Hyd/UBR5 defines a tumor suppressor pathway that links Polycomb repressive complex to regulated protein degradation in tissue growth control and tumorigenesis.

Tumor suppressor genes play critical roles in normal tissue homeostasis, and their dysregulation underlies human diseases including cancer. Besides human genetics, model organisms such as Drosophila have been instrumental in discovering tumor suppressor pathways that were subsequently shown to be highly relevant in human cancer. Here we show that hyperplastic disc (Hyd), one of the first tumor suppressors isolated genetically in Drosophila and encoding an E3 ubiquitin ligase with hitherto unknown substrates, and Lines (Lin), best known for its role in embryonic segmentation, define an obligatory tumor suppressor protein complex (Hyd-Lin) that targets the zinc finger-containing oncoprotein Bowl for ubiquitin-mediated degradation, with Lin functioning as a substrate adaptor to recruit Bowl to Hyd for ubiquitination. Interestingly, the activity of the Hyd-Lin complex is directly inhibited by a micropeptide encoded by another zinc finger gene, drumstick (drm), which functions as a pseudosubstrate by displacing Bowl from the Hyd-Lin complex, thus stabilizing Bowl. We further identify the epigenetic regulator Polycomb repressive complex1 (PRC1) as a critical upstream regulator of the Hyd-Lin-Bowl pathway by directly repressing the transcription of the micropeptide drm Consistent with these molecular studies, we show that genetic inactivation of Hyd, Lin, or PRC1 resulted in Bowl-dependent hyperplastic tissue overgrowth in vivo. We also provide evidence that the mammalian homologs of Hyd (UBR5, known to be recurrently dysregulated in various human cancers), Lin (LINS1), and Bowl (OSR1/2) constitute an analogous protein degradation pathway in human cells, and that OSR2 promotes prostate cancer tumorigenesis. Altogether, these findings define a previously unrecognized tumor suppressor pathway that links epigenetic program to regulated protein degradation in tissue growth control and tumorigenesis.

Meet the authors: Meiling Wang, Wenjing Li, and Weixing Zhao.

Molecular Cell talks to co-first authors Meiling Wang and Wenjing Li with co-corresponding author Weixing Zhao about their paper, "Crucial roles of the BRCA1-BARD1 E3 ubiquitin ligase activity in homology-directed DNA repair" (in this issue of Molecular Cell) and what motivates their scientific pursuits.

Crucial roles of the BRCA1-BARD1 E3 ubiquitin ligase activity in homology-directed DNA repair.

The tumor-suppressor breast cancer 1 (BRCA1) in complex with BRCA1-associated really interesting new gene (RING) domain 1 (BARD1) is a RING-type ubiquitin E3 ligase that modifies nucleosomal histone and other substrates. The importance of BRCA1-BARD1 E3 activity in tumor suppression remains highly controversial, mainly stemming from studying mutant ligase-deficient BRCA1-BARD1 species that we show here still retain significant ligase activity. Using full-length BRCA1-BARD1, we establish robust BRCA1-BARD1-mediated ubiquitylation with specificity, uncover multiple modes of activity modulation, and construct a truly ligase-null variant and a variant specifically impaired in targeting nucleosomal histones. Cells expressing either of these BRCA1-BARD1 separation-of-function alleles are hypersensitive to DNA-damaging agents. Furthermore, we demonstrate that BRCA1-BARD1 ligase is not only required for DNA resection during homology-directed repair (HDR) but also contributes to later stages for HDR completion. Altogether, our findings reveal crucial, previously unrecognized roles of BRCA1-BARD1 ligase activity in genome repair via HDR, settle prior controversies regarding BRCA1-BARD1 ligase functions, and catalyze new efforts to uncover substrates related to tumor suppression.

BRCA1/BARD1 intrinsically disordered regions facilitate chromatin recruitment and ubiquitylation.

