Electric Double Layer Oriented Eutectic Additive Design toward Stable Zn Anodes with a High Depth of Discharge.

ZnSO4-based electrolytes for aqueous zinc ion batteries fail to meet practical application metrics due to hydrogen evolution reaction (HER) and dendrite growth. In this work, a highly polarized eutectic additive, glycerophosphorylcholine (GPC) is rationally designed, to regulate the electric double layer (EDL) structure for stable Zn anodes with a high depth of discharge (DOD). On one hand, GPC molecules with abundant hydroxyl groups can precisely regulate the hydrogen bond network in EDL to suppress HER. On the other hand, the enrichment of GPC at the interface is positively responsible for the negative charge density on the Zn surface, which leads to the formation of a robust ZnxPyOz-rich solid-electrolyte interphase and terminates dendrite growth in the charge-rich sites. This EDL-oriented eutectic additive engineering enables highly reversible and selectively (002)-textured Zn anodes to operate for over 1450 h at a high DOD of 45.3%. Meanwhile, a high-capacity (185.7 mAh g-1) aqueous Zn||VS2 full cell shows remarkable cycling stability over 220 cycles with an excellent capacity retention of 90.4% even at a low current density of 0.1 A g-1 (0.5 C). This work sheds light on electrolyte design and interface engineering for high-performance aqueous batteries.

Carbonated Beverage Chemistry for High-Voltage Battery Cathodes.

Advanced lithium-ion batteries utilize high upper cut-off voltages up to 4.8 V versus lithium metal to reach extraordinary energy densities. Such a harsh environment challenges the cathode stability and requires the construction of robust cathode electrolyte interphases at their electrochemical interface. Inspired by carbonated beverages with supersaturated CO2, here, a surface modification strategy that produces effective passivation layer of low modulus from the weakest link, is proposed CO2 bubbles preferentially nucleate and grow at rough surfaces, which in oxide cathodes, are also the local regions offering fast degradation pathway. Metal ion exchange on carbonated layer assists the construction of highly elastic interface under the guidance of packing factor. This method enables surface reconstruction at both primary and secondary particle levels for various cathodes exemplified by high-voltage LiNi0.8Co0.1Mn0.1O2 (NCM811) and LiCoO2 (LCO). Remarkably, with ultra-high upper cut-off voltage of 4.8 V versus Li+/Li, over 235 mAh g-1 discharge capacity, and over 900 W h kg-1 discharge energy at cathode level, ≈90% capacity retention can be obtained for LiNi0.8Co0.1Mn0.1O2 over 100 cycles at 0.5 C with commercial carbonate electrolytes. This carbonated beverage chemistry is promising for constructing high-quality surface passivation in many extreme-condition applications beyond battery cathodes.

Acyltransferase zinc finger DHHC-type containing 2 aggravates gastric carcinoma growth by targeting Nrf2 signaling: A mechanism-based multicombination bionic nano-drug therapy.

The significant regulatory role of palmitoylation modification in cancer-related targets has been demonstrated previously. However, the biological functions of Nrf2 in stomach cancer and whether the presence of Nrf2 palmitoylation affects gastric cancer (GC) progression and its treatment have not been reported. Several public datasets were used to look into the possible link between the amount of palmitoylated Nrf2 and the progression and its outcome of GC in patients. The palmitoylated Nrf2 levels in tumoral and peritumoral tissues from GC patients were also evaluated. Both loss-of-function and gain-of-function via transgenic experiments were performed to study the effects of palmitoylated Nrf2 on carcinogenesis and the pharmacological function of 2-bromopalmitate (2-BP) on the suppression of GC progression in vitro and in vitro. We discovered that Nrf2 was palmitoylated in the cytoplasmic domain, and this lipid posttranslational modification causes Nrf2 stabilization by inhibiting ubiquitination, delaying Nrf2 destruction via the proteasome and boosting nuclear translocation. Importantly, we also identify palmitoyltransferase zinc finger DHHC-type palmitoyltransferase 2 (DHHC2) as the primary acetyltransferase required for the palmitoylated Nrf2 and indicate that the suppression of Nrf2 palmitoylation via 2-bromopalmitate (2-BP), or the knockdown of DHHC2, promotes anti-cancer immunity in vitro and in mice model-bearing xenografts. Of note, based on the antineoplastic mechanism of 2-BP, a novel anti-tumor drug delivery system ground 2-BP and oxaliplatin (OXA) dual-loading gold nanorods (GNRs) with tumor cell membrane coating biomimetic nanoparticles (CM@GNRs-BO) was established. In situ photothermal therapy is done using near-infrared (NIR) laser irradiation to help release high-temperature-triggered drugs from the CM@GNRs-BO reservoir when needed. This is done to achieve photothermal/chemical synergistic therapy. Our findings show the influence and linkage of palmitoylated Nrf2 with tumoral and peritumoral tissues in GC patients, the underlying mechanism of palmitoylated Nrf2 in GC progression, and novel possible techniques for addressing Nrf2-associated immune evasion in cancer growth. Furthermore, the bionic nanomedicine developed by us has the characteristics of dual drugs delivery, homologous tumor targeting, and photothermal and chemical synergistic therapy, and is expected to become a potential platform for cancer treatment.

