The Shigella kinase effector OspG modulates host ubiquitin signaling to escape septin-cage entrapment.

Shigella flexneri is a Gram-negative bacterium causing severe bloody dysentery. Its pathogenesis is largely dictated by a plasmid-encoded type III secretion system (T3SS) and its associated effectors. Among these, the effector OspG has been shown to bind to the ubiquitin conjugation machinery (E2~Ub) to activate its kinase activity. However, the cellular targets of OspG remain elusive despite years of extensive efforts. Here we show by unbiased phosphoproteomics that a major target of OspG is CAND1, a regulatory protein controlling the assembly of cullin-RING ubiquitin ligases (CRLs). CAND1 phosphorylation weakens its interaction with cullins, which is expected to impact a large panel of CRL E3s. Indeed, global ubiquitome profiling reveals marked changes in the ubiquitination landscape when OspG is introduced. Notably, OspG promotes ubiquitination of a class of cytoskeletal proteins called septins, thereby inhibiting formation of cage-like structures encircling cytosolic bacteria. Overall, we demonstrate that pathogens have evolved an elaborate strategy to modulate host ubiquitin signaling to evade septin-cage entrapment.

High-Throughput Identification of Single Nanoparticles via Electrochemically Assisted High-Resolution Plasmonic Scattering Interferometric Microscopy.

The identification of nanoparticles within heterogeneous mixtures poses significant challenges due to the similarity in physical properties among different nanomaterials. Here, we present electrochemically assisted high-resolution plasmonic scattering interferometric microscopy (HR-PSIM). This technique allows for the high-throughput identification of nanoparticles by accurately measuring the refractive index of individual nanoparticles without interference from background signals. Through elimination of parabolic scattering interference and employing electrochemical modulation, HR-PSIM demonstrates high spatial resolution and stability against background noise, enabling the differentiation of nanoparticles with closely matched refractive indices, such as Au and Ag nanoparticles. The efficacy of this method is demonstrated through its application in real-time, label-free imaging of nanoparticle electrochemical activity, providing a platform for the precise and high-throughput characterization of nanomaterials. The robustness of our approach against electrochemical interference and its high spatial resolution mark a significant advancement in the field of nanomaterial analysis, promising wide-ranging applications in nanoparticle research and beyond.

A novel strategy for enhancing the stability of aptamer conformations in heavy metal ion detection.

BACKGROUND: Detection methods based on aptamer probes have great potential and progress in the field of rapid detection of heavy metal ions. However, the unstable conformation of aptamers often results in poor sensitivity due to the dissociation of aptamer-target complex in real environments. RESULTS: In this study, we developed a locking aptamer probe and combined it with AgInZnS quantum dots for the first time to detect cadmium ions. When cadmium ions are combined with the probe, the cadmium ions are fixed in the core-locking position, forming a stable cavity structure. The limit of detection (LOD) was achieved at a concentration of 6.9 nmol L-1, with a broad detection range from 10 nmol L-1 to 1000 µmol L-1, and good recovery rates (92.93%-102.8 %) were achieved in aquatic product testing. The locking aptamer probe with stable conformation effectively enhances the stability of the aptamer-target complex and remains good stability in four buffer environments as well as a 600 mmol L-1 salt solution; it also exhibits good stability at pH 6.5-7.5 and temperatures ranging from 25 °C to 35 °C. SIGNIFICANCE: Overall, our study presented a general, simple, and cost-effective strategy for stabilizing aptamer conformations, and used for highly sensitive detection of cadmium ions.

Modulation of host lipid metabolism by virus infection leads to exoskeleton damage in shrimp.

The arthropod exoskeleton provides protection and support and is vital for survival and adaption. The integrity and mechanical properties of the exoskeleton are often impaired after pathogenic infection; however, the detailed mechanism by which infection affects the exoskeleton remains largely unknown. Here, we report that the damage to the shrimp exoskeleton is caused by modulation of host lipid profiles after infection with white spot syndrome virus (WSSV). WSSV infection disrupts the mechanical performance of the exoskeleton by inducing the expression of a chitinase (Chi2) in the sub-cuticle epidermis and decreasing the cuticle chitin content. The induction of Chi2 expression is mediated by a nuclear receptor that can be activated by certain enriched long-chain saturated fatty acids after infection. The damage to the exoskeleton, an aftereffect of the induction of host lipogenesis by WSSV, significantly impairs the motor ability of shrimp. Blocking the WSSV-caused lipogenesis restored the mechanical performance of the cuticle and improved the motor ability of infected shrimp. Therefore, this study reveals a mechanism by which WSSV infection modulates shrimp internal metabolism resulting in phenotypic impairment, and provides new insights into the interactions between the arthropod host and virus.