BRCA1/BARD1 is a tumor suppressor E3 ubiquitin (Ub) ligase with roles in DNA damage repair and in transcriptional regulation. BRCA1/BARD1 RING domains interact with nucleosomes to facilitate mono-ubiquitylation of distinct residues on the C-terminal tail of histone H2A. These enzymatic domains constitute a small fraction of the heterodimer, raising the possibility of functional chromatin interactions involving other regions such as the BARD1 C-terminal domains that bind nucleosomes containing the DNA damage signal H2A K15-Ub and H4 K20me0, or portions of the expansive intrinsically disordered regions found in both subunits. Herein, we reveal novel interactions that support robust H2A ubiquitylation activity mediated through a high-affinity, intrinsically disordered DNA-binding region of BARD1. These interactions support BRCA1/BARD1 recruitment to chromatin and sites of DNA damage in cells and contribute to their survival. We also reveal distinct BRCA1/BARD1 complexes that depend on the presence of H2A K15-Ub, including a complex where a single BARD1 subunit spans adjacent nucleosome units. Our findings identify an extensive network of multivalent BARD1-nucleosome interactions that serve as a platform for BRCA1/BARD1-associated functions on chromatin.

Spatial transcriptomics reveals light-induced chlorenchyma cells involved in promoting shoot regeneration in tomato callus.

Callus is a reprogrammed cell mass involved in plant regeneration and gene transformation in crop engineering. Pluripotent callus cells develop into fertile shoots through shoot regeneration. The molecular basis of the shoot regeneration process in crop callus remains largely elusive. This study pioneers the exploration of the spatial transcriptome of tomato callus during shoot regeneration. The findings reveal the presence of highly heterogeneous cell populations within the callus, including epidermis, vascular tissue, shoot primordia, inner callus, and outgrowth shoots. By characterizing the spatially resolved molecular features of shoot primordia and surrounding cells, specific factors essential for shoot primordia formation are identified. Notably, chlorenchyma cells, enriched in photosynthesis-related processes, play a crucial role in promoting shoot primordia formation and subsequent shoot regeneration. Light is shown to promote shoot regeneration by inducing chlorenchyma cell development and coordinating sugar signaling. These findings significantly advance our understanding of the cellular and molecular aspects of shoot regeneration in tomato callus and demonstrate the immense potential of spatial transcriptomics in plant biology.

MMiKG: a knowledge graph-based platform for path mining of microbiota-mental diseases interactions.

The microbiota-gut-brain axis denotes a two-way system of interactions between the gut and the brain, comprising three key components: (1) gut microbiota, (2) intermediates and (3) mental ailments. These constituents communicate with one another to induce changes in the host's mood, cognition and demeanor. Knowledge concerning the regulation of the host central nervous system by gut microbiota is fragmented and mostly confined to disorganized or semi-structured unrestricted texts. Such a format hinders the exploration and comprehension of unknown territories or the further advancement of artificial intelligence systems. Hence, we collated crucial information by scrutinizing an extensive body of literature, amalgamated the extant knowledge of the microbiota-gut-brain axis and depicted it in the form of a knowledge graph named MMiKG, which can be visualized on the GraphXR platform and the Neo4j database, correspondingly. By merging various associated resources and deducing prospective connections between gut microbiota and the central nervous system through MMiKG, users can acquire a more comprehensive perception of the pathogenesis of mental disorders and generate novel insights for advancing therapeutic measures. As a free and open-source platform, MMiKG can be accessed at http://yangbiolab.cn:8501/ with no login requirement.

Abscisic acid-induced transcription factor PsMYB306 negatively regulates tree peony bud dormancy release.

Bud dormancy is a crucial strategy for perennial plants to withstand adverse winter conditions. However, the regulatory mechanism of bud dormancy in tree peony (Paeonia suffruticosa) remains largely unknown. Here, we observed dramatically reduced and increased accumulation of abscisic acid (ABA) and bioactive gibberellins (GAs) GA1 and GA3, respectively, during bud endodormancy release of tree peony under prolonged chilling treatment. An Illumina RNA sequencing study was performed to identify potential genes involved in the bud endodormancy regulation in tree peony. Correlation matrix, principal component, and interaction network analyses identified a downregulated MYB transcription factor gene, PsMYB306, the expression of which positively correlated with 9-CIS-EPOXYCAROTENOID DIOXYGENASE 3 (PsNCED3) expression. Protein modeling analysis revealed 4 residues within the R2R3 domain of PsMYB306 to possess DNA binding capability. Transcription of PsMYB306 was increased by ABA treatment. Overexpression of PsMYB306 in petunia (Petunia hybrida) inhibited seed germination and plant growth, concomitant with elevated ABA and decreased GA contents. Silencing of PsMYB306 accelerated cold-triggered tree peony bud burst and influenced the production of ABA and GAs and the expression of their biosynthetic genes. ABA application reduced bud dormancy release and transcription of ENT-KAURENOIC ACID OXIDASE 1 (PsKAO1), GA20-OXIDASE 1 (PsGA20ox1), and GA3-OXIDASE 1 (PsGA3ox1) associated with GA biosynthesis in PsMYB306-silenced buds. In vivo and in vitro binding assays confirmed that PsMYB306 specifically transactivated the promoter of PsNCED3. Silencing of PsNCED3 also promoted bud break and growth. Altogether, our findings suggest that PsMYB306 negatively modulates cold-induced bud endodormancy release by regulating ABA production.

