Ultrafast Formation of a Delocalized Triplet-Excited State in an Epigenetically Modified DNA Duplex under Direct UV Excitation.

Epigenetic modifications impart important functionality to nucleic acids during gene expression but may increase the risk of photoinduced gene mutations. Thus, it is crucial to understand how these modifications affect the photostability of duplex DNA. In this work, the ultrafast formation (<20 ps) of a delocalized triplet charge transfer (CT) state spreading over two stacked neighboring nucleobases after direct UV excitation is demonstrated in a DNA duplex, d(G5fC)9•d(G5fC)9, made of alternating guanine (G) and 5-formylcytosine (5fC) nucleobases. The triplet yield is estimated to be 8 ± 3%, and the lifetime of the triplet CT state is 256 ± 22 ns, indicating that epigenetic modifications dramatically alter the excited state dynamics of duplex DNA and may enhance triplet state-induced photochemistry.

The identification of signature genes and their relationship with immune cell infiltration in age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is a prevalent source of visual impairment among the elderly population, and its incidence has risen in tandem with the increasing longevity of humans. Despite the progress made with anti-VEGF therapy, clinical outcomes have proven to be unsatisfactory. METHOD: We obtained differentially expressed genes (DEGs) of AMD patients and healthy controls from the GEO database. GO and KEGG analyses were used to enrich the DEGs. Weighted gene coexpression network analysis (WGCNA) was used to identify modules related to AMD. SVM, random forest, and least absolute shrinkage and selection operator (LASSO) were employed to screen hub genes. Gene set enrichment analysis (GSEA) was used to explore the pathways in which these hub genes were enriched. CIBERSORT was utilized to analyze the relationship between the hub genes and immune cell infiltration. Finally, Western blotting and RT‒PCR were used to explore the expression of hub genes in AMD mice. RESULTS: We screened 1084 DEGs in GSE29801, of which 496 genes were upregulated. These 1084 DEGs were introduced into the WGCNA, and 94 genes related to AMD were obtained. Seventy-nine overlapping genes were obtained by the Venn plot. These 79 genes were introduced into three machine-learning methods to screen the hub genes, and the genes identified by the three methods were TNC, FAP, SREBF1, and TGF-ß2. We verified their diagnostic function in the GSE29801 and GSE103060 datasets. Then, the hub gene co-enrichment pathways were obtained by GO and KEGG analyses. CIBERSORT analysis showed that these hub genes were associated with immune cell infiltration. Finally, we found increased expression of TNC, FAP, SREBF1, and TGF-ß2 mRNA and protein in the retinas of AMD mice. CONCLUSION: We found that four hub genes, namely, FAP, TGF-ß2, SREBF1, and TNC, have diagnostic significance in patients with AMD and are related to immune cell infiltration. Finally, we determined that the mRNA and protein expression of these hub genes was upregulated in the retinas of AMD mice.

Ultrafast spectroscopy study of DNA photophysics after proflavine intercalation.

Proflavine (PF), an acridine DNA intercalating agent, has been widespread applied as an anti-microbial and topical antiseptic agent due to its ability to suppress DNA replication. On the other hand, various studies show that PF intercalation to DNA can increase photogenotoxicity and has potential chances to induce carcinomas of skin appendages. However, the effects of PF intercalation on the photophysical and photochemical properties of DNA have not been sufficiently explored. In this study, the excited state dynamics of the PF intercalated d(GC)9 • d(GC)9 and d(AT)9 • d(AT)9 DNA duplex are investigated in an aqueous buffer solution. Under 267 nm excitation, we observed ultrafast charge transfer (CT) between PF and d(GC)9 • d(GC)9 duplex, generating a CT state with an order of magnitude longer lifetime compared to that of the intrinsic excited state reported for the d(GC)9 • d(GC)9 duplex. In contrast, no excited state interaction was detected between PF and d(AT)9 • d(AT)9. Nevertheless, a localized triplet state with a lifetime over 5 µs was identified in the PF-d(AT)9 • d(AT)9 duplex.

Dual Stimuli-Responsive [2]Rotaxanes with Tunable Vibration-Induced Emission and Switchable Circularly Polarized Luminescence.

