Asymmetric dearomatization of benzyl 1-naphthyl ethers via [1,3] O-to-C rearrangement.

A catalytic asymmetric dearomatization reaction of benzyl 1-naphthyl ethers accelerated by a chiral N,N'-dioxide/Co(II) complex is disclosed. The reaction proceeds via an enantioselective [1,3] O-to-C rearrangement through a tight ion-pair pathway, providing a wide array of α-naphthalenone derivatives bearing an all-carbon quaternary center in high yields with excellent ee values.

Unraveling Mechanism for Microstructure Engineering toward High-Capacity Nickel-Rich Cathode Materials.

Microstructural engineering on nickel-rich layered oxide (NRLO) cathode materials is considered a promising approach to increase both the capacity and lifespan of lithium-ion batteries by introducing high valence-state elements. However, rational regulation on NRLO microstructures based on a deep understanding of its capacity enhancement mechanism remains challenging. Herein for the first time, it is demonstrated that an increase of 14 mAh g-1 in reversible capacity at the first cycle can be achieved via tailoring the micro and nano structure of NRLO through introducing tungsten. Aberration-corrected scanning transmission electron microscopy (STEM) characterization reveals that the formation of a modified microstructure featured as coherent spinel twin boundaries. Theoretical modeling and electrochemical investigations further demonstrate that the capacity increase mechanism is related to such coherent spinel twin boundaries, which can lower the Li+ diffusion barrier and thus allow more Li+ to participate in deeper phase transitions. Meanwhile, the surface and grain boundaries of NRLOs are found to be modified by generating a dense and uniform LiWxOy phase, which further extends its cycle life by reducing side reactions with electrolytes. This work enables a comprehensive understanding of the capacity-increased mechanism and endows the remarkable potential of microstructural engineering for capacity- and lifespan-increased NRLOs.

Lipidomics reveals the serum profiles of pediatric allergic rhinitis and its severity.

Allergic rhinitis (AR) is a prevalent upper airway chronic inflammatory disease in children worldwide. The role of bioactive lipids in the regulation of AR has been recognized, but the underlying serum lipidomic basis of its pathology remains unclear. We utilized ultra-performance liquid chromatography (UPLC)-Q-Exactive Orbitrap/mass spectrometry (MS) to investigate the serum lipidomic profiles of children with AR. The lipidomic analysis identified 42 lipids that were differentially expressed (p < 0.05, fold change > 2) between the AR (n = 75) and normal control groups (n = 44). Specifically, the serum levels of diacylglycerol (DG), triacylglycerol (TG), fatty acid (FA), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine, phosphatidyl-ethanolamine, and cardiolipins were significantly higher in the AR group. The diagnostic potential of the identified lipids was further evaluated using receiver operating characteristic curve analysis. The analysis revealed that five lipids, including FA 30:7, LPC O-18:1, LPC 18:0, LPC 16:0, and DG 34:0, had area under the curve values greater than 0.9 (p < 0.05). Furthermore, serum levels of IgE and IL-33, markers of AR severity, were found to have a significant positive correlation (p < 0.05) with DGs, LPCs, TGs, and FAs in AR patients. This study revealed the lipid disorders associated with AR and its severity, providing new insights into the pathological process of AR.

Sludge reduction and hydrogen production in a microbial photoelectrochemical cell with a g-C3N4/CQDs/BiOBr composite photocathode.