Weakly Solvating Few-Layer-Carbon Interface toward High Initial Coulombic Efficiency and Cyclability Hard Carbon Anodes.

The carbonaceous anodes in sodium ion batteries suffer from low initial Coulombic efficiency (ICE) and poor cyclability due to rampant solid electrolyte interface (SEI) growth. The concept of the weakly solvating electrolyte (WSE) has been popularized for SEI regulation on the anode by adjusting the cation solvation structure. Nevertheless, the effects on the solvation sheath from the electrode/electrolyte interface are ignored in most WSE applications. In this work, we extend the WSE from the bulk electrolyte to the electrolyte/carbon interface. By recycling asphalt wastes into sp2 C enriched few-layer carbon on hard carbon, a weakly solvating interface is fabricated with lower adsorption energy to electrolyte solvent molecules than a pristine anode (-0.89 vs -1.08 eV for Na/diglyme). Accordingly, more anionic groups are attracted into the solvent-weakened solvation sheath during sodiation (2.30 vs 1.96 coordination number for PF6-). The anion-mediated contact ion pairs facilitate a thin, inorganic-rich SEI layer with a homogeneous distribution, which confers a high ICE of 97.9% and a high capacity of 335.6 mA h g-1 at 1 C (89.5% retention, 1000 cycles). The full battery also manifests an energy density of 209 W h kg-1. This interfacial design is applicable in both ether- and ester-based electrolytes, which is promising in cost-effective modification for carbonaceous electrodes.

KBTBD2 promotes proliferation and migration of gastric cancer via activating EGFR signaling pathway.

BACKGROUND: To explore the role of Kelch repeat and BTB (POZ) domain containing 2 (KBTBD2) in Gastric cancer(GC) via studying the level of KBTBD2 and its impact on GC cells and mice model. METHODS: Expression of KBTBD2 in GC was analyzed by analysis of TCGA data, Western blotting and Real-time quantitative polymerasechain reaction (RT-qPCR). The role of KBTBD2 on GC cells proliferation, viability, invasion, migration and apoptosis in vitro were assessed by using western blotting，RT-qPCR，CCK-8, EDU, Colony Formation Assay, Wound healing assay, Transwell, JC-1 mitochondrial membrane potential and flow cytometry assay, respectively. And levels of Bcl-2, BAX, PARP, E-cadherin, Vimentin, N-cadherin, EGFR, SOS1, NROS, BRAF,ERK1/2 and GAPDH were tested by western blotting. Relation of KBTBD2 and epidermal growth factor receptor (EGFR) was predicted by KEGG analysis. KBTBD2 gene GSEA enrichment was analyzed by using R language. Moreover, CCK-8, western blotting, and wound healing assays were used to verify the correlation of KBTBD2 and EGFR pathway. Finally, tumor growth in mice was also investigated. Cells proliferation, migration and apoptosis were detected by Ki67 staining, Tunnel staining and mouse lung metastasis model. RESULTS: KBTBD2 was highly expressed in GC, and was related to poor prognosis. Moreover, silencing KBTBD2 suppressed GC cell proliferation, migration and invasion, while also inhibited the EMT, but promoted apoptosis. At the same time, KBTBD2 overexpression showed opposite results. In addition, KBTBD2 regulated the EGFR pathway. Further, silencing KBTBD2 inhibited tumor growth, cell proliferation and migration but promoted apoptosis in vivo, and KBTBD2 overexpression showed opposite results. CONCLUSIONS: KBTBD2 was highly expressed in GC. KBTBD2 promotes the progress of GC by activating EGFR signal pathway. KBTBD2 may thus be a novel target for treating GC.

