Proton-coupled electron transfer of macrocyclic ring hydrogenation: The chlorinphlorin.

SignificanceThe chemical reduction of unsaturated bonds occurs by hydrogenation with H2 as the reductant. Conversely, in biology, the unavailability of H2 engenders the typical reduction of unsaturated bonds with electrons and protons from different cofactors, requiring olefin hydrogenation to occur by proton-coupled electron transfer (PCET). Moreover, the redox noninnocence of tetrapyrrole macrocycles furnishes unusual PCET intermediates, including the phlorin, which is an intermediate in tetrapyrrole ring reductions. Whereas the phlorin of a porphyrin is well established, the phlorin of a chlorin is enigmatic. By controlling the PCET reactivity of a chlorin, including the use of a hangman functionality to manage the proton transfer, the formation of a chlorinphlorin by PCET is realized, and the mechanism for its formation is defined.

Development of recombinase amplification assays for the rapid detection of infectious myonecrosis virus.

Infectious myonecrosis virus (IMNV) has affected shrimp farming in many countries, such as northeastern Brazil and southeast Asia, and poses a serious threat to the global shrimp industry. Reverse transcription enzymatic recombinant amplification technology (RT-ERA) is a rapid DNA amplification assay with high specificity in isothermal conditions and has been widely applied to the pathogen's detection. In this study, two novel ERA assays of IMNV, real-time RT-ERA and an RT-ERA combined with lateral flow dipsticks assay (RT-ERA-LFD), were developed and evaluated. The real-time RT-ERA assay could be carried out at 38-42 °C and had the highest end-point fluorescence value and the smallest Ct value at 41 °C. The brightness and width of the detection line were at a maximum at 39 °C and 30 min, and these conditions were selected in RT-ERA-LFD. Both real-time RT-ERA and RT-ERA-LFD produced positive results with IMNV standard plasmids only and showed no cross-reaction with Vibrio parahaemolyticus, which causes acute hepatopancreatic necrosis disease (VpAHPND); white spot syndrome virus (WSSV); infectious hypodermal and hematopoietic necrosis virus (IHHNV); or Ecytonucleospora hepatopenaei (EHP). Meanwhile, we compared the sensitivities of nested RT-PCR, real-time RT-PCR, real-time RT-ERA, and RT-ERA-LFD. The sensitivities of real-time RT-ERA and RT-ERA-LFD were both 101 copies/µL. The detection sensitivities of nested RT-PCR and real-time RT-PCR were 100 and 102 copies/µL, respectively. As a result, two ERA assays were determined to be specific, sensitive, and economical methods for the on-site diagnosis of IMNV infection, showing great potential for the control of IMNV infections.

[Epidemiological characteristics of cardio-metabolic risk factors in women aged 15-49 years in 4 provinces of China in 2018].