Hydrogen (H2) remains a pivotal clean energy source, and the emergence of Solar-powered Microbial Photoelectrochemical Cells (MPECs) presents promising avenues for H2 production while concurrently aiding organic matter degradation. This study introduces an MPEC system employing a g-C3N4/CQDs/BiOBr photocathode and a bioanode, successfully achieving simultaneous H2 production and sludge reduction. The research highlights the effective formation of a Z-type heterojunction in the g-C3N4/CQDs/BiOBr photocathode, substantially enhancing the photocurrent response under light conditions. Operating at - 0.4 V versus RHE, it demonstrated a current density of - 3.25 mA·cm-2, surpassing that of g-C3N4/BiOBr (-2.25 mA·cm-2) by 1.4 times and g-C3N4 (-2.04 mA·cm-2) by 1.6 times. When subjected to visible light irradiation and a 0.8 V applied bias voltage, the MPEC system achieved a current density of 1.0 mA·cm-2. The cumulative H2 production of the MPEC system reached 8.9 mL, averaging a production rate of 0.13 mL·h-1. In the anode chamber, the degradation rates of total chemical oxygen demand (TCOD), soluble chemical oxygen demand (SCOD), total suspended solids (TSS), volatile suspended solids (VSS), proteins, polysaccharides, and volatile fatty acids (VFA) in the sludge were recorded at 57.18%, 82.64%, 64.98%, 86.39%, 42.81%, 67.34%, and 29.01%, respectively.

Investigating the effects of dexamethasone on pulmonary surfactant lipids based on lipidomics studies.

Dexamethasone, a glucocorticoid commonly used in pediatric patients, has potent anti-inflammatory and immunosuppressive properties. However, it is associated with side effects such as reduced lung function and decreased immunity. Pulmonary surfactant lipids are closely linked to lung disease and play a role in reducing surface tension, immune response and antiviral activity. The dysregulation of lipid metabolism is closely associated with lung disease. Hence, untargeted lipidomics may be instrumental in elucidating the effects of dexamethasone on pulmonary surfactant lipids. We obtained surfactant lipid samples from the bronchoalveolar lavage fluid of young mice injected subcutaneously with dexamethasone and conducted a comprehensive lipidomic analysis, comparing them with a control group. We observed a decrease in lipids, such as phosphatidylcholine, phosphatidylglycerol and phosphatidylethanolamine, and an increase in ceramide, fatty acid, diacylglycerol and monoglyceride, which may impact lung health. This study revealed the influence of dexamethasone on pulmonary surfactant lipids, offering new insights into adverse reactions in clinical settings.

Theoretical insights on highly efficient X-shaped near-infrared thermal activation delayed fluorescence emitter.

The near-infrared (NIR) thermally activated delayed fluorescence (TADF) molecules hold practical application value in various fields, including biological imaging, anti-counterfeiting, sensors, telemedicine, photomicrography, and night vision display. These molecules have emerged as a significant development direction in organic electroluminescent devices, offering exciting possibilities for future technological advancements. Despite the remarkable potential of NIR-TADF molecules in various applications, the development of molecules that exhibit both long-wavelength emission and high efficiency remains a significant challenge. Herein, based on T-type and Y-type TADF molecules BCN-TPA and ECN-TPA, a novel X-type TADF molecule X-ECN-TPA is theoretically designed through a molecular fusion strategy. Utilizing first-principles calculations and the thermal vibration correlation function (TVCF) method, the photophysical properties and luminescent mechanisms of these three molecules in both solvent and solid (doped films) are revealed. A comparison of the luminescent properties of isomeric BCN-TPA and ECN-TPA shows that the enhanced luminescence efficiency of BCN-TPA in the solid states is attributed to higher radiative rates and lower non-radiative rates. Furthermore, compared to BCN-TPA and ECN-TPA, X-ECN-TPA exhibits significant conjugation extension, resulting in a pronounced redshift, reaching 831 nm and 813 nm in solvent and solid states, respectively. Importantly, molecular fusion significantly increases the transition dipole moment density between the donor and acceptor, leading to a substantial increase in radiative transition rates. Additionally, molecular fusion effectively reduces the energy gap between the first singlet excited state (S1) and the first triplet excited state (T1), facilitating the improvement of the reverse intersystem crossing (RISC) process. In addition, the calculation of Marcus formula shows that the triplet energy transfer from CBP to BCN-TPA, ECN-TPA and X-ECN-TPA is very effective. This work not only designs a novel efficient NIR-TADF molecule but also proposes a strategy for designing efficient NIR-TADF molecules. This principle offers unique insights for optimizing traditional molecular frameworks, opening up new possibilities for future advancements.

