DNA-controlled protein fluorescence: Design of aptamer-split peptide hetero-modulator for GFP to respond to intracellular ATP levels.

Enabling the precise control of protein functions with artificially programmed reaction patterns is beneficial for investigating biological processes. Although several strategies have been established that employ the programmability of nucleic acid, they have been limited to DNA hybridization without external stimuli or target binding. Here, we report an approach for the DNA-mediated control of the tripartite split-GFP assembly via aptamers with responsiveness to intracellular small molecules as stimuli. We designed a novel structure-switching aptamer-peptide conjugate as a hetero modulator for split GFP in response to ATP. By conjugating two peptides (S10/11) derived from the tripartite split-GFP to ATP aptamer, we achieved GFP reassembly using only ATP as a trigger molecule. The response to ATP at ≥4 mM concentrations indicated that it can be applied to respond to intracellular ATP in live cells. Furthermore, our hetero-modulator exhibited high and long-term stability, with a half-life of approximately four days in a serum stability assay, demonstrating resistance to nuclease degradation. We validated that our aptamer-modulator split GFP was successfully reconstituted in the cell in response to intracellular ATP levels. Our aptamer-modulated split GFP platform can be utilized to monitor a wide range of intracellular metabolites by replacing the aptamer sequence.

Quantitative, Regiospecific, and Stereoselective Radical Ring-Opening Polymerization of Monosaccharide Cyclic Ketene Acetals.

Cyclic ketene acetals (CKAs) are among the most well-studied monomers for radical ring-opening polymerization (rROP). However, ring-retaining side reactions and low reactivities in homopolymerization and copolymerization remain significant challenges for the existing CKAs. Here, we report that a class of monosaccharide CKAs can be facilely prepared from a short and scalable synthetic route and can undergo quantitative, regiospecific, and stereoselective rROP. NMR analyses and degradation experiments revealed a reaction mechanism involving a propagating radical at the C2 position of pyranose with different monosaccharides exhibiting distinct stereoselectivity in the radical addition of the monomer. Furthermore, the addition of maleimide was found to improve the incorporation efficiency of monosaccharide CKA in the copolymerization with vinyl monomers and produced unique degradable terpolymers with carbohydrate motifs in the polymer backbone.

Precision Cellulose from Living Cationic Polymerization of Glucose 1,2,4-Orthopivalates.

Cellulose serves as a sustainable biomaterial for a wide range of applications in biotechnology and materials science. While chemical and enzymatic glycan assembly methods have been developed to access modest quantities of synthetic cellulose for structure-property studies, chemical polymerization strategies for scalable and well-controlled syntheses of cellulose remain underdeveloped. Here, we report the synthesis of precision cellulose via living cationic ring-opening polymerization (CROP) of glucose 1,2,4-orthopivalates. In the presence of dibutyl phosphate as an initiator and triflic acid as a catalyst, precision cellulose with well-controlled molecular weights, defined chain-end groups, and excellent regio- and stereospecificity was readily prepared. We further demonstrated the utility of this method through the synthesis of precision native d-cellulose and rare precision l-cellulose.

A highly oxidized germacranolide from elephantopus tomentosus inhibits the growth of hepatocellular carcinoma cells by targeting EGFR in vitro and in vivo.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with high mortality and poor prognosis. WBDC-1 is a novel highly oxidized germacranolide from the Elephantopus tomentosus in our previous work, which has excellent anti-HCC activity, but the detailed mechanism is still unclear. In this study, we found that WBDC-1 was able to inhibit the proliferation and colony formation of Hep3B and HepG2 cells, as well as the cell migration ability and EMT. In addition, WBDC-1 showed no obvious toxicity to normal liver epithelial cells L-02. The potential targets of WBDC-1 were predicted by network pharmacology, and the following verified experiments showed that WBDC-1 exerted anti-HCC effect by targeting EGFR. Mechanismly, subsequent biological analysis showed that WBDC-1 can inhibit EGFR and its downstream RAS/RAF/MEK/ERK and PI3K/AKT signaling pathways. Overexpression of EGFR reversed the anticancer properties of WBDC-1. Consistent with in vitro experiments, WBDC-1 was able to inhibit tumor growth and was non-toxic in xenograft tumor models. In summary, this study revealed a potential tumor suppressive mechanism of WBDC-1 and provided a novel strategy for HCC treatment. It also laid a foundation for further research on the anti-tumor effect of highly oxidized germacranolides.