Anionic Ionomer: Released Surface-Immobilized Cations and an Established Hydrophobic Microenvironment for Efficient and Durable CO2-to-Ethylene Electrosynthesis at High Current over One Month.

Electrosynthesis of multicarbon products, such as C2H4, from CO2 reduction on copper (Cu) catalysts holds promise for achieving carbon neutrality. However, maintaining a steady high current-level C2H4 electrosynthesis still encounters challenges, arising from unstable alkalinity and carbonate precipitation caused by undesired ion migration at the cathode under a repulsive electric field. To address these issues, we propose a universal "charge release" concept by incorporating tiny amounts of an oppositely charged anionic ionomer (e.g., perfluorinated sulfonic acid, PFSA) into a cationic covalent organic framework on the Cu surface (cCOF/PFSA). This strategy effectively releases the hidden positive charge within the cCOF, enhancing surface immobilization of cations to impede both outward migration of generated OH- and inward migration of cations, inhibiting carbonate precipitation and creating a strong alkaline microenvironment. Meanwhile, the ionomer's hydrophobic chains create a hydrophobic environment within the cCOF, facilitating efficient gas transport. In situ characterizations and theoretical calculations demonstrate that the cCOF/PFSA catalyst establishes a hydrophobic strong alkaline microenvironment, optimizing the adsorption strength and configuration of *CO intermediates to promote the C2H4 formation. The optimized catalyst achieves a 70.5% Faradaic efficiency for C2H4 with a partial current density over 470 mA cm-2. Notably, it delivers a high single-pass carbon efficiency of 96.5% for CO2RR and sustains an exceptional stability over 760 h. When implemented in a large-area MEA electrolyzer and a 5-cell MEA stack, the system achieves an industrial current of 15 A and continuous C2H4 production exceeding 19 mL min-1, marking a significant step toward industrial feasibility in CO2RR-to-C2H4 conversion.

Tumour-intrinsic PDL1 signals regulate the Chk2 DNA damage response in cancer cells and mediate resistance to Chk1 inhibitors.

BACKGROUND: Aside from the canonical role of PDL1 as a tumour surface-expressed immune checkpoint molecule, tumour-intrinsic PDL1 signals regulate non-canonical immunopathological pathways mediating treatment resistance whose significance, mechanisms, and therapeutic targeting remain incompletely understood. Recent reports implicate tumour-intrinsic PDL1 signals in the DNA damage response (DDR), including promoting homologous recombination DNA damage repair and mRNA stability of DDR proteins, but many mechanistic details remain undefined. METHODS: We genetically depleted PDL1 from transplantable mouse and human cancer cell lines to understand consequences of tumour-intrinsic PDL1 signals in the DNA damage response. We complemented this work with studies of primary human tumours and inducible mouse tumours. We developed novel approaches to show tumour-intrinsic PDL1 signals in specific subcellular locations. We pharmacologically depleted tumour PDL1 in vivo in mouse models with repurposed FDA-approved drugs for proof-of-concept clinical translation studies. RESULTS: We show that tumour-intrinsic PDL1 promotes the checkpoint kinase-2 (Chk2)-mediated DNA damage response. Intracellular but not surface-expressed PDL1 controlled Chk2 protein content post-translationally and independently of PD1 by antagonising PIRH2 E3 ligase-mediated Chk2 polyubiquitination and protein degradation. Genetic tumour PDL1 depletion specifically reduced tumour Chk2 content but not ATM, ATR, or Chk1 DDR proteins, enhanced Chk1 inhibitor (Chk1i) synthetic lethality in vitro in diverse human and murine tumour models, and improved Chk1i efficacy in vivo. Pharmacologic tumour PDL1 depletion with cefepime or ceftazidime replicated genetic tumour PDL1 depletion by reducing tumour Chk2, inducing Chk1i synthetic lethality in a tumour PDL1-dependent manner, and reducing in vivo tumour growth when combined with Chk1i. CONCLUSIONS: Our data challenge the prevailing surface PDL1 paradigm, elucidate important and previously unappreciated roles for tumour-intrinsic PDL1 in regulating the ATM/Chk2 DNA damage response axis and E3 ligase-mediated protein degradation, suggest tumour PDL1 as a biomarker for Chk1i efficacy, and support the rapid clinical potential of pharmacologic tumour PDL1 depletion to treat selected cancers.

