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1.
J Am Chem Soc ; 146(5): 2977-2985, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38284994

ABSTRACT

The recently surged halide-based solid electrolytes (SEs) are great candidates for high-performance all-solid-state batteries (ASSBs), due to their decent ionic conductivity, wide electrochemical stability window, and good compatibility with high-voltage oxide cathodes. In contrast to the crystalline phases in halide SEs, amorphous components are rarely understood but play an important role in Li-ion conduction. Here, we reveal that the presence of amorphous component is common in halide-based SEs that are prepared via mechanochemical method. The fast Li-ion migration is found to be associated with the local chemistry of the amorphous proportion. Taking Zr-based halide SEs as an example, the amorphization process can be regulated by incorporating O, resulting in the formation of corner-sharing Zr-O/Cl polyhedrons. This structural configuration has been confirmed through X-ray absorption spectroscopy, pair distribution function analyses, and Reverse Monte Carlo modeling. The unique structure significantly reduces the energy barriers for Li-ion transport. As a result, an enhanced ionic conductivity of (1.35 ± 0.07) × 10-3 S cm-1 at 25 °C can be achieved for amorphous Li3ZrCl4O1.5. In addition to the improved ionic conductivity, amorphization of Zr-based halide SEs via incorporation of O leads to good mechanical deformability and promising electrochemical performance. These findings provide deep insights into the rational design of desirable halide SEs for high-performance ASSBs.

2.
Angew Chem Int Ed Engl ; 63(2): e202314181, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38009453

ABSTRACT

Glassy Na-ion solid-state electrolytes (GNSSEs) are an important group of amorphous SSEs. However, the insufficient ionic conductivity of state-of-the-art GNSSEs at room temperature lessens their promise in the development of all-solid-state Na-ion batteries (ASSNIBs) with high energy density and improved safety. Here we report the discovery of a new sodium superionic glass, 0.5Na2 O2 -TaCl5 (NTOC), based on dual-anion sublattice of oxychlorides. The unique local structures with abundant bridging and non-bridging oxygen atoms contributes to a highly disordered Na-ion distribution as well as low Na+ migration barrier within NTOC, enabling an ultrahigh ionic conductivity of 4.62 mS cm-1 at 25 °C (more than 20 times higher than those of previously reported GNSSEs). Moreover, the excellent formability of glassy NTOC electrolyte and its high electrochemical oxidative stability ensure a favourable electrolyte-electrode interface, contributing to superior cycling stability of ASSNIBs for over 500 cycles at room temperature. The discovery of glassy NTOC electrolyte would reignite research enthusiasm in superionic glassy SSEs based on multi-anion chemistry.

3.
Angew Chem Int Ed Engl ; : e202403331, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728142

ABSTRACT

The evolution of inorganic solid electrolytes has revolutionized the field of sustainable organic cathode materials, particularly by addressing the dissolution problems in traditional liquid electrolytes. However, current sulfide-based all-solid-state lithium-organic batteries still face challenges such as high working temperatures, high costs, and low voltages. Here, we design an all-solid-state lithium battery based on a cost-effective organic cathode material phenanthrenequinone (PQ) and a halide solid electrolyte Li2ZrCl6. Thanks to the good compatibility between PQ and Li2ZrCl6, the PQ cathode achieved a high specific capacity of 248 mAh g-1 (96 % of the theoretical capacity), a high average discharge voltage of 2.74 V (vs. Li+/Li), and a good capacity retention of 95 % after 100 cycles at room temperature (25 °C). Furthermore, the interactions between the high-voltage carbonyl PQ cathode and both sulfide and halide solid electrolytes, as well as the redox mechanism of the PQ cathode in all-solid-state batteries, were carefully studied by a variety of advanced characterizations. We believe such a design and the corresponding investigations into the underlying chemistry give insights for the further development of practical all-solid-state lithium-organic batteries.

4.
Angew Chem Int Ed Engl ; 63(27): e202401373, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38659181

ABSTRACT

Inorganic solid-state electrolytes (SSEs) play a vital role in high-energy all-solid-state batteries (ASSBs). However, the current method of SSE preparation usually involves high-energy mechanical ball milling and/or a high-temperature annealing process, which is not suitable for practical application. Here, a facile strategy is developed to realize the scalable synthesis of cost-effective aluminum-based oxyhalide SSEs, which involves a self-propagating method by the exothermic reaction of the raw materials. This strategy enables the synthesis of various aluminum-based oxyhalide SSEs with tunable components and high ionic conductivities (over 10-3 S cm-1 at 25 °C) for different cations (Li+, Na+, Ag+). It is elucidated that the amorphous matrix, which mainly consists of various oxidized chloroaluminate species that provide numerous sites for smooth ion migration, is actually the key factor for the achieved high conductivities. Benefit from their easy synthesis, low cost, and low weight, the aluminum-based oxyhalide SSEs synthesized by our approach could further promote practical application of high-energy-density ASSBs.