Tracking the changes of dissolved organic matter throughout the city water supply system with optical indices.

Dissolved organic matter (DOM) is important in determining the drinking water treatment and the supplied water quality. However, a comprehensive DOM study for the whole water supply system is lacking and the potential effects of secondary water supply are largely unknown. This was studied using dissolved organic carbon (DOC), absorption spectroscopy, and fluorescence excitation-emission matrices-parallel factor analysis (EEM-PARAFAC). Four fluorescent components were identified, including humic-like C1-C2, tryptophan-like C3, and tyrosine-like C4. In the drinking water treatment plants, the advanced treatment using ozone and biological activated carbon (O3-BAC) was more effective in removing DOC than the conventional process, with the removals of C1 and C3 improved by 17.7%-25.1% and 19.2%-27.0%. The absorption coefficient and C1-C4 correlated significantly with DOC in water treatments, suggesting that absorption and fluorescence could effectively track the changes in bulk DOM. DOM generally remained stable in each drinking water distribution system, suggesting the importance of the treated water quality in determining that of the corresponding network. The optical indices changed notably between distribution networks of different treatment plants, which enabled the identification of changing water sources. A comparison of DOM in the direct and secondary water supplies suggested limited impacts of secondary water supply, although the changes in organic carbon and absorption indices were detected in some locations. These results have implications for better understanding the changes of DOM in the whole water supply system to help ensure the supplied water quality.

Evolution of fermented grain yeast communities in strong-flavored baijiu and functional validation of yeasts that produce superior-flavored substances.

BACKGROUND: Baijiu is a well-known alcoholic beverage in China and the quality is determined by various microorganisms during the fermentation process. Yeast is one of the most important microorganisms in the fermentation of baijiu. It has a strong esterification capacity and also affects the aroma. RESULTS: High-throughput sequencing results showed that the fermented grains (jiupei) during baijiu production were mainly composed of eight highly abundant yeast species. The species and abundance of yeasts changed significantly with the fermentation process. The flavor of 30 yeast strains in the jiupei was determined by a sniffing test and gas chromatography-mass spectrometry (GC-MS). The strain with the highest flavor substance content (2.34 mg L-1), named YX3205, was identified as Clavispora lusitaniae. Tolerance results showed that C. lusitaniae YX3205 can tolerate up to 15% (v v-1) ethanol. In a solid-state simulated fermentation experiment, the content of 24 flavor substances was significantly increased in the fortified group, and the total ester content reached 4240.73 µg kg-1, which was 2.8 times higher than that of the control group. CONCLUSION: The present study demonstrated the potential of C. lusitaniae YX3205 to enhance the flavor of baijiu, thereby serving as a valuable strain for the improvement of the flavor quality of baijiu. © 2024 Society of Chemical Industry.

Orexin recruits non-selective cationic conductance and endocannabinoid to dynamically modulate firing of caudal pontine reticular nuclear neurones.

