Naked mesoporous rhodium nanospheres with glutathione depletion and photothermal capabilities for tumor therapy.

Pancreatic and colon cancer are malignant tumors of the digestive system that currently lack effective treatments. In cancer cells, a high level of glutathione (GSH) is indispensable to scavenge excessive reactive oxygen species (ROS) and detoxify xenobiotics, which make it a potential target for cancer therapy. GSH depletion has been proved to improve the therapeutic efficacy of photodynamic therapy. Here, we reported that naked mesoporous rhodium nanospheres (Rh MNs), prepared by soft template redox method, can act as GSH depletion agent and photothermal conversion agent to achieve synergistic therapy respectively. Different from conventional nanoagents, Rh MNs with the characteristics of easy synthesis, simple structure and multiple functions can decrease the GSH level in tumor and depict excellent photothermal ability with a high photothermal conversion efficiency (PTCE) up to 39%. Notably, multiple anti-tumor mechanisms in CT26 and BxPC-3 tumor models, include inhibited anti-apoptosis, DNA replication repair, and GSH synthesis are revealed, and the pancreatic tumor cure rate of the cooperative treatment group is 80%. Collectively, we developed Rh MNs to combine GSH depletion with photothermal therapy for cancer treatment.

Quantitative predictions of protein and total flavonoids content in Tartary and common buckwheat using near-infrared spectroscopy and chemometrics.

A rapid method was developed for determining the total flavonoid and protein content in Tartary buckwheat by employing near-infrared spectroscopy (NIRS) and various machine learning algorithms, including partial least squares regression (PLSR), support vector regression (SVR), and backpropagation neural network (BPNN). The RAW-SPA-CV-SVR model exhibited superior predictive accuracy for both Tartary and common buckwheat, with a high coefficient of determination (R2p = 0.9811) and a root mean squared error of prediction (RMSEP = 0.1071) for flavonoids, outperforming both PLSR and BPNN models. Additionally, the MMN-SPA-PSO-SVR model demonstrated exceptional performance in predicting protein content (R2p = 0.9247, RMSEP = 0.3906), enhancing the effectiveness of the MMN preprocessing technique for preserving the original data distribution. These findings indicate that the proposed methodology could efficiently assess buckwheat adulteration analysis. It can also provide new insights for the development of a promising method for quantifying food adulteration and controlling food quality.

Preoperative markers for identifying CT ≤2 cm solid nodules of lung adenocarcinoma based on image deep learning.

BACKGROUND: The solid pattern is a highly malignant subtype of lung adenocarcinoma. In the current era of transitioning from lobectomy to sublobar resection for the surgical treatment of small lung cancers, preoperative identification of this subtype is highly important for patient surgical approach selection and long-term prognosis. METHODS: A total of 1489 patients with clinical stage IA1-2 primary lung adenocarcinoma were enrolled. Based on patient clinical characteristics and lung imaging features obtained via deep learning, highly correlated diagnostic factors were identified through LASSO regression and decision tree analysis. Subsequently, a logistic model and nomogram were constructed. A restricted cubic spline (RCS) was used to calculate the optimal inflection point of quantitative data and the differences between the groups. RESULTS: The three-dimensional proportion of solid component (PSC), sex, and smoking status was identified as being highly correlated diagnostic factors for solid predominant adenocarcinoma. The logistic model had good prediction efficiency, and the area under the ROC curve was 0.85. Decision curve analysis demonstrated that the application of diagnostic factors can improve patient outcomes. RCS analysis indicated that the proportion of solid adenocarcinomas increased by 4.6 times when the PSC was ≥72%. A PSC of 72% is a good cutoff point. CONCLUSION: The preoperative diagnosis of solid-pattern adenocarcinoma can be confirmed by typical imaging features and clinical characteristics, assisting the thoracic surgeon in developing a more precise surgical plan.

Oxidation-induced graded bandgap narrowing in Two-dimensional tin sulfide for high-sensitivity broadband photodetection.