Stable Axially Chiral Cyclohexylidenes from Catalytic Asymmetric Knoevenagel Condensation.

Axially chiral cycloalkylidenes are interesting but less developed axially chiral molecules. Here, a bispidine-based chiral amine catalytic system was developed to promote efficiently the asymmetric Knoevenagel condensation of N-protected oxindoles and benzofuranones with 4-substituted cyclohexanones. A variety of alkylidenecycloalkanes with stable axial chirality were obtained in good yields and fairly good er (enantiomeric ratio). Based on the absolute configuration determination of product and DFT calculations, a possible mechanism of stereoselective induction was proposed.

Cucumber PGIP2 is involved in resistance to gray mold disease.

Polygalacturonase inhibitor protein (PGIP) restricts fungal growth and colonization and functions in plant immunity. Gray mold in cucumber is a common fungal disease caused by Botrytis cinerea, and is widespread and difficult to control in cucumber (Cucumis sativus L.) production. In this study, Cucumis sativus polygalacturonase-inhibiting protein 2 (CsPGIP2) was found to be upregulated in response to gray mold in cucumber. CsPGIP2 was detected in the endoplasmic reticulum, cell membrane, and cell wall after transient transformation of protoplasts and tobacco. A possible interaction between Botrytis cinerea polygalacturonase 3 (BcPG3) and CsPGIP2 was supported by protein interaction prediction and BiFC analysis. Transgenic Arabidopsis plants expressing CsPGIP2 were constructed and exhibited smaller areas of gray mold infection compared to wild type (WT) plants after simultaneous inoculation. Evans blue dye (EBD) confirmed greater damage for WT plants, with more intense dyeing than for the transgenic Arabidopsis. Interestingly, compared to WT, transgenic Arabidopsis exhibited higher superoxide dismutase (AtSOD1) expression, antioxidant enzyme activities, lignin content, net photosynthetic rate (Pn), and photochemical activity. Our results suggest that CsPGIP2 stimulates a variety of plant defense mechanisms to enhance transgenic Arabidopsis resistance against gray mold disease.

Application of Online-Offline Teaching Combined with SimMan 3G Simulation Teaching Model in Critical Illness Teaching in a Department of Cardiology.

Objective: To explore the effectiveness of online-offline teaching combined with SimMan 3G simulation teaching in improving theoretical knowledge and practical skills for critical illnesses in cardiology among undergraduate students. Methods: This randomized controlled trial compared traditional bedside teaching (control group, n=120) with an innovative approach combining online education and SimMan 3G simulation teaching (experimental group, n=120) among 240 undergraduate clinical medicine students. The control group received traditional bedside teaching, while the experimental Group received a combination of online teaching plus a SimMan 3G simulation teaching. Subsequently, the theoretical and clinical practice scores and the students' satisfaction scores about the teaching methods and teaching effects were collected and analyzed. Results: The experimental group demonstrated a statistically significant improvement in both theoretical (89.42±11.28 vs. 76.49±17.42) and clinical practice scores (18.04±4.32 vs. 15.33±3.94) compared to the control group, alongside a higher satisfaction score. Conclusions: The integration of online-offline teaching with SimMan 3G simulation teaching offers a promising model for enhancing cardiology education, suggesting a valuable direction for curriculum development in medical training programs.

Factors affecting the oral health of patients on maintenance hemodialysis and recommendations for standardized nursing care: a multicenter study.