The neuropeptide orexin is involved in motor circuit function. However, its modulation on neuronal activities of motor structures, integrating orexin's diverse downstream molecular cascades, remains elusive. By combining whole-cell patch-clamp recordings and neuropharmacological methods, we revealed that both non-selective cationic conductance (NSCC) and endocannabinoids (eCBs) are recruited by orexin signalling on reticulospinal neurones in the caudal pontine reticular nucleus (PnC). The orexin-NSCC cascade provides a depolarizing force that proportionally enhances the firing-responsive gain of these neurones. Meanwhile, the orexin-eCB cascade selectively attenuates excitatory synaptic strength in these neurones by activating presynaptic cannabinoid receptor type 1. This cascade restrains the firing response of the PnC reticulospinal neurones to excitatory inputs. Intriguingly, non-linear or linear interactions between orexin postsynaptic excitation and presynaptic inhibition can influence the firing responses of PnC reticulospinal neurones in different directions. When presynaptic inhibition is in the lead, non-linear interactions can prominently downregulate or even gate the firing response. Conversely, linear interactions occur to promote the firing response, and these linear interactions can be considered a proportional reduction in the contribution of depolarization to firing by presynaptic inhibition. Through the dynamic employment of these interactions, adaptive modulation may be achieved by orexin to restrain or even gate the firing output of the PnC to weak/irrelevant input signals and facilitate those to salient signals. KEY POINTS: This study investigated the effects of orexin on the firing activity of PnC reticulospinal neurones, a key element of central motor control. We found that orexin recruited both the non-selective cationic conductances (NSCCs) and endocannabinoid (eCB)-cannabinoid receptor type 1 (CB1R) system to pontine reticular nucleus (PnC) reticulospinal neurones. The orexin-NSCC cascade exerts a postsynaptic excitation that enhances the firing response, whereas the orexin-eCB-CB1R cascade selectively attenuates excitatory synaptic strength that restrains the firing response. The postsynaptic and presynaptic actions of orexins occur in an overlapping time window and interact to dynamically modulate firings in PnC reticulospinal neurones. Non-linear interactions occur when presynaptic inhibition of orexin is in the lead, and these interactions can prominently downregulate or even gate firing responses in PnC reticulospinal neurones. Linear interactions occur when postsynaptic excitation of orexin is in the lead, and these interactions can promote the firing response. These linear interactions can be considered a proportional reduction of the contribution of depolarization to firing by presynaptic inhibition.

Fluorosulfate as a Latent Sulfate in Peptides and Proteins.

Sulfation widely exists in the eukaryotic proteome. However, understanding the biological functions of sulfation in peptides and proteins has been hampered by the lack of methods to control its spatial or temporal distribution in the proteome. Herein, we report that fluorosulfate can serve as a latent precursor of sulfate in peptides and proteins, which can be efficiently converted to sulfate by hydroxamic acid reagents under physiologically relevant conditions. Photocaging the hydroxamic acid reagents further allowed for the light-controlled activation of functional sulfopeptides. This work provides a valuable tool for probing the functional roles of sulfation in peptides and proteins.

Combined metabolomics and machine learning algorithms to explore metabolic biomarkers for diagnosis of acute myocardial ischemia.

Acute myocardial ischemia (AMI) remains the leading cause of death worldwide, and the post-mortem diagnosis of AMI represents a current challenge for both clinical and forensic pathologists. In the present study, the untargeted metabolomics based on ultra-performance liquid chromatography combined with high-resolution mass spectrometry was applied to analyze serum metabolic signatures from AMI in a rat model (n = 10 per group). A total of 28 endogenous metabolites in serum were significantly altered in AMI group relative to control and sham groups. A set of machine learning algorithms, namely gradient tree boosting (GTB), support vector machine (SVM), random forest (RF), logistic regression (LR), and multilayer perceptron (MLP) models, was used to screen the more valuable metabolites from 28 metabolites to optimize the biomarker panel. The results showed that classification accuracy and performance of MLP model were better than other algorithms when the metabolites consisting of L-threonic acid, N-acetyl-L-cysteine, CMPF, glycocholic acid, L-tyrosine, cholic acid, and glycoursodeoxycholic acid. Finally, 17 blood samples from autopsy cases were applied to validate the classification model's value in human samples. The MLP model constructed based on rat dataset achieved accuracy of 88.23%, and ROC of 0.89 for predicting AMI type II in autopsy cases of sudden cardiac death. The results demonstrated that MLP model based on 7 molecular biomarkers had a good diagnostic performance for both AMI rats and autopsy-based blood samples. Thus, the combination of metabolomics and machine learning algorithms provides a novel strategy for AMI diagnosis.

Niche Differentiation of Biofilm Microorganisms in a Full-scale Municipal Drinking Water Distribution System in China and Their Implication for Biofilm Control.