Two-dimensional (2D) layered group-IV monochalcogenides with large surface-to-volume ratio and high surface activity make that their structural and optoelectronic properties are sensitive to air oxidation. Here, we report the utilization of oxidation-induced gradient doping to modulate electronic structures and optoelectronic properties of 2D group-IV monochalcogenides by using SnS nanoplates grown by physical vapor deposition as a model system. By a precise control of oxidation time and temperature, the structural transition from SnS to SnSOx could be driven by the layer-by-layer oxygen doping and intercalation. The resulting SnSOx with a graded narrowing bandgap exhibits the enhanced optical absorption and photocurrent, leading to the fabricated SnSOx photodetector with remarkable photoresponsivity and fast response speed (<64 µs) at a broadband spectrum range of 520-1550 nm. The peak responsivity (7294 A/W) and detectivity (9.54 × 109 Jones) of SnSOx device are at least two orders of magnitude larger than those of SnS photodetector. Moreover, its photodetection performance can be competed with state-of-the-art of 2D materials-based photodetectors. This work suggests that the air oxidation could be utilized as an efficient strategy to engineer the electronic and optical properties of SnS and other 2D group-IV monochalcogenides for the development of high-performance broadband photodetectors.

Designing Contact Independent High-Performance Low-Cost Flexible Electronics.

Organic semiconductors enable low-cost solution processing of optoelectronic devices on flexible substrates. Their use in contemporary applications, however, is sparse due to persistent challenges in achieving the requisite performance levels in a reliable and reproducible manner. A critical bottleneck is the inefficiency associated with charge injection. Here, large-scale simulations are employed to identify operational windows where key device parameters that are difficult to control experimentally, such as the contact resistance, become less consequential to overall device functionality. This design methodology overcomes injection barrier limitations in organic field-effect transistors (OFETs), leading to high charge carrier mobility and significantly expanding the range of suitable electrode materials. Leveraging this new understanding, all-organic, solution-deposited OFETs are successfully fabricated on flexible substrates. These devices incorporate printed contacts and showcase mobilities exceeding 5 cm2 Vs-1. These results provide a route for accessing the fundamental limits of material properties even in the absence of ideal contacts - a critical step in establishing reliable structure/property relationships and optimal material design paradigms. While reducing the injection barrier and contact resistance remains critical for achieving high OFET performance, this work demonstrates a path toward consistently achieving high charge carrier mobility through device geometry design, ultimately reducing processing complexity and cost.

Establishing a Robust Nonlinear Targeted Switch for C1 Electroproduction in Atomic Alloy Cox/Pd Bimetallenes.

Establishing a targeted switch for CO2 conversion under electric drive is essential for achieving carbon-balance by enabling selective chemicals. However, engineering the topological assembly of active sites to precisely regulate the competing pathways for various intermediates has been plagued by unclear structure-function relationships. To tailor the CO/formate pathways, herein we established a robust nonlinear targeted switch with tunable active Cox sites integrated into Pd metallene, which involves Co1/Pd single-atom alloy (favoring CO) and Co2/Pd diatomic alloy (favoring formate). Transitioning from Co1/Pd to Co2/Pd atomic alloy bimetallenes resulted in a nonlinear, high-contrast flip in selectivity, surpassing 94% for CO and formate productions in both H-cell and flow cell. Furthermore, the superior selectivity and current efficiency for CO (> 80 %) and formate (> 88%) were consistently maintained at -150 mA cm-2 over continuous 200 h. Theoretical simulations and in-situ spectroscopy analyses unveiled that appropriate adjacent metal site combinations (Pd-Pd, Pd-Co and Co-Co) lead to tunable dz2 band center and a nonlinear shift in preferred adsorption configurations of intermediates, dictating the C1 pathways. Our finding reveals a desired switch in C1 selectivity and robust stability within Cox/Pd system, providing a new perspective for fine-tuning energy conversion processes through specific topological assembly.

Near-infrared spectroscopy combined with support vector machine for the identification of Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn) adulteration using wavelength selection algorithms.

The frequent occurrence of adulterating Tartary buckwheat powder with crop flours in the market necessitates an urgent need for a simple analysis method to ensure the quality of Tartary buckwheat. This study employed near-infrared spectroscopy (NIRS) for the collection of spectral data from Tartary buckwheat samples adulterated with whole wheat, oat, soybean, barley, and sorghum flours. The competitive adaptive reweighted sampling (CARS) and successive projection algorithm (SPA) were deployed to identify informative wavelengths. By integrating support vector machine (SVM) and partial least squares discriminant analysis (PLS-DA), we constructed qualitative models to discern Tartary buckwheat adulteration. The PLS-DA model exhibited prediction accuracies between 89.78 % and 94.22 %, while the mean-centering (MC)-PLS-DA model showcased impressive predictive accuracy of 93.33 %. Notably, the feature-based Autoscales-CARS-CV-SVM model achieved more excellent identification accuracy. These findings exhibit the excellent potential of chemometrics as a powerful tool for detecting food product adulteration.