Kindlin2 regulates neural crest specification via integrin-independent regulation of the FGF signaling pathway.

The focal adhesion protein Kindlin2 is essential for integrin activation, a process that is fundamental to cell-extracellular matrix adhesion. Kindlin 2 (Fermt2) is widely expressed in mouse embryos, and its absence causes lethality at the peri-implantation stage due to the failure to trigger integrin activation. The function of kindlin2 during embryogenesis has not yet been fully elucidated as a result of this early embryonic lethality. Here, we showed that kindlin2 is essential for neural crest (NC) formation in Xenopus embryos. Loss-of-function assays performed with kindlin2-specific morpholino antisense oligos (MOs) or with CRISPR/Cas9 techniques in Xenopus embryos severely inhibit the specification of the NC. Moreover, integrin-binding-deficient mutants of Kindlin2 rescued the phenotype caused by loss of kindlin2, suggesting that the function of kindlin2 during NC specification is independent of integrins. Mechanistically, we found that Kindlin2 regulates the fibroblast growth factor (FGF) pathway, and promotes the stability of FGF receptor 1. Our study reveals a novel function of Kindlin2 in regulating the FGF signaling pathway and provides mechanistic insights into the function of Kindlin2 during NC specification.

Comparison of two single-pill dual combination antihypertensive therapies in Chinese patients: a randomized, controlled trial.

BACKGROUND: Current hypertension guidelines recommend combination of an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker with a calcium-channel blocker or thiazide diuretic as initial antihypertensive therapy in patients with monotherapy uncontrolled hypertension. However, to what extent these two different combinations are comparable in blood pressure (BP)-lowering efficacy and safety remains under investigation, especially in the Chinese population. We investigated the BP-lowering efficacy and safety of the amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies in Chinese patients. METHODS: In a multi-center, randomized, actively controlled, parallel-group trial, we enrolled patients with stage 1 or 2 hypertension from July 2018 to June 2021 in 20 hospitals and community health centers across China. Of the 894 screened patients, 560 eligible patients were randomly assigned to amlodipine/benazepril 5/10 mg (n = 282) or benazepril/hydrochlorothiazide 10/12.5 mg (n = 278), with 213 and 212 patients, respectively, who completed the study and had a valid repeat ambulatory BP recording during follow-up and were included in the efficacy analysis. The primary outcome was the change from baseline to 24 weeks of treatment in 24-h ambulatory systolic BP. Adverse events including symptoms and clinically significant changes in physical examinations and laboratory findings were recorded for safety analysis. RESULTS: In the efficacy analysis (n = 425), the primary outcome, 24-h ambulatory systolic BP reduction, was - 13.8 ± 1.2 mmHg in the amlodipine/benazepril group and - 12.3 ± 1.2 mmHg in the benazepril/hydrochlorothiazide group, with a between-group difference of - 1.51 (p = 0.36) mmHg. The between-group differences for major secondary outcomes were - 1.47 (p = 0.18) in 24-h diastolic BP, - 2.86 (p = 0.13) and - 2.74 (p = 0.03) in daytime systolic and diastolic BP, and - 0.45 (p = 0.82) and - 0.93 (p = 0.44) in nighttime systolic and diastolic BP. In the safety analysis (n = 560), the incidence rate of dry cough was significantly lower in the amlodipine/benazepril group than in the benazepril/hydrochlorothiazide group (5.3% vs 10.1%, p = 0.04). CONCLUSIONS: The amlodipine/benazepril and benazepril/hydrochlorothiazide dual therapies were comparable in ambulatory systolic BP lowering. The former combination, compared with the latter, had a greater BP-lowering effect in the daytime and a lower incidence rate of dry cough. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03682692. Registered on 18 September 2018.

Proximity ligation-triggered DNAzyme for selective fluorescent aptasensing of methicillin-resistant Staphylococcus aureus.