OBJECTIVE: To analyze the prevalence of cardio-metabolic(CM) risk in women aged 15-49 years in 4 provinces of China and the influence of socioeconomic factors on them. METHODS: A total of 2851 women aged 15-49 years from Community-based Cohort Study on Nervous System Disease in 2018 were selected. Obesity, central obesity, elevated triglyceride(TG), elevated total cholesterol(TC), decreased high-density lipoprotein cholesterol(HDL-C), elevated low-density lipoprotein cholesterol(LDL-C), elevated blood pressure, elevated blood glucose and risk factor aggregation were analyzed. χ~2 test was used for univariate analysis, multinomial Logit model was used to evaluate the relationship between socioeconomic factors and CM risk factors, and Cochran-Armitage trend test was used for trend analysis. RESULTS: The detection rate of CM risk factors in this study from high to low were central obesity(26.76%), overweight(22.41%), pre central obesity(17.47%), decreased HDL-C(15.36%), elevated TG(11.78%), borderline elevated TC(11.40%), borderline elevated TG(11.12%), elevated blood pressure(9.71%) and hypertension(9.12%). The prevalence rates of CM risk factors were different among different age groups, income groups and education levels(P<0.05). In addition to decreased HDL-C, the prevalence of other metabolic risk factors increased with age(P_(trend)<0.05). With the improvement of educational level, the prevalence rates of overweight, obesity, central obesity, central obesity, elevated TG, decreased HDL-C, elevated blood pressure, hypertension, elevated blood pressure and diabetes showed a downward trend(P_(trend)<0.05). Multinomial Logit model showed that the rick of metabolic risk factors in the age group of 40 to 49 years old was higher than that in the younger age group aged 15-29 years, and was more significant in hypertension, elevated blood pressure and elevated blood glucose, which were 8.51 times(95% CI 5.45-13.27), 3.14 times(95%CI 2.20-4.48)and 2.66(95% CI 1.52-4.66)times of the younger age group, respectively. Women with high-income level have a higher risk of borderline elevated TC, elevated TC and borderline elevated LDL-C(OR=1.85, 95% CI 1.44-2.38;OR=2.01, 95% CI 1.25-3.22;OR=2.16, 95% CI 1.61-2.90), but the lower risk of overweight and elevated blood pressure(OR=0.79, 95% CI 0.64-0.98;OR=0.69, 95% CI 0.50-0.94). The risk of obesity, hypertension and diabetes of people with college degree or above was about 50% lower than those with junior high school education or below(OR=0.52, 95% CI 0.35-0.78;OR=0.43, 95% CI 0.27-0.67; OR=0.52, 95% CI 0.28-0.96). CONCLUSION: Central obesity, overweight, pre central obesity and HDL-C decrease were prominent CM risk factors in women aged 15-49 years in four provinces of China in 2018. The detection rate of CM risk factors is higher in women of high age group or low education level.

[Consumption status and growth trends of dairy products among children and adolescents in China from 1991 to 2018].

OBJECTIVE: To explore the dairy consumption among children and adolescents aged 7-17 in China. METHODS: 10 rounds of follow-up data from the "China Health and Nutrition Survey" from 1991 to 2018 were collected, and individuals aged 7-17 were selected as the study subjects. Dietary data was collected by using 3-day 24-hour dietary review method and household weighing accounting method(edible oils and seasonings). Dairy consumption was calculated by converting various dairy products into liquid milk intake using the China Food Composition. After excluding those with missing demographic information, missing data from the "3 days and 24 hours" dietary survey, and abnormal daily energy intake, 18 529 participants were included in the final analysis. Joinpoint regression model was used to analyze the trend of changes in dairy intake. RESULTS: The dairy consumption rate increased from 2.8% in 1991 to 42.3% in 2018, while it increased from 8.4% to 58.8% in urban and from 0.9% to 32.1% in rural areas. Meanwhile, the proportion of people whose dairy intake reaches the recommended intake(300 g/d) increased from 0.2% to 3.0%, and the proportion in rural area was 2.0%, which was lower than that in urban areas(4.9%). From 1991 to 2018, dairy intake increased at a rate of 12.97%(P=0.02), and the growth rate of urban and rural areas were 9.79%(P=0.03) and 15.67%(P<0.01), respectively. There was a faster growth trend from 1991-2004 compared to 2004-2018. The growth rate in urban and rural areas also showed different growth trends. CONCLUSION: The dairy intake of children and adolescents aged 7-17 in China improved significantly from 1991 to 2018, with higher consumption rate in urban areas than in rural areas, but it still need to be improved for health.

[Analysis of food carbon footprint and its socio-demographic disparities in China in 2018].