High-Entropy Layered Oxide Cathode Enabling High-Rate for Solid-State Sodium-Ion Batteries.

Na-ion O3-type layered oxides are prospective cathodes for Na-ion batteries due to high energy density and low-cost. Nevertheless, such cathodes usually suffer from phase transitions, sluggish kinetics and air instability, making it difficult to achieve high performance solid-state sodium-ion batteries. Herein, the high-entropy design and Li doping strategy alleviate lattice stress and enhance ionic conductivity, achieving high-rate performance, air stability and electrochemically thermal stability for Na0.95Li0.06Ni0.25Cu0.05Fe0.15Mn0.49O2. This cathode delivers a high reversible capacity (141 mAh g-1 at 0.2C), excellent rate capability (111 mAh g-1 at 8C, 85 mAh g-1 even at 20C), and long-term stability (over 85% capacity retention after 1000 cycles), which is attributed to a rapid and reversible O3-P3 phase transition in regions of low voltage and suppresses phase transition. Moreover, the compound remains unchanged over seven days and keeps thermal stability until 279 ℃. Remarkably, the polymer solid-state sodium battery assembled by this cathode provides a capacity of 92 mAh g-1 at 5C and keeps retention of 96% after 400 cycles. This strategy inspires more rational designs and could be applied to a series of O3 cathodes to improve the performance of solid-state Na-ion batteries.

PKNOX1 acts as a transcription factor of DHH and promotes the progression of stomach adenocarcinoma by regulating the Hedgehog signalling pathway.

BACKGROUND: This study explored the effects and potential mechanism by which PBX/knotted 1 homeobox 1 (PKNOX1) may exacerbate stomach adenocarcinoma (STAD). METHODS: For the in silico analysis, we examined TCGA-PKNOX1 expression using the UALCAN website, as well as its expression patterns in the GSE172032 and GSE174237 datasets, obtained from the GEO database. The associated patient survival curves, were analysed via the KMplot webtool. In vitro, we measured cell viability, proliferation, migration, and invasion using cell counting kit-8, colony formation, wound healing, and cell migration assays, respectively. Real time qPCR and western blotting assessed the mRNA and protein levels of PKNOX1, Snail, vimentin, N-cadherin, E-cadherin, desert hedgehog (DHH), cyclin D2, glioma-associated oncogene homolog 1, and smoothened. Gene Set Enrichment Analysis was performed using LinkedOmics webtools and the clusterProfiler package in R. Dual-luciferase reporter assay was used to examine the interactions of PKNOX1 with DHH, and of TEA domain transcription factor 4 (TEAD4) with PKNOX1. RESULTS: PKNOX1 was highly expressed in STAD and linked to poor patient survival. Downregulation of PKNOX1 inhibited STAD cell viability, proliferation, migration, invasion, and epithelial-mesenchymal transition. Upregulation of TEAD4 promoted colony formation and migration, while these effects were reversed by PKNOX1 depletion. Furthermore, PKNOX1 regulated the activation of the hedgehog signalling pathway at the gene level, as we identified PKNOX1 to be a putative transcription factor for DHH that promotes its expression. CONCLUSION: Our results show that PKNOX1 acts as a candidate transcription factor for DHH and facilitates STAD development by regulating the hedgehog signalling pathway.

Competitive dynamics of E2 and SN2 reaction driven by collision energy and leaving group.

The competition between E2 and SN2 reactions is essential in organic chemistry. In this paper, the reaction mechanism of F- + CH3CH2Cl is investigated utilizing direct dynamics simulations, and unravel how the collision energy (Ecoll) and the leaving group affect the competition between SN2 and E2 in the F- + CH3CH2Y (Y = Cl and Br) reactions. Simulation results for F- + CH3CH2Cl reaction show that the anti-E2 channel is dominant, but with the increase of Ecoll from 0.04 to 1.9 eV the branching ratio of the anti-E2 pathway significantly decreases by 21%, and the SN2 pathway becomes more important. A transition from indirect to direct reaction has been revealed when Ecoll is increased from 0.04 to 1.90 eV. At lower Ecoll, a large ratio of indirect events occurs via a long-lived hydrogen-bonded complex, and as the collision energy is increased, the lifetimes of the hydrogen-bonded complexes are shortened, due to an initial faster relative velocity. The simulation results of F- + CH3CH2Cl are further compared with the F- + CH3CH2Br reaction at Ecoll of 0.04 eV. Changing the leaving group from Cl to Br drastically suppresses the indirect events of anti-E2 with a branching ratio decreasing from 0.46 to 0.36 due to the mass effect, and promotes direct rebound mechanism resulting from a looser transition state geometry caused by varied electronegativity.