OBJECTIVE: To determine the oral health status of patients on maintenance hemodialysis (MHD) and to identify the factors influencing their oral health. METHODS: This observational study included 1,186 patients with chronic kidney disease who received MHD across 33 hospitals in China. The patients were recruited for a questionnaire survey between April and August 2023 at Beijing Chaoyang Hospital using stratified sampling. Data collection tools included the General Information Questionnaire for Maintenance Hemodialysis Patients, the Oral Health Assessment Tool, the Pittsburgh Sleep Quality Index, and the Hospital Anxiety and Depression Scale. Spearman's rank correlation coefficients were used to assess the relationships between the oral health of patients on MHD and continuous variables such as sleep quality and emotional status. Multiple linear regression analysis was employed to explore the relationship between oral health and various variables. RESULTS: The oral health scores of the patients ranged from 8 to 22, with a mean score of 12.54 ± 2.63. The final model of the multiple linear regression analysis indicated a goodness of fit of 22.19%. Independent factors affecting the oral health of patients included smoking, the proportion of medical expenses, water consumption, sleep quality, and anxiety scores (all P < 0.05). High levels of smoking, substantial medical expenses, poor sleep quality, and elevated anxiety scores were risk factors for poor oral health (all P < 0.05). Adequate daily water intake served as a protective factor for oral health (P < 0.05). CONCLUSION: This study proposes targeted interventions to enhance the management and improvement of oral health in patients on hemodialysis, aiming to provide highly personalised and effective oral health care. These interventions are expected to improve oral health outcomes in future clinical practice.

Role of Bridging Groups in Regulating the Luminescence and Charge Transfer Properties of Thermally Activated Delayed Fluorescence Molecules: A Theoretical Perspective.

Organic emitters with a simultaneous combination of aggregation-induced emission (AIE) and thermally activated delayed fluorescence (TADF) characteristics are in great demand due to their excellent comprehensive performances toward efficient organic light-emitting diodes (OLEDs), biomedical imaging, and the telecommunications field. However, the development of efficient AIE-TADF materials remains a substantial challenge. In this work, light-emitting properties of two AIE-TADF molecules with different bridging groups ICz-BP and ICz-DPS are theoretically investigated in the solid state with the combined quantum mechanics/molecular mechanics (QM/MM) method and the thermal vibration correlation function (TVCF) theory. The research indicates that the C═O bridging bond in ICz-BP is more favorable than the S═O bridging bond in ICz-DPS for enhancing the planarity of the acceptor, increasing conjugation, and thereby elevating the transition dipole moment density. Simultaneously, the stacking pattern of ICz-BP in the solid facilitates a reduction in energy gap between S1 and T1 (ΔEST), achieving rapid reverse intersystem crossing rate (kRISC). Furthermore, compared to toluene, the stacking patterns of ICz-BP and ICz-DPS in the solid effectively suppress the out-of-plane wagging vibration of the acceptor, thereby inhibiting the loss of nonradiative energy in the excited state and realizing aggregation-induced emission. Moreover, the charge transport properties of both electrons and holes in ICz-BP are found to be higher than the corresponding rates in ICz-DPS, attributed to the smaller internal reorganization energy of ICz-BP in the solid state. Additionally, the calculations reveal a more balanced charge transport characteristic in ICz-BP, contributing to efficient exciton recombination and emission and ultimately mitigating efficiency roll-off. Based on these computational results, we aim to unveil the relationship between molecular structure and light-emitting properties, aiding in the design and development of efficient AIE-TADF devices.

Thermally stable Ni foam-supported inverse CeAlOx/Ni ensemble as an active structured catalyst for CO2 hydrogenation to methane.

Nickel is the most widely used inexpensive active metal center of the heterogeneous catalysts for CO2 hydrogenation to methane. However, Ni-based catalysts suffer from severe deactivation in CO2 methanation reaction due to the irreversible sintering and coke deposition caused by the inevitable localized hotspots generated during the vigorously exothermic reaction. Herein, we demonstrate the inverse CeAlOx/Ni composite constructed on the Ni-foam structure support realizes remarkable CO2 methanation catalytic activity and stability in a wide operation temperature range from 240 to 600 °C. Significantly, CeAlOx/Ni/Ni-foam catalyst maintains its initial activity after seven drastic heating-cooling cycles from RT to 240 to 600 °C. Meanwhile, the structure catalyst also shows water resistance and long-term stability under reaction condition. The promising thermal stability and water-resistance of CeAlOx/Ni/Ni-foam originate from the excellent heat and mass transport efficiency which eliminates local hotspots and the formation of Ni-foam stabilized CeAlOx/Ni inverse composites which effectively anchored the active species and prevents carbon deposition from CH4 decomposition.