OBJECTIVE: To analyze food carbon footprint and its socio-demographic disparities among adults in China. METHODS: A total of 12 777 adults aged 18 years and above from the China Health and Nutrition Survey in 2018 who have completed dietary and socio-demographic data were analyzed. The information of food intake were collected by 24 h recalls combined with the weighing of household seasonings. Food consumption was converted into energy intake by the China Food Composition Table. Carbon footprint of 26 food groups were calculated by the food carbon footprint database based on life-cycle assessment(LCA), multinomial logit model was used to analyze the association of socio-demographic factors and food carbon footprint. RESULTS: Average food carbon footprint were decreased with increasing age while increased with increasing income and education levels, and was higher among male than that among female, was higher among urban residents than that among rural residents, was higher in the south than that in the north. Multinomial logit analysis showed that compared with people aged 18-44, the likelihood of occurring high carbon footprint in 60y and above group were 29%(OR=0.71, 95%CI 0.61-0.83) lower than that occurring low carbon footprint. Women were 11%(OR=0.89, 95%CI 0.81-0.99) and 25%(OR=0.75, 95%CI 0.67-0.84) less likely to appear medium and high carbon footprint than low carbon footprint, compared with their male counterparts. In comparison to people living in cities, rural dwellers were 24%(OR=0.76, 95%CI 0.69-0.85) and 38%(OR=0.62, 95%CI 0.55-0.70) less likely to appear medium and high carbon footprint than low carbon footprint. People in the south were 3.89 times(95%CI 3.52-4.30) and 11.35 times(95%CI 10.01-12.88) more likely to occur medium and high carbon footprint than low carbon footprint, compared with people in the north. Participants were more likely to occur medium carbon footprint and high carbon footprint with the increasing income level(OR>1), and were more likely to occur high carbon footprint with the increasing education level(OR>1). CONCLUSION: The food carbon footprint of adults in China in 2018 show different socio-demographic disparities, gender, income and education level are significant factors.

[Change of dietary pattern among young people aged 18-35 in China from 1989 to 2018].

OBJECTIVE: To analyze the dietary patterns changes of young people aged 18-35 in 15 provinces(autonomous regions, municipalities) from 1989 to 2018. METHODS: Using the data of China Health and Nutrition Survey, a total of 25 400 young people aged 18-35 with complete dietary and sociodemographic information from 1989 to 2018 in 15 provinces(autonomous regions, municipalities) were selected as the research objects. Nutrition survey was carried out by using 3 consecutive days of 24-hour review method combined with weighing accounting method. Energy and nutrient intake was calculated based on food composition list. The principal component cluster analysis was used to select food groups and K-mean cluster was uesd to extract dietary patterns. Dwass-Steel-Critchlow-Fligner was used to test the difference of food intake in different dietary patterns. Cochran-Armitage trend test was to analyze the change of dietary patterns with the years. Chi-square test was to analyze the difference of people with different dietary patterns in 2018. RESULTS: The dietary patterns of young people aged 18-35 in 15 provinces(autonomous regions, municipalities) were mainly divided into three categories: "traditional rice", "traditional pasta" and "high-quality protein". In 2018, the proportion of "traditional rice" dietary patterns was higher for men than for women, and the proportion of "high-quality protein" dietary patterns was lower than for women. The proportion of "traditional pasta" dietary pattern in people aged 25-35 was higher than that aged 18-24, and the proportion of "high-quality protein" dietary pattern was lower than that aged 18-24. The proportion of people in urban with "traditional rice" dietary pattern was lower than that in rural areas, and the proportion of "high-quality protein" dietary pattern was higher than that in rural areas. The northern region was dominated by "traditional pasta" dietary pattern, while the southern region was dominated by "traditional rice" dietary pattern, and the proportion of people with "high-quality protein" dietary pattern was higher in the northern region than in the southern region. With the increase of education level and income level, the proportion of people with "high-quality protein" dietary pattern showed an increasing trend. From 1989 to 2018, the "traditional rice" dietary pattern had always maintained a high proportion among young people aged 18-35 in 15 provinces(autonomous regions, municipalities) in China, and the "traditional pasta" dietary pattern had been decreasing since 2009, and the "high-quality protein" dietary pattern had significantly increased since 2011. CONCLUSION: From 1989 to 2018, the proportion of young people aged 18-35 with reasonable dietary pattern has increased in 15 provinces(autonomous regions, municipalities), but the traditional dietary pattern still needs to be improved.