5.
Angew Chem Int Ed Engl ; 63(12): e202316360, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38243690

ABSTRACT

Halide solid electrolytes (SEs) have attracted significant attention due to their competitive ionic conductivity and good electrochemical stability. Among typical halide SEs (chlorides, bromides, and iodides), substantial efforts have been dedicated to chlorides or bromides, with iodide SEs receiving less attention. Nevertheless, compared with chlorides or bromides, iodides have both a softer Li sublattice and lower reduction limit, which enable iodides to possess potentially high ionic conductivity and intrinsic anti-reduction stability, respectively. Herein, we report a new series of iodide SEs: Lix YI3+x (x=2, 3, 4, or 9). Through synchrotron X-ray/neutron diffraction characterizations and theoretical calculations, we revealed that the Lix YI3+x SEs belong to the high-symmetry cubic structure, and can accommodate abundant vacancies. By manipulating the defects in the iodide structure, balanced Li-ion concentration and generated vacancies enables an optimized ionic conductivity of 1.04 × 10-3  S cm-1 at 25 °C for Li4 YI7 . Additionally, the promising Li-metal compatibility of Li4 YI7 is demonstrated via electrochemical characterizations (particularly all-solid-state Li-S batteries) combined with interface molecular dynamics simulations. Our study on iodide SEs provides deep insights into the relation between high-symmetry halide structures and ionic conduction, which can inspire future efforts to revitalize halide SEs.

6.
Plant J ; 110(4): 1144-1165, 2022 05.
Article in English | MEDLINE | ID: mdl-35277905

ABSTRACT

Tea (Camellia sinensis) is concocted from tea plant shoot tips that produce catechins, caffeine, theanine, and terpenoids, which collectively determine the rich flavors and health benefits of the infusion. However, little is known about the integrated regulation of shoot tip development and characteristic secondary metabolite biosynthesis in tea plants. Here, we demonstrate that MYB transcription factors (TFs) play key and yet diverse roles in regulating leaf and stem development, secondary metabolite biosynthesis, and environmental stress responses in tea plants. By integrating transcriptomic and metabolic profiling data in different tissues at a series of developmental stages or under various stress conditions, alongside biochemical and genetic analyses, we predicted the MYB TFs involved in regulating shoot development (CsMYB2, 98, 107, and 221), epidermal cell initiation (CsMYB184, 41, 139, and 219), stomatal initiation (CsMYB113 and 153), and the biosynthesis of flavonoids (including catechins, anthocyanins, and flavonols; CsMYB8 and 99), caffeine (CsMYB85 and 86), theanine (CsMYB9 and 49), carotenoids (CsMYB110), mono-/sesquiterpenoid volatiles (CsMYB68, 147, 148, and 193), lignin (CsMYB164 and 192), and indolic compounds (CsMYB139, 162, and 198), as well as the MYB TFs that are likely involved in hormone signaling-mediated environmental stress and defense responses. We characterized the functions of some key MYBs in regulating flavonoid and carotenoid biosynthesis for tea quality and flavor. This study provides a cross-family analysis of MYBs in tea alongside new insights into the coordinated regulation of tea plant shoot development and secondary metabolism, paving the way towards understanding of tea quality trait formation and genetic improvement of quality tea plants.


Subject(s)
Camellia sinensis , Catechin , Anthocyanins/metabolism , Caffeine/metabolism , Camellia sinensis/genetics , Camellia sinensis/metabolism , Catechin/metabolism , Flavonoids/metabolism , Gene Expression Regulation, Plant , Plant Leaves/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Secondary Metabolism/genetics , Tea/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
7.
J Am Chem Soc ; 145(21): 11701-11709, 2023 May 31.
Article in English | MEDLINE | ID: mdl-37195646

ABSTRACT

Inorganic solid-state electrolytes (SSEs) have gained significant attention for their potential use in high-energy solid-state batteries. However, there is a lack of understanding of the underlying mechanisms of fast ion conduction in SSEs. Here, we clarify the critical parameters that influence ion conductivity in SSEs through a combined analysis approach that examines several representative SSEs (Li3YCl6, Li3HoCl6, and Li6PS5Cl), which are further verified in the xLiCl-InCl3 system. The scaling analysis on conductivity spectra allowed the decoupled influences of mobile carrier concentration and hopping rate on ionic conductivity. Although the carrier concentration varied with temperature, the change alone cannot lead to the several orders of magnitude difference in conductivity. Instead, the hopping rate and the ionic conductivity present the same trend with the temperature change. Migration entropy, which arises from lattice vibrations of the jumping atoms from the initial sites to the saddle sites, is also proven to play a significant role in fast Li+ migration. The findings suggest that the multiple dependent variables such as the Li+ hopping frequency and migration energy are also responsible for the ionic conduction behavior within SSEs.

8.
J Am Chem Soc ; 145(4): 2183-2194, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36583711

ABSTRACT

The revival of ternary halides Li-M-X (M = Y, In, Zr, etc.; X = F, Cl, Br) as solid-state electrolytes (SSEs) shows promise in realizing practical solid-state batteries due to their direct compatibility toward high-voltage cathodes and favorable room-temperature ionic conductivities. Most of the reported superionic halide SSEs have a structural pattern of [MCl6]x- octahedra and generate a tetrahedron-assisted Li+ ion diffusion pathway. Here, we report a new class of zeolite-like halide frameworks, SmCl3, for example, in which 1-dimensional channels are enclosed by [SmCl9]6- tricapped trigonal prisms to provide a short jumping distance of 2.08 Å between two octahedra for Li+ ion hopping. The fast Li+ diffusion along the channels is verified through ab initio molecular dynamics simulations. Similar to zeolites, the SmCl3 framework can be grafted with halide species to obtain mobile ions without altering the base structure, achieving an ionic conductivity over 10-4 S cm-1 at 30 °C with LiCl as the adsorbent. Moreover, the universality of the interface-bonding behavior and ionic diffusion in a class of framework materials is demonstrated. It is suggested that the ionic conductivity of the MCl3/halide composite (M = La-Gd) is likely in correlation with the ionic conductivity of the grafted halide species, interfacial bonding, and framework composition/dimensions. This work reveals a potential class of halide structures for superionic conductors and opens up a new frontier for constructing zeolite-like frameworks in halide-based materials, which will promote the innovation of superionic conductor design and contribute to a broader selection of halide SSEs.

9.
Angew Chem Int Ed Engl ; 62(5): e202215680, 2023 Jan 26.
Article in English | MEDLINE | ID: mdl-36446742

ABSTRACT

Sulfide electrolytes with high ionic conductivities are one of the most highly sought for all-solid-state lithium batteries (ASSLBs). However, the non-negligible electronic conductivities of sulfide electrolytes (≈10-8  S cm-1 ) lead to electron smooth transport through the sulfide electrolyte pellets, resulting in Li dendrite directly depositing at the grain boundaries (GBs) and serious self-discharge. Here, a grain-boundary electronic insulation (GBEI) strategy is proposed to block electron transport across the GBs, enabling Li-Li symmetric cells with 30 times longer cycling life and Li-LiCoO2 full cells with three times lower self-discharging rate than pristine sulfide electrolytes. The Li-LiCoO2 ASSLBs deliver high capacity retention of 80 % at 650 cycles and stable cycling performance for over 2600 cycles at 0.5 mA cm-2 . The innovation of the GBEI strategy provides a new direction to pursue high-performance ASSLBs via tailoring the electronic conductivity.

10.
New Phytol ; 234(3): 902-917, 2022 05.
Article in English | MEDLINE | ID: mdl-35167117

ABSTRACT

Tea trichomes synthesize numerous specialized metabolites to protect plants from environmental stresses and contribute to tea flavours, but little is known about the regulation of trichome development. Here, we showed that CsMYB1 is involved in the regulation of trichome formation and galloylated cis-catechins biosynthesis in tea plants. The variations in CsMYB1 expression levels are closely correlated with trichome indexes and galloylated cis-catechins contents in tea plant populations. Genome resequencing showed that CsMYB1 may be selected in modern tea cultivars, since a 192-bp insertion in CsMYB1 promoter was found exclusively in modern tea cultivars but not in the glabrous wild tea Camellia taliensis. Several enhancers in the 192-bp insertion increased CsMYB1 transcription in modern tea cultivars that coincided with their higher galloylated cis-catechins contents and trichome indexes. Biochemical analyses and transgenic data showed that CsMYB1 interacted with CsGL3 and CsWD40 and formed a MYB-bHLH-WD40 (MBW) transcriptional complex to activate the trichome regulator genes CsGL2 and CsCPC, and the galloylated cis-catechins biosynthesis genes anthocyanidin reductase and serine carboxypeptidase-like 1A. CsMYB1 integratively regulated trichome formation and galloylated cis-catechins biosynthesis. Results suggest that CsMYB1, trichome and galloylated cis-catechins are coincidently selected during tea domestication by harsh environments for improved adaption and by breeders for better tea flavours.


Subject(s)
Catechin , Trichomes , Catechin/metabolism , Domestication , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Tea , Trichomes/metabolism
11.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(2): 127-132, 2021 Feb.
Article in Zh | MEDLINE | ID: mdl-33627205

ABSTRACT

OBJECTIVE: To study the changes and clinical significance of amplitude-integrated electroencephalography (aEEG) in preterm infants with bronchopulmonary dysplasia (BPD). METHODS: A total of 156 preterm infants with a gestational age of ≤ 32+6 weeks who were diagnosed with BPD were enrolled as the BPD group, and 156 preterm infants without BPD who were hospitalized during the same period of time were enrolled as the control group. The aEEG scoring system for preterm infants was used to compare aEEG results between the two groups during hospitalization. A stratified analysis was conducted based on the examination time (at the corrected gestational age of ≤ 28+6 weeks, 29-30+6 weeks, 31-32+6 weeks, 33-34+6 weeks, 35-36+6 weeks, and 37-38+6 weeks). RESULTS: Compared with the non-BPD group, the BPD group had a significantly lower total aEEG score at the corrected gestational age of 33-34+6 weeks (P < 0.001). The mild BPD group had a significantly lower total aEEG score than the non-BPD group at the corrected gestational age of 33-34+6 weeks (P < 0.05); the moderate BPD group had a significantly lower total aEEG score than the non-BPD group at the corrected gestational ages of 31-32+6 weeks, 33-34+6 weeks, and 35-36+6 weeks (P < 0.05); the severe BPD group had a significantly lower total aEEG score than the non-BPD group at all corrected gestational ages except ≤ 28+6 weeks and 29-30+6 weeks (P < 0.05). CONCLUSIONS: Preterm infants with BPD (especially moderate to severe BPD) have a lower aEEG score than those without BPD, suggesting that their nervous system development may lag behind that of non-BPD preterm infants with the same gestational age. Therefore, early nervous system evaluation and intervention are necessary for preterm infants with BPD.


Subject(s)
Bronchopulmonary Dysplasia , Bronchopulmonary Dysplasia/diagnosis , Electroencephalography , Gestational Age , Hospitalization , Humans , Infant , Infant, Newborn , Infant, Premature
12.
Int J Cancer ; 143(8): 2039-2052, 2018 10 15.
Article in English | MEDLINE | ID: mdl-29752722

ABSTRACT

The activity of negative immune regulatory molecules, such as indoleamine 2,3-oxygenase (IDO), significantly attenuates DC (Dendritic cells)-mediated immunotherapy. We have previously reported that knockdown of IDO using siRNA can reinstall anti-tumor immunity. However, a DC-targeted siRNA delivery system for in vivo mobilized DCs remains to be developed, while gene silencing in mobilized DCs for cancer immunotherapy has never been explored. In our study, we developed a novel DC-targeted siRNA delivery system, man-GNR-siIDO, using as a nanocarrier of siRNA specific for IDO (siIDO) and mannose (man) as a guide molecule for targeting DCs. We explored the immunostimulatory man-GNR-siIDO nano-construct in DCs mobilized by Flt3-L, a receptor-type tyrosine kinase ligand, for lung cancer immunotherapy. In vivo DC-targeted gene silencing of IDO resulted in robust anti-tumor immunity as evidenced by promoting DC maturation, up-regulating tumor antigen-specific T-cell proliferation and enhancing tumor-specific cytotoxicity. A combinatorial treatment for Lewis Lung Carcinoma (LLC)-bearing mice, with man-GNR-siIDO and Flt3-L, significantly attenuated tumor growth and delayed tumor formation, suggesting the treatment feasibility of the man-GNR-siIDO system in Flt3-L mobilized DCs in the immunotherapy of lung cancer. Therefore, our study highlights a clinical potential for a first-in-class anti-cancer immunotherapy through simultaneous DC-mobilization and DC-targeted gene silencing of IDO with man-GNR-siIDO and Flt3-L treatments.


