Assessment of the correlation between KAP scores regarding sugar-sweetened beverage consumption and hyperuricemia amongst Chinese young adults.

BACKGROUND: The prevalence of hyperuricemia in China has been consistently increasing, particularly among the younger generation. The excessive consumption of sugar-sweetened beverages is associated with hyperuricemia. This study examined the knowledge, attitudes, and practices (KAP) of Chinese young adults regarding sugar-sweetened beverage consumption and the correlation with hyperuricemia. METHODS: This cross-sectional investigation was conducted from June 28th, 2023, to July 21st, 2023, and enrolled Chinese young adults. Demographics and KAP were evaluated using a questionnaire (Cronbach's α = 0.787). Factors influencing KAP scores were analyzed using multivariable analyses. RESULTS: A total of 1288 valid questionnaires were analyzed. The median knowledge, attitude, and practice scores were 16 (12,19)/22, 22 (20,24)/30, and 27.5 (23,31.75)/40. The multivariable analysis showed that bachelor's/associate education (OR = 1.912, 95%CI: 1.128-3.239), white collar/employee (OR = 0.147, 95%CI: 0.105-0.206), educator (OR = 0.300, 95%CI: 0.174-0.518), healthcare worker (OR = 0.277, 95%CI: 0.188-0.407), not suffering from hyperuricemia (OR = 0.386, 95%CI: 0.253-0.590), and not having gout (OR = 0.456, 95%CI: 0.282-0.736) were independently associated with knowledge. Age 26-30 (OR = 1.470, 95%CI: 1.052-2.052), age 31-35 (OR = 1.489, 95%CI: 1.097-2.022), age 36-40 (OR = 0.328, 95%CI: 1.010-1.746), age 41-44 (OR = 1.548, 95%CI: 1.091-2.198), and not having hyperuricemia (OR = 0.512, 95%CI: 0.345-0.760) were independently associated with attitude. White collar/employee (OR = 0.386, 95%CI: 0.285-0.521), educator (OR = 0.534, 95%CI: 0.317-0.899), healthcare worker (OR = 0.341, 95%CI: 0.236-0.493), having siblings (OR = 0.725, 95%CI: 0.573-0.917), and not suffering from hyperuricemia (OR = 0.442, 95%CI: 0.296-0.659), were independently associated with practice. CONCLUSION: Chinese young adults display moderate KAP toward sugar-sweetened beverages. Notably, an association was observed between hyperuricemia and each KAP dimension.

Flexible TAM requirement of TnpB enables efficient single-nucleotide editing with expanded targeting scope.

TnpBs encoded by the IS200/IS605 family transposon are among the most abundant prokaryotic proteins from which type V CRISPR-Cas nucleases may have evolved. Since bacterial TnpBs can be programmed for RNA-guided dsDNA cleavage in the presence of a transposon-adjacent motif (TAM), these nucleases hold immense promise for genome editing. However, the activity and targeting specificity of TnpB in homology-directed gene editing remain unknown. Here we report that a thermophilic archaeal TnpB enables efficient gene editing in the natural host. Interestingly, the TnpB has different TAM requirements for eliciting cell death and for facilitating gene editing. By systematically characterizing TAM variants, we reveal that the TnpB recognizes a broad range of TAM sequences for gene editing including those that do not elicit apparent cell death. Importantly, TnpB shows a very high targeting specificity on targets flanked by a weak TAM. Taking advantage of this feature, we successfully leverage TnpB for efficient single-nucleotide editing with templated repair. The use of different weak TAM sequences not only facilitates more flexible gene editing with increased cell survival, but also greatly expands targeting scopes, and this strategy is probably applicable to diverse CRISPR-Cas systems.

A fully validated LC­MS/MS method for quantifying bevacizumab in plasma samples from patients with NSCLC and its implications in therapeutic drug monitoring.

Given the increasing use of bevacizumab in combinatorial drug therapy for a multitude of different cancer types, there is a need for therapeutic drug monitoring to analyze the possible correlation between drug trough concentration, and therapeutic effect and adverse reactions. An ultra-performance liquid chromatography tandem-mass spectrometry method was then developed and validated to determine bevacizumab levels in human plasma samples. Chromatographic separation was achieved on a Shimadzu InertSustainBio C18 HP column, whereas subsequent mass spectrometric analysis was performed using a Shimadzu 8050CL triple quadrupole mass spectrometer equipped with an electro-spray ionization source in the positive ion mode. In total, three multiple reaction monitoring transitions of each of the surrogate peptides were chosen with 'FTFSLDTSK' applied as the quantification peptide whereas 'VLIYFTSSLHSGVPSR' and 'STAYLQMNSLR' were designated as the verification peptides using the Skyline software. This analytical method was then fully validated, with specificity, linearity, lower limit of quantitation, accuracy, precision, stability, matrix effect and recovery calculated. The linearity of this method was developed to be within the concentration range 5-400 µg/ml for bevacizumab in human plasma. Subsequently, eight patients with non-small cell lung cancer (NSCLC) were recruited and injected with bevacizumab over three periods of treatment to analyze their steady-state trough concentration and differences. To conclude, the results of the present study suggest that bevacizumab can be monitored in a therapeutic setting in patients with NSCLC.

An exploratory study on the association of multiple metals in serum with preeclampsia.

Background: Individual metal levels are potential risk factors for the development of preeclampsia (PE). However, understanding of relationship between multiple metals and PE remains elusive. Purpose: The purpose of this study was to explore whether eight metals [zinc (Zn), manganese (Mn), copper (Cu), nickel (Ni), lead (Pb), arsenic (As), cadmium (Cd), and mercury (Hg)] in serum had a certain relationship with PE. Methods: A study was conducted in Dongguan, China. The concentrations of metals in maternal serum were assessed using inductively coupled plasma mass spectrometry (ICP-MS). Data on various factors were collected through a face-to-face interview and hospital electronic medical records. The unconditional logistic regression model, principal component analysis (PCA) and Bayesian Kernel Machine Regression (BKMR) were applied in our study. Results: The logistic regression model revealed that the elevated levels of Cu, Pb, and Hg were associated with an increased risk of PE. According to PCA, principal component 1 (PC1) was predominated by Hg, Pb, Mn, Ni, Cu, and As, and PC1 was associated with an increased risk of PE, while PC2 was predominated by Cd and Zn. The results of BKMR indicated a significant positive cumulative effect of serum metals on PE risk, with Ni and Cu exhibiting a significant positive effect. Moreover, BKMR results also revealed the nonlinear effects of Ni and Cd. Conclusion: The investigation suggests a potential positive cumulative impact of serum metals on the occurrence of PE, with a particular emphasis on Cu as a potential risk factor for the onset and exacerbation of PE. These findings offer valuable insights for guiding future studies on this concern.

A general strategy for the enhanced H2 production performance of CdS/noble metal sulfide nanorods photocatalysts by cation exchange.

In this work, we report a series of noble metal (Ag, Au, Pt, etc.) sulfides that act as co-catalysts anchoring on CdS nanorods (NRs) obtained via a cation exchange strategy to promote photocatalytic hydrogen evolution. CdS NRs are first generated via a hydrothermal routine, noble metal sulfides are then in-situ grown on CdS NRs by a cation exchange method. CdS/Ag2S, CdS/Au2S and CdS/PtS NRs show improved hydrogen production rates (2506.88, 1513.17 and 1004.54 µmol g-1h-1, respectively), approximately 18, 11 and 7 times higher than CdS NRs (138.27 µmol g-1h-1). Among CdS/noble metal sulfide NRs, CdS/Ag2S NRs present the best H2 production performance. The apparent quantum efficiency (AQE) of CdS/Ag2S NRs achieves 3.11 % at λ = 370 nm. The improved photocatalytic performance of CdS/noble metal sulfide NRs dues to the following points: i) Noble metal sulfides on CdS NRs are beneficial for elevating light-absorbing and light-utilizing capacities, contributing to generating more photoexcited charges; ii) Noble metal sulfides are in-situ grown on CdS NRs as electron acceptors by a cation exchange method, thus the photoexcited electrons generated by CdS NRs rapidly migrate to the surface of noble metal sulfides, successfully accelerating the carriers separation efficiency. This series of noble metal sulfides acting as co-catalysts anchoring on CdS NRs offer new insights into the construction principles of high-performance photocatalytic hydrogen evolution catalysts.