Development of a real-time enzymatic recombinase amplification assay for rapid detection of infectious hypodermal and hematopoietic necrosis virus (IHHNV) in shrimp Penaeus vannamei.

Infectious hypodermal and hematopoietic necrosis virus (IHHNV) is classified as a reportable crustacean disease by the World Organisation for Animal Health (WOAH), which causes poor growth in Penaeus vannamei. According to genome sequence alignment analysis, enzymatic recombinase amplification (ERA) primers and probe were designed based on the ORF1 region of IHHNV, and a real-time ERA assay for IHHNV detection (IHHNV-ERA) was established. The experimental results show that IHHNV-F2/IHHNV-R2 and IHHNV-Probe can effectively amplify the target gene, and the sensitivity is 1.4 × 101 copies/µL within 14.97 ± 0.19 min, while the qPCR using primers 309F/309R could reach the detection limit of 1.4 × 101 copies/µL within 21.76 ± 0.63 min, and the sensitivity results of one-step PCR could be as low as 1.4 copies/µL with expense of time and false positives. The IHHNV-ERA system can effectively amplify the target gene at 42 ℃ within 20 min, and has no cross-reaction with white spot syndrome virus (WSSV), Ecytonucleospora hepatopenaei (EHP), Vibrio parahaemolyticus causing acute hepatopancreatic necrosis disease (VpAHPND), and healthy shrimp genomic DNA. Test results of practical samples showed that the detection rate of IHHNV-ERA (18/20) was better than the industrial standard qPCR assay (17/20). Compared with the existing technology, the useful results of this detection assay are: (1) get rid of the dependence on the thermal cycle instrument in the PCR process; (2) the experimental procedure is simple, time-consuming and fast; (3) the detection sensitivity is high. This study provides an ERA based detection assay for IHHNV, which can be used not only for the rapid detection of IHHNV infection, but also for the field screening of pathogens. This assay can also be applied to clinical inspection, customs detection, enterprise quality inspection and other fields, and has obvious practical application value.

Inverted Molding with Porous Skeleton Nickel Foam for Preparing Flexible Multi-Wall Carbon Nanotubes Pressure Sensors.

The application of traditional pressure sensors in health monitoring is limited by their initial rigidity. Flexible pressure sensors have thus received extensive attention owing to their excellent device flexibility. In this paper, we demonstrate a method of constructing flexible pressure sensors by inverting porous skeleton nickel foam based on multi-wall carbon nanotubes (MWCNTs) and polydimethylsiloxane (PDMS). MWCNTs and PDMS were mixed to form a composite conductive film, and the mass fraction of MWCNTs was optimized by evaluating the resistance change rate of the composite film. The optimized value of the mass fraction was 5%, which was used to prepare the flexible pressure sensors. The response, hysteresis, and stability of the sensors were further characterized. Pulse signals of humans were detected through flexible sensors, which can be used to evaluate cardiovascular conditions of the human body. These performance characteristics and the application demonstration show that our flexible pressure sensors have good prospects in human health care.

Single-Atom Zinc Sites with Synergetic Multiple Coordination Shells for Electrochemical H2 O2 Production.

Precise manipulation of the coordination environment of single-atom catalysts (SACs), particularly the simultaneous engineering of multiple coordination shells, is crucial to maximize their catalytic performance but remains challenging. Herein, we present a general two-step strategy to fabricate a series of hollow carbon-based SACs featuring asymmetric Zn-N2 O2 moieties simultaneously modulated with S atoms in higher coordination shells of Zn centers (n≥2; designated as Zn-N2 O2 -S). Systematic analyses demonstrate that the synergetic effects between the N2 O2 species in the first coordination shell and the S atoms in higher coordination shells lead to robust discrete Zn sites with the optimal electronic structure for selective O2 reduction to H2 O2 . Remarkably, the Zn-N2 O2 moiety with S atoms in the second coordination shell possesses a nearly ideal Gibbs free energy for the key OOH* intermediate, which favors the formation and desorption of OOH* on Zn sites for H2 O2 generation. Consequently, the Zn-N2 O2 -S SAC exhibits impressive electrochemical H2 O2 production performance with high selectivity of 96 %. Even at a high current density of 80 mA cm-2 in the flow cell, it shows a high H2 O2 production rate of 6.924 mol gcat -1 h-1 with an average Faradaic efficiency of 93.1 %, and excellent durability over 65 h.

