Microelectrochemical Sensor Reveals Tunneling Nanotube-Mediated Intercellular Communication of Endothelial Mechanotransduction.

The intercellular communication of mechanotransduction has a significant impact on various cellular processes. Tunneling nanotubes (TNTs) have been documented to possess the capability of transmitting mechanical stimulation between cells, thereby triggering an influx of Ca2+ ions. However, the related kinetic information on the TNT-mediated intercellular mechanotransduction communication is still poorly explored. Herein, we developed a classic and sensitive Pt-functionalized carbon fiber microelectrochemical sensor (Pt/CF) to study the intercellular communication of endothelial mechanotransduction through TNTs. The experimental findings demonstrate that the transmission of mechanical stimulation from stimulated human umbilical vein endothelial cells (HUVECs) to recipient HUