A Translation-Activating Function of MIWI/piRNA during Mouse Spermiogenesis.

Spermiogenesis is a highly orchestrated developmental process during which chromatin condensation decouples transcription from translation. Spermiogenic mRNAs are transcribed earlier and stored in a translationally inert state until needed for translation; however, it remains largely unclear how such repressed mRNAs become activated during spermiogenesis. We previously reported that the MIWI/piRNA machinery is responsible for mRNA elimination during late spermiogenesis in preparation for spermatozoa production. Here we unexpectedly discover that the same machinery is also responsible for activating translation of a subset of spermiogenic mRNAs to coordinate with morphological transformation into spermatozoa. Such action requires specific base-pairing interactions of piRNAs with target mRNAs in their 3' UTRs, which activates translation through coupling with cis-acting AU-rich elements to nucleate the formation of a MIWI/piRNA/eIF3f/HuR super-complex in a developmental stage-specific manner. These findings reveal a critical role of the piRNA system in translation activation, which we show is functionally required for spermatid development.

Ubiquitination-Deficient Mutations in Human Piwi Cause Male Infertility by Impairing Histone-to-Protamine Exchange during Spermiogenesis.

Genetic studies have elucidated critical roles of Piwi proteins in germline development in animals, but whether Piwi is an actual disease gene in human infertility remains unknown. We report germline mutations in human Piwi (Hiwi) in patients with azoospermia that prevent its ubiquitination and degradation. By modeling such mutations in Piwi (Miwi) knockin mice, we demonstrate that the genetic defects are directly responsible for male infertility. Mechanistically, we show that MIWI binds the histone ubiquitin ligase RNF8 in a Piwi-interacting RNA (piRNA)-independent manner, and MIWI stabilization sequesters RNF8 in the cytoplasm of late spermatids. The resulting aberrant sperm show histone retention, abnormal morphology, and severely compromised activity, which can be functionally rescued via blocking RNF8-MIWI interaction in spermatids with an RNF8-N peptide. Collectively, our findings identify Piwi as a factor in human infertility and reveal its role in regulating the histone-to-protamine exchange during spermiogenesis.

Photo-Stimulated Zn-based Batteries: Progress, Challenges, and Perspectives.

Solar energy, as a renewable energy source, dominates the vast majority of human energy, which can be harvested and converted by photovoltaic solar cells. However, the intermittent availability of solar energy restricts the actual utilization circumstances of solar cells. Integrating photo-responsive electrodes into an energy storage device emerges as a dependable and executable strategy, fostering the creation of photo-stimulated batteries that seamlessly amalgamate the process of solar energy collection, conversion, and storage in one system. Endowed by virtues such as cost-effectiveness, facile manufacturing, safety, and environmental friendliness, photo-stimulated Zn-based batteries have attracted considerable attention. The progress report furnishes a brief overview, summarizing various photo-stimulated Zn-based batteries. Their configurations, operational principles, advancements, and the intricate engineering of photoelectrode designs are introduced, respectively. Through rigorous architectural design, photo-stimulated Zn-based batteries exhibit the ability to initiate charging by saving electricity usage, and in certain instances, even without the need for external electrical grids under illumination. Furthermore, the compensation of solar energy can be explored to improve the output electric energy. At last, opportunities and challenges toward photo-stimulated Zn-based batteries in the process of development are proposed and discussed in the hope of expanding their application scenarios and accelerating the commercialization progress.

Engineered Macrophages Tune Intratumoral Cytokines through Precisely Controlled Self-Pyroptosis to Enhance Bladder Cancer Immunotherapy.

Engineered macrophages are a promising tool for drug delivery and immunotherapy in cancer treatment. However, simultaneous targeted enrichment and controllable immunological activation of these macrophages at the tumor site remains challenging. As a solution, macrophages loaded with an advanced nanoparticle encapsulating CpG-conjugated magnetic nanoclusters (MNC) with indocyanine green (ICG) and nigericin (NIG) (MNC-ICG-NIG@SiO2 (MINS)), utilizing Se─Se bond-modified SiO2, are designed and applied in bladder cancer, which is typically managed surgically, followed by Bacillus Calmette-Guerin (BCG) adjuvant instillation therapy. Upon intravenous administration, BCG-mediated tumor-localized inflammation leads to targeted accumulation of MINS@MΦ. MINS@MΦ accumulates within the tumor tissue and is immunologically activated through laser irradiation, leading to ICG-mediated generation of reactive oxygen species, Se─Se bond cleavage, and subsequent NIG release to induce self-pyroptosis. Consequently, MINS@MΦ releases Fe2+ ions and CpG, thus promoting the M1 polarization of tumor-associated macrophages and secretion of appropriate antitumor cytokines. However, without intervention, MINS@MΦ undergoes apoptosis in the bloodstream after 48 h without eliciting any immune response. Therefore, this innovative approach optimizes and enhances the efficacy of BCG immunotherapy by precisely modulating the cytokines for effective bladder cancer treatment without inducing a systemic inflammatory response.

Electrically tunable metasurface in TN LC configuration with enhanced quality factor and metaatom-induced alignment.

Dynamic metasurface with subwavelength dimensions has emerged as a key optical technology in recent years. Although various active tuning mechanisms are being proposed, liquid crystal-based dynamic metasurface remains attractive due to its large index variation, electrical tunability, reliability, and mass fabricability. In this work, we report a dynamic metasurface for amplitude modulation in reflection, with twisted nematic liquid crystal configuration to reduce broadband reflection in the off state. The metasurface consists of coupled subwavelength grating fingers, which provide alignment for the liquid crystal without the need for an additional alignment material or process. The alignment of liquid crystal materials was examined between crossed polarizers, and the twist of nematic liquid crystal was confirmed. The coupled grating fingers exhibit a resonance quality factor of 27 at telecommunication wavelength and an amplitude modulation depth of 8 times of the minimum at 1630 nm. This work highlights the potential of liquid crystal-based tunable metasurface, combining polarization control via liquid crystal and spectrum control via metasurface. Furthermore, it also shows a way in which the interaction between liquid crystal and metasurface is used for an alignment layer-free cell assembly process.

Targeting tumour surface collage with hydrogel probe: a new strategy to enhance intraoperative imaging sensitivity and stability of bladder cancer.

PURPOSE: The incomplete resection of non-muscle invasive bladder cancer (NMIBC) augments the risk of disease recurrence. Imaging-guided surgery by molecular probes represents a pivotal strategy for mitigating postoperative recurrence. Traditional optical molecular probes, primarily composed of antibodies/peptides targeting tumour cells and fluorescent groups, are challenged by the high heterogeneity of NMIBC cells, leading to inadequate probe sensitivity. We have developed a collagen-adhesive probe (CA-P) to target the collagen within the tumour microenvironment, aiming to address the issue of insufficient imaging sensitivity. METHODS: The distribution characteristics of collagen in animal bladder cancer models and human bladder cancer tissues were explored. The synthesis and properties of CA-P were validated. In animal models, the imaging performance of CA-P was tested and compared with our previously reported near-infrared probe PLSWT7-DMI. The clinical translational potential of CA-P was assessed using human ex vivo bladder tissues. RESULTS: The distribution of collagen on the surface of tumour cells is distinct from its expression in normal urothelium. In vitro studies have demonstrated the ability of the CA-P to undergo a "sol-gel" transition upon interaction with collagen. In animal models and human ex vivo bladder specimens, CA-P exhibits superior imaging performance compared to PLSWT7-DMI. The sensitivity of this probe is 94.1%, with a specificity of 81%. CONCLUSION: CA-P demonstrates the capability to overcome tumour cell heterogeneity and enhance imaging sensitivity, exhibiting favorable imaging outcomes in preclinical models. These findings provide a theoretical basis for the application of CA-P in intraoperative navigation for NMIBC.

Electron Donor-Acceptor Complex Driven Photocatalyst-Free Trifluoromethylation of Heterocycles.

Heterocyclic trifluoromethylation is efficiently initiated through a photochemical reaction utilizing an electron donor-acceptor (EDA) complex, proceeding smoothly without the use of photocatalysts, transition-metal catalysts, or additional oxidants. This method has been optimized through extensive experimentation, demonstrating its versatility and efficacy across various substrates, including quinoxalinones, coumarins, and indolones. Notably, this approach enables the practical synthesis of trifluoromethylated quinoxalinones on a gram scale. Mechanistic investigations that incorporate radical trapping and ultraviolet/visible spectroscopy, confirmed the formation of the an EDA complex and elucidated the reaction pathways. This study highlights the crucial role of EDA photoactivation in trifluoromethylation, significantly expanding the application scope of EDA complexes in chemical synthesis.