Aiming at the construction of novel stimuli-responsive fluorescent system with precisely tunable emissions, the typical 9,14-diphenyl-9,14-dihydrodibenzo[a, c]phenazine (DPAC) luminogen with attractive vibration-induced emission (VIE) behavior has been introduced into [2]rotaxane as a stopper. Taking advantage of their unique dual stimuli-responsiveness towards solvent and anion, the resultant [2]rotaxanes reveal both tunable VIE and switchable circularly polarized luminescence (CPL). Attributed to the formation of mechanical bonds, DPAC-functionalized [2]rotaxanes display interesting VIE behaviors including white-light emission upon the addition of viscous solvent, as evaluated in detail by femtosecond transient absorption (TA) spectra. In addition, ascribed to the regulation of chirality information transmission through anion-induced motions of chiral wheel, the resolved chiral [2]rotaxanes reveal unique switchable CPL upon the addition of anion, leading to significant increase in the dissymmetry factors (glum ) values with excellent reversibility. Interestingly, upon doping the chiral [2]rotaxanes in stretchable polymer, the blend films reveal remarkable emission change from white light to light blue with significant 6.5-fold increase in glum values up to -0.035 under external tensile stresses. This work provides not only a new design strategy for developing molecular systems with fluorescent tunability but also a novel platform for the construction of smart chiral luminescent materials for practical use.

Unraveling the Origin of Multichannel Circularly Polarized Luminescence in a Pyrene-Functionalized Topologically Chiral [2]Catenane.

Mechanically interlocked molecules (MIMs) are promising platform for developing functionalized artificial molecular machines. The construction of chiral MIMs with appealing circularly polarized luminescence (CPL) properties has boosted their potential application in biomedicine and optical industry. However, there is currently little knowledge about the CPL emission mechanism as well as the emission dynamics of these related MIMs. Herein, we demonstrate that time-resolved circularly polarized luminescence (TRCPL) spectroscopy combined with transient absorption (TA) spectroscopy offers a feasible approach to elucidate the origins of CPL emission in pyrene-functionalized topologically chiral [2]catenane as well as in a series of pyrene-functionalized chiral molecules. For the first time, direct evidence differentiating the chiroptical signals originating from either topological (local state emission) or Euclidean chirality (excimer state emission) in these pyrene-functionalized chiral molecules has been discovered. Our work not only establishes a novel and ideal methodology to study CPL mechanism, but also provides a theoretical foundation for the rational design of novel chiral materials in the future.

A Carbon-Caged Rhodamine Generating Nitrosoperoxycarbonate for Photoimmunotherapy.

Photoimmunotherapy is a promising cancer treatment modality. While potent 1-e- oxidative species are known to induce immunogenic cell death (ICD), they are also associated with unspecific oxidation and collateral tissue damage. This difficulty may be addressed by post-generation radical reinforcement. Namely, non-oxidative radicals are first generated and subsequently activated into powerful oxidative radicals to induce ICD. Here, we developed a photo-triggered molecular donor (NPCD565) of nitrosoperoxycarbonate (ONOOCO2 -), the first of its class to our knowledge, and further evaluated its feasibility for immunotherapy. Upon irradiation of NPCD565 by light within a broad spectral region from ultraviolet to red, ONOOCO2 - is released along with a bright rhodamine dye (RD565), whose fluorescence is a reliable and convenient build-in reporter for the localization, kinetics, and dose of ONOOCO2 - generation. Upon photolysis of NPCD565 in 4T1 cells, damage-associated molecular patterns (DAMPs) indicative of ICD were observed and confirmed to exhibit immunogenicity by induced maturation of dendritic cells. In vivo studies with a bilateral tumor-bearing mouse model showcased the potent tumor-killing capability of NPCD565 of the primary tumors and growth suppression of the distant tumors. This work unveils the potent immunogenicity of ONOOCO2 -, and its donor (NPCD565) has broad potential for photo-immunotherapy of cancer.

Rigid and Photostable Shortwave Infrared Dye Absorbing/Emitting beyond 1200 nm for High-Contrast Multiplexed Imaging.

The shortwave infrared (SWIR) spectral region beyond 1200 nm offers optimal tissue penetration depth and has broad potential in diagnosis, therapy, and surgery. Here, we devised a novel class of fluorochromic scaffold, i.e., a tetra-benzannulated xanthenoid (EC7). EC7 absorbs/emits maximally at 1204/1290 nm in CH2Cl2 and exhibits an unparalleled molar absorptivity of 3.91 × 105 cm-1 M-1 and high transparency to light at 400-900 nm. It also exhibited high resistance toward both photobleaching and symmetry breaking due to its unique structural rigidity. It is feasible for in vivo bioimaging and particularly suitable to couple with the shorter-wavelength analogues for high-contrast multiplexing. High-contrast dual-channel intraoperative imaging of the hepatobiliary system and three-channel in vivo imaging of the intestine, the stomach, and the vasculature were showcased. EC7 is a benchmark fluorochrome for facile biomedical exploitation of the SWIR region beyond 1200 nm.

Identification of Alkoxy Radicals as Hydrogen Atom Transfer Agents in Ce-Catalyzed C-H Functionalization.

The intermediacy of alkoxy radicals in cerium-catalyzed C-H functionalization via H-atom abstraction has been unambiguously confirmed. Catalytically relevant Ce(IV)-alkoxide complexes have been synthesized and characterized by X-ray diffraction. Operando electron paramagnetic resonance and transient absorption spectroscopy experiments on isolated pentachloro Ce(IV) alkoxides identified alkoxy radicals as the sole heteroatom-centered radical species generated via ligand-to-metal charge transfer (LMCT) excitation. Alkoxy-radical-mediated hydrogen atom transfer (HAT) has been verified via kinetic analysis, density functional theory (DFT) calculations, and reactions under strictly chloride-free conditions. These experimental findings unambiguously establish the critical role of alkoxy radicals in Ce-LMCT catalysis and definitively preclude the involvement of chlorine radical. This study has also reinforced the necessity of a high relative ratio of alcohol vs Ce for the selective alkoxy-radical-mediated HAT, as seemingly trivial changes in the relative ratio of alcohol vs Ce can lead to drastically different mechanistic pathways. Importantly, the previously proposed chlorine radical-alcohol complex, postulated to explain alkoxy-radical-enabled selectivities in this system, has been examined under scrutiny and ruled out by regioselectivity studies, transient absorption experiments, and high-level calculations. Moreover, the peculiar selectivity of alkoxy radical generation in the LMCT homolysis of Ce(IV) heteroleptic complexes has been analyzed and back-electron transfer (BET) may have regulated the efficiency and selectivity for the formation of ligand-centered radicals.

Ultrafast Electron Transfer Dynamics of Organic Polymer Nanoparticles with Graphene Oxide.

We prepared organic polymer poly-3-hexylthiophene (p3ht) nanoparticles (NPs) and graphene oxide (GO)/reduced graphene oxide (RGO) composites p3ht NPs-GO/RGO by using the reprecipitation method. We demonstrated that GO/RGO could improve the ordering and planarity of p3ht chains as well as the formation of p3ht NPs, and confirmed the effects of GO/RGO on the fluorescence and carrier transport dynamics of p3ht NPs by using femtosecond fluorescence upconversion and transient absorption (TA) techniques. Ultrafast electron transfer (∼1 ps) between GO/RGO and p3ht NPs quenched the fluorescence of p3ht NPs, indicating excellent properties of p3ht NPs-GO/RGO as the charge transfer complexes. Efficient electron transfer may promote the applications of p3ht NPs-GO/RGO composites in organic polymer solar cells and photocatalysis. Moreover, RGO had stronger interfacial interactions and more matched conduction band energy levels with p3ht NPs than GO did, which implied that p3ht NPs-RGO might have greater application values than p3ht NPs-GO.

Ultrafast Förster resonance energy transfer from tyrosine to tryptophan in monellin: potential intrinsic spectroscopic ruler.

Ultrafast Förster Resonance Energy Transfer (FRET) between tyrosine (Tyr) and tryptophan (Trp) residues in the protein monellin has been investigated using picosecond and femtosecond time-resolved fluorescence spectroscopy. Decay associated spectra (DAS) and time-resolved emission spectra (TRES) taken with the different excitation wavelengths of 275, 290 and 295 nm were constructed via global analysis. At two of those three excitation loci (275 and 290 nm), earmarks of energy transfer from Tyr to Trp in monellin are seen, and particularly when the excitation is 275 nm, the energy transfer between Tyr and Trp clearly changes the signature emission DAS shape to that indicating excited state reaction (especially on the red side of fluorescence emission, near 380 nm). Those FRET signatures may overlap with the conventional signatory DAS in heterogeneous systems. When overlap and addition occur between FRET type DAS and "full positive" QSSQ (quasi-static self-quenching), mixed DAS shapes will emerge that still show "positive blue side and negative red sides", just with zero crossing shifted. In addition, excitation decay associated spectra (EDAS) taken with the different emission wavelengths of 330, 350 and 370 nm were constructed. In the study of protein dynamics, ultrafast FRET between Tyr and Trp could provide a basis for an intrinsic (non-perturbing) "spectroscopic ruler", potentially a powerful tool to detect even slight changes in protein structures.