Exploring the influence of spiritual leadership, leader - member exchange, and traditionality orientation on employee voice behavior.

This research builds on the idea that the exchange of resources between leaders and followers can influence the behavior of employees. Specifically, the study investigates how leaders can develop strong leader-member exchange (LMX) with their followers, and how this exchange can lead to increased employee voice behavior. The study analyzed data collected from 365 individual employees working in Chinese organization. The findings indicate that LMX acts as a mediator between spiritual leadership and employee voice behavior. The strength of this mediation, however, depends on the followers' level of traditionality orientation. Notably, the findings indicate that the effect is significant only among individuals who exhibit low traditionality. Theoretical contributions and implications for practice are discussed in later sections.

Octave-wide broadening of ultraviolet dispersive wave driven by soliton-splitting dynamics.

Coherent dispersive wave emission, as an important phenomenon of soliton dynamics, manifests itself in multiple platforms of nonlinear optics from fibre waveguides to integrated photonics. Limited by its resonance nature, efficient generation of coherent dispersive wave with ultra-broad bandwidth has, however, proved difficult to realize. Here, we unveil a new regime of soliton dynamics in which the dispersive wave emission process strongly couples with the splitting dynamics of the driving pulse. High-order dispersion and self-steepening effects, accumulated over soliton self-compression, break the system symmetry, giving rise to high-efficiency generation of coherent dispersive wave in the ultraviolet region. Simultaneously, asymmetric soliton splitting results in the appearance of a temporally-delayed ultrashort pulse with high intensity, overlapping and copropagating with the dispersive wave pulse. Intense cross-phase modulations lead to octave-wide broadening of the dispersive wave spectrum, covering 200-400 nm wavelengths. The highly-coherent, octave-wide ultraviolet spectrum, generated from the simple capillary fibre set-up, is in great demand for time-resolved spectroscopy, ultrafast electron microscopy and frequency metrology applications, and the critical role of the secondary pulse in this process reveals some new opportunities for all-optical control of versatile soliton dynamics.

Long noncoding RNA AK144717 exacerbates pathological cardiac hypertrophy through modulating the cellular distribution of HMGB1 and subsequent DNA damage response.

DNA damage induced by oxidative stress during cardiac hypertrophy activates the ataxia telangiectasia mutated (ATM)-mediated DNA damage response (DDR) signaling, in turn aggravating the pathological cardiomyocyte growth. This study aims to identify the functional associations of long noncoding RNA (lncRNAs) with cardiac hypertrophy and DDR. The altered ventricular lncRNAs in the mice between sham and transverse aortic constriction (TAC) group were identified by microarray analysis, and a novel lncRNA AK144717 was found to gradually upregulate during the development of pathological cardiac hypertrophy induced by TAC surgery or angiotensin II (Ang II) stimulation. Silencing AK144717 had a similar anti-hypertrophic effect to that of ATM inhibitor KU55933 and also suppressed the activated ATM-DDR signaling induced by hypertrophic stimuli. The involvement of AK144717 in DDR and cardiac hypertrophy was closely related to its interaction with HMGB1, as silencing HMGB1 abolished the effects of AK144717 knockdown. The binding of AK144717 to HMGB1 prevented the interaction between HMGB1 and SIRT1, contributing to the increased acetylation and then cytosolic translocation of HMGB1. Overall, our study highlights the role of AK144717 in the hypertrophic response by interacting with HMGB1 and regulating DDR, hinting that AK144717 is a promising therapeutic target for pathological cardiac growth.

Multifunctional MnGA Nanozymes for the Treatment of Ulcerative Colitis by Reducing Intestinal Inflammation and Regulating the Intestinal Flora.