Effects of Methyl Substitution and Leaving Group on E2/SN2 Competition for Reactions of F- with RY (R = CH3, C2H5, iC3H7, tC4H9; Y = Cl, I).

The competition between base-induced elimination (E2) and bimolecular nucleophilic substitution (SN2) is of significant importance in organic chemistry and is influenced by many factors. The electronic structure calculations for the gas-phase reactions of F- + RY (R = CH3, C2H5, iC3H7, tC4H9, and Y = Cl, I) are executed at the MP2 level with aug-cc-pVDZ or ECP/d basis set to investigate the α-methyl substitution effect. The variation in barrier height, reaction enthalpy, and competition of SN2/E2 as a function of methyl-substitution and leaving group ability has been emphasized. And the nature of these rules has been explored. As the degree of methyl substitution on α-carbon increases, the E2 channel becomes more competitive and dominant with R varying from C2H5, iC3H7, to tC4H9. Energy decomposition analysis offers new insights into the competition between E2 and SN2 processes, which suggests that the drop in interaction energy with an increasing degree of substitution cannot compensate for the rapid growth of preparation energy, leading to a rapid increase in the SN2 energy barrier. By altering the leaving group from Cl to I, the barriers of both SN2 and E2 monotonically decrease, and, with the increased number of substituents, they reduce more dramatically, which is attributed to the looser transition state structures with the stronger leaving group ability. Interestingly, ∆E0‡ exhibits a positive linear correlation with reaction enthalpy (∆H) and halogen electronegativity. With the added number of substituents, the differences in ∆E0‡ and ∆H between Y = Cl and I likewise exhibit good linearity.

A fish image segmentation methodology in aquaculture environment based on multi-feature fusion model.

Underwater fish image processing is one of the key technologies to realize intelligent aquaculture. However, due to the complexity of marine environments, underwater fish images usually have the characteristics of color cast, unbalanced contrast, and blur. Current underwater fish image segmentation methods lack adaptive models and have low segmentation accuracy. Hence, this paper constructs a convolutional neural network-based image segmentation model. This paper first proposes a fish image preprocessing method based on pixel threshold segmentation. To enhance the important features in a fish image, this method uses the minimum Euclidean distance between the original image peaks to redefine the threshold and fuses the thresholded image with the original image. Second, to strengthen the extraction of high-level semantic features of images, the multiscale attentional feature extraction module (MAFEM), which fuses the adaptive channel attention mechanism with the hybrid dilated convolutional pyramid pooling module, is proposed. In this paper, a data set in voc format is produced based on underwater fish images, and this data set is used to verify the model in this paper. The mean intersection over union (MIoU) reaches 92.6%. Compared with other traditional segmentation models, the MIoU, mean pixel accuracy (MPA), and balanced F score (F1-score) of the segmentation results of the model in this paper are increased by averages of 1.84%, 0.785%, and 1.18%, respectively. The experimental results show that this model has a better segmentation effect than other models and provides a theoretical basis for intelligent monitoring of underwater fish body length measurement, weight estimation, and discrimination of growth and health statuses.

Single-cell analysis of gastric signet ring cell carcinoma reveals cytological and immune microenvironment features.

Gastric signet ring cell carcinoma (GSRC) is a special subtype of gastric cancer (GC) associated with poor prognosis, but an in-depth and systematic study of GSRC is lacking. Here, we perform single-cell RNA sequencing to assess GC samples. We identify signet ring cell carcinoma (SRCC) cells. Microseminoprotein-beta (MSMB) can be used as a marker gene to guide the identification of moderately/poorly differentiated adenocarcinoma and signet ring cell carcinoma (SRCC). The upregulated differentially expressed genes in SRCC cells are mainly enriched in abnormally activated cancer-related signalling pathways and immune response signalling pathways. SRCC cells are also significantly enriched in mitogen-activated protein kinase and oestrogen signalling pathways, which can interact and promote each other in a positive feedback loop. SRCC cells are shown to have lower cell adhesion and higher immune evasion capabilities as well as an immunosuppressive microenvironment, which may be closely associated with the relatively poor prognosis of GSRC. In summary, GSRC exhibits unique cytological characteristics and a unique immune microenvironment, which may be advantageous for accurate diagnosis and treatment.