There is an urgent need for novel strategies to accurately and reliably detect pathogenic bacteria to address the global epidemic of antibiotic resistance. This study proposes an innovative approach combining dual aptamer-based target recognition and proximity ligation assay (PLA) triggered DNAzyme recycling cleavage. This method allows for the precise identification and reliable detection of methicillin-resistant Staphylococcus aureus (MRSA). The fluorescence probe labeled with a fluorophore is modified on gold nanoparticles (AuNPs), resulting in the quenching of the fluorescent signal by the AuNPs. The interaction between MRSA and two aptamers leads to forming a Mg2+-dependent DNAzyme. The DNAzyme cleaves the fluorescence probe, causing the fluorescent fragment to detach from the surface of the AuNPs, in which the quenched fluorescence signal in the fluorescence probe reappears. The DNAzyme-assisted cleavage and rebinding process generates a processive strolling along the surface track of AuNPs. Consequently, the fluorescence intensity experiences a substantial recovery. A strong linear correlation is observed between the fluorescence intensity and MRSA concentration within 50 cfu/mL to 106 cfu/mL. We believe that implementing the novel integrated strategy will broaden the range of bacterial detection methods in the battlefield environment and stimulate the creation of potential new drugs in the future.

Application of N-doped NiCo2O4/NiO/Co3O4composites rich in oxygen vacancies in electromagnetic wave absorption.

In this work, N-doped and oxygen vacancy-rich NiCo2O4/NiO/Co3O4composites are synthesized by the direct calcination method. Noticeably, by changing the additive concentrations of urea dissolved in DMF (N-N dimethylformamide), the electromagnetic wave (EMW) absorption abilities of NiCo2O4/NiO/Co3O4composite effectively. A maximum reflection loss (RLmax) value at 12.94 GHz for a 2.8 mm thick sheet is -29.76 dB, while its effective absorption bandwidth (RL < -10 dB) reaches 4.21 GHz. In-depth research of possible mechanisms of EMW absorption enhancement. Owing to its simple preparation method and superb EMW absorption properties, the NiCo2O4/NiO/Co3O4composites have a chance to be suitable candidates for high-property EMW absorbers.

Multi-instance learning based artificial intelligence model to assist vocal fold leukoplakia diagnosis: A multicentre diagnostic study.

OBJECTIVE: To develop a multi-instance learning (MIL) based artificial intelligence (AI)-assisted diagnosis models by using laryngoscopic images to differentiate benign and malignant vocal fold leukoplakia (VFL). METHODS: The AI system was developed, trained and validated on 5362 images of 551 patients from three hospitals. Automated regions of interest (ROI) segmentation algorithm was utilized to construct image-level features. MIL was used to fusion image level results to patient level features, then the extracted features were modeled by seven machine learning algorithms. Finally, we evaluated the image level and patient level results. Additionally, 50 videos of VFL were prospectively gathered to assess the system's real-time diagnostic capabilities. A human-machine comparison database was also constructed to compare the diagnostic performance of otolaryngologists with and without AI assistance. RESULTS: In internal and external validation sets, the maximum area under the curve (AUC) for image level segmentation models was 0.775 (95 % CI 0.740-0.811) and 0.720 (95 % CI 0.684-0.756), respectively. Utilizing a MIL-based fusion strategy, the AUC at the patient level increased to 0.869 (95 % CI 0.798-0.940) and 0.851 (95 % CI 0.756-0.945). For real-time video diagnosis, the maximum AUC at the patient level reached 0.850 (95 % CI, 0.743-0.957). With AI assistance, the AUC improved from 0.720 (95 % CI 0.682-0.755) to 0.808 (95 % CI 0.775-0.839) for senior otolaryngologists and from 0.647 (95 % CI 0.608-0.686) to 0.807 (95 % CI 0.773-0.837) for junior otolaryngologists. CONCLUSIONS: The MIL based AI-assisted diagnosis system can significantly improve the diagnostic performance of otolaryngologists for VFL and help to make proper clinical decisions.

Effects of Phase â Cardiac Rehabilitation Combined with Cognitive Behavioural Therapy on Cardiac Function, Exercise Capacity and Mental Health in Patients after Aortic Valve Replacement: A Retrospective Study.