Phage defence system CBASS is regulated by a prokaryotic E2 enzyme that imitates the ubiquitin pathway.

The cyclic-oligonucleotide-based anti-phage signalling system (CBASS) is a type of innate prokaryotic immune system. Composed of a cyclic GMP-AMP synthase (cGAS) and CBASS-associated proteins, CBASS uses cyclic oligonucleotides to activate antiviral immunity. One major class of CBASS contains a homologue of eukaryotic ubiquitin-conjugating enzymes, which is either an E1-E2 fusion or a single E2. However, the functions of single E2s in CBASS remain elusive. Here, using biochemical, genetic, cryo-electron microscopy and mass spectrometry investigations, we discover that the E2 enzyme from Serratia marcescens regulates cGAS by imitating the ubiquitination cascade. This includes the processing of the cGAS C terminus, conjugation of cGAS to a cysteine residue, ligation of cGAS to a lysine residue, cleavage of the isopeptide bond and poly-cGASylation. The poly-cGASylation activates cGAS to produce cGAMP, which acts as an antiviral signal and leads to cell death. Thus, our findings reveal a unique regulatory role of E2 in CBASS.

Water conservation pattern of Fangcheng River Basin in Beibu Gulf and its response to precipitation.

Assessing the spatiotemporal patterns of watershed water conservation under the influence of the South Asian monsoon climate and its response to precipitation is essential for revealing the evolving patterns of water conservation under different temporal scales. Following the principles of water balance and using the Soil and Water Assessment Tool (SWAT) model, we investigated the spatiotemporal patterns of water conservation and its response to precipitation in the Fangcheng River Basin of Beibu Gulf. The results showed that water conservation in Fangcheng River Basin calculated by SWAT model were 1637.4 mm·a-1, accounting for 50.7% of the mean annual precipitation. The variation of water conservation in different sub-basins was obviously different. Sub-basins with high forest coverage and steep slopes exhibited higher water conservation, while sub-basins with other land use types (such as cropland and grassland), gentle slopes, and intense human activities showed lower water conservation. At the monthly scale, both water conservation and its variation showed similar response characteristics to precipitation in the basin. The response of water conservation variation to sub-precipitation events could be classified into two types. For the short-term rainfall events (duration≤2 days), water conservation variation showed a linear relationship. For the medium to long-term rainfall events (2 days

Enhancing the Flame Retardancy of Polyester/Cotton Blend Fabrics Using Biobased Urea-Phytate Salt.

The use of biobased flame-retardant (FR) agents for reducing the flammability of polyester/cotton (T/C) blend fabrics is highly desirable. In this study, a novel and sustainable phosphorus/nitrogen-containing FR, namely, phytic acid-urea (PA-UR) salt, was synthesized. The PA-UR salt was further used to enhance the FR performance of T/C fabric through surface modification. We further explored the potential chemical structure of PA-UR and the surface morphology, thermal stability, heat release capacity, FR properties, and mode of action of the coated fabric. The coated fabric achieved self-extinguishing and exhibited an increased limiting oxygen index of 31.8%. Moreover, the coated T/C blend fabric demonstrated a significantly reduced heat release capacity, indicating a decreased fire hazard. Thermogravimetric analysis revealed the anticipated decomposition of the coated T/C blend fabric and a subsequent increase in thermal stability. The burned char residues also maintained their fiber shape structures, suggesting the presence of condensed FR actions in the PA-UR-coated T/C blend fabric.

Newborn genetic screening for Fabry disease: Insights from a retrospective analysis in Nanjing, China.