Rapid cycle deliberate practice: application in forceps simulation training for gynecology and obstetrics residents.

BACKGROUND: Rapid Cycle Deliberate Practice (RCDP) has gained prominence in recent years as an innovative teaching method in simulation-based training for adult and pediatric emergency medical skills. However, its application in the training of forceps delivery skills among obstetrics and gynecology residents remains unexplored. This study aimed to assess the impact of RCDP in this domain. METHODS: Conducted in March 2021, this randomized controlled study involved 60 second-year obstetrics and gynecology residents undergoing standardized training. Participants were randomly assigned to the RCDP group or the traditional teaching method (TTM) group, each comprising 30 residents. The RCDP group followed the RCDP practice mode, while the TTM group adhered to conventional simulation teaching. Post-training assessment of operational proficiency was conducted immediately and after one year. Independent operational confidence and training satisfaction were evaluated through questionnaire surveys and the Satisfaction with Simulation Experience (SSE) scale. Data analysis utilized SPSS 23.0. RESULTS: The RCDP group displayed significantly higher immediate post-training forceps operation scores compared to the TTM group (92.00 [range: 90.00-94.00] vs. 88.00 [range: 86.75-92.00]; z = 3.79; p < .001). However, no significant difference emerged in forceps operation scores after one year (86.00 [range: 85.00-88.00] vs. 85.50 [range: 84.00-88.25]; z = 0.54; p = .59). The RCDP group exhibited notable performance improvement over the TTM group (z = 3.49; p < .001). Independent operation confidence showed no significant discrepancy (p > .05). Importantly, the RCDP group reported higher satisfaction scores, particularly in the Debriefing and Reflection subscale (44.00 [range: 43.00-45.00] vs. 41.00 [range: 41.50-43.00]; z = 5.24; p < .001), contributing to an overall superior SSE score (z = 4.74; p < .001). CONCLUSIONS: RCDP exhibits immediate efficacy in elevating forceps delivery skills among residents. However, sustained skill enhancement necessitates innovative approaches, while RCDP's value lies in tailored feedback and reflection for enriched medical education.

Rapid Cycle Deliberate Practice (RCDP) demonstrates immediate effectiveness in enhancing forceps delivery skills among obstetrics and gynecology residents, leading to improved immediate performance, which also increased their satisfaction with the teaching process and operational confidence.Long-term skill retention through RCDP appears limited, highlighting the importance of ongoing reinforcement to prevent skill decay and maintain proficiency.

Combining CRISPR/Cas9 and natural excision for the precise and complete removal of mobile genetic elements in bacteria.

Horizontal gene transfer, facilitated by mobile genetic elements (MGEs), is an adaptive evolutionary process that contributes to the evolution of bacterial populations and infectious diseases. A variety of MGEs not only can integrate into the bacterial genome but also can survive or even replicate like plasmids in the cytoplasm, thus requiring precise and complete removal for studying their strategies in benefiting host cells. Existing methods for MGE removal, such as homologous recombination-based deletion and excisionase-based methods, have limitations in effectively eliminating certain MGEs. To overcome these limitations, we developed the Cas9-NE method, which combines the CRISPR/Cas9 system with the natural excision of MGEs. In this approach, a specialized single guide RNA (sgRNA) element is designed with a 20-nucleotide region that pairs with the MGE sequence. This sgRNA is expressed from a plasmid that also carries the Cas9 gene. By utilizing the Cas9-NE method, both the integrative and circular forms of MGEs can be precisely and completely eliminated through Cas9 cleavage, generating MGE-removed cells. We have successfully applied the Cas9-NE method to remove four representative MGEs, including plasmids, prophages, and genomic islands, from Vibrio strains. This new approach not only enables various investigations on MGEs but also has significant implications for the rapid generation of strains for commercial purposes.IMPORTANCEMobile genetic elements (MGEs) are of utmost importance for bacterial adaptation and pathogenicity, existing in various forms and multiple copies within bacterial cells. Integrated MGEs play dual roles in bacterial hosts, enhancing the fitness of the host by delivering cargo genes and potentially modifying the bacterial genome through the integration/excision process. This process can lead to alterations in promoters or coding sequences or even gene disruptions at integration sites, influencing the physiological functions of host bacteria. Here, we developed a new approach called Cas9-NE, allowing them to maintain the natural sequence changes associated with MGE excision. Cas9-NE allows the one-step removal of integrated and circular MGEs, addressing the challenge of eliminating various MGE forms efficiently. This approach simplifies MGE elimination in bacteria, expediting research on MGEs.