Rapid Fabrication of Large-Grain Opal Films and Photonic Crystal Hydrogel Sensors by a Filter Paper-Enhanced Evaporation Chip.

Developing a rapid fabrication method for crack-free opal films is a significant challenge with broad applications. We developed a microfluidic platform known as the "filter paper-enhanced evaporation microfluidic chip" (FPEE-chip) for the fabrication of photonic crystal and inverse opal hydrogel (IOPH) films. The chip featured a thin channel formed by bonding double-sided adhesive poly(ethylene terephthalate) with a polymethyl methacrylate cover and a glass substrate. This channel was then filled with nanosphere colloids. The water was guided to evaporate rapidly at the surface of the filter paper, allowing the nanospheres to self-assemble and accumulate within the channel under capillary forces. Experimental results confirmed that the self-assembly method based on the FPEE-chip was a rapid platform for producing high-quality opal, with centimeter-sized opal films achievable in less than an hour. Furthermore, the filter paper altered the stress release mechanism of the opal films during drying, resulting in fewer cracks. This platform was proven capable of producing large-grain, crack-free opal films of up to 30 mm2 in size. We also fabricated crack-free IOPH pH sensors that exhibited color and size responsiveness to pH changes. The coefficient of variation of the gray color distribution for crack-free IOPH ranged from 0.03 to 0.07, which was lower than that of cracked IOPH (ranging from 0.07 to 0.14). Additionally, the grayscale peak value in 1 mm2 of the crack-free IOPH was more than twice that of the cracked IOPH at the same pH. The FPEE-chip demonstrated potential as a candidate for developing vision sensors.

Mechanism of p-Type Heteroatom Doping of Lithium Stannate for the Photodegradation of 2,4-Dichlorophenol: Enhanced Hole Oxidative Capability and Concentrations.

A systematic evaluation of enhancing photocatalysis via aliovalent cation doping is conducted. Cation In3+, being p-type-doped, was chosen to substitute the Sn site (Sn4+) in Li2SnO3, and the photodegradation of 2,4-dichlorophenol was applied as a model reaction. Specifically, Li2Sn0.90In0.10O3 exhibited superior catalytic performance; the photodegradation efficiency reached about 100% within only 12 min. This efficiency is far greater than that of pure Li2SnO3 under identical conditions. Density functional theory calculations reveal that introducing In3+ increased the electron mobility, yet decreased the hole mobility, leading to photogenerated carrier separation. However, photoluminescence and time-resolved photoluminescence suggest that In3+ induced nonradiative coupling in the matrix, reducing the photogenerated carrier separation ratio compared with that of Li2SnO3. The optical band gap of Li2Sn0.90In0.10O3 was almost unchanged compared with that of Li2SnO3 via ultraviolet-visible absorption. The increased photocatalytic efficiency was ascribed to the lower valence band position and enhanced hole concentrations by valence band X-ray photoelectron spectroscopy and electrochemical measurements. Finally, a 2,4-dichlorophenol degradation pathway, an intermediate toxicity assessment, and a photocatalytic mechanism were proposed. This work offers insights into designing and optimizing semiconductor photocatalysts with high performance.

Development of a sensitive direct competitive chemiluminescent enzyme immunoassay for gentamicin based on the construction of a specific single-chain variable fragment-alkaline phosphatase fusion protein.

A sensitive chemiluminescent enzyme immunoassay (CLEIA) was established for the determination of gentamicin (GEN) residue levels in animal tissue. This assay is based on a fusion protein of single-chain variable fragment (scFv) and alkaline phosphatase (AP). Initially, VL and VH derived from anti-gentamicin monoclonal antibody were linked by a short peptide to construct a scFv. Subsequently, the constructed scFv sequence was accessed into the pLIP6/GN vector, and a soluble scFv-AP fusion protein was generated. The scFv-AP fusion protein was used to develop a direct competitive CLEIA (dcCLEIA) for the determination of gentamicin. In the dcCLEIA, the half inhibitory concentration (IC50) and limit of detection (LOD) were 1.073 ng/mL and 0.380 ng/mL, respectively. The average recoveries of gentamicin spiked in animal tissue samples ranged from 78% to 96%. These results showed a strong correlation with ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The above results suggest that the anti-GEN scFv-AP fusion protein is suitable for detecting gentamicin residues in edible animal tissues.