In ulcerative colitis (UC), the formation of an inflammatory environment is due to the combined effects of excess production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), overproduction of proinflammatory cytokines, and disruption of immune system function. There are many kinds of traditional drugs for the clinical treatment of UC, but long-term drug use can cause toxic side effects and drug resistance and can also reduce patient compliance and other drawbacks. Hence, in light of the clinical challenges associated with UC, including the limitations of existing treatments, intense adverse reactions and the development of resistance to medications, no novel therapeutic agents that offer effective relief and maintain a high level of biosafety are urgently needed. Although many anti-inflammatory nanomedicines have been developed by researchers, the development of efficient and nontoxic nanomedicines is still a major challenge in clinical medicine. Using the natural product gallic acid and the metal compound manganese chloride, a highly effective and nontoxic multifunctional nanoenzyme was developed for the treatment of UC. Nanozymes can effectively eliminate ROS and RNS to reduce the inflammation of intestinal epithelial cells caused by oxidation, facilitate the restoration of the intestinal epithelial barrier through the upregulation of tight junction protein expression, and balance the intestinal microbiota to maintain the stability of the intestinal environment. Using a rodent model designed to mimic UC, we monitored body weight, colon length, the spleen index, and the degree of tissue damage and demonstrated that manganese gallate (MnGA) nanoparticles can reduce intestinal inflammation by clearing ROS and active nitrogen. Intestinal flora sequencing revealed that MnGA nanoparticles could regulate the intestinal flora, promote the growth of beneficial bacteria and decrease the levels of detrimental bacteria within the intestinal tract in a mouse model of UC. Thus, MnGA nanoparticles can maintain the balance of the intestinal flora. This study demonstrated that MnGA nanoparticles are excellent antioxidant and effective anti-inflammatory agents, have good biosafety, and can effectively treat UC.

Drug-Drug Cocrystal Alloy and Nanoformulation of Cytarabine: Optimized Biopharmaceutical Property and Synergistic Antitumor Efficacy.

An integrated strategy by combining cocrystallization with nanotechnology is developed to optimize in vitro/vivo performances of marine antitumor drug cytarabine (ARA) and further obtain innovative insights into the exploitation of cocrystal alloy nanoformulation. Therein, the optimization of properties and synergistic effects of ARA mainly depends on assembling with uracil (U) and antitumor drug 5-fluorouracil (FU) into the same crystal by cocrystallization technology, while the long-term efficacy is primarily maintained by playing the superiority of nanotechnology. Along this line, the first cocrystal alloy of ARA, viz., ARA-FU-U (0.6:0.4), is successfully obtained and then transformed into a nanocrystal. Single-crystal X-ray diffraction analysis demonstrates that this cocrystal alloy consists of two isomorphic cocrystals of ARA, namely, ARA-FU and ARA-U, in 0.6:0.4 ratio. An R22(8) hydrogen-bonding cyclic system formed by a cytosine fragment of ARA with U or FU can protect and stabilize the amine group on ARA, laying the foundation for regulating its properties. The in vitro/in vivo properties of the cocrystal alloy and its nanocrystals are investigated by theoretical and experimental means. It reveals that both the alloy and nanocrystal can improve physicochemical properties and promote drug absorption, thus bringing to optimized pharmacokinetic behaviors. The nanocrystal produces superior effects than the alloy that helps to extend therapeutic time and action. Particularly, relative to the corresponding binary cocrystal, the synergistic antitumor activity of ARA and FU in the cocrystal alloy is heightened obviously. It may be that U contributes to reducing the degradation of FU, specifically increasing its concentration in tumors to enhance the synergistic effects of FU and ARA. These findings provide new thoughts for the application of cocrystal alloys in the marine drug field and break fresh ground for cocrystal alloy formulations to optimize drug properties.

Ultrasensitive mass spectrometric quantitation of apurinic/apyrimidinic sites in genomic DNA of mammalian cell lines exposed to genotoxic reagents.

The apurinic/apyrimidinic (AP) site is an important intermediate in the DNA base excision repair (BER) pathway, having the potential of being a biomarker for DNA damage. AP sites could lead to the stalling of polymerases, the misincorporation of bases and DNA strand breaks, which might affect physiological function of cells. However, the abundance of AP sites in genomic DNA is very low (less than 2 AP sites/106 nts), which requires a sensitive and accurate method to meet its detection requirements. Here, we described an ultrasensitive quantification method based on a hydrazine-s-triazine reagent (i-Pr2N) labeling for AP sites combining with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The limit of detection reached an ultralow level (40 amol), realizing the most sensitive MS-based quantification for the AP site. To guarantee the accuracy of the quantitative results, the labeling reaction was carried out directly on DNA strands instead of labeling after DNA enzymatic digestion to reduce artifacts that might be produced during the enzymatic process of DNA strands. And selective detection was realized by MS to avoid introducing the false-positive signals from other aldehyde species, which could also react with i-Pr2N. Genomic DNA samples from different mammalian cell lines were successfully analyzed using this method. There were 0.4-0.8 AP sites per 106 nucleotides, and the values would increase 16.1 and 2.75 times when cells were treated with genotoxic substances methyl methanesulfonate and 5-fluorouracil, respectively. This method has good potential in the analysis of a small number of cell samples and clinical samples, is expected to be useful for evaluating the damage level of DNA bases, the genotoxicity of compounds and the drug resistance of cancer cells, and provides a new tool for cell function research and clinical precise treatment.