Ecological barriers: An approach to ecological conservation and restoration in China.

The Chinese government has pursued comprehensive ecological conservation and restoration by establishing an ecological barrier system. However, the majority of international research tends to focus on the connectivity between habitats, overlooking the functions that ecological barriers play in ecological conservation and restoration. The existing literature lacks a systematic exploration of the theory and practice of ecological barriers. This study employed the literature analysis tool CiteSpace to present the theoretical and developmental trends in ecological barriers from various perspectives, including research fields, historical evolution, research hotspots, and major research nations. By analyzing the differences in the understanding of ecological barriers between China and other countries, examining the ecological barriers construction history in China, and exploring the types and functions of ecological barriers, this study summarizes the framework of China's ecological barriers construction system as "features-functions-problems." Constructing an ecological barrier system can help achieve ecological conservation and restoration goals in China.

Applications of Circulating Tumor DNA in Myelodysplastic Syndromes and Acute Myeloid Leukemia: Promises and Challenges.

The term 'liquid biopsy' has become widely used by clinicians with the development of non-invasive diagnostic and monitoring techniques for malignancies. Liquid biopsy can provide genetic information for early diagnosis, risk stratification, treatment selection and postoperative follow-up. In the era of personalized medicine, liquid biopsy is an important research direction. In recent years, research on circulating tumour DNA (ctDNA) in hematological malignancies has also made great progress. This review provides an overview of the current understanding of circulating tumour DNA in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Additionally, recent advancements in the monitoring of minimal/measurable residual disease (MRD) through ctDNA are discussed.

Photo-Assisted Li-N2 Batteries with Enhanced Nitrogen Fixation and Energy Conversion.

Li-N2 batteries have received widespread attention for their potential to integrate N2 fixation, energy storage, and conversion. However, because of the low activity and poor stability of cathode catalysts, the electrochemical performance of Li-N2 batteries is suboptimal, and their electrochemical reversibility has rarely been proven. In this study, a novel bifunctional photo-assisted Li-N2 battery system was established by employing a plasmonic Au nanoparticles (NPs)-modified defective carbon nitride (Au-Nv -C3 N4 ) photocathode. The Au-Nv -C3 N4 exhibits strong light-harvesting, N2 adsorption, and N2 activation abilities, and the photogenerated electrons and hot electrons are remarkably beneficial for accelerating the discharge and charge reaction kinetics. These advantages enable the photo-assisted Li-N2 battery to achieve a low overpotential of 1.32 V, which is the lowest overpotential reported to date, as well as superior rate capability and prolonged cycle stability (≈500 h). Remarkably, a combination of theoretical and experimental results demonstrates the high reversibility of the photo-assisted Li-N2 battery. The proposed novel strategy for developing efficient cathode catalysts and fabricating photo-assisted battery systems breaks through the overpotential bottleneck of Li-N2 batteries, providing important insights into the mechanism underlying N2 fixation and storage.

Incorporation of cellulose nanocrystals to improve the physicochemical and bioactive properties of pectin-konjac glucomannan composite films containing clove essential oil.