Nucleophile Effects on the E2/SN2 Competition for the X- + CH3CH2Cl Reactions: A Theoretical Study.

The effect of nucleophiles on the gas-phase E2/SN2 competition is still not completely elucidated, despite its importance in chemistry. In the current work, the electronic structure calculations of prototypical reactions X- + CH3CH2Cl (X = OH, F, Cl, Br, and I) are performed at the MP2 level with aug-cc-pVDZ or ECP/d. The effects of nucleophiles on the competing E2 and SN2 reactions in terms of the correlation between the barrier height and reaction energy, electronegativity of X, bond length, charge distribution, and proton affinity of anionic nucleophile X- are explored and emphasized. As the nucleophile changes from OH- to I-, both SN2 and E2 reactions become more exothermic, with the reaction energy in the ranges from -51.9 to 10.8 kcal mol-1 (SN2) and -36.8 to 38.0 kcal mol-1(E2). For X- = F- and OH-, the sequence of reactivity for the four pathways is ret-SN2 < syn-E2 < anti-E2 ∼ inv-SN2. However, for X- = Cl-, Br-, and I-, the anti-E2 barrier is much higher in energy (17.1-29.4 kcal mol-1) than that of inv-SN2. Energy decomposition analysis illustrates that the anti-E2 pathway possesses the highly destabilizing characteristic distortion, resulting in a larger reaction barrier and hence becoming a more unfavorable pathway than inv-SN2. More interestingly, only ion-dipole complex exists in the entrance channel for reactions involving OH-, Cl-, Br-, and I-, and in contrast, a significant hydrogen-bonded complex formation is also revealed for X- = F-, which can further affect E2/SN2 competition and atomic-level mechanisms, especially, for the isoelectronic nucleophile F- and OH-. It has been revealed here that electronegativity of central atoms in X and ionic radii of nucleophiles are the important factors affecting the entrance channel complex.

Loss of cancer-associated fibroblast-derived exosomal DACT3-AS1 promotes malignant transformation and ferroptosis-mediated oxaliplatin resistance in gastric cancer.

AIMS: Long non-coding RNAs (lncRNAs), as one of the components of exosomes derived from cancer-associated fibroblasts (CAFs), exhibit a crucial role in the pathogenesis and chemoresistance of gastric cancer (GC). Herein, we investigated the role and mechanism of a novel lncRNA disheveled binding antagonist of beta catenin3 antisense1 (DACT3-AS1) and its involvement in GC. METHODS: DACT3-AS1 was identified by RNA-sequencing and verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The functional role of DACT3-AS1 in GC was evaluated using in vitro and in vivo experiments including Transwell assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay, immunoblotting, and xenograft tumor mouse model. Dual-luciferase reporter assay was performed to assess the association between genes. RESULTS: DACT3-AS1 was downregulated and involved in poor prognosis of patients with GC. The results from both in vitro and in vivo experiments showed that DACT3-AS1 suppressed cell proliferation, migration, and invasion through targeting miR-181a-5p/sirtuin 1 (SIRT1) axis. Additionally, DACT3-AS1 was transmitted from CAFs to GC cells mainly via exosomes. Exosomal DACT3-AS1 alleviated xenograft tumor growth. DACT3-AS1 conferred sensitivity of cancer cells to oxaliplatin through SIRT1-mediated ferroptosis both in vitro and in vivo. CONCLUSIONS: CAFs-derived exosomal DACT3-AS1 is a suppressive regulator in malignant transformation and oxaliplatin resistance. DACT3-AS1 could be used for diagnosis and treatment of GC.

OASL knockdown inhibits the progression of stomach adenocarcinoma by regulating the mTORC1 signaling pathway.