Fabry disease (FD), an X-linked disorder resulting from dysfunction of α-galactosidase A, can result in significant complications. Early intervention yields better outcomes, but misdiagnosis or delayed diagnosis is common, impacting prognosis. Thus, early detection is crucial in the clinical diagnosis and treatment of FD. While newborn screening for FD has been implemented in certain regions, challenges persist in enzyme activity detection techniques, particularly for female and late-onset patients. Further exploration of improved screening strategies is warranted. This study retrospectively analyzed genetic screening results for pathogenic GLA variants in 17,171 newborns. The results indicated an estimated incidence of FD in the Nanjing region of China of approximately 1 in 1321. The most prevalent pathogenic variant among potential FD patients was c.640-801G > A (46.15 %). Furthermore, the residual enzyme activity of the pathogenic variant c.911G > C was marginally higher than that of other variants, and suggesting that genetic screening may be more effective in identifying potential female and late-onset patients compared to enzyme activity testing. This research offers initial insights into the effectiveness of GLA genetic screening and serves as a reference for early diagnosis, treatment, and genetic counseling in FD.

Deep-Learning Driven, High-Precision Plasmonic Scattering Interferometry for Single-Particle Identification.

Label-free probing of the material composition of (bio)nano-objects directly in solution at the single-particle level is crucial in various fields, including colloid analysis and medical diagnostics. However, it remains challenging to decipher the constituents of heterogeneous mixtures of nano-objects with high sensitivity and resolution. Here, we present deep-learning plasmonic scattering interferometric microscopy, which is capable of identifying the composition of nanoparticles automatically with high throughput at the single-particle level. By employing deep learning to decode the quantitative relationship between the interferometric scattering patterns of nanoparticles and their intrinsic material properties, this technique is capable of high-throughput, label-free identification of diverse nanoparticle types. We demonstrate its versatility in analyzing dynamic surface chemical reactions on single nanoparticles, revealing its potential as a universal platform for nanoparticle imaging and reaction analysis. This technique not only streamlines the process of nanoparticle characterization, but also proposes a methodology for a deeper understanding of nanoscale dynamics, holding great potential for addressing extensive fundamental questions in nanoscience and nanotechnology.

To explore the pathogenesis of anterior resection syndrome by magnetic resonance imaging rectal defecography.

BACKGROUND: Over 90% of rectal cancer patients develop low anterior resection syndrome (LARS) after sphincter-preserving resection. The current globally recognized evaluation method has many drawbacks and its subjectivity is too strong, which hinders the research and treatment of LARS. AIM: To evaluate the anorectal function after colorectal cancer surgery by quantifying the index of magnetic resonance imaging (MRI) defecography, and pathogenesis of LARS. METHODS: We evaluated 34 patients using the standard LARS score, and a new LARS evaluation index was established using the dynamic images of MRI defecography to verify the LARS score. RESULTS: In the LARS score model, there were 10 (29.41%) mild and 24 (70.58%) severe cases of LARS. The comparison of defecation rate between the two groups was 29.36 ± 14.17% versus 46.83 ± 18.62% (P = 0.004); and MRI-rectal compliance (MRI-RC) score was 3.63 ± 1.96 versus 7.0 ± 3.21 (P = 0.001). Severe and mild LARS had significant differences using the two evaluation methods. There was a significant negative correlation between LARS and MRI-RC score (P < 0.001), and they had a negative correlation with defecation rate (P = 0.028). CONCLUSION: MRI defecography and standard LARS score can both be used as an evaluation index to study the pathogenesis of LARS.

Graves' disease and systemic lupus erythematosus: a Mendelian randomization study.

Introduction: Previous observational studies have established a correlation between Graves' disease(GD) and systemic lupus erythematosus(SLE). However, whether a causal relationship exists between these two diseases remains unknown.We utilized Mendelian randomization to infer the causal association between GD and SLE. Methods: This study employed GWAS summary statistics of GD and SLE in individuals of Asian descent. The random effect inverse variance weighted (IVW) method was utilized to aggregate the causal effect estimates of all SNPs. Cochran's Q values were computed to evaluate the heterogeneity among instrumental variables. Sensitivity analyses such as MR-Egger method, median weighting method, leave-one-out method, and MR-PRESSO method were used to test whether there was horizontal pleiotropy of instrumental variables. Results: Our study found genetically predicted GD may increase risk of SLE (OR=1.17, 95% CI 0.99-1.40, p=0.069). Additionally, genetically predicted SLE elevated the risk of developing GD by 15% (OR=1.15, 95% CI 1.05-1.27, p= 0.004). After correcting for possible horizontal pleiotropy by excluding outlier SNPs, the results suggested that GD increased the risk of SLE (OR=1.27, 95% CI 1.09-1.48, p =0.018), while SLE also increased the risk of developing GD (OR=1.13, 95% CI 1.05-1.22, p =0.003). Conclusion: The findings of the study indicate that there may be a correlation between GD and SLE, with each potentially increasing the risk of the other. These results have important implications for the screening and treatment of patients with co-morbidities in clinical settings, as well as for further research into the molecular mechanisms underlying the relationship between GD and SLE.