Theoretical Insights into the Photophysical Properties of 4CzIPN Doped in Different Hosts: A Multiscale Study.

As a typical thermally activated delayed fluorescence (TADF) emitter with green emission, 4CzIPN has attracted much attention recently. Most studies indicated that 4CzIPN doped in different hosts presented different performances; thus, the hosts should have an obvious influence on its photophysical properties. Herein, the influence of four kinds of hosts, including m-CzPym, m-CzTrz, p-CzPym, and p-CzTrz, on the photophysical properties of 4CzIPN is investigated. Molecular dynamics simulations were performed to simulate the host-guest conformations, and the photophysical properties were studied using the combined quantum mechanics/molecular mechanics method coupled with the thermal-vibration correlation function method. It is found that 4CzIPN in doped films has larger transition dipole moments and spin-orbital coupling constants compared to that in nondoped films. Faster radiative decay, intersystem crossing rates, and higher fluorescence efficiency could be obtained in doped films. Our work helps to better understand the photophysical properties of 4CzIPN in doped films and may favor the design of new hosts.

Synergistic Effects of Amine Functional Groups and Enriched-Atomic-Iron Sites in Carbon Dots for Industrial-Current-Density CO2 Electroreduction.

Metal phthalocyanine molecules with Me-N4 centers have shown promise in electrocatalytic CO2 reduction (eCO2R) for CO generation. However, iron phthalocyanine (FePc) is an exception, exhibiting negligible eCO2R activity due to a higher CO2 to *COOH conversion barrier and stronger *CO binding energy. Here, amine functional groups onto atomic-Fe-rich carbon dots (Af-Fe-CDs) are introduced via a one-step solvothermal molecule fusion approach. Af-Fe-CDs feature well-defined Fe-N4 active sites and an impressive Fe loading (up to 8.5 wt%). The synergistic effect between Fe-N4 active centers and electron-donating amine functional groups in Af-Fe-CDs yielded outstanding CO2-to-CO conversion performance. At industrial-relevant current densities exceeding 400 mA cm-2 in a flow cell, Af-Fe-CDs achieved >92% selectivity, surpassing state-of-the-art CO2-to-CO electrocatalysts. The in situ electrochemical FTIR characterization combined with theoretical calculations elucidated that Fe-N4 integration with amine functional groups in Af-Fe-CDs significantly reduced energy barriers for *COOH intermediate formation and *CO desorption, enhancing eCO2R efficiency. The proposed synergistic effect offers a promising avenue for high-efficiency catalysts with elevated atomic-metal loadings.

Water-enabling strategies for asymmetric catalysis.

Water possesses unique advantages, including abundance, environmental friendliness and mild effects. Undoubtedly, it is an ideal solvent or reagent in chemical syntheses. Water also shows unique abilities in catalytic asymmetric synthesis. It can accelerate reaction rates, improve diastereo- or enantioselectivities, initiate reactions, diversify chemo, diastereo- or enantioselectivities through various effects (hydrophobic, hydrogen bonding, protonation). Several reviews have demonstrated the positive effects of water in asymmetric synthesis. In this review, we summarize water-enabling strategies in the last decade, and focus on advances which reveal how water affects a reaction.

Modulation of luminescence properties of circularly polarized thermally activated delayed fluorescence molecules with axial chirality by donor engineering.