Distinct doorway states lead to triplet excited state generation in epigenetic RNA nucleosides.

N 6-Hydroxymethyladenosine (hm6A) and N6-formyladenosine (f6A) are two important intermediates during the demethylation process of N6-methyladenosine (m6A), which has been proven to show epigenetic function in mRNA. However, there is no knowledge about how the chemical integrity and stability could be altered when these two nucleosides are exposed to ultraviolet (UV) radiation. Herein, we report the first study on excited state dynamics of hm6A and f6A in solutions by using femtosecond time-resolved spectroscopy and quantum chemistry calculations. Surprisingly, triplet excited species are clearly identified in both hm6A and f6A after UV excitation, which is in sharp contrast to the 10-3 level triplet yield of adenosine scaffolds. Moreover, the doorway states leading to triplet states are found to be an intramolecular charge transfer state and a lower-lying dark nπ* state in hm6A and f6A, respectively. These discoveries pave the way to further study their effects on RNA strands and provide insight for understanding RNA photochemistry.

Excitation localization/delocalization induced intramolecular singlet fission in cyclopentadithiophene-based quinoidal derivatives.

Two triplet excitons are generated through an ultrafast photophysical process, namely singlet fission (SF), providing a solution for efficient solar energy usage. In this work, we provide an effective guideline for designing SF materials by adjusting the planarity in cyclopentadithiophene (CPDT) derivatives. A practical strategy is proposed for tuning the quinoidal-biradical resonance structures by varying the electron push-pull groups of CPDTs for SF. The localized, delocalized, and intermediate charge-transfer excited configurations are predicted in the singlet excited state via computational simulations, which is further confirmed by ultrafast spectroscopy. Deduced from the potential energy surfaces in the low-lying excited states and transient absorption, the delocalized excited state is formed in 2.1 ps via postulated intramolecular SF in a polar solvent, followed by the ultrafast formation of the free triplet state with a lifetime of 6.8 ps. In comparison with different cross-conjugated chromophores, it is found that the increase in the charge separation could enhance the triplet-pair generation for iSF. We expect that by introducing symmetry-breaking modifications in the electronic configurations and adjusting the separation between the push-pull groups of CPDTs, it should be possible to prolong the duration of the free triplet state by preventing recombination within the triplet-pair excited configuration.

An ultrafast phototrigger of the Trp5CN-Trp motif in a ß-hairpin peptide.

Phototriggers are useful molecular tools to initiate reactions in enzymes by light for the purpose of photoenzymatic design and mechanistic investigations. Here, we incorporated the non-natural amino acid 5-cyanotryptophan (W5CN) in a polypeptide scaffold and resolved the photochemical reaction of the W5CN-W motif using femtosecond transient UV/Vis and mid-IR spectroscopy. We identified a marker band of ∼2037 cm-1 from the CN stretch of the electron transfer intermediate W5CN·- in the transient IR measurement and found UV/Vis spectroscopic evidence for the W·+ radical at 580 nm. Through kinetic analysis, we characterized that the charge separation between the excited W5CN and W occurs in 253 ps, with a charge-recombination lifetime of 862 ps. Our study highlights the potential use of the W5CN-W pair as an ultrafast phototrigger to initiate reactions in enzymes that are not light-sensitive, making downstream reactions accessible to femtosecond spectroscopic detection.

Resistance mechanisms and remediation potential of hexavalent chromium in Pseudomonas sp. strain AN-B15.