This study aimed to investigate the effectiveness of cellulose nanocrystals (CNC) isolated from cotton in augmenting pectin (PEC)/konjac glucomannan (KGM) composite films containing clove essential oil (CEO) for food packaging application. The effects of CNC dosage on film properties were examined by analyzing the rheology of film-forming solutions and the mechanical, barrier, antimicrobial, and CEO-release properties of the films. Rheological and FTIR analysis revealed the enhanced interactions among the film components after CNC incorporation due to its high aspect ratio and abundant hydroxyl groups, which can also prevent CEO droplet aggregation, contributing to form a compact microstructure as confirmed by SEM and 3D surface topography observations. Consequently, the addition of CNC reinforced the polysaccharide matrix, increasing the tensile strength of the films and improving their barrier properties to water vapor. More importantly, antibacterial, controlled release and kinetic simulation experiments proved that the addition of CNC could further slow down the release rate of CEO, prolonging the antimicrobial properties of the films. PEC/KGM/CEO composite films with 15 wt% CNC was found to have relatively best comprehensive properties, which was also most effective in delaying deterioration of grape quality during the storage of 9 days at 25 °C.

Development of a novel HER2-CAR monocyte cell therapy with controllable proliferation and enhanced anti-tumor efficacy.

BACKGROUND: One of the significant challenges for cell therapies, such as chimeric antigen receptor (CAR)-T cell therapy, is the poor infiltration of immune cells into tumor tissues. CAR-monocytes/macrophages (CAR-M) are promising therapies because of their enrichment in the tumor microenvironment. Thus, we constructed a novel CAR-M to facilitate the infiltration of T cells and other immune cells. METHODS: The suicide gene inducible caspase-9 (iCasp9) and anti-erb-b2 receptor tyrosine kinase 2 (HER2) CAR elements were transfected into THP1 (an immortalized human monocyte cell line) by lentivirus. The suicide efficiency and specific anti-tumor efficacy were assessed using flow cytometry, inCucyte, and tumor-bearing BALB/c-nude mouse models. The activation of related signaling pathways in CAR-THP1 activation was explored by transcriptome sequencing. Finally, the synergistic therapeutic efficacy of CAR-THP1 combined with RAK cell treatment was demonstrated in tumor-bearing NOD.CB17-Prkdcscid Il2rgtm1/Bcgen mouse models. RESULTS: We developed a novel CAR-THP1 which incorporated iCasp9, CD3ζ and CD147 intracellular segments, based on the first-generation HER2-CAR backbone. By constructing and comparing a series of CARs with different permutations, CAR-CD3ζ-CD147-iCasp9-THP1 was selected as the optimal combination. CAR-CD3ζ-CD147-iCasp9-THP1 initiated suicide quickly and efficiently under the control of iCasp9 gene, which enabled us to achieve controlled proliferation of CAR-THP1. CAR-THP1 also exhibited robust specific anti-tumor efficacy independently of T cells in vitro and in vivo. Through transcriptional sequencing, we found that CAR-THP1 tended to differentiate into the M1 phenotype and bridged innate and adaptive immunity. A combination of CAR-THP1 and Retronectin actived killer cells (RAKs) showed better therapeutic efficiency, as the metalloproteinases (MMPs) secreted by CAR-THP1 facilitated the degradation of the dense tumor matrix. This further assisted intratumoral infiltration of T cells and augmented the anti-tumor immune response. CONCLUSION: CAR-THP1 might be effective against HER2-positive tumor cells and has great potential for combination therapy with other immune cells.

Analysis of maternal genetic structure of mitochondrial DNA control region from Tai-Kadai-speaking Buyei population in southwestern China.

BACKGROUND: Even though the Buyei are a recognised ethnic group in southwestern China, there hasn't been much work done on forensic population genetics, notably using mitochondrial DNA. The sequences and haplogroups of mitochondrial DNA control regions of the Buyei peoples were studied to provide support for the establishment of a reference database for forensic DNA analysis in East Asia. METHODS AND RESULTS: The mitochondrial DNA control region sequences of 200 Buyei individuals in Guizhou were investigated. The haplotype frequencies and haplogroup distribution of the Buyei nationality in Guizhou were calculated. At the same time, the paired Fst values of the study population and other populations around the world were computed, to explore their genetic polymorphism and population relationship. A total of 179 haplotypes were detected in the Buyei population, with frequencies of 0.005-0.015. All haplotypes were assigned to 89 different haplogroups. The haplotype diversity and random matching probability were 0.999283 and 0.0063, respectively. The paired Fst genetic distances and correlation p-values among the 54 populations revealed that the Guizhou Buyei was most closely related to the Henan Han and the Guizhou Miao, and closer to the Hazara population in Pakistan and the Chiang Mai population. CONCLUSIONS: The study of mitochondrial DNA based on the maternal genetic structure of the Buyei nationality in Guizhou will benefit the establishment of an East Asian forensic DNA reference database and provide a reference for anthropological research in the future.