Biofilms on the inner surface of a drinking water distribution system (DWDS) affect water quality and stability. Understanding the niche differentiation of biofilm microbial communities is necessary for the efficient control of DWDS biofilms. However, biofilm studies are difficult to conduct in the actual DWDS because of inaccessibility to the pipes buried underground. Taking the opportunity of infrastructure construction and relevant pipeline replacement in China, biofilms in a DWDS (a water main and its branch pipes) were collected in situ, followed by analysis on the abundances and community structures of bacterial and archaeal using quantitative PCR and high-throughput sequencing, respectively. Results showed that archaea were detected only in the biofilms of the water main, with a range of 9.4×103~1.1×105 copies/cm2. By contrast, bacteria were detected in the biofilms of branch pipes and the distal part of the water main, with a range of 8.8×103~9.6×106 copies/cm2. Among the biofilm samples, the archaeal community in the central part of the water main showed the highest richness and diversity. Nitrosopumilus was found to be predominant (86.22%) in the biofilms of the proximal part of the water main. However, Methanobrevibacter (87.15%) predominated in the distal part of the water main. The bacterial community of the water main and branch pipes was primarily composed of Firmicutes and Proteobacteria at the phylum level, respectively. Regardless of archaea or bacteria, only few operational taxonomic units (OTUs) (<0.5% of total OTUs) were shared by all the biofilms, indicating the niche differentiation of biofilm microorganisms. Moreover, the high Mn content in the biofilms of the distal sampling location (D3) in the water main was linked to the predominance of Bacillus. Functional gene prediction revealed that the proportion of infectious disease-related genes was 0.44-0.67% in the tested biofilms. Furthermore, functional genes related to the resistance of the bacterial community to disinfections and antibiotics were detected in all the samples, that is, glutathione metabolism-relating genes (0.14-0.65%) and beta-lactam resistance gene (0.01-0.05%). The results of this study indicate the ubiquity of archaea and bacteria in the biofilms of water main and branch pipes, respectively, and pipe diameters could be a major influencing factor on bacterial community structure. In the water main, the key finding was the predominant existence of archaea, particularly Nitrosopumilus and methanogen. Hence, their routine monitoring and probable influences on water quality in pipelines with large diameter should be given more attention. Besides, since Mn-related Bacillus and suspected pathogenic Enterococcus were detected in the biofilm, supplementation of disinfectant may be a feasible strategy for inhibiting their growth and ensuring water quality. In addition, the monitoring on their abundance variation could help to determine the frequency and methods of pipeline maintenance.

Early succession of biofilm bacterial communities in newly built drinking water pipelines via multi-area analysis.

Biofilms inhabiting pipeline walls are critical to drinking water quality and safety. With massive pipeline replacement underway, however, biofilm formation process in newly built pipes and its effects on water quality are unclear. Moreover, differences and connections between biofilms in newly built and old pipes are unknown. In this study, early succession (≤ 120 days) of biofilm bacterial communities (abundance and diversity) in upper, middle and bottom areas of a newly built cement-lined ductile iron pipeline were evaluated using improved Propella™ biofilm reactor and multi-area analysis. A comparison with old pipelines (grey cast iron, 10 years) was performed. In the newly built pipeline, the abundance of biofilm bacteria did not change significantly between 40 and 80 days, but increased significantly between 80 and 120 days. The biofilm bacterial abundance (per unit area) in the bottom area was always higher than that in the upper and middle areas. Based on alpha diversity index and PCoA results, biofilm bacterial community richness, diversity and composition did not change significantly during the 120-day operation. Besides, biofilm shedding from the walls of newly built pipeline significantly increased bacterial abundance in the outlet water. Opportunistic pathogen-containing genera, such as Burkholderia, Acinetobacter and Legionella, were identified in both water and biofilm samples from newly built pipelines. The comparison between new and old pipelines suggested a higher bacterial abundance per unit area at the middle and bottom areas in old pipelines. Moreover, the bacterial community composition of biofilms in old pipelines was similar to that of newly built pipelines. These results contribute to accurate prediction and management of biofilm microbial communities in drinking water pipelines, ensuring the biosafety of drinking water. KEY POINTS: • Biofilm bacterial communities in different areas of pipe wall were revealed. • The abundance of biofilm bacteria increased significantly between 80 and 120 days. • Biofilm bacterial community compositions of newly built and old pipes were similar.

The risk of endometriosis by early menarche is recently increased: a meta-analysis of literature published from 2000 to 2020.