AcousticRobots: Smart acoustically powered micro-/nanoswimmers for precise biomedical applications.

Although nanotechnology has evolutionarily progressed in biomedical field over the past decades, achieving satisfactory therapeutic effects remains difficult with limited delivery efficiency. Ultrasound could provide a deep penetration and maneuverable actuation to efficiently power micro-/nanoswimmers with little harm, offering an emerging and fascinating alternative to the active delivery platform. Recent advances in novel fabrication, controllable concepts like intelligent swarm and the integration of hybrid propulsions have promoted its function and potential for medical applications. In this review, we will summarize the mechanisms and types of ultrasonically propelled micro/nanorobots (termed here as "AcousticRobots"), including the interactions between AcousticRobots and acoustic field, practical design considerations (e.g., component, size, shape), the synthetic methods, surface modification, controllable behaviors, and the advantages when combined with other propulsion approaches. The representative biomedical applications of functional AcousticRobots are also highlighted, including drug delivery, invasive surgery, eradication on the surrounding bio-environment, cell manipulation, detection, and imaging, etc. We conclude by discussing the challenges and outlook of AcousticRobots in biomedical applications.

Molecular mechanisms of selenite reduction by Lactiplantibacillus plantarum BSe: An integrated genomic and transcriptomic analysis.

The reduction of selenite [Se(Ⅳ)] by microorganisms is a green and efficient detoxification strategy. We found that Se(Ⅳ) inhibited exopolysaccharide and protein secretion by Lactiplantibacillus plantarum BSe and compromised cell integrity. In this study, L. plantarum BSe reduced Se(Ⅳ) by increasing related enzyme activity and electron transfer. Genomic analysis demonstrated that L. plantarum BSe should be able to reduce Se(Ⅳ). Further transcriptome analysis showed that L. plantarum BSe enhanced its tolerance to Se(Ⅳ) by upregulating the expression of surface proteins and transporters, thus reducing the extracellular Se(Ⅳ) concentration through related enzymatic reactions and siderophore-mediated pathways. Lactiplantibacillus plantarum BSe was able to regulate the expression of related genes involved in quorum sensing and a two-component system and then select appropriate strategies for Se(Ⅳ) transformation in response to varying environmental Se(Ⅳ) concentrations. In addition, azo reductase was linked to the reduction of Se(Ⅳ) for the first time. The present study established a multipath model for the reduction of Se(Ⅳ) by L. plantarum, providing new insights into the biological reduction of Se(Ⅳ) and the biogeochemical cycle of selenium.

Utility, benefits, and risks of newborn genetic screening carrier reports for families.

Background: Newborn genetic screening (NBGS) based on next-generation sequencing offers enhanced disease detection and better detection rates than traditional newborn screening. However, challenges remain, especially around reporting the NBGS carrier results. Therefore, we aimed to investigate the NBGS carrier parents' views on NBGS and NBGS reports in China. Methods: We distributed a survey querying demographic information, knowledge and perceptions of NBGS, the impact of NBGS on a total of 2930 parents, and their decision-making to parents of newborns reported as carriers in NBGS in Nanjing, China in 2022. Results: The average age of the survey respondents was 30.7 years (standard deviation = 3.6). Most (68.38%) felt informed about NBGS, especially women, the highly educated, and high earners. Nearly all (98.74%) saw NBGS as crucial for early disease detection, with 73.18% believing it positively impacts their future. However, 19.16% felt it might cause anxiety, especially among the less educated. Concerns included potential discrimination due to exposed genetic data and strained family ties. Many suggested NBGS coverage by medical insurance to ease financial burdens. Conclusions: Through our study, we gained insights into parents' perspectives and concerns regarding the NBGS carrier result reporting, thus providing relevant information for further refinement and clinical promotion of the NBGS project.

Shigella induces stress granule formation by ADP-riboxanation of the eIF3 complex.