MYCT1 inhibits hematopoiesis in diffuse large B-cell lymphoma by suppressing RUNX1 transcription.

BACKGROUND: The abnormality of chromosomal karyotype is one factor causing poor prognosis of lymphoma. In the analysis of abnormal karyotype of lymphoma patients, three smallest overlap regions were found, in which MYCT1 was located. MYCT1 is the first tumor suppressor gene cloned by our research team, but its studies relating to the occurrence and development of lymphoma have not been reported. METHODS: R banding analyses were employed to screen the abnormality of chromosomal karyotype in clinical specimen and MYCT1 over-expression cell lines. FISH was to monitor MYCT1 copy number aberration. RT-PCR and Western blot were to detect the mRNA and protein levels of the MYCT1 and RUNX1 genes, respectively. The MYCT1 and RUNX1 protein levels in clinical specimen were evaluated by immunohistochemical DAB staining. The interaction between MYCT1 and MAX proteins was identified via Co-IP and IF. The binding of MAX on the promoter of the RUNX1 gene was detected by ChIP and Dual-luciferase reporter assay, respectively. Flow cytometry and CCK-8 assay were to explore the effects of MYCT1 and RUNX1 on the cell cycle and proliferation, respectively. RESULTS: MYCT1 was located in one of three smallest overlap regions of diffuse large B-cell lymphoma, it altered chromosomal instability of diffuse large B-cell lymphoma cells. MYCT1 negatively correlated with RUNX1 in lymphoma tissues of the patients. MAX directly promoted the RUNX1 gene transcription by binding to its promoter region. MYCT1 may represses RUNX1 transcription by binding MAX in diffuse large B-cell lymphoma cells. MYCT1 binding to MAX probably suppressed RUNX1 transcription, leading to the inhibition of proliferation and cell cycle of the diffuse large B-cell lymphoma cells. CONCLUSION: This study finds that there is a MYCT1-MAX-RUNX1 signaling pathway in diffuse large B-cell lymphoma. And the study provides clues and basis for the in-depth studies of MYCT1 in the diagnosis, treatment and prognosis of lymphoma.

Aprotic Lithium-Oxygen Batteries Based on Nonsolid Discharge Products.

Aprotic lithium-oxygen (Li-O2) batteries are considered to be a promising alternative option to lithium-ion batteries for high gravimetric energy storage devices. However, the sluggish electrochemical kinetics, the passivation, and the structural damage to the cathode caused by the solid discharge products have greatly hindered the practical application of Li-O2 batteries. Herein, the nonsolid-state discharge products of the off-stoichiometric Li1-xO2 in the electrolyte solutions are achieved by iridium (Ir) single-atom-based porous organic polymers (termed as Ir/AP-POP) as a homogeneous, soluble electrocatalyst for Li-O2 batteries. In particular, the numerous atomic active sites act as the main nucleation sites of O2-related discharge reactions, which are favorable to interacting with O2-/LiO2 intermediates in the electrolyte solutions, owing to the highly similar lattice-matching effect between the in situ-formed Ir3Li and LiO2, achieving a nonsolid LiO2 as the final discharge product in the electrolyte solutions for Li-O2 batteries. Consequently, the Li-O2 battery with a soluble Ir/AP-POP electrocatalyst exhibits an ultrahigh discharge capacity of 12.8 mAh, an ultralow overpotential of 0.03 V, and a long cyclic life of 700 h with the carbon cloth cathode. The manipulation of nonsolid discharge products in aprotic Li-O2 batteries breaks the traditional growth mode of Li2O2, bringing Li-O2 batteries closer to being a viable technology.