OBJECTIVE: To explore the application effect of phase Ⅰ cardiac rehabilitation (CR-Ⅰ) combined with cognitive behavioural therapy (CBT) on patients after aortic valve replacement (AVR). METHODS: This study retrospectively analysed the data of 441 patients after AVR in our hospital from January 2020 to May 2023. A total of 38 patients who did not meet the inclusion criteria were excluded. A total of 403 patients were included. In accordance with different postoperative management schemes, the included patients were divided into the reference group (n = 202, received CR-Ⅰ) and the observation group (n = 201, received CR-Ⅰ+CBT). The cardiac function, exercise capacity and mental health of the two groups were compared. RESULTS: Before management, both groups had no significant differences in left ventricular end diastolic diameter (LVEDD), left ventricular end systolic dimension (LVESD), left ventricular ejection fraction (LVEF) and six-minute walking test (6MWT) scores (p > 0.05). At discharge and 3 months after discharge, the observation group had significantly lower LVEDD and LVESD and remarkably higher LVEF and 6MWT scores than the reference group (p < 0.001). The proportions of autonomous activity in bed within 3-4 days after surgery, autonomous out-of-bed activity within 8-10 days after surgery and autonomous walking 200 m within 12-15 days after surgery were distinctly higher (p < 0.001) and the incidence of adverse reactions was overtly lower (p < 0.001) in the observation group than in the reference group. Before management, both groups had no significant difference in their scores on the State-Trait Anxiety Inventory (STAI) (p > 0.05). At discharge and 3 months after discharge, the observation group had lower STAI scores than the reference group (p < 0.001). CONCLUSION: CR-Ⅰ combined with CBT effectively improves the cardiac function, independent exercise capacity and mental health level of patients after AVR and provides a new direction for the formulation and selection of follow-up clinical management.

Analysis of postoperative nausea and vomiting in patients with lung cancer undergoing thoracoscopic surgery under general anesthesia and its influencing factors: a observational study.

OBJECTIVE: To investigate the current situation and influencing factors of postoperative nausea and vomiting (PONV) in lung cancer patients undergoing thoracoscopic surgery under general anesthesia, providing a reference for developing targeted PONV prevention and management strategies. METHODS: Using a consecutive sampling method, 200 lung cancer patients who underwent their first thoracoscopic surgery under general anesthesia between November 18, 2021, and March 1, 2022, at a tertiary class A cancer hospital in Liaoning Province, China, were selected. The occurrence of PONV within 24 h post-operation was assessed using WHO Postoperative Nausea and Vomiting Rating Criteria. Patient general information, surgical and medication data were systematically collected to analyze the independent influencing factors of PONV. RESULTS: Among the 200 patients undergoing thoracoscopic lung cancer surgery under general anesthesia, 75 (37.5%) experienced PONV. Logistic regression analysis indicated that being female, having a history of motion sickness, and a history of PONV were independent risk factors for the occurrence of PONV in these patients. Long-acting antiemetics such as penehyclidine hydrochloride and methylprednisolone were protective factors against PONV. CONCLUSION: The incidence of PONV in patients undergoing thoracoscopic lung cancer surgery under general anesthesia is relatively high. Nursing staff should focus on female patients and those with a history of motion sickness and PONV. Comprehensive preoperative assessments should be conducted, exploring multimodal analgesia and applying integrated prevention measures to reduce the occurrence of PONV and promote the rapid recovery of patients.

Physicochemical Synergistic Separator Coating Induces Uniform and Rapid Deposition of Li and Zn Ions.

Li and Zn metal batteries are the most promising candidates to replace conventional Li-ion batteries. However, a series of issues, especially dendrites caused by uneven deposition of cations during charge-discharge cycles, hinder their practical application. Here, we proposed a facile separator modification method which combines physical and chemical forces to regulate uniform and rapid deposition of both Li+ and Zn2+. Physically, the electronegativity of modified separators drives rapid transport of metal ions via a surface diffusion mode. Chemically, the polar surface functional groups on coated separators induce uniform deposition of metal ions so that the dendrite growth is effectively inhibited. As a result, the Li and Zn metal anodes employing modified separators can cycle stably for over 1000 h under a large current density of 10 mA cm-2.

Defect-Engineered VS2 Electrocatalysts for Lithium-Sulfur Batteries.