Syntheses and Properties of Metalated Tetradehydrocorrins.

The monoanionic tetrapyrrolic macrocycle B,C-tetradehydrocorrin (TDC) resides chemically between corroles and corrins. This chemical space remains largely unexplored due to a lack of reliable synthetic strategies. We now report the preparation and characterization of Co(II)- and Ni(II)-metalated TDC derivatives ([Co-TDC]+ and [Ni-TDC]+, respectively) with a combination of crystallographic, electrochemical, computational, and spectroscopic techniques. [Ni-TDC]+ was found to undergo primarily ligand-centered electrochemical reduction, leading to hydrogenation of the macrocycle under cathodic electrolysis in the presence of acid. Transient absorption (TA) spectroscopy reveals that [Ni-TDC]+ and the two-electron-reduced [Ni-TDC]- possess long-lived excited states, whereas the excited state of singly reduced [Ni-TDC] exhibits picosecond dynamics. The Co(I) compound [Co-TDC] is air stable, highlighting the notable property of the TDC ligand to stabilize low-valent metal centers in contradistinction to other tetrapyrroles such as corroles, which typically stabilize metals in higher oxidation states.

Alleviated built-in electric field in the active region of AlGaN deep-ultraviolet light-emitting diodes with locally embedded p-i-n junctions.

The strong polarization-induced electric field in the multi-quantum well region reduces the radiative recombination rates by separating the electron and hole wave functions, which is one of the most detrimental factors that is to blame for the low luminous efficiency of AlGaN deep-ultraviolet light-emitting diodes (DUV LEDs). In this work, we redesigned the active region by incorporating Si and Mg doping at the vicinity of the quantum wells, forming a series of embedded p-i-n junctions in the multi-quantum well region. The additional electric field induced by the fixed charges from the embedded doping-induced junctions can effectively compensate for the intrinsic polarization-induced electric fields in the quantum well region and give rise to the improved overlap of hole and electron wave function, hence enhancing the radiative recombination rates and the external quantum efficiency and optical power of DUV LEDs. The mechanism behind the alleviated polarization electric field is comprehensively discussed and analyzed. The embedded p-i-n junctions can also alter the band diagram structure of the active region, decrease the effective barrier heights for holes, and diminish the electron leakage into the p-type region. In addition, different thicknesses and doping concentrations of the embedded p- and n- layers were designed, and their influence on the performance of DUV LEDs was numerically analyzed. The proposed structure with embedded p-i-n junctions provides an alternative way to achieve efficient DUV LEDs.

Promotion of cell autophagy and apoptosis in cervical cancer by inhibition of long noncoding RNA LINC00511 via transcription factor RXRA-regulated PLD1.