Highly Stable Organic Molecular Porous Solid Electrolyte with One-Dimensional Ion Migration Channel for Solid-State Lithium-Oxygen Battery.

Solid-state lithium-oxygen (Li-O2 ) batteries have been widely recognized as one of the candidates for the next-generation of energy storage batteries. However, the development of solid-state Li-O2 batteries has been hindered by the lack of solid-state electrolyte (SSE) with high ionic conductivity at room temperature, high Li+ transference number, and the high stability to air. Herein, the organic molecular porous solid cucurbit[7]uril (CB[7]) with one-dimensional (1D) ion migration channels is developed as the SSE for solid-state Li-O2 batteries. Taking advantage of the 1D ion migration channel for Li+ conduction, CB[7] SSE achieves high ionic conductivity (2.45 × 10-4 S cm-1 at 25 °C). Moreover, the noncovalent interactions facilitated the immobilization of anions, realizing a high Li+ transference number (tLi + = 0.81) and Li+ uniform distribution. The CB[7] SSE also shows a wide electrochemical stability window of 0-4.65 V and high thermal stability and chemical stability, as well as realizes stable Li+ plating/stripping (more than 1000 h at 0.3 mA cm-2 ). As a result, the CB[7] SSE endows solid-state Li-O2 batteries with superior rate capability and long-term discharge/charge stability (up to 500 h). This design strategy of CB[7] SSE paves the way for stable and efficient solid-state Li-O2 batteries toward practical applications.

Single-cell analysis reveals that cryptic prophage protease LfgB protects Escherichia coli during oxidative stress by cleaving antitoxin MqsA.

Although toxin/antitoxin (TA) systems are ubiquitous, beyond phage inhibition and mobile element stabilization, their role in host metabolism is obscure. One of the best-characterized TA systems is MqsR/MqsA of Escherichia coli, which has been linked previously to protecting gastrointestinal species during the stress it encounters from the bile salt deoxycholate as it colonizes humans. However, some recent whole-population studies have challenged the role of toxins such as MqsR in bacterial physiology since the mqsRA locus is induced over a hundred-fold during stress, but a phenotype was not found upon its deletion. Here, we investigate further the role of MqsR/MqsA by utilizing single cells and demonstrate that upon oxidative stress, the TA system MqsR/MqsA has a heterogeneous effect on the transcriptome of single cells. Furthermore, we discovered that MqsR activation leads to induction of the poorly characterized yfjXY ypjJ yfjZF operon of cryptic prophage CP4-57. Moreover, deletion of yfjY makes the cells sensitive to H2O2, acid, and heat stress, and this phenotype was complemented. Hence, we recommend yfjY be renamed to lfgB (less fatality gene B). Critically, MqsA represses lfgB by binding the operon promoter, and LfgB is a protease that degrades MqsA to derepress rpoS and facilitate the stress response. Therefore, the MqsR/MqsA TA system facilitates the stress response through cryptic phage protease LfgB.IMPORTANCEThe roles of toxin/antitoxin systems in cell physiology are few and include phage inhibition and stabilization of genetic elements; yet, to date, there are no single-transcriptome studies for toxin/antitoxin systems and few insights for prokaryotes from this novel technique. Therefore, our results with this technique are important since we discover and characterize a cryptic prophage protease that is regulated by the MqsR/MqsA toxin/antitoxin system in order to regulate the host response to oxidative stress.

Unlocking Synthesis of Polyhedral Oligomeric Silsesquioxane-Based Three-Dimensional Polycubane Covalent Organic Frameworks.