Under stress conditions, translationally stalled mRNA and associated proteins undergo liquid-liquid phase separation and condense into cytoplasmic foci called stress granules (SGs). Many viruses hijack SGs for their pathogenesis; however, whether pathogenic bacteria also exploit this pathway remains unknown. Here, we report that members of the OspC family of Shigella flexneri induce SG formation in infected cells. Mechanistically, the OspC effectors target multiple subunits of the host translation initiation factor 3 complex by ADP-riboxanation. The modification of eIF3 leads to translational arrest and thus the formation of SGs. Furthermore, OspC-mediated SGs are beneficial for S. flexneri replication within infected host cells, and bacterial strains unable to induce SGs are attenuated for virulence in a murine model of infection. Our findings reveal a mechanism by which bacterial pathogens induce SG assembly by inactivating host translational machinery and promote bacterial proliferation in host cells.

Ammonia stress-induced heat shock factor 1 enhances white spot syndrome virus infection by targeting the interferon-like system in shrimp.

Disease emergence is the consequence of host-pathogen-environment interactions. Ammonia is a key stress factor in aquatic environments that usually increases the risk of pathogenic diseases in aquatic animals. However, the molecular regulatory mechanisms underlying the enhancement of viral infection following ammonia stress remain largely unknown. Here, we found that ammonia stress enhances white spot syndrome virus infection in kuruma shrimp (Marsupenaeus japonicus) by targeting the antiviral interferon-like system through heat shock factor 1 (Hsf1). Hsf1 is an ammonia-induced transcription factor. It regulates the expression of Cactus and Socs2, which encode negative regulators of NF-κB signaling and Jak/Stat signaling, respectively. By inhibiting these two pathways, ammonia-induced Hsf1 suppressed the production and function of MjVago-L, an arthropod interferon analog. Therefore, this study revealed that Hsf1 is a central regulator of suppressed antiviral immunity after ammonia stress and provides new insights into the molecular regulation of immunity in stressful environments. IMPORTANCE: Ammonia is the end product of protein catabolism and is derived from feces and unconsumed foods. It threatens the health and growth of aquatic animals. In this study, we demonstrated that ammonia stress suppresses shrimp antiviral immunity by targeting the shrimp interferon-like system and that heat shock factor 1 (Hsf1) is a central regulator of this process. When shrimp are stressed by ammonia, they activate Hsf1 for stress relief and well-being. Hsf1 upregulates the expression of negative regulators that inhibit the production and function of interferon analogs in shrimp, thereby enhancing white spot syndrome viral infection. Therefore, this study, from a molecular perspective, explains the problem in the aquaculture industry that animals living in stressed environments are more susceptible to pathogens than those living in unstressed conditions. Moreover, this study provides new insights into the side effects of heat shock responses and highlights the complexity of achieving cellular homeostasis under stressful conditions.

[Clinical Value of Detecting ABL Kinase Domain Mutations in Patients with Chronic Myeloid Leukemia Based on High-Throughput Sequencing Technology].

OBJECTIVE: To compare the efficacy and clinical value of high-throughput sequencing (HTS) and Sanger sequencing in detecting ABL kinase domain mutations in patients with chronic myeloid leukemia (CML). METHODS: A total of 198 samples of 147 CML patients from July 2017 to March 2021 in Henan Cancer Hospital were collected and underwent high-throughput sequencing and Sanger sequencing to detect the mutations in ABL kinase domain, and the relevant clinical data were collected for comparative analysis. RESULTS: The proportion of total mutations and ≥2 mutations detected by high-throughput sequencing were significantly higher than those detected by Sanger sequencing (P =0.01; P =0.046). ≥2 mutations were detected in 22 cases, of which 5 cases (22.7%) had compound mutations. High-throughput sequencing can detect low level mutations that cannot be detected by Sanger sequencing. In 198 samples, 25 (12.6%) were low level mutations, 33 (16.7%) were high level mutations and 10 (5.1%) were mixed high and low level mutations. In the analysis of related clinical factors, the total mutation rate and the low level mutation rate in the optimal period, failure period and warning period were gradually increased (total mutation rate, P =0.016; low level mutation rate, P =0.005). The mutation rate of the samples with additional chromosomal abnormalities was also significantly increased (P =0.009). The mutation rate of patients who received first- and second-line treatment was significantly lower than that of patients who received third- or higher-line treatment (P =0.006). Analysis based on variant allele frequency (VAF) of the mutation site was helpful to visually evaluate the clonal evolution status of TKI-resistance CML cells. CONCLUSION: High-throughput sequencing is more sensitive and accurate than Sanger sequencing in mutation detection, which is helpful to accurately and visually evaluate TKI treatment response and optimize treatment strategy for CML.

