging as new solid fillers and show great promise to regulate ion migration. Herein, by using a Co-based MOF, a high-performance CPE is initially prepared and studied. Benefiting from the sufficient interactions and pore confinement from MOF, the obtained CPE shows both high ionic conductivity and a high Li+ transference number (0.41). The MOF-incorporated CPE then enables a uniform Li deposition and stable interfacial condition. Accordingly, the as-assembled solid batteries demonstrate a high reversible capacity and good cycling performance. This work verifies the practicability of MOFs as solid fillers to produce advanced CPEs, presenting their promising prospect for practical application.

A thermo-sensitive and injectable hydrogel derived from a decellularized amniotic membrane to prevent intrauterine adhesion by accelerating endometrium regeneration.

Objective To investigate the effect of the injectable hydrogel generated from a decellularized amniotic membrane (dAM)-gel on preventing the development of an intrauterine adhesion (IUA) on a rat model. Methods The dAM-gel was developed from an amniotic membrane (AM) by a process of decellularization, lyophilization, and enzyme digestion. Histological analysis, residual component determination, electronic microscopy and turbidimetric gelation kinetics analysis were performed to characterize the dAM-gel. The proliferation and migration of endometrial cells on the dAM-gel coated surface was examined. IUA was surgically created in rats and received dAM-gel injection immediately after wound creation. Gene profiles of epithelial cells cultured on the dAM-gel coated surface were evaluated by RNA-sequencing. Results The collagen content was retained in the dAM-gel, while the GAG content decreased significantly compared with fresh AM (fAM). Gelation of the gel was temperature-sensitive and showed a matrix concentration-dependent manner. Transplantation of the dAM-gel significantly reduced fibrosis of IUA with a recovered uterine cavity, regenerated endometrium and increased microvascular density, along with elevated pregnancy rate compared with endometrium damage groups. Migration of epithelial cells was greatly promoted by the dAM-gel in a surgically created uterine wound model. By comparing the RNA-sequence data of epithelial cells that were cultured on dAM-gel coated and non-coated surfaces, respectively, distinct gene profiles relative to the cellular migration, adhesion and angiogenesis and involved signaling pathway were identified. Conclusions The injectable dAM-gel developed from AM offers a promising option for preventing endometrial fibrosis by promotion of the re-epithelialization of the damaged endometrium.

Bio-Inspired Binder Design for a Robust Conductive Network in Silicon-Based Anodes.

Due to the severe volume variations during electrochemical processes, Si-based anodes suffer from poor cycling performance as the result of a collapsed conductive network. In this regard, a key strategy for fully exploiting the capacity potential of Si-based anodes is to construct a robust conductive network through rational binder design. In this work, a bio-inspired conductive binder (PFPQDA) is designed by introducing dopamine-functionalized fluorene structure units (DA) into a conductivity enhanced polyfluorene-typed copolymer (PFPQ) to enhance its mechanical properties. Through constructing hierarchical binding networks and resilient electron transportations within both nano-sized Si and micro-sized SiOx electrodes via interweaved interactions, the PFPQDA successfully suppresses the electrode expansion and maintains the integrity of conductive pathways. Consequently, owing to the favorable properties of PFPQDA, Si-based anodes exhibit improved cycling performance and rate capability with an areal capacity over 2.5 mAh cm-2 .

Elastic Lattice Enabling Reversible Tetrahedral Li Storage Sites in a High-Capacity Manganese Oxide Cathode.

The key to breaking through the capacity limitation imposed by intercalation chemistry lies in the ability to harness more active sites that can reversibly accommodate more ions (e.g., Li+ ) and electrons within a finite space. However, excessive Li-ion insertion into the Li layer of layered cathodes results in fast performance decay due to the huge lattice change and irreversible phase transformation. In this study, an ultrahigh reversible capacity is demonstrated by a layered oxide cathode purely based on manganese. Through a wealth of characterizations, it is clarified that the presence of low-content Li2 MnO3 domains not only reduces the amount of irreversible O loss; but also regulates Mn migration in LiMnO2 domains, enabling elastic lattice with high reversibility for tetrahedral sites Li-ion storage in Li layers. This work utilizes bulk cation disorder to create stable Li-ion-storage tetrahedral sites and an elastic lattice for layered materials, with a reversible capacity of 600 mA h g-1 , demonstrated in th range 0.6-4.9 V versus Li/Li+ at 10 mA g-1 . Admittedly, discharging to 0.6 V might be too low for practical use, but this exploration is still of great importance as it conceptually demonstrates the limit of Li-ions insertion into layered oxide materials.

Strontium mineralized silk fibroin porous microcarriers with enhanced osteogenesis as injectable bone tissue engineering vehicles.

In this paper, silk fibroin (SF) porous microcarriers containing strontium were constructed as injectable bone tissue engineering vehicles. The effects of SF concentration and strontium content on micromorphology, element distribution, strontium ion release and cellular behavior of the constructed microcarriers were investigated. The microcarriers with an open interconnected pore can be fabricated by controlling the concentration of SF. The strontium functionalized SF microcarriers showed the sustained release of strontium ion and allowed bone mesenchymal stem cells (BMSCs) to attach, proliferate and secrete extracellular matrix. Furthermore, the strontium functionalized SF microcarriers improved the osteogenic capability of BMSCs in vitro compared with those microcarriers without sustained release of strontium ion. This study presents a valuable approach to fabricate polymeric microcarriers with the capability of sustained release of strontium ion that show potential in bone tissue engineering applications.