Subject(s)
Carcinoma, Lewis Lung/therapy , Dendritic Cells/immunology , Gene Silencing/immunology , Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics , Animals , Antigens, Neoplasm/genetics , Antigens, Neoplasm/immunology , Carcinoma, Lewis Lung/genetics , Carcinoma, Lewis Lung/immunology , Cell Line , Cell Line, Tumor , Cell Proliferation/genetics , Humans , Immunotherapy/methods , Indoleamine-Pyrrole 2,3,-Dioxygenase/immunology , Male , Membrane Proteins/genetics , Membrane Proteins/immunology , Mice , Mice, Inbred C57BL , RNA, Small Interfering/genetics , RNA, Small Interfering/immunology
14.
Biomolecules ; 14(6)2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38927074

ABSTRACT

Diabetes imposes a huge burden worldwide. Islet transplantation is an alternative therapy for diabetes. However, tacrolimus, a kind of immunosuppressant after organ transplantation, is closely related to post-transplant diabetes mellitus. Mesenchymal stem cells (MSCs) have attracted interest for their potential to alleviate diabetes. In vivo experiments revealed that human menstrual blood-derived stem cells (MenSCs) treatment improved tacrolimus-induced blood glucose, body weight, and glucose tolerance disorders in mice. RNA sequencing was used to analyze the potential therapeutic targets of MenSCs. In this study, we illustrated that cystathionine ß-synthase (CBS) contributed to tacrolimus -induced islet dysfunction. Using ß-cell lines (MIN6, ß-TC-6), we demonstrated that MenSCs ameliorated tacrolimus-induced islet dysfunction in vitro. Moreover, MenSC reduced the tacrolimus-induced elevation of CBS levels and significantly enhanced the viability, anti-apoptotic ability, glucose-stimulated insulin secretion (GSIS), and glycolytic flux of ß-cells. We further revealed that MenSCs exerted their therapeutic effects by inhibiting CBS expression to activate the IL6/JAK2/STAT3 pathway. In conclusion, we showed that MenSCs may be a potential strategy to improve tacrolimus-induced islet dysfunction.


Subject(s)
Cystathionine beta-Synthase , Interleukin-6 , STAT3 Transcription Factor , Tacrolimus , Humans , STAT3 Transcription Factor/metabolism , Tacrolimus/pharmacology , Interleukin-6/metabolism , Animals , Mice , Female , Cystathionine beta-Synthase/metabolism , Islets of Langerhans/drug effects , Islets of Langerhans/metabolism , Janus Kinase 2/metabolism , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Menstruation/blood , Menstruation/drug effects , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/cytology , Signal Transduction/drug effects , Insulin Secretion/drug effects , Cell Line
15.
Adv Mater ; 36(3): e2308012, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37848393

ABSTRACT

The development of solid-state sodium-ion batteries (SSSBs) heavily hinges on the development of an superionic Na+ conductor (SSC) that features high conductivity, (electro)chemical stability, and deformability. The construction of heterogeneous structures offers a promising approach to comprehensively enhancing these properties in a way that differs from traditional structural optimization. Here, this work exploits the structural variance between high- and low-coordination halide frameworks to develop a new class of halide heterogeneous structure electrolytes (HSEs). The halide HSEs incorporating a UCl3 -type high-coordination framework and amorphous low-coordination phase achieves the highest Na+ conductivity (2.7 mS cm-1 at room temperature, RT) among halide SSCs so far. By discerning the individual contribution of the crystalline bulk, amorphous region, and interface, this work unravels the synergistic ion conduction within halide HSEs and provides a comprehensive explanation of the amorphization effect. More importantly, the excellent deformability, high-voltage stability, and expandability of HSEs enable effective SSSB integration. Using a cold-pressed cathode electrode composite of uncoated Na0.85 Mn0.5 Ni0.4 Fe0.1 O2 and HSEs, the SSSBs present stable cycle performance with a capacity retention of 91.0% after 100 cycles at 0.2 C.