Overall survival and disease-free survival prediction in Chinese women with breast cancer aged 70 years or older by using nomograms.

PURPOSE: By analyzing the existing data of this study, a prediction tool for the overall breast cancer survival and disease-free survival (DFS) of elderly women was established. PATIENTS AND METHODS: Clinicopathologic data were collected from elderly women with BC who were admitted to the Tianjin Medical University Cancer Institute and Hospital from August 2014 to December 2017. Independent prognostic factors for BC in elderly patients were confirmed using the Cox proportional hazards model. Nomograms were developed with these factors for predicting the 3- and 5-year overall survival (OS) as well as DFS. The nomograms' discrimination ability and calibration were assessed through the area under the curve (AUC), concordance index (C-index), decision curve analysis (DCA), and calibration plots. RESULTS: We enroled 889 elderly patients with BC, and the results showed that the 3-year OS rate was 93.4% (95%CI = 91.8%-95.1%), the 3-year DFS rate was 87.8% (95%CI = 85.7%-90.0%), the 5-year OS rate was 85.6% (95%CI = 83.3%-87.9%), and the 5-year DFS rate was 80.1%(95%CI = 77.5%-82.8%). The corrected C-indices of the OS and DFS nomograms were 0.799 and 0.667, respectively (95%CI = 0.767-0.830 and 0.632-0.702, respectively). Relatively high AUC values were shown by the nomograms for estimating OS and DFS. The DCA revealed that the constructed nomograms had net benefits for clinical application. The calibration curves demonstrated an excellent correspondence between the data predicted by the nomograms and the actual survival data. Survival curves indicated that risk stratification could differentiate OS and DFS. CONCLUSIONS: This study developed novel and practical nomograms for individual prediction of DFS and OS in elderly BC patients. These nomograms can predict 3- and 5-year OS as well as DFS in the elderly BC patient population, thereby enabling personalized risk assessment and risk-based therapy.

Hepatotoxic assessment in a microphysiological system: Simulation of the drug absorption and toxic process after an overdosed acetaminophen on intestinal-liver-on-chip.

To compensate the limitation of animal models, new models were proposed for drug safety evaluation to refine and reduce existing models. To mimic drug absorption and metabolism and predict toxicokinetic and toxic effects in an in vitro intestinal-liver microphysiological system (MPS), we constructed an intestinal-liver-on-chip and detected the acute liver injury process after an overdose of acetaminophen (APAP). Caco-2 and HT29-MTX-E12 cell lines were utilized to establish intestinal equivalents, along with HepG2, HUVEC-T1, and THP-1 induced by PMA and human hepatic stellate cell to establish liver equivalents. The APAP concentration was determined using high-performance liquid chromatography, and the toxicokinetic parameters were fitted using the non-compartmental analysis method by Phoenix. Changes in liver injury biomarkers aspartate aminotransferase and alanine aminotransferase, and liver function marker albumin indicated that the short-term culture of the two organs-on-chip model was stable for 4 days. Reactive oxygen species signaling was enhanced after APAP administration, along with decreased mitochondrial membrane potential, activated caspase-3, and enhanced p53 signaling, indicating a toxic response induced by APAP overdose. In the gut-liver MPS model, we fitted the toxicokinetic parameters and simulated the hepatotoxicity procedure following an APAP overdose, which will facilitate the organ-on-chips application in drug toxicity assays.

Achieving Ultra-Narrow-Band Deep-Red Electroluminescence By a Soliton-type Dye Squaraine.

Due to the soliton-like electronic structural characteristics, cyanine dyes typically exhibit spectral behaviors such as large molar extinction coefficients, narrow spectra, and high fluorescence efficiency. However, their extensive applications as emitters in electroluminescence are largely ignored due to their serious emission quenching in the aggregation state. Herein, it is reported a squaraine dye (a type of cyanine) SQPhEt. At different solution concentrations, the unusual decrease in full-width at half-maxima (FWHM) with increasing Stokes shift indicates the fluorescence quenching of SQPhEt in the aggregated state is because of the strong self-absorption effect. A sensitized device structure can help to reduce the doping concentration of dye, which can effectively suppress self-absorption. Benefitting from the large molar extinction coefficient of SQPhEt, even at low doping concentrations of 0.1 wt%, efficient Förster energy transfer can be achieved. The corresponding spin-coating sensitized device based on SQPhEt as the dopant exhibits favorable deep-red emission at 668 nm with a small FWHM of 0.10 eV.