Defective two-dimensional transition metal dichalcogenides can be effective electrocatalysts for Li-S batteries, but the relationship between defect types and battery performance is unclear. In this work, we designed S vacancy-type SV-VS2 and V self-intercalated-type VI-VS2 and measured their catalytic activities in Li-S batteries. Compared with self-intercalating V atoms, S vacancies accelerated Li+ diffusion and SV-VS2 as a Li+ "reservoir" promoted the sulfur conversion kinetics significantly. In addition, the presence of sulfur vacancies promoted the lithiation behavior of SV-VS2 during discharge, leading to an enhancement of the catalytic ability of SV-VS2. However, this lithiation phenomenon weakened the catalytic activity of VI-VS2. Overall, SV-VS2 had better adsorption and catalytic activity. Li-S batteries with SV-VS2-coated separators delivered high rate performance and excellent cycling stability, with a capacity decay rate of 0.043% over 880 cycles at 1.0 C. This work provides an effective strategy for designing efficient Li-S battery electrocatalysts using defect engineering.

Two-Dimensional Organic-Inorganic Heterostructure as a Multifunctional Protective Layer for High Performance Zinc Metal Anode.

Dendrite growth and side reactions of Zn metal anodes remain unresolved obstacles for practical application of aqueous Zn ion batteries. Herein, a two-dimensional (2D) organic-inorganic heterostructure with controlled thickness was constructed as a protective layer for a Zn metal anode. The reduction of uniformly distributed polyoxometalate in the layer causes a negative charge density gradient, which can accelerate zinc ion transfer, homogenize zinc deposition, and shield sulfates at the electrode interface, while the exposed hydrophobic alkyl chain of the layer can isolate the direct contact of water with the Zn anode. As a result of the synergetic effect, this 2D organic-inorganic heterostructure enables high Zn plating/stripping reversibility, with high average Coulombic efficiencies of 99.97% for 3700 cycles at 2 mA cm-2. Under high Zn utilization conditions, a high areal-capacity full cell with hundreds of cycles was demonstrated.

Transcriptomic Analysis of the Response of the Dioryctria abietella Larva Midgut to Bacillus thuringiensis 2913 Infection.

Dioryctria abietella Denis Schiffermuller (Lepidoptera: Pyralidae) is an oligophagous pest that mainly damages Pinaceae plants. Here, we investigated the effects of the Bacillus thuringiensis 2913 strain (Bt 2913), which carries the Cry1Ac, Cry2Ab, and Vip3Aa genes, on the D. abietella midgut transcriptome at 6, 12, and 24 h after infection. In total, 7497 differentially expressed genes (DEGs) were identified from the midgut transcriptome of D. abietella larvae infected with Bt 2913. Among these DEGs, we identified genes possibly involved in Bt 2913-induced perforation of the larval midgut. For example, the DEGs included 67 genes encoding midgut proteases involved in Cry/Vip toxin activation, 74 genes encoding potential receptor proteins that bind to insecticidal proteins, and 19 genes encoding receptor NADH dehydrogenases that may bind to Cry1Ac. Among the three transcriptomes, 88 genes related to metabolic detoxification and 98 genes related to immune defense against Bt 2913 infection were identified. Interestingly, 145 genes related to the 60S ribosomal protein were among the DEGs identified in the three transcriptomes. Furthermore, we performed bioinformatic analysis of zonadhesin, GST, CYP450, and CarE in the D. abietella midgut to determine their possible associations with Bt 2913. On the basis of the results of this analysis, we speculated that trypsin and other serine proteases in the D. abietella larval midgut began to activate Cry/Vip prototoxin at 6 h to 12 h after Bt 2913 ingestion. At 12 h after Bt 2913 ingestion, chymotrypsin was potentially involved in degrading the active core fragment of Vip3Aa toxin, and the detoxification enzymes in the larvae contributed to the metabolic detoxification of the Bt toxin. The ABC transporter and several other receptor-protein-related genes were also downregulated to increase resistance to Bt 2913. However, the upregulation of 60S ribosomal protein and heat shock protein expression weakened the resistance of larvae to Bt 2913, thereby enhancing the expression of NADH dehydrogenase and other receptor proteins that are highly expressed in the larval midgut and bind to activating toxins, including Cry1Ac. At 24 h after Bt 2913 ingestion, many activated toxins were bound to receptor proteins such as APN in the larval midgut, resulting in membrane perforation. Here, we clarified the mechanism of Bt 2913 infection in D. abietella larvae, as well as the larval immune defense response to Bt 2913, which provides a theoretical basis for the subsequent control of D. abietella using B. thuringiensis.