An increasing number of studies have explored the relationship of long noncoding RNAs (lncRNAs) with cervical cancer, yet the role of LINC00511 in cervical cancer still remains elusive. The current dissertation was intended to explore the effect of LINC00511 on cervical cancer development by regulating phospholipase D1 (PLD1) expression through transcription factor retinoic X receptor alpha (RXRA). Differentially expressed lncRNA and messenger RNA related to cervical cancer were screened by microarray-based expression profiling. Cervical cancer and paracancerous tissues were harvested to determine the LINC00511 expression using reverse transcription-quantitative polymerase chain reaction and western blot analysis. The relationship among LINC00511, PLD1 promoter activity, and RXRA were determined via RNA immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays. Proliferation, autophagy, and apoptosis of cervical cancer cells were detected with a series of experiments. Tumor xenograft in nude mice was employed to determine the influence of LINC00511 and PLD1 on tumor formation and growth of cervical cancer in vivo. LINC00511 might influence the occurrence of cervical cancer by upregulating PLD1 expression via recruiting transcription factor RXRA. LINC00511 and PLD1 expressions were remarkably high in cervical cancer tissues and cells. LINC00511 combined with RXRA, and overexpression of LINC00511 in cervical cancer cells elevated PLD1 expression. Si-LINC00511, si-RXRA or si-PLD1 triggered repression of proliferation and promotion of autophagy and apoptosis of cervical cancer cells. In vivo experiment, si-LINC00511, or si-PLD1 inhibited the tumorigenic ability of nude mice. Collectively, this study suggests that LINC00511 acts as an oncogenic lncRNA in cervical cancer via the promotion of transcription factor RXRA-regulated PLD1.

Synthesis of Hangman Chlorins.

Two complementary rational synthetic routes have been developed in order to synthesize hangman chlorins, which differ with regard to the order of the installation (pre- and post-formation of the chlorin macrocycle) and position of the xanthene backbone about the chlorin periphery. The versatility of the synthetic method is demonstrated with the preparation of ten new hangman chlorins bearing a xanthene backbone and a pendant carboxylic acid. Cyclic voltammograms of hangman chlorins exhibit a hangman effect derived from intermolecular proton transfer. This hangman effect is manifested in catalytic hydrogen evolution production.

SMAD3 inducing the transcription of STYK1 to promote the EMT process and improve the tolerance of ovarian carcinoma cells to paclitaxel.

OBJECTIVE: To figure out the relationship between SMAD3 and serine-threonine tyrosine kinase (STYK1) in ovarian carcinoma cell's paclitaxel resistance. METHODS: The quantitative reverse transcription-polymerase chain reactpostion and Western blot analysis were used to analyze RNA and protein content of SMAD3 and STYK1, respectively. The chromatin immunoprecipitation assay was used to confirm the binding site of SMAD3 to the STYK1 promoter region. Transwell assay was used to detect cell invasion and migration, and Western Blot was used to detect the marker proteins (vimentin and E-cadherin) of epithelial-mesenchymal transition (EMT) process. MTT and apoptosis assay were used to, respectively, measure cell vitality and apoptosis. In vivo experiments, rats were subcutaneously implanted with A2780 cells to establish an animal model of ovarian cancer and the survival curve was drawn. RESULTS: Upregulating SMAD3 induced the expression of STYK1 in ovarian cancer cell lines. STYK1 is a direct transcriptional target of SMAD3. Upregulating STYK1 improved the paclitaxel resistance of ovarian carcinoma cells. Upregulating STYK1 promoted cell invasion, migration, and the EMT process, and SMAD3 had the same effect with STYK1 on cell invasion, cell migration, and the EMT process. The animal assay showed that downregulating STYK1 inhibited the EMT process and the paclitaxel resistance, further promoting the treatment of cervical cancer. CONCLUSION: SMAD3 combined with the promoter region of STYK1 to promote the transcription process of STYK1, thereby promoting the EMT process and paclitaxel resistance of ovarian cancer cells.

Ligand Noninnocence in Nickel Porphyrins: Nickel Isobacteriochlorin Formation under Hydrogen Evolution Conditions.