Reticular chemistry effectively yields porous structures with distinct topological lattices for a broad range of applications. Polyhedral oligomeric silsesquioxane (POSS)-based octatopic building blocks with a rare Oh symmetric configuration and attracting inorganic features have great potential for creating three-dimensional (3D) covalent organic frameworks (COFs) with new topologies. However, the intrinsic flexibility and intensive motion of cubane-type POSS molecules make the construction of 3D regular frameworks challenging. Herein, by fastening three or four POSS cores with per aromatic rigid linker from rational steric directions, we successfully developed serial crystalline 3D COFs with unpresented "the" and scu topologies. Both the experimental and theoretical results proved the formation of target 3D POSS-based COFs. The resultant hybrid networks with designable chemical skeletons and high surface areas maintain the superiorities of both the inorganic and organic components, such as their high compatibility with inorganic salts, abundant periodic electroactive sites, excellent thermal stability, and open multilevel nanochannels. Consequently, the polycubane COFs could serve as outstanding solid electrolytes with a high ionic conductivity of 1.23 × 10-4 S cm-1 and a lithium-ion transference number of 0.86 at room temperature. This work offers a pathway to generate ordered lattices with multiconnected flexible cube motifs and enrich the topologies of 3D COFs for potential applications.

Polyoxometalate Li3 PW12 O40 and Li3 PMo12 O40 Electrolytes for High-energy All-solid-state Lithium Batteries.

Solid-state lithium (Li) batteries promise both high energy density and safety while existing solid-state electrolytes (SSEs) fail to satisfy the rigorous requirements of battery operations. Herein, novel polyoxometalate SSEs, Li3 PW12 O40 and Li3 PMo12 O40 , are synthesized, which exhibit excellent interfacial compatibility with electrodes and chemical stability, overcoming the limitations of conventional SSEs. A high ionic conductivity of 0.89 mS cm-1 and a low activation energy of 0.23 eV are obtained due to the optimized three-dimensional Li+ migration network of Li3 PW12 O40 . Li3 PW12 O40 exhibits a wide window of electrochemical stability that can both accommodate the Li anode and high-voltage cathodes. As a result, all-solid-state Li metal batteries fabricated with Li/Li3 PW12 O40 /LiNi0.5 Co0.2 Mn0.3 O2 display a stable cycling up to 100 cycles with a cutoff voltage of 4.35 V and an areal capacity of more than 4 mAh cm-2 , as well as a cost-competitive SSEs price of $5.68 kg-1 . Moreover, Li3 PMo12 O40 homologous to Li3 PW12 O40 was obtained via isomorphous substitution, which formed a low-resistance interface with Li3 PW12 O40 . Applications of Li3 PW12 O40 and Li3 PMo12 O40 in Li-air batteries further demonstrate that long cycle life (650 cycles) can be achieved. This strategy provides a facile, low-cost strategy to construct efficient and scalable solid polyoxometalate electrolytes for high-energy solid-state Li metal batteries.

The Interplay Between HIF-1α and EZH2 in Lung Cancer and Dual-Targeted Drug Therapy.

Interactions between oncogenic proteins contribute to the phenotype and drug resistance. Here, EZH2 (enhancer of zest homolog 2) is identified as a crucial factor that mediates HIF-1 (hypoxia-inducible factor) inhibitor resistance. Mechanistically, targeting HIF-1 enhanced the activity of EZH2 through transcription activation of SUZ12 (suppressor of zest 12 protein homolog). Conversely, inhibiting EZH2 increased HIF-1α transcription, but not the transcription of other HIF family members. Additionally, the negative feedback regulation between EZH2 and HIF-1α is confirmed in lung cancer patient tissues and a database of cell lines. Moreover, molecular prediction showed that a newly screened dual-target compound, DYB-03, forms multiple hydrogen bonds with HIF-1α and EZH2 to effectively inhibit the activity of both targets. Subsequent studies revealed that DYB-03 could better inhibit migration, invasion, and angiogenesis of lung cancer cells and HUVECs in vitro and in vivo compared to single agent. DYB-03 showed promising antitumor activity in a xenograft tumor model by promoting apoptosis and inhibiting angiogenesis, which could be almost abolished by the deletion of HIF-1α and EZH2. Notably, DYB-03 could reverse 2-ME2 and GSK126-resistance in lung cancer. These findings clarified the molecular mechanism of cross-regulation of HIF-1α and EZH2, and the potential of DYB-03 for clinical combination target therapy.