16.
Stem Cells Int ; 2023: 2988907, 2023.
Article in English | MEDLINE | ID: mdl-36895784

ABSTRACT

Human menstrual blood-derived mesenchymal stem cells (MenSCs) and their secreted small extracellular vesicles (EVs) had been proven to relieve inflammation, tissue damage, and fibrosis in various organs. The microenvironment induced by inflammatory cytokines can promote mesenchymal stem cells (MSCs) to secrete more substances (including EVs) that could regulate inflammation. Inflammatory bowel disease (IBD) is a chronic idiopathic intestinal inflammation, the etiology and mechanism of which are unclear. At present, the existing therapeutic methods are ineffective for many patients and have obvious side effects. Hence, we explored the role of tumor necrosis factor α- (TNF-α-) pretreated MenSC-derived small EV (MenSCs-sEVTNF-α ) in a mouse model of dextran sulfate sodium- (DSS-) induced colitis, expecting to find better therapeutic alterations. In this research, the small EVs of MenSCs were obtained by ultracentrifugation. MicroRNAs of small EVs derived from MenSCs before and after TNF-α treatment were sequenced, and the differential microRNAs were analyzed by bioinformatics. The small EVs secreted by TNF-α-stimulating MenSCs were more effective in colonic mice than those secreted directly by MenSCs, as evidenced by the results of histopathology analysis of colonic tissue, immunohistochemistry for tight junction proteins, and enzyme-linked immunosorbent assay (ELISA) for cytokine expression profiles in vivo. The process of MenSCs-sEVTNF-α relieving colonic inflammation was accompanied by the polarization of M2 macrophages in the colon and miR-24-3p upregulation in small EVs. In vitro, both MenSC-derived sEV (MenSCs-sEV) and MenSCs-sEVTNF-α reduced the expression of proinflammatory cytokines, and MenSCs-sEVTNF-α can increase the portion of M2 macrophages. In conclusion, after TNF-α stimulation, the expression of miR-24-3p in small EVs derived from MenSCs was upregulated. MiR-24-3p was proved to target and downregulate interferon regulatory factor 1 (IRF1) expression in the murine colon and then promoted the polarization of M2 macrophages. The polarization of M2 macrophages in colonic tissues then reduced the damage caused by hyperinflammation.

17.
Stem Cell Res Ther ; 14(1): 58, 2023 04 01.
Article in English | MEDLINE | ID: mdl-37005657

ABSTRACT

BACKGROUND: Sorafenib is a first-line drug targeting the RTK-MAPK signalling pathway used to treat advanced hepatocellular carcinoma (HCC). However, tumour cells readily develop sorafenib resistance, limiting long-term therapy with this drug. In our previous study, we found that human menstrual blood-derived stem cells (MenSCs) altered the expression of some sorafenib resistance-associated genes in HCC cells. Therefore, we wanted to further explore the feasibility of MenSC-based combination therapy in treating sorafenib-resistant HCC (HCC-SR) cells. METHODS: The therapeutic efficiency of sorafenib was determined using CCK-8 (Cell Counting Kit-8), Annexin V/PI and clone formation assays in vitro and a xenograft mouse model in vivo. DNA methylation was determined using RT‒PCR and methylated DNA immunoprecipitation (MeDIP). Autophagy was detected by measuring LC3-II degradation and autophagosome maturation. Transmission electron microscopy identified autophagosomes and mitochondria. Physiological functions of mitochondria were assessed by measuring the ATP content, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP). RESULTS: The tumour suppressor genes BCL2 interacting protein 3 (BNIP3) and BCL2 interacting protein 3 like (BNIP3L) were silenced by promoter methylation and that BNIP3 and BNIP3L levels correlated negatively with sorafenib resistance in HCC-SR cells. Strikingly, MenSCs reversed sorafenib resistance. MenSCs upregulated BNIP3 and BNIP3L expression in HCC-SR cells via tet methylcytosine dioxygenase 2 (TET2)-mediated active demethylation. In HCC-SR cells receiving sorafenib and MenSC combination therapy, pressure from sorafenib and elevated BNIP3 and BNIP3L levels disrupted balanced autophagy. Hyperactivation of mitophagy significantly caused severe mitochondrial dysfunction and eventually led to the autophagic death of HCC-SR cells. CONCLUSIONS: Our research suggests that combining sorafenib and MenSCs may be a potentially new strategy to reverse sorafenib resistance in HCC-SR cells.


Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Animals , Mice , Sorafenib/pharmacology , Sorafenib/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Mitophagy/genetics , Stem Cells/pathology , Proto-Oncogene Proteins c-bcl-2 , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use
18.
Nat Commun ; 14(1): 7615, 2023 Nov 22.
Article in English | MEDLINE | ID: mdl-37993459

ABSTRACT

Motivated by the high-performance solid-state lithium batteries enabled by lithium superionic conductors, sodium superionic conductor materials have great potential to empower sodium batteries with high energy, low cost, and sustainability. A critical challenge lies in designing and discovering sodium superionic conductors with high ionic conductivities to enable the development of solid-state sodium batteries. Here, by studying the structures and diffusion mechanisms of Li-ion versus Na-ion conducting solids, we reveal the structural feature of face-sharing high-coordination sites for fast sodium-ion conductors. By applying this feature as a design principle, we discover a number of Na-ion conductors in oxides, sulfides, and halides. Notably, we discover a chloride-based family of Na-ion conductors NaxMyCl6 (M = La-Sm) with UCl3-type structure and experimentally validate with the highest reported ionic conductivity. Our findings not only pave the way for the future development of sodium-ion conductors for sodium batteries, but also consolidate design principles of fast ion-conducting materials for a variety of energy applications.

19.
Vet Sci ; 11(1)2023 Dec 25.
Article in English | MEDLINE | ID: mdl-38250917

ABSTRACT

The aim of this experiment was to investigate the effect of Laminaria japonica polysaccharide (LJP) supplementation at levels of 100, 200, or 400 mg/kg on the growth performance, faecal digestive enzyme activity, and serum biochemistry and amino acids of weaned piglets. One hundred and twenty weaned piglets (Barkshire × Licha Black, 21 days old, 6.13 ± 0.16 kg) were randomly divided into four groups with five replicates of six piglets in each group based on body weight. Piglets were fed with different levels (0, 100, 200, and 400 mg/kg) of LJP for a 21-day trial. On day 21, faecal and blood samples were collected from one piglet per pen. The results showed that the supplementation of the 200 and 400 mg/kg LJP significantly increased average daily gain (ADG) and average daily feed intake (ADFI) compared to the control group (p = 0.007; p = 0.002), and dietary LJP linearly increased ADG and ADFI (p = 0.002; p < 0.001). In addition, the supplementation of the 200 and 400 mg/kg LJP significantly increased faecal amylase activity (p < 0.001) compared to the control group, and dietary LJP linearly increased faecal amylase and lipase activities (p = 0.001; p = 0.037). Moreover, dietary LJP at 400 mg/kg increased serum histidine content compared to the other groups (p = 0.002), and dietary LJP linearly increased the contents of serum histidine and asparagine in piglets (p < 0.001; p = 0.046). In conclusion, supplementation of 200 and 400 mg/kg LJP could enhance growth performance and faecal digestive enzyme activity and modulate the serum amino acid content of weaned piglets, potentially contributing to the health of weaned piglets.

20.
Nat Commun ; 14(1): 3780, 2023 Jun 24.
Article in English | MEDLINE | ID: mdl-37355635

ABSTRACT

Solid electrolyte is vital to ensure all-solid-state batteries with improved safety, long cyclability, and feasibility at different temperatures. Herein, we report a new family of amorphous solid electrolytes, xLi2O-MCly (M = Ta or Hf, 0.8 ≤ x ≤ 2, y = 5 or 4). xLi2O-MCly amorphous solid electrolytes can achieve desirable ionic conductivities up to 6.6 × 10-3 S cm-1 at 25 °C, which is one of the highest values among all the reported amorphous solid electrolytes and comparable to those of the popular crystalline ones. The mixed-anion structural models of xLi2O-MCly amorphous SEs are well established and correlated to the ionic conductivities. It is found that the oxygen-jointed anion networks with abundant terminal chlorines in xLi2O-MCly amorphous solid electrolytes play an important role for the fast Li-ion conduction. More importantly, all-solid-state batteries using the amorphous solid electrolytes show excellent electrochemical performance at both 25 °C and -10 °C. Long cycle life (more than 2400 times of charging and discharging) can be achieved for all-solid-state batteries using the xLi2O-TaCl5 amorphous solid electrolyte at 400 mA g-1, demonstrating vast application prospects of the oxychloride amorphous solid electrolytes.


Subject(s)
Body Fluids , Lithium , Electrolytes , Chlorides , Chlorine
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