An electron-deficient nickel porphyrin complex undergoes facile ring reduction to form a nickel isobacteriochlorin complex under hydrogen evolution conditions. Spectroscopic experiments indicate that the reduced nickel porphyrin undergoes subsequent reduction and protonation to form a phlorin anion rather than a metal hydride, demonstrating that the key initial proton-coupled electron transfer step is directed toward the ligand versus the metal. The phlorin anion facilely converts to the isobacteriochlorin in the presence of two-electron and three-proton equivalents. Cyclic voltammetry (CV) and spectroscopic experiments reveal that the four-electron, four-proton electrochemical reduction of nickel porphyrin to isobacteriochlorin occurs promptly in the presence of the strong proton donor tosic acid, followed by hydrogen evolution reaction (HER) catalysis at slightly more negative potentials. CVs of independently synthesized Ni isobacteriochlorin show a catalytic HER at the same potentials as those observed for the HER in CVs of the Ni porphyrin. We find that, under strongly acidic conditions, the HER catalysis arises from conversion of the Ni isobacteriochlorin into a nickel-containing, catalytically active electrode-adsorbed species. These results show that Ni porphyrin converts to Ni isobacteriochlorin under HER catalysis conditions via a ligand-based PCET process and that it is the isobacteriochlorin complex which gives rise to an active HER catalysis.

Array MEMS Vector Hydrophone Oriented at Different Direction Angles.

A new type of array MEMS (Microelectro Mechanical Systems) vector hydrophone has been proposed to solve the left-right ambiguity problem that is commonly found in current ones. Meanwhile, the advantages of good sensitivity and low fabrication cost are maintained. The array MEMS vector hydrophone is integrated by four units oriented at different direction angles. By the aid of this kind of vector hydrophone, not only the exact direction of the sound source can be measured, but also the position obtained. The working principle of the array microstructure has been analyzed and simulated. The result shows that the position of the sound source can be well determined. The prototype of the hydrophone is fabricated based on standard MEMS technology, and its performance is tested in a standing wave tube and an anechoic tank. The testing results show that the array hydrophone exhibits a good consistency of all the four units and satisfactory performance. More importantly, this array hydrophone exhibits excellent ability of positioning with the relatively small angle error. Thus, a MEMS hydrophone with multiple functions and relatively high performance is realized, which has important theoretical and practical significance in relevant applications such as the small-size underwater vehicles.

Seizures and Sleep in the Thalamus: Focal Limbic Seizures Show Divergent Activity Patterns in Different Thalamic Nuclei.

The thalamus plays diverse roles in cortical-subcortical brain activity patterns. Recent work suggests that focal temporal lobe seizures depress subcortical arousal systems and convert cortical activity into a pattern resembling slow-wave sleep. The potential simultaneous and paradoxical role of the thalamus in both limbic seizure propagation, and in sleep-like cortical rhythms has not been investigated. We recorded neuronal activity from the central lateral (CL), anterior (ANT), and ventral posteromedial (VPM) nuclei of the thalamus in an established female rat model of focal limbic seizures. We found that population firing of neurons in CL decreased during seizures while the cortex exhibited slow waves. In contrast, ANT showed a trend toward increased neuronal firing compatible with polyspike seizure discharges seen in the hippocampus. Meanwhile, VPM exhibited a remarkable increase in sleep spindles during focal seizures. Single-unit juxtacellular recordings from CL demonstrated reduced overall firing rates, but a switch in firing pattern from single spikes to burst firing during seizures. These findings suggest that different thalamic nuclei play very different roles in focal limbic seizures. While limbic nuclei, such as ANT, appear to participate directly in seizure propagation, arousal nuclei, such as CL, may contribute to depressed cortical function, whereas sleep spindles in relay nuclei, such as VPM, may interrupt thalamocortical information flow. These combined effects could be critical for controlling both seizure severity and impairment of consciousness. Further understanding of differential effects of seizures on different thalamocortical networks may lead to improved treatments directly targeting these modes of impaired function.SIGNIFICANCE STATEMENT Temporal lobe epilepsy has a major negative impact on quality of life. Previous work suggests that the thalamus plays a critical role in thalamocortical network modulation and subcortical arousal maintenance, but its precise seizure-associated functions are not known. We recorded neuronal activity in three different thalamic regions and found divergent activity patterns, which may respectively participate in seizure propagation, impaired level of conscious arousal, and altered relay of information to the cortex during focal limbic seizures. These very different activity patterns within the thalamus may help explain why focal temporal lobe seizures often disrupt widespread network function, and can help guide future treatments aimed at restoring normal thalamocortical network activity and cognition.