Multifunctional thermally activated delayed fluorescence (TADF) materials are currently a trending research subject for luminescence layer materials of organic light-emitting diodes (OLEDs). Among these, circularly polarized thermally activated delayed fluorescence (CP-TADF) materials have the advantage of being able to directly achieve highly efficient circularly polarized luminescence (CPL). The simultaneous integration of outstanding luminescence efficiency and excellent luminescence asymmetry factor (glum) is a major constraint for the development of CP-TADF materials. Therefore, on the basis of first-principles calculations in conjunction with the thermal vibration correlation function (TVCF) method, we study CP-TADF molecules with different donors to explore the feasibility of using the donor substitution strategy for optimizing the CPL and TADF properties. The results indicate that molecules with the phenothiazine (PTZ) unit as the donor possess small energy difference, a great spin-orbit coupling constant and a rapid reverse intersystem crossing rate, which endow them with remarkable TADF features. Meanwhile, compared with the reported molecules, the three designed molecules exhibit better CPL properties with higher glum values. Effective molecular design strategies by donor engineering to modulate the CPL and TADF properties are theoretically proposed. Our findings reveal the relationship between molecular structures and luminescence properties of CP-TADF molecules and further provide theoretical design strategies for optimizing the CPL and TADF properties.

Transposable elements impact the population divergence of rice blast fungus Magnaporthe oryzae.

Dynamic transposition of transposable elements (TEs) in fungal pathogens has significant impact on genome stability, gene expression, and virulence to the host. In Magnaporthe oryzae, genome plasticity resulting from TE insertion is a major driving force leading to the rapid evolution and diversification of this fungus. Despite their importance in M. oryzae population evolution and divergence, our understanding of TEs in this context remains limited. Here, we conducted a genome-wide analysis of TE transposition dynamics in the 11 most abundant TE families in M. oryzae populations. Our results show that these TEs have specifically expanded in recently isolated M. oryzae rice populations, with the presence/absence polymorphism of TE insertions highly concordant with population divergence on Geng/Japonica and Xian/Indica rice cultivars. Notably, the genes targeted by clade-specific TEs showed clade-specific expression patterns and are involved in the pathogenic process, suggesting a transcriptional regulation of TEs on targeted genes. Our study provides a comprehensive analysis of TEs in M. oryzae populations and demonstrates a crucial role of recent TE bursts in adaptive evolution and diversification of the M. oryzae rice-infecting lineage. IMPORTANCE: Magnaporthe oryzae is the causal agent of the destructive blast disease, which caused massive loss of yield annually worldwide. The fungus diverged into distinct clades during adaptation toward the two rice subspecies, Xian/Indica and Geng/Japonica. Although the role of TEs in the adaptive evolution was well established, mechanisms underlying how TEs promote the population divergence of M. oryzae remain largely unknown. In this study, we reported that TEs shape the population divergence of M. oryzae by differentially regulating gene expression between Xian/Indica-infecting and Geng/Japonica-infecting populations. Our results revealed a TE insertion-mediated gene expression adaption that led to the divergence of M. oryzae population infecting different rice subspecies.

Integrated network pharmacology, molecular docking, and lipidomics to reveal the regulatory effect of Qingxuan Zhike granules on lipid metabolism in lipopolysaccharide-induced acute lung injury.

Qingxuan Zhike granules (QXZKG), a traditional Chinese patent medication, has shown therapeutic potential against acute lung injury (ALI). However, the precise mechanism underlying its lung-protective effects requires further investigation. In this study, integrated network pharmacology, molecular docking, and lipidomics were used to elucidate QXZKG's regulatory effect on lipid metabolism in lipopolysaccharide-induced ALI. Animal experiments were conducted to substantiate the efficacy of QXZKG in reducing pro-inflammatory cytokines and mitigating pulmonary pathology. Network pharmacology analysis identified 145 active compounds that directly targeted 119 primary targets of QXZKG against ALI. Gene Ontology function analysis emphasized the roles of lipid metabolism and mitogen-activated protein kinase (MAPK) cascade as crucial biological processes. The MAPK1 protein exhibited promising affinities for naringenin, luteolin, and kaempferol. Lipidomic analysis revealed that 12 lipids showed significant restoration following QXZKG treatment (p < 0.05, FC >1.2 or <0.83). Specifically, DG 38:4, DG 40:7, PC O-40:8, TG 18:1_18:3_22:6, PI 18:2_20:4, FA 16:3, FA 20:3, FA 20:4, FA 22:5, and FA 24:5 were downregulated, while Cer 18:0;2O/24:0 and SM 36:1;2O/34:5 were upregulated in the QXZKG versus model groups. This study enhances our understanding of the active compounds and targets of QXZKG, as well as the potential of lipid metabolism in the treatment of ALI.