Examining the linkage between economic policy uncertainty, coal price, and carbon pricing in China: Evidence from pilot carbon markets.

Economic policies affect companies' production decisions. And the energy consumption volume is an intuitive reflection of the enterprise's production decisions. In China, coal is the main source of carbon emissions and the most important energy source. Therefore, the coal market and the uncertainty of economic policies are both directly tied to the carbon market. This study explores both the direct impact of economic policy uncertainty and coal price on carbon prices as well as the indirect impact of economic policy uncertainty on carbon prices through coal prices by utilizing the DCC-GARCH model and the NARDL model. The findings indicate that the dynamic correlations between coal prices and the CEPU are always negative and that those between the price of carbon and the CEPU vary by area. Meanwhile, the dynamic correlations between coal and carbon prices are only positive in Shenzhen and Beijing. Both coal prices and economic policy uncertainty produce asymmetrical impacts on carbon prices. Some policy implications are provided for developing the carbon markets in light of the results drawn from the study.

Design, Synthesis, Antifungal Activity, and 3D-QSAR Study of Novel Quinoxaline-2-Oxyacetate Hydrazide.

Plant pathogenic fungi pose a major threat to global food security, ecosystem services, and human livelihoods. Effective and broad-spectrum fungicides are needed to combat these pathogens. In this study, a novel antifungal 2-oxyacetate hydrazide quinoxaline scaffold as a simple analogue was designed and synthesized. Their antifungal activities were evaluated against Botrytis cinerea (B. cinerea), Altemaria solani (A. solani), Gibberella zeae (G. zeae), Rhizoctonia solani (R. solani), Colletotrichum orbiculare (C. orbiculare), and Alternaria alternata (A. alternata). These results demonstrated that most compounds exhibited remarkable inhibitory activities and possessed better efficacy than ridylbacterin, such as compound 15 (EC50 = 0.87 µg/mL against G. zeae, EC50 = 1.01 µg/mL against C. orbiculare) and compound 1 (EC50 = 1.54 µg/mL against A. alternata, EC50 = 0.20 µg/mL against R. solani). The 3D-QSAR analysis of quinoxaline-2-oxyacetate hydrazide derivatives has provided new insights into the design and optimization of novel antifungal drug molecules based on quinoxaline.

[Expert consensus on the application of digital PCR non-invasive prenatal screening technology for the preliminary implementation of fetal chromosomal disease screening].

Clinical application of serological screening and non-invasive prenatal testing (NIPT) both have difficulties to attain high detection rate and low cost. For its advantages of high detection rate, high sensitivity, simplicity, short turnaround time and low cost, digital PCR (dPCR) has provided a new choice for prenatal screening of trisomies 21, 18 and 13. To standardize the application of dPCR for prenatal screening, we have formulated this consensus by referring to relevant guidelines, expert consensus and latest literature, which has covered the basic requirements, application scope, pre-testing service, testing procedure, report interpretation, genetic counseling, and limitations for this technology.

A Self-Disguised Nanospy for Improving Drug Delivery Efficiency via Decreasing Drug Protonation.

Nanoscale drug carriers play a crucial role in reducing side effects of chemotherapy drugs. However, the mononuclear phagocyte system (MPS) and the drug protonation after nanoparticles (NPs) burst release still limit the drug delivery efficiency. In this work, a self-disguised Nanospy is designed to overcome this problem. The Nanospy is composed of: i) poly (lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) loading doxorubicin is the core structure of the Nanospy. ii) CD47 mimic peptides (CD47p) is linked to NPs which conveyed the "don't eat me" signal. iii) 4-(2-aminoethyl) benzenesulfonamide (AEBS) as the inhibitor of Carbonic anhydrase IX (CAIX) linked to NPs. Briefly, when the Nanospy circulates in the bloodstream, CD47p binds to the regulatory protein α (SIRPα) on the surface of macrophages, which causes the Nanospy escapes from phagocytosis. Subsequently, the Nanospy enriches in tumor and the AEBS reverses the acidic microenvironment of tumor. Due to above characteristics, the Nanospy reduces liver macrophage phagocytosis by 25% and increases tumor in situ DOX concentration by 56% compared to PLGA@DOX treatment. In addition, the Nanospy effectively inhibits tumor growth with a 63% volume reduction. This work presents a unique design to evade the capture of MPS and overcomes the influence of acidic tumor microenvironment (TME) on weakly alkaline drugs.