Restoring Conscious Arousal During Focal Limbic Seizures with Deep Brain Stimulation.

Impaired consciousness occurs suddenly and unpredictably in people with epilepsy, markedly worsening quality of life and increasing risk of mortality. Focal seizures with impaired consciousness are the most common form of epilepsy and are refractory to all current medical and surgical therapies in about one-sixth of cases. Restoring consciousness during and following seizures would be potentially transformative for these individuals. Here, we investigate deep brain stimulation to improve level of conscious arousal in a rat model of focal limbic seizures. We found that dual-site stimulation of the central lateral nucleus of the intralaminar thalamus (CL) and the pontine nucleus oralis (PnO) bilaterally during focal limbic seizures restored normal-appearing cortical electrophysiology and markedly improved behavioral arousal. In contrast, single-site bilateral stimulation of CL or PnO alone was insufficient to achieve the same result. These findings support the "network inhibition hypothesis" that focal limbic seizures impair consciousness through widespread inhibition of subcortical arousal. Driving subcortical arousal function would be a novel therapeutic approach to some forms of refractory epilepsy and may be compatible with devices already in use for responsive neurostimulation. Multisite deep brain stimulation of subcortical arousal structures may benefit not only patients with epilepsy but also those with other disorders of consciousness.

Chlorophyll-Inspired Red-Region Fluorophores: Building Block Synthesis and Studies in Aqueous Media.

Fluorophores that absorb and emit in the red spectral region (600-700 nm) are of great interest in photochemistry and photomedicine. Eight new target chlorins (and 19 new chlorins altogether)-analogues of chlorophyll-of different polarities have been designed and synthesized for various applications; seven of the chlorins are equipped with a bioconjugatable tether. Hydrophobic or amphiphilic chlorins in a non-polar organic solvent (toluene), polar organic solvent (DMF), and aqueous or aqueous micellar media show a sharp emission band in the red region and modest fluorescence quantum yield (Φf = 0.2-0.3). A Poisson analysis implies most micelles are empty and few contain >1 chlorin. Water-soluble chlorins each bearing three PEG (oligoethyleneglycol) groups exhibit narrow emission bands (full-width-at-half maximum <25 nm). The lifetime of the lowest singlet excited state and the corresponding yields and rate constants for depopulation pathways (fluorescence, intersystem crossing, internal conversion) are generally little affected by the PEG groups or dissolution in aqueous or organic media. A set of chlorin-avidin conjugates revealed a 2-fold increase in Φf with increased average chlorin/avidin ratio (2.3-12). In summary, the chlorins of various polarities described herein are well suited as red-emitting fluorophores for applications in aqueous or organic media.

The Development of the Differential MEMS Vector Hydrophone.

To solve the problem that MEMS vector hydrophones are greatly interfered with by the vibration of the platform and flow noise in applications, this paper describes a differential MEMS vector hydrophone that could simultaneously receive acoustic signals and reject acceleration signals. Theoretical and simulation analyses have been carried out. Lastly, a prototype of the differential MEMS vector hydrophone has been created and tested using a standing wave tube and a vibration platform. The results of the test show that this hydrophone has a high sensitivity, Mv = -185 dB (@ 500 Hz, 0 dB reference 1 V/µPa), which is almost the same as the previous MEMS vector hydrophones, and has a low acceleration sensitivity, Mv = -58 dB (0 dB reference 1 V/g), which has decreased by 17 dB compared with the previous MEMS vector hydrophone. The differential MEMS vector hydrophone basically meets the requirements of acoustic vector detection when it is rigidly fixed to a working platform, which lays the foundation for engineering applications of MEMS vector hydrophones.