Identification of the tumor metastasis-related tumor subgroups overexpressed NENF in triple-negative breast cancer by single-cell transcriptomics.

Tumor metastasis is a continuous and dynamic process and is a major cause of tumor-related death in triple-negative breast cancer. However, this biological process remains largely unknown in triple-negative breast cancer. The emergence of single-cell sequencing enables a deeper understanding of the tumor microenvironment and provides a new strategy for discovering the potential mechanism of tumor metastasis. Herein, we integrated the single-cell expression profiling of primary and metastatic triple-negative breast cancer by Seurat package. Nine tumor cell subgroups were identified. Enrichment analysis suggested tumor subgroups (C0, C4) were associated with tumor metastasis with poor prognosis in TNBC. Weighted gene co-expression network was constructed and identified NENF was a metastasis-related gene. Subsequently, RT-qPCR, Immunohistochemistry, and western blot confirmed NENF is highly expressed in TNBC tissues. And cell function assays indicated NENF promote cell invasion and migration through regulating EMT in TNBC. Finally, TIDE and Connectivity Map database suggest the candidate drugs for targeting NENF. In conclusion, our findings provide a new insight into the progression and metastasis of TNBC and uncover NENF may be a prognostic biomarker and potential therapy targets.

A novel synthesis method of medium- and long-chain triglyceride lipids from rubber seed oil catalyzed by enzymatic interesterification and its metabolism mechanism.

Medium- and long-chain triglyceride (MLCT) is a striking structural lipid for the supply of energy and essential fatty free acids (FFAs) in the food field. This study aimed to prepare MLCT by enzymatic interesterification of rubber seed oil (RSO) and medium-chain triglyceride (MCT). Fortunately, the conversion of synthesized MLCT could reach 75.4% by the catalysis of Novozym 40086 (7 wt% to MCT) at a temperature of 40 °C with the substrate mole ratio of 1 : 0.7 (RSO : MCT). The as-synthesized MLCT contained unsaturated fatty acid (USFA, 50.13%) at the sn-2 position and exhibited superior performance on the acid value, peroxide value and iodine value in contrast to grade III soybean oil. Moreover, it exhibited the simultaneous release of LCFAs and MCFAs, extremely facilitating the reduction of body weight gain and control of the level of lipids in the blood. Finally, the preferred hepatic metabolism process of the obtained MLCT was proven to be the main cause of the reduced body weight and improved lipid levels by the in vivo deposition experiments. Therefore, our study suggested that the outstanding performance of the MLCT synthesized by RSO in foods as functional lipids.

A Click Chemistry Strategy Toward Spin-Polarized Transition-Metal Single Site Catalysts for Dynamic Probing of Sulfur Redox Electrocatalysis.

Catalytic conversion of lithium polysulfides (LiPSs) is a crucial approach to enhance the redox kinetics and suppress the shuttle effect in lithium-sulfur (Li-S) batteries. However, the roles of a typical heterogenous catalyst cannot be easily identified due to its structural complexity. Compared with the distinct sites of single atom catalysts (SACs), each active site of single site catalysts (SSCs) is identical and uniform in their spatial energy, binding mode, and coordination sphere, etc. Benefiting from the well-defined structure, iron phthalocyanine (FePc) is covalently clicked onto CuO nanosheet to prepare low spin-state Fe SSCs as the model catalyst for Li-S electrochemistry. The periodic polarizability evolution of Fe-N bonding is probed during sulfur redox reaction by in situ Raman spectra. Theoretical analysis shows the decreased d-band center gap of Fe (Δd) and delocalization of dxz/dyz after the axial click confinement. Consequently, Li-S batteries with Fe SSCs exhibit a capacity decay rate of 0.029% per cycle at 2 C. The universality of this methodological approach is demonstrated by a series of M SSCs (M = Mn, Co, and Ni) with similar variation of electronic configuration. This work provides guidance for the design of efficient electrocatalysis in Li-S batteries.