Facile Synthesis of Clickable Unnatural Sugars in the Unprotected and 1,6-Di-O-Acylated Forms for Metabolic Glycan Labeling.

Clickable unnatural sugars have been widely used in studying glycosylation in living systems via the metabolic glycan labelling (MGL) strategy. Partial protection of unnatural sugars by 1,6-di-O-acylation increases the labelling efficiency while avoiding the non-specific S-glyco-modification. Herein, we report the facile synthesis of a series of clickable unnatural sugars in both the unprotected and 1,6-di-O-acylated forms at the ten-gram scale. By evaluation of the labelling specificity, efficiency, and biocompatibility of various 1,6-di-O-acylated sugars for MGL in cell lines and living mice, we demonstrate that 1,6-di-O-propionylated unnatural sugars are optimal chemical reporters for glycan labelling. The synthetic routes developed in this work should facilitate the widespread use of MGL with no artificial S-glyco-modification for investigating the functional roles of glycans.

Comprehensive analysis and validation of SNX7 as a novel biomarker for the diagnosis, prognosis, and prediction of chemotherapy and immunotherapy response in hepatocellular carcinoma.

BACKGROUND: Studies have demonstrated that Sorting nexin 7 (SNX7) functions as an anti-apoptotic protein in liver tissue and plays a crucial role in the survival of hepatocytes during early embryonic development. However, its diagnostic and prognostic value as well as the predictive value of chemotherapy and immunotherapy have not been reported in hepatocellular carcinoma (HCC). METHODS: SNX7 mRNA expression and its diagnostic efficacy were examined in GEO datasets, and the findings were further confirmed in TCGA, ICGC cohorts, and cell lines. The protein level of SNX7 was determined using CPTAC and HPA databases, and the results were validated through immunohistochemistry (IHC). Survival analyses were performed in TCGA and ICGC cohorts, and the results were subsequently validated via Kaplan-Meier Plotter. The response to chemotherapy and immunotherapy was predicted via GDSC dataset and TIDE algorithm, respectively. R packages were employed to explore the relationship between SNX7 expression and immune infiltration, m6A modification, as well as the functional enrichment of differentially expressed genes (DEGs). RESULTS: The expression of SNX7 at both mRNA and protein levels was significantly upregulated in HCC tissues. SNX7 exhibited superior diagnostic efficacy compared to AFP alone for HCC detection, and combining it with AFP improved the diagnostic accuracy for HCC. High SNX7 was associated with unfavorable outcomes, including poor overall survival, disease-specific survival, progression-free survival, and advanced pathological stage, in patients with HCC, and SNX7 was identified as an independent risk factor for HCC. Moreover, elevated SNX7 expression was positively correlated with increased sensitivity to various chemotherapy drugs, including sorafenib, while it was associated with resistance to immunotherapy in HCC patients. Correlation analysis revealed a relationship between SNX7 and multiple m6A-related genes and various immune cells. Finally, enrichment analysis demonstrated strong associations of SNX7 with critical biological processes, such as cell cycle regulation, cellular senescence, cell adhesion, DNA replication, and mismatch repair pathway in HCC. CONCLUSIONS: Our study highlights the association of SNX7 with the immune microenvironment and its potential influence on HCC progression. SNX7 emerges as a promising novel biomarker for the diagnosis, prognosis, and prediction of response to chemotherapy and immunotherapy in patients with HCC.

The change of eosinophils in the perioperative period is significantly associated with the prognosis in patients with lung cancer.

Background: This research focuses on the relationship between the changes in peripheral blood eosinophils (PBEs) perioperatively and the prognosis of lung cancer. Methods: The study included 414 lung cancer patients. These patients were divided into the DOWN (186 patients) and UP (209 patients) groups according to perioperative changes in PBEs. Furthermore, overall survival was compared based on pathological stage, pathological type, tumor location, age and sex. Furthermore, the authors analyzed the prediction of PBEs on the prognosis of chemotherapy. Results: The results showed that lung cancer patients in the DOWN group had a better prognosis (p = 0.0121; 95% CI: 0.6915 [0.5184-0.9224]), and the DOWN group patients with normal postoperative PBEs had a better prognosis (p = 0.0115; 95% CI: 0.6721 [0.4938-0.9148]). Conclusion: Lung cancer patients whose postoperative PBEs were lower than preoperative PBEs had a better prognosis.