New techniques to identify the tissue of origin for cancer of unknown primary in the era of precision medicine: progress and challenges.

Despite a standardized diagnostic examination, cancer of unknown primary (CUP) is a rare metastatic malignancy with an unidentified tissue of origin (TOO). Patients diagnosed with CUP are typically treated with empiric chemotherapy, although their prognosis is worse than those with metastatic cancer of a known origin. TOO identification of CUP has been employed in precision medicine, and subsequent site-specific therapy is clinically helpful. For example, molecular profiling, including genomic profiling, gene expression profiling, epigenetics and proteins, has facilitated TOO identification. Moreover, machine learning has improved identification accuracy, and non-invasive methods, such as liquid biopsy and image omics, are gaining momentum. However, the heterogeneity in prediction accuracy, sample requirements and technical fundamentals among the various techniques is noteworthy. Accordingly, we systematically reviewed the development and limitations of novel TOO identification methods, compared their pros and cons and assessed their potential clinical usefulness. Our study may help patients shift from empirical to customized care and improve their prognoses.

A novel therapeutic approach to modulate the inflammatory cascade: A timely exogenous local inflammatory response attenuates the sepsis-induced cytokine storm.

BACKGROUND: The emergence of severe sepsis is contingent upon the occurrence of a cytokine storm (CS), a multifaceted process intricately entwined with the temporal dimension, thereby rendering the infection response remarkably intricate. Consequently, it becomes imperative to discern and accurately identify the optimal timing for interventions, predicated upon the dynamic timeline of inflammatory changes. Moreover, the administration of exogenous low-dose pro-inflammatory agents has exhibited the potential to impede the relentless progression of the inflammatory cascade. Hence, the present study aims to scrutinize the impact of exogenous Local Inflammatory Response (eLIR) on the body surface in the context of the inflammatory cascade during sepsis, within a temporal framework, with a particular emphasis on the point of exacerbation of inflammation. METHODS: Rats were induced sterile sepsis by intraperitoneal injection of zymosan (ZY) at an appropriate dosage. The temporal progression of inflammatory changes and eLIR effects were described based on the trend of serum crucial inflammatory cytokines, tring to quest time-point of inflammatory aggravation in sepsis. Then, the varying degrees of surface inflammation caused by eLIR on this time point leading to the final effects on the inflammatory cascade response were explored. In addition, given the authentic pathological progression of sepsis, further observation was conducted on the impact of another intervention timing of eLIR on the inflammatory cascade. The survival rate was measured. Serum and organ related inflammatory cytokines were detected, and organ histopathology was investigated. RESULTS: In present study, a dosage of 600 mg/kg ZY was found to be optimal for the sterile sepsis model. Initiating eLIR 6 h prior to ZY injection, the maximum effect point of eLIR could be precisely align with the inflammatory aggravation point of sterile sepsis. Initiating eLIR at this time, 3 sessions of eLIR were found to be more effective than 1 or 2 sessions in mitigating inflammatory responses during the initial stage of inflammation and the peak of inflammation. Notably, the findings also suggested that this intervention improve survival rate. In addition, the anti-inflammatory efficacy has been substantially diminished by the prompt initiation of 3 sessions of eLIR immediately after ZY injection at the onset of sepsis. Similarly, the current findings did not demonstrate a statistically significant enhancement in survival rates with eLIR at this time point. CONCLUSIONS: Compared with the initial stage of inflammation, low-scale inflammation caused by a certain intensity of eLIR (3 sessions) on the body surface can more effectively pry the inflammation aggravation time-point, thereby shifting the pro-inflammatory to anti-inflammatory milieu, impeding the disproportionate cytokines release in inflammatory diseases, slowing down the inflammatory cascade, and improving the survival rate of sepsis.