The present study investigated the effects of 2'-5' oligoadenylate synthetase-like (OASL) on the biological functions of stomach adenocarcinoma (STAD) cells and tumor formation in nude mice. The differential expression levels of OASL in the different cancer types from TCGA dataset were analyzed using gene expression profiling interactive analysis. Overall survival and the receiver operating characteristic were analyzed using the KM plotter and R, respectively. Furthermore, OASL expression and its effects on the biological functions of STAD cells were detected. The possible upstream transcription factors of OASL were predicted using JASPAR. The downstream signaling pathways of OASL were analyzed using GSEA. Tumor formation experiments were performed to evaluate the effect of OASL on tumor formation in nude mice. The results showed that OASL was highly expressed in STAD tissues and cell lines. OASL knockdown markedly inhibited cell viability, proliferation, migration, and invasion and accelerated STAD cell apoptosis. Conversely, OASL overexpression had the opposite effect on STAD cells. JASPAR analysis revealed that STAT1 is an upstream transcription factor of OASL. Furthermore, GSEA showed that OASL activated the mTORC1 signaling pathway in STAD. The protein expression levels of p-mTOR and p-RPS6KB1 were suppressed by OASL knockdown and promoted by OASL overexpression. The mTOR inhibitor, rapamycin, markedly reversed the effect of OASL overexpression on STAD cells. Additionally, OASL promoted tumor formation and increased tumor weight and volume in vivo. In conclusion, OASL knockdown suppressed the proliferation, migration, invasion, and tumor formation of STAD cells by inhibiting the mTOR signaling pathway.

A Heteroanionic Zinc Ion Conductor for Dendrite-Free Zn Metal Anodes.

Although zinc-based batteries are promising candidates for eco-friendly and cost-effective energy storage devices, their performance is severely retarded by dendrite formation. As the simplest zinc compounds, zinc chalcogenides, and halides are individually applied as a Zn protection layer due to high zinc ion conductivity. However, the mixed-anion compounds are not studied, which constrains the Zn2+ diffusion in single-anion lattices to their own limits. A heteroanionic zinc ion conductor (Zny O1- x Fx ) coating layer is designed by in situ growth method with tunable F content and thickness. Strengthened by F aliovalent doping, the Zn2+ conductivity is enhanced within the wurtzite motif for rapid lattice Zn migration. Zny O1- x Fx also affords zincophilic sites for oriented superficial Zn plating to suppress dendrite growth. Therefore, Zny O1- x Fx -coated anode exhibits a low overpotential of 20.4 mV for 1000 h cycle life at a plating capacity of 1.0 mA h cm-2 during symmetrical cell test. The MnO2 //Zn full battery further proves high stability of 169.7 mA h g-1 for 1000 cycles. This work may enlighten the mixed-anion tuning for high-performance Zn-based energy storage devices.

A zinc-conducting chalcogenide electrolyte.

A solid-state zinc-ion battery can fundamentally eliminate dendrite formation and hydrogen evolution on the zinc anode from aqueous systems. However, enabling fast zinc ion + conduction in solid crystals is thought to be impossible. Here, we demonstrated a fluorine-doping approach to achieving fast Zn2+ transport in mesoporous ZnyS1-xFx. The substitutional doping of fluoride ion with sulfide substantially reduces Zn2+ migration barrier in a crystalline phase, while mesopore channels with bounded dimethylformamide enable nondestructive Zn2+ conduction along inner pore surface. This mesoporous conductor features a high room-temperature Zn2+ conductivity (0.66 millisiemens per centimeter, compared with 0.01 to 1 millisiemens per centimeter for lithium solid-state electrolyte) with a superior cycling performance (89.5% capacity retention over 5000 cycles) in a solid zinc-ion battery and energy density (0.04 watt-hour per cubic centimeter) in a solid zinc-ion capacitor. The universality of this crystal engineering approach was also verified in other mesoporous zinc chalcogenide materials, which implies various types of potential Zn2+-conducting solid electrolytes.

A Highly Efficacious Electrical Biofilm Treatment System for Combating Chronic Wound Bacterial Infections.

Biofilm infection has a high prevalence in chronic wounds and can delay wound healing. Current treatment using debridement and antibiotic administration imposes a significant burden on patients and healthcare systems. To address their limitations, a highly efficacious electrical antibiofilm treatment system is described in this paper. This system uses high-intensity current (75 mA cm-2 ) to completely debride biofilm above the wound surface and enhance antibiotic delivery into biofilm-infected wounds simultaneously. Combining these two effects, this system uses short treatments (≤2 h) to reduce bacterial count of methicillin-resistant S. aureus (MRSA) biofilm-infected ex vivo skin wounds from 1010 to 105.2 colony-forming units (CFU) g-1 . Taking advantage of the hydrogel ionic circuit design, this system enhances the in vivo safety of high-intensity current application compared to conventional devices. The in vivo antibiofilm efficacy of the system is tested using a diabetic mouse-based wound infection model. MRSA biofilm bacterial count decreases from 109.0 to 104.6 CFU g-1 at 1 day post-treatment and to 103.3 CFU g-1 at 7 days post-treatment, both of which are below the clinical threshold for infection. Overall, this novel technology provides a quick, safe, yet highly efficacious treatment to chronic wound biofilm infections.