PURPOSE: The relationship between menarche age and endometriosis has been studied extensively; however, the results were inconsistent due to differences in study dates, populations, and methodology. The goal of this meta-analysis was to see how different research populations, dates, and types affected the estimated risk of endometriosis in early menarche. METHODS: The terms "endometriosis", "early menarche", and other pertinent terms were searched in PubMed, Medline, and Embase. This meta-analysis comprised 16 papers published between 2000 and 2020, with a start year ranging from 1989 to 2017. Random effects were used to examine endometriosis risks in these articles. Study start years, countries, types (case-control and cohort studies), and quality (Newcastle-Ottawa scale, NOS) were all taken into account in further stratified analysis and meta-regression analyses. RESULTS: Early menarche (< 12 years) was associated with a significant pooled risk of endometriosis with high heterogeneity (OR = 1.34, 95% CI 1.16-1.54, I2 = 72.0%). Stratified analysis showed that this risk was increased in studies started after 2000 (OR = 1.62, 95% CI 0.96-1.35, I2 = 74.4%), compared to those before 2000 (OR = 1.13, 95% CI 1.16-1.54, I2 = 40.7%); additionally, this risk was higher in low-income countries (OR = 2.11, 95% CI 1.55-2.87, I2 = 0%) than in other countries (OR = 1.25, 95% CI 1.09-1.43, I2 = 70.6%). These results were further confirmed by meta-regression analysis (both P values < 0.1). No significant differences were found between different study types and NOS scores. CONCLUSION: Our results suggested an increasing risk of endometriosis with early menarche, which was more noticeable in low-income countries. Large-scale studies are warranted.

Four Pairs of Neuroprotective Aryldihydronaphthalene-Type Lignanamide Enantiomers from the Herbs of Solanum lyratum.

Four pairs of aryldihydronaphthalene-type lignanamide enantiomers were isolated from Solanum lyratum (Solanaceae). The enantiomeric separation was accomplished by chiral-phase HPLC, and five undescribed compounds were elucidated. Analysis by various spectroscopy and ECD calculations, the structures of undescribed compounds were illuminated. The neuroprotective effects of all compounds were evaluated using H2 O2 -induced human neuroblastoma SH-SY5Y cells and AchE inhibition activity. Among them, compound 4 a exhibited remarkable neuroprotective effects at high concentrations of 25 and 50 µmol/L comparable to Trolox. Compound 1 a showed the highest AchE inhibition with the IC50 value of 3.06±2.40 µmol/L. Molecular docking of the three active compounds was performed and the linkage between the compounds and the active site of AchE was elucidated.

Ortho-Alkoxy-benzamide Directed Formation of a Single Crystalline Hydrogen-bonded Crosslinked Organic Framework and Its Boron Trifluoride Uptake and Catalysis.

Boron trifluoride (BF3 ) is a highly corrosive gas widely used in industry. Confining BF3 in porous materials ensures safe and convenient handling and prevents its degradation. Hence, it is highly desired to develop porous materials with high adsorption capacity, high stability, and resistance to BF3 corrosion. Herein, we designed and synthesized a Lewis basic single-crystalline hydrogen-bond crosslinked organic framework (HC OF-50) for BF3 storage and its application in catalysis. Specifically, we introduced self-complementary ortho-alkoxy-benzamide hydrogen-bonding moieties to direct the formation of highly organized hydrogen-bonded networks, which were subsequently photo-crosslinked to generate HC OFs. The HC OF-50 features Lewis basic thioether linkages and electron-rich pore surfaces for BF3 uptake. As a result, HC OF-50 shows a record-high 14.2 mmol/g BF3 uptake capacity. The BF3 uptake in HC OF-50 is reversible, leading to the slow release of BF3 . We leveraged this property to reduce the undesirable chain transfer and termination in the cationic polymerization of vinyl ethers. Polymers with higher molecular weights and lower polydispersity were generated compared to those synthesized using BF3 ⋅ Et2 O. The elucidation of the structure-property relationship, as provided by the single-crystal X-ray structures, combined with the high BF3 uptake capacity and controlled sorption, highlights the molecular understanding of framework-guest interactions in addressing contemporary challenges.

Estimating the time of skeletal muscle contusion based on the spatial distribution of neutrophils: a practical approach to forensic problems.