Microwave-responsive gadolinium metal-organic frameworks nanosystem for MRI-guided cancer thermotherapy and synergistic immunotherapy.

The clinical application of cancer immunotherapy is unsatisfied due to low response rates and systemic immune-related adverse events. Microwave hyperthermia can be used as a synergistic immunotherapy to amplify the antitumor effect. Herein, we designed a Gd-based metal-organic framework (Gd-MOF) nanosystem for MRI-guided thermotherapy and synergistic immunotherapy, which featured high performance in drug loading and tumor tissue penetration. The PD-1 inhibitor (aPD-1) was initially loaded in the porous Gd-MOF (Gd/M) nanosystem. Then, the phase change material (PCM) and the cancer cell membrane were further sequentially modified on the surface of Gd/MP to obtain Gd-MOF@aPD-1@CM (Gd/MPC). When entering the tumor microenvironment (TME), Gd/MPC induces immunogenic death of tumor cells through microwave thermal responsiveness, improves tumor suppressive immune microenvironment and further enhances anti-tumor ability of T cells by releasing aPD-1. Meanwhile, Gd/MPC can be used for contrast-enhanced MRI. Transcriptomics data revealed that the downregulation of MSK2 in cancer cells leads to the downregulation of c-fos and c-jun, and ultimately leads to the apoptosis of cancer cells after treatment. In general, Gd/MPC nanosystem not only solves the problem of system side effect, but also achieves the controlled drug release via PCM, providing a promising theranostic nanoplatform for development of cancer combination immunotherapy.

Molecular basis of threonine ADP-ribosylation of ubiquitin by bacterial ARTs.

Ubiquitination plays essential roles in eukaryotic cellular processes. The effector protein CteC from Chromobacterium violaceum blocks host ubiquitination by mono-ADP-ribosylation of ubiquitin (Ub) at residue T66. However, the structural basis for this modification is unknown. Here we report three crystal structures of CteC in complexes with Ub, NAD+ or ADP-ribosylated Ub, which represent different catalytic states of CteC in the modification. CteC adopts a special 'D-E' catalytic motif for catalysis and binds NAD+ in a half-ligand binding mode. The specific recognition of Ub by CteC is determined by a relatively separate Ub-targeting domain and a long loop L6, not the classic ADP-ribosylating turn-turn loop. Structural analyses with biochemical results reveal that CteC represents a large family of poly (ADP-ribose) polymerase (PARP)-like ADP-ribosyltransferases, which harbors chimeric features from the R-S-E and H-Y-E classes of ADP-ribosyltransferases. The family of CteC-like ADP-ribosyltransferases has a common 'D-E' catalytic consensus and exists extensively in bacteria and eukaryotic microorganisms.

Rechargeable Zinc-Air Batteries: Advances, Challenges, and Prospects.

Rechargeable zinc-air batteries (Re-ZABs) are one of the most promising next-generation batteries that can hold more energy while being cost-effective and safer than existing devices. Nevertheless, zinc dendrites, non-portability, and limited charge-discharge cycles have long been obstacles to the commercialization of Re-ZABs. Over the past 30 years, milestone breakthroughs have been made in technical indicators (safety, high energy density, and long battery life), battery components (air cathode, zinc anode, and gas diffusion layer), and battery configurations (flexibility and portability), however, a comprehensive review on advanced design strategies for Re-ZABs system from multiple angles is still lacking. This review underscores the progress and strategies proposed so far to pursuit the high-efficiency Re-ZABs system, including the aspects of rechargeability (from primary to rechargeable), air cathode (from unifunctional to bifunctional), zinc anode (from dendritic to stable), electrolytes (from aqueous to non-aqueous), battery configurations (from non-portable to portable), and industrialization progress (from laboratorial to practical). Critical appraisals of the advanced modification approaches (such as surface/interface modulation, nanoconfinement catalysis, defect electrochemistry, synergistic electrocatalysis, etc.) are highlighted for cost-effective flexible Re-ZABs with good sustainability and high energy density. Finally, insights are further rendered properly for the future research directions of advanced zinc-air batteries.