AKAP8L enhances the stemness and chemoresistance of gastric cancer cells by stabilizing SCD1 mRNA.

Gastric cancer (GC) remains the third leading cause of cancer-related deaths. Chemoresistance is the major determinant of GC treatment failure. To explore the molecular mechanisms of GC chemoresistance, mass spectrometry was performed to detect the genes altered in expression between chemoresistant and chemosensitive GC. PRKA kinase anchor protein 8L (AKAP-8L) was identified as one of the top upregulated genes in chemoresistant GC tissues. Moreover, the higher AKAP-8L expression was associated with the lower survival rate in GC patients. Overexpression of AKAP-8L enhanced the GC cell stemness and chemoresistance of oxaliplatin in vivo and in vitro. AKAP-8L deficiency obtained the opposite results. Mechanistically, AKAP-8L interacted with Stearoyl-CoA desaturase 1 (SCD1) mRNA and IGF2BP1 protein, and regulated SCD1 mRNA stability via IGF2BP1-dependent manner. SCD1 played a critical role in mediating the function of AKAP-8L in GC cell stemness and chemoresistance. Clinically, AKAP-8L and SCD1 protein levels was positively associated with human GC chemoresistance. Taken together, our results demonstrated that AKAP-8L facilitates GC chemoresistance via regulating SCD1-mediated stemness of GC cells. AKAP8L may represent a novel therapeutic target to overcome GC chemoresistance.

Synergistic Effects of B-F/B-S and Nitrogen Vacancy Co-Doping on g-C3N4 and Photocatalytic CO2 Reduction Mechanisms: A DFT Study.

Nonmetallic co-doping and surface hole construction are simple and efficient strategies for improving the photocatalytic activity and regulating the electronic structure of g-C3N4. Here, the g-C3N4 catalysts with B-F or B-S co-doping combined with nitrogen vacancies (Nv) are designed. Compared to the pristine g-C3N4, the direction of the excited electron orbit for the B-F-co-doped system is more matching (N2pz→C2pz), facilitating the separation of electrons and holes. Simultaneously, the introduced nitrogen vacancy can further reduce the bandgap by generating impurity states, thus improving the utilization rate of visible light. The doped S atoms can also narrow the bandgap of the B-S-Nv-co-doped g-C3N4, which originates from the p-orbital hybridization between C, N, and S atoms, and the impurity states are generated by the introduction of N vacancies. The doping of B-F-Nv and B-S-Nv exhibits a better CO2 reduction activity with a reduced barrier for the rate-determining step of around 0.2 eV compared to g-C3N4. By changing F to S, the origin of the rate-determining step varies from *CO2→*COOH to *HCHO→*OCH3, which eventually leads to different products of CH3OH and CH4, respectively.

Reaction mechanism conversion induced by the contest of nucleophile and leaving group.

Direct dynamic simulations have been employed to investigate the OH- + CH3Cl reaction with the chosen B3LYP/aug-cc-pVDZ method. The calculated rate coefficient for the bimolecular nucleophilic substitution reaction (SN2), 1.0 × 10-9 cm3 mol-1 s-1 at 300 K, agrees well with the experimental result of (1.3-1.6) × 10-9 cm3 mol-1 s-1. The simulations reveal that the majority of the SN2 reactions are temporarily trapped in the hydrogen-bonded complex at Ecoll = 0.89 kcal mol-1. Importantly, the influences of the leaving group and nucleophile have been discussed by comparisons of X- + CH3Y (X = F, OH; Y = Cl, I) reactions. For the X = F- reactions, the reaction probability of SN2 increases along the increased leaving group ability Cl < I, suggesting that the thermodynamic factor plays a key role. The indirect mechanisms were found to be dominant for both reactions. In contrast, for X = OH-, the fraction of SN2 drops with the enhanced leaving group ability. In particular, a dramatic transition occurs for the dominant atomic reaction mechanisms, i.e., from complex-mediated indirect to direct, implying an interesting contest between the leaving group and the nucleophile and the importance of the dynamic factors, i.e., the dipole moment, steric hindrance, and electronegativity.