Suppressing Polysulfide Shuttling in Lithium-Sulfur Batteries via a Multifunctional Conductive Binder.

Exhibiting high specific energy and low cost, lithium-sulfur batteries are considered promising candidates for the next-generation battery. However, its wide applications are limited by the insulating nature of the sulfur, dissolution of polysulfide species, and large volume change of the sulfur cathode. In this work, a conductive binder, crosslinked polyfluorene (C-PF) is synthesized and employed in Li-S batteries to enhance the overall electrochemical performance from the following three aspects: 1) possessing high electronic conductivity, C-PF facilitates lowered areal resistance for the sulfur electrode and leads to an improved rate capability; 2) owing to the cross-linked polymer structure, favorable mechanical properties of the electrode can be achieved, hence the well-preserved electrode integrity; 3) forming strong binding with various polysulfide species, C-PF manages to trap them from diffusing to the Li anode, which greatly improves the cycling stability of Li-S cells. Through designing a multifunctional binder to comprehensively enhance the Li-S cathode, this proposed approach could be broadly applied to fully harness the energy from S redox in addition to cathode material modifications.

Acoustic study on the outbreak of Creseise acicula nearby the Daya Bay Nuclear Power Plant Base during the summer of 2020.

From the mid-June to mid-July 2020, there was a massive bloom of Creseise acicula nearby the waters of Daya Bay Nuclear Power Plant Base (DNPP base). In order to find out the spatiotemporal dynamic characteristics of C. acicula and the main factors related to its outbreak and extinction, acoustic surveys and in-situ observations were performed. The results showed that the average abundance of C. acicula at the in-situ observation site fluctuated with the tidal rhythm. Furthermore, a horizontal migration pattern during ebb tide and a vertical subsidence trend of C. acicula was found. The outbreak of C. acicula bloom nearby the waters of DNPP base was the result of the joint action of water temperature, salinity and food availability etc. The extinction of C. acicula was mainly related to the adhesion of Licmophora, predation pressure from phytoplanktivorous fishes (such as Sardinella lemuru and Dussumieria elopsoides) and human intervention.

Oxygen-Deficient ß-MnO2@Graphene Oxide Cathode for High-Rate and Long-Life Aqueous Zinc Ion Batteries.

Recent years have witnessed a booming interest in grid-scale electrochemical energy storage, where much attention has been paid to the aqueous zinc ion batteries (AZIBs). Among various cathode materials for AZIBs, manganese oxides have risen to prominence due to their high energy density and low cost. However, sluggish reaction kinetics and poor cycling stability dictate against their practical application. Herein, we demonstrate the combined use of defect engineering and interfacial optimization that can simultaneously promote rate capability and cycling stability of MnO2 cathodes. ß-MnO2 with abundant oxygen vacancies (VO) and graphene oxide (GO) wrapping is synthesized, in which VO in the bulk accelerate the charge/discharge kinetics while GO on the surfaces inhibits the Mn dissolution. This electrode shows a sustained reversible capacity of ~ 129.6 mAh g-1 even after 2000 cycles at a current rate of 4C, outperforming the state-of-the-art MnO2-based cathodes. The superior performance can be rationalized by the direct interaction between surface VO and the GO coating layer, as well as the regulation of structural evolution of ß-MnO2 during cycling. The combinatorial design scheme in this work offers a practical pathway for obtaining high-rate and long-life cathodes for AZIBs.

Determination of the volatile constituents in radix Flemingiae Philippinensis by GC-MS and a heuristic evolving latent projection method.

With the help of chemometric resolution methods, a technique for qualitative and quantitative determination of the volatile chemical constituents in radix Flemingiae Philippinensis by chromatography-mass spectrometry was developed. After the overlapping chromatographic peaks were resolved into pure chromatograms and spectra using a heuristic evolving latent projections (HELP) method, qualitative analysis was performed by similarity search of the obtained pure mass spectrum of each component in the NIST library and the quantitative results were obtained by calculating the total two-way response volume. A total of 63 components were separated and 55 components were identified, accounting for 90.62% of the total content. The main components were farnesol isomer and beta-caryophyllene, accounting for 31.33% and 12.60% of the total content, respectively. The obtained results can provide useful information for further study and development of radix Flemingiae Philippinensis.

Enhanced production of CoQ10 by newly isolated Sphingomonas sp. ZUTEO3 with a coupled fermentation-extraction process.

The use of coenzyme Q(10) (CoQ(10)) as a complementary therapy in heart failure will increase in proportion to the growth of the ageing population and the expansion of statins consumption. Economical production of CoQ(10) by microbes will become more important due to the growing demands of the pharmaceutical industry. Process simplification and integration might be one desirable pathway for economic production of CoQ(10) by microbial fermentation. In this report, the effect of a coupled fermentation-extraction process on CoQ(10) production by newly isolated Sphingomonas sp. ZUTEO3 was evaluated. It was found that the CoQ(10) yield of the coupled process was significantly higher than that of the traditional process. As optimal conditions in our experiment, 2% soybean oil was added to the original culture to enhance cell membrane permeability, and 50 mL hexane was added to the 30 h culture as an extracting solvent for the subsequent coupled fermentation-extraction process. The maximal yield of CoQ(10) reached 43.2 mg/L and 32.5 mg/g dry cell weight after 38 h of total fermentation period. The coupled process represents one potential pathway for CoQ(10) production with even higher yield and lower cost. This is the first report of CoQ(10) production by Sphingomonas sp. using a coupled fermentation-extraction process.