The understanding of bacterial resistance to hexavalent chromium [Cr(VI)] are crucial for the enhancement of Cr(VI)-polluted soil bioremediation. However, the mechanisms related to plant-associated bacteria remain largely unclear. In this study, we investigate the resistance mechanisms and remediation potential of Cr(VI) in a plant-associated strain, AN-B15. The results manifested that AN-B15 efficiently reduced Cr(VI) to soluble organo-Cr(III). Specifically, 84.3 % and 56.5 % of Cr(VI) was removed after 48 h in strain-inoculated solutions supplemented with 10 and 20 mg/L Cr(VI) concentrations, respectively. Transcriptome analyses revealed that multiple metabolic systems are responsible for Cr(VI) resistance at the transcriptional level. In response to Cr(VI) exposure, strain AN-B15 up-regulated the genes involved in central metabolism, providing the reducing power by which enzymes (ChrR and azoR) transformed Cr(VI) to Cr(III) in the cytoplasm. Genes involved in the alleviation of oxidative stress and DNA repair were significantly up-regulated to neutralize Cr(VI)-induced toxicity. Additionally, genes involved in organosulfur metabolism and certain ion transporters were up-regulated to counteract the starvation of sulfur, molybdate, iron, and manganese induced by Cr(VI) stress. Furthermore, a hydroponic culture experiment showed that toxicity and uptake of Cr(VI) by plants under Cr(VI) stress were reduced by strain AN-B15. Specifically, strain AN-B15 inoculation increased the fresh weights of the wheat root and shoot by 55.5 % and 18.8 %, respectively, under Cr(VI) stress (5 mg/L). The elucidation of bacterial resistance to Cr(VI) has an important implication for exploiting microorganism for the effective remediation of Cr(VI)-polluted soils.

Mechanisms involved in the sequestration and resistance of cadmium for a plant-associated Pseudomonas strain.

Understanding Cd-resistant bacterial cadmium (Cd) resistance systems is crucial for improving microremediation in Cd-contaminated environments. However, these mechanisms are not fully understood in plant-associated bacteria. In the present study, we investigated the mechanisms underlying Cd sequestration and resistance in the strain AN-B15. These results showed that extracellular Cd sequestration by complexation in strain AN-B15 was primarily responsible for the removal of Cd from the solution. Transcriptome analyses have shown that the mechanisms of Cd resistance at the transcriptional level involve collaborative processes involving multiple metabolic pathways. The AN-B15 strain upregulated the expression of genes related to exopolymeric substance synthesis, metal transport, Fe-S cluster biogenesis, iron recruitment, reactive oxygen species oxidative stress defense, and DNA and protein repair to resist Cd-induced stress. Furthermore, inoculation with AN-B15 alleviated Cd-induced toxicity and reduced Cd uptake in the shoots of wheat seedlings, indicating its potential for remediation. Overall, the results improve our understanding of the mechanisms involved in Cd resistance in bacteria and thus have important implications for improving microremediation.

Excited State Kinetics of Benzo[a]pyrene Is Affected by Oxygen and DNA.

Benzo[a]pyrene is a widespread environmental pollutant and a strong carcinogen. It is important to understand its bio-toxicity and degradation mechanism. Herein, we studied the excited state dynamics of benzo[a]pyrene by using time-resolved fluorescence and transient absorption spectroscopic techniques. For the first time, it is identified that benzo[a]pyrene in its singlet excited state could react with oxygen, resulting in fluorescence quenching. Additionally, effective intersystem crossing can occur from its singlet state to the triplet state. Furthermore, the interaction between the excited benzo[a]pyrene and ct-DNA can be observed directly and charge transfer between benzo[a]pyrene and ct-DNA may be the reason. These results lay a foundation for further understanding of the carcinogenic mechanism of benzo[a]pyrene and provide insight into the photo-degradation mechanism of this molecule.

Plasmon-Induced Charge Transfer-Enhanced Raman Scattering on a Semiconductor: Toward Amplification-Free Quantification of SARS-CoV-2.

Semiconductors demonstrate great potentials as chemical mechanism-based surface-enhanced Raman scattering (SERS) substrates in determination of biological species in complex living systems with high selectivity. However, low sensitivity is the bottleneck for their practical applications, compared with that of noble metal-based Raman enhancement ascribed to electromagnetic mechanism. Herein, a novel Cu2 O nanoarray with free carrier density of 1.78×1021  cm-3 comparable to that of noble metals was self-assembled, creating a record in enhancement factor (EF) of 3.19×1010 among semiconductor substrates. The significant EF was mainly attributed to plasmon-induced hot electron transfer (PIHET) in semiconductor which was never reported before. This Cu2 O nanoarray was subsequently developed as a highly sensitive and selective SERS chip for non-enzyme and amplification-free SARS-CoV-2 RNA quantification with a detection limit down to 60 copies/mL within 5 min. This unique Cu2 O nanoarray demonstrated the significant Raman enhancement through PIHET process, enabling rapid and sensitive point-of-care testing of emerging virus variants.