Gut microbial signatures of patients with primary hepatocellular carcinoma and their healthy first-degree relatives.

AIMS: The gut microbiome has been recognized as a significant contributor to primary hepatocellular carcinoma (HCC), with mounting evidence indicating associations between bacterial components and cancers of the digestive system. METHODS AND RESULTS: Here, to characterize gut bacterial signature in patients with primary HCC and to assess the diagnostic potential of bacterial taxa for primary HCC, 21 HCC patients and 21 healthy first-degree relatives (control group) were enrolled in this study. Bacterial DNA in the fecal samples was quantified by 16S rRNA gene sequencing. We found that 743 operational taxonomic units (OTUs) were shared between patients with primary HCC and healthy controls. Of these, 197 OTUs were unique to patients with primary HCC, while 95 OTUs were unique to healthy subjects. Additionally, we observed significant differences in the abundance of Ruminococcaceae_UCG-014 and Romboutsia between patients with primary HCC and their healthy first-degree relatives. Besides, the relative abundance of Ruminococcaceae_UCG-014 and Prevotella_9 was positively correlated with physiological indicators including AST, ALT, ALB, or TBIL. Signature bacterial taxa could serve as non-invasive biomarkers, of which Romboutsia and Veillonella were identified as differential taxa in fecal samples from patients with HCC compared to healthy controls. Romboutsia showed a strong association with HCC (AUC = 0.802). Additionally, the combination of Romboutsia and Veillonella (AUC = 0.812) or the grouping of Fusobacterium, Faccalibacterium, and Peptostreptococcacae together (AUC = 0.762) exhibited promising outcomes for the diagnosis of HCC. CONCLUSIONS: The composition of gut microbes in patients with HCC was found to be significantly altered. Differential taxa Romboutsia, Veillonella, and Peptostreptococcacae could be tested for identification of HCC.

Nonvolatile and Nonflammable Sulfolane-Based Electrolyte Achieving Effective and Safe Operation of the Li-O2 Battery in Open O2 Environment.

The Li-O2 battery should operate effectively/safely in an open O2 environment for practical applications, but not trapped in sealed/closed atmosphere. However, the typical use of volatile and flammable electrolyte restricts Li-O2 battery to be able to be running in open O2 environment. We report herein, for the first time, a highly electrochemical reversible Li-O2 battery operated in an open O2 environment, i.e., under the condition of keeping O2 flowing continuously based on a nonvolatile and nonflammable sulfolane (TMS) solvent. The electrochemical irreversibility of Li2O2/O2 conversion and incompatibility between Li metal anodes and electrolyte have been addressed via dissolving LiNO3 in concentrated TMS electrolyte. The tuned electrolyte not only enables a stable solid electrolyte interphase (SEI) with conformal inorganic components (including LiF, LiNxOy, and Li2O) that promotes a uniform Li electro-plating/stripping process but also results in a low charge overpotential, a stable discharge terminal plateau, and reversible O2 generation of the Li-O2 battery conducted in an open O2 environment.

Titration Mass Spectroscopy (TMS): A Quantitative Analytical Technology for Rechargeable Batteries.

Development of high-energy-density rechargeable battery systems not only needs advanced qualitative characterizations for mechanism exploration but also requires accurate quantification technology to quantitatively elucidate products and fairly assess numerous modification strategies. Herein, as a reliable quantification technology, titration mass spectroscopy (TMS) is developed to accurately quantify O-related anionic redox reactions (Li-O2 battery and nickel-cobalt-manganese (NCM)/Li-rich cathodes), parasitic carbonate deposition and decomposition (derived from air-exposure degradation and electrolyte oxidation), and dead Li0 formation (Li-metal battery and over-discharged graphite anode). TMS technology can harvest key information on products (e.g., quantification of oxidized lattice oxygen and solid electrolyte interphase (SEI)/cathode electrolyte interphase (CEI) components) and guide corresponding design strategy by enhancing understanding of the mechanism (e.g., clearly distinguish the catalytic target of highly oxidative Ni4+ on the NCM cathode). Not limited as a rigid quantification tool for widely known products/mechanisms, TMS technology has been demonstrated as a powerful and versatile tool for the investigations of advanced batteries.