The study aimed to explore the neutrophil's spatial distributions used to estimate the histological age of contused skeletal muscle, and assessed the accuracy of various indicators, such as the proportion of neutrophils, "neutrophil mean distance," and distribution of neutrophils in areas of "contiguous contour lines." Fifty-five Sprague-Dawley rats were divided randomly into a control group and contusion groups at 1, 1.5, 2, 3, 4, and 6 h, as well as 1, 3, 5, and 15 days, post-injury (n = 5 per group). Nuclei and neutrophils were detected by hematoxylin and eosin (HE) staining and immunohistochemical (IHC) staining. At 0-24 h after injury, the distribution of neutrophils at distances of 100, 200, 300, 400, 500, and 600 µm from adjacent blood vessels was determined, and the best samples were screened to estimate wound age. To estimate wound age as accurately as possible, Fisher discriminant analysis (FDA) of the proportion of neutrophils, neutrophil mean distance, and distribution of neutrophils was performed, and 100.0% and 95.0% of the original and cross-validated cases were correctly classified, respectively. The spatial distribution of neutrophils at different distances from adjacent blood vessels showed a strong correlation with the histological age of contusion skeletal muscle, and the combination of the proportion of neutrophils, neutrophil mean distance, and distribution of neutrophils could be used to accurately estimate wound age.

Prevalence of depression and anxiety and their predictors among patients undergoing maintenance hemodialysis in Northern China: a cross-sectional study.

OBJECTIVE: To investigate the prevalence of depression and anxiety in patients undergoing maintenance hemodialysis (MHD) in Hohhot, a large city on the northern border of China, and to identify independent risk factors for depression and anxiety in these patients. METHODS: Patients receiving MHD for >3 months were enrolled in the four largest hemodialysis centers between September 2020 and December 2020. Depression and anxiety were assessed using the Zung self-rated depression scale (SDS) and Zung self-rated anxiety scale (SAS), respectively, with demographic and other data collected for logistic regression analyses. RESULTS: Among 305 MHD patients included in this study, the prevalence of depression was 55.1%, including 27.5%, 21.0%, and 6.6% with mild, moderate and severe cases, respectively. The prevalence of anxiety was 25.9%, with 20.0%, 4.6%, and 1.3% having mild, moderate, and severe cases, respectively. An independent protective factor for depression was family income of ≥1415 US dollars/month relative to <157 US dollars/month (odds ratio [OR] 0.209, 95% confidence interval [CI] 0.065-0.673), and predictors of depression included ≥3 comorbidities (OR 18.527, 95% CI 1.674-205.028) and severe pruritus (OR 15.971, 95% CI 5.173-49.315). Independent predictors of anxiety included infrequent exercise (OR 3.289, 95% CI 1.411-7.664) and severe pruritus (OR 5.912, 95% CI 1.733-20.168). The correlation between depression and anxiety in these patients was significant (rs = 0.775, p < 0.001). CONCLUSION: MHD patients in Northern China had high prevalence rates of depression (55.1%) and anxiety (25.9%). Lower family income, more comorbidities, and a higher degree of pruritus were predictors of depression, while infrequent exercise and severe pruritus were predictors of anxiety. Depression correlated significantly with anxiety. Attention should be given to family income, comorbidity, exercise, and pruritus severity for improved management of depression and anxiety among MHD patients.

Degradable Vinyl Random Copolymers via Photocontrolled Radical Ring-Opening Cascade Copolymerization.

Degradable vinyl polymers by radical ring-opening polymerization are promising solutions to the challenges caused by non-degradable vinyl plastics. However, achieving even distributions of labile functional groups in the backbone of degradable vinyl polymers remains challenging. Herein, we report a photocatalytic approach to degradable vinyl random copolymers via radical ring-opening cascade copolymerization (rROCCP). The rROCCP of macrocyclic allylic sulfones and acrylates or acrylamides mediated by visible light at ambient temperature achieved near-unity comonomer reactivity ratios over the entire range of the feed compositions. Experimental and computational evidence revealed an unusual reversible inhibition of chain propagation by in situ generated sulfur dioxide (SO2 ), which was successfully overcome by reducing the solubility of SO2 . This study provides a powerful approach to degradable vinyl random copolymers with comparable material properties to non-degradable vinyl polymers.