Sequential Multistep Excited-State Structural Transformations in N,N'-Diphenyl-dihydrodibenzo[a,c]phenazine Fluorophores.

We demonstrate that a single polycyclic π-scaffold can undergo sequential multistep excited-state structural evolution along the bent, planar, and twisted conformers, which coexist to produce intrinsic multiple fluorescence emissions in room-temperature solution. By installing a methyl or trifluoromethyl group on the ortho-site of N,N'-diphenyl-dihydrodibenzo[a,c]phenazine (DPAC), the enhanced steric effects change the fluorescence emission of DPAC from a dominant red band to well-resolved triple bands. The ultra-broadband triple emissions of ortho-substituted DPACs range from ≈350 to ≈850 nm, which is unprecedented for small fluorophores with molecular weight of <500. Ultrafast spectroscopy and theoretical calculations clearly reveal that the above dramatic changes originate from the influence of steric hindrance on the shape of excited state potential energy surface (S1 PES). Compared to the steep S1 PES of parental DPAC, the introduction of ortho-substituent is shown to make the path of structural evolution in S1 wider and flatter, so the ortho-substituted derivatives exhibit slower structural transformations from bent to planar and then to twisted forms, yielding intrinsic triple emission. The results provide the proof of concept that the bent, planar, and twisted emissive states can coexist in the same S1 PES, which greatly expand the fundamental understanding of the excited-state structural relaxation.

Stable, Bright, and Long-Fluorescence-Lifetime Dyes for Deep-Near-Infrared Bioimaging.

Near-infrared (NIR) fluorophores absorbing maximally in the region beyond 800 nm, i.e., deep-NIR spectral region, are actively sought for biomedical applications. Ideal dyes are bright, nontoxic, photostable, biocompatible, and easily derivatized to introduce functionalities (e.g., for bioconjugation or aqueous solubility). The rational design of such fluorophores remains a major challenge. Silicon-substituted rhodamines have been successful for bioimaging applications in the red spectral region. The longer-wavelength silicon-substituted congeners for the deep-NIR spectral region are unknown to date. We successfully prepared four silicon-substituted bis-benzannulated rhodamine dyes (ESi5a-ESi5d), with an efficient five-step cascade on a gram-scale. Because of the extensive overlapping of their HOMO-LUMO orbitals, ESi5a-ESi5d are highly absorbing (λabs ≈ 865 nm and ε > 105 cm-1 M-1). By restraining both the rotational freedom via annulation and the vibrational freedom via silicon-imparted strain, the fluorochromic scaffold of ESi5 is highly rigid, resulting in an unusually long fluorescence lifetime (τ > 700 ps in CH2Cl2) and a high fluorescence quantum yield (ϕ = 0.14 in CH2Cl2). Their half-lives toward photobleaching are 2 orders of magnitude longer than the current standard (ICG in serum). They are stable in the presence of biorelevant concentration of nucleophiles or reactive oxygen species. They are minimally toxic and readily metabolized. Upon tail vein injection of ESi5a (as an example), the vasculature of a nude mouse was imaged with a high signal-to-background ratio. ESi5 dyes have broad potentials for bioimaging in the deep-NIR spectral region.

Pathogenesis of sepsis-associated encephalopathy: more than blood-brain barrier dysfunction.

Sepsis-associated encephalopathy is a common neurological complication of sepsis and is responsible for higher mortality and poorer long-term outcomes in septic patients. Sepsis-associated encephalopathy symptoms can range from mild delirium to deep coma, which occurs in up to 70% of patients in intensive care units. The pathological changes in the brain associated with sepsis include cerebral ischaemia, cerebral haemorrhage, abscess and progressive multifocal necrotic leukoencephalopathy. Several mechanisms are involved in the pathogenesis of sepsis-associated encephalopathy, such as blood-brain barrier dysfunction, cerebral blood flow impairment, glial cell activation, leukocyte transmigration, and neurotransmitter disturbances. These events are interrelated and influence each other, therefore they do not act as independent factors. This review is focused on new evidence showing the pathological process of sepsis-associated encephalopathy.