Sevoflurane Post-Conditioning Ameliorates Neuronal Deficits and Axon Demyelination After Neonatal Hypoxic Ischemic Brain Injury: Role of Microglia/Macrophage.

Microglia/macrophages have been identified to be highly polarized after ischemia. Interestingly, the polarization of these microglia/macrophages varies immensely under differing disease conditions. Post-conditioning using sevoflurane, a volatile anesthetic, could provide long-term neuroprotection to neonatal rats after hypoxic-ischemic brain injury (HIBI). Thus, the current study aimed at investigating the effects of sevoflurane post-conditioning (SPC) on microglia/macrophage polarization after HIBI induction in neonatal rats. Additionally, we aimed at identifying the underpinning mechanisms specifically related to autophagy and lysosomal protease enzyme, cathepsin B. To develop a HIBI model, 7-day-old Sprague-Dawley rats underwent left common carotid artery ligation followed by 2 h of hypoxia. The role of microglia/macrophages in the neuroprotection conferred by SPC was examined by left-side intra-cerebroventricular injection with adenovirus vector carrying catB-GFP or rapamycin. The number of interleukin (IL)-1ß+ cells, cathepsin B+ cells, light chain 3B positive (LC3B+) cells among ionized calcium binding adaptor molecule 1(Iba1+)cells to investigate microglia polarization, neuronal apoptosis to assess neuronal death in the acute phase were tested at 24 h after HIBI. Behavioral tests including suspension test, Morris water maze tests were performed to investigate the long-term effects of SPC, at 21 to 34 days post HIBI. Nissl staining and myelin basic protein (MBP) immunostaining to assess the long-term neuronal and myelin damage were performed at 34 days after HIBI. Based on the obtained results post HIBI, we observed the cells that were positive for IL-1ß, cathepsin B, and LC3B among Iba1 positive cell population in the hippocampus were significantly decreased after SPC treatment. SPC significantly attenuated the HIBI-induced increase in neuronal apoptosis, improved long-term cognitive function, and attenuated HI-induced decrease of Nissl-positive cells and MBP expression. However, these trends were reversed by injection of adenovirus vector carrying catB-GFP and rapamycin. SPC attenuated microglia polarization towards neurotoxic phenotypes, alleviates neuronal death and axon demyelination after HIBI in neonatal rats by regulating microglia autophagy and cathepsin B expression, and therefore provided long-term cognitive, learning and memory protection.

Metathesis Cascade-Triggered Depolymerization of Enyne Self-Immolative Polymers*.

A novel class of enyne self-immolative polymers (SIPs) capable of metathesis cascade-triggered depolymerization is reported. Studies on model compounds established 1,6-enyne structures for efficient metathesis cascade reactions. SIPs incorporating the optimized 1,6-enyne motif were prepared via both polycondensation and iterative exponential growth approaches. These SIPs demonstrated excellent stability in strong acid, base, nucleophiles, or at elevated temperatures, and can undergo efficient and complete depolymerization once triggered by a metathesis catalyst. Further studies revealed that introducing a terminal alkene to the chain end of the enyne SIPs improved the depolymerization efficiency, and established their potential as stimuli-responsive materials.

Electrochemically Triggered Chain Reactions for the Conversion of Furan Derivatives.

We report an electrochemical method for coupling biomass-derived C5/C6 compounds to value-added fuel precursors. Using only 2 % of equivalent charges, 2-methylfuran (2-MF) was oxidized to yield a cation radical, which readily reacted with 3-hexene-2,5-dione, a derivate of 2,5-dimethylfuran, to produce 3-(5-methylfuran-2-yl)hexane-2,5-dione. The product was converted to 4-ethylnonane (a component of biodiesel/jet fuel) in a single step in excellent yield. Importantly, the reaction was not sensitive to oxygen, and a trace amount of water was found to promote the reaction. Detailed mechanistic studies confirmed the proposed reaction pathways. Key to the mechanism is the radical generation that is enabled by electrochemistry. The radical is regenerated at the end of a reaction cycle to ensure chain propagation for an average of ca. 47 times, resulting in an apparent Faradaic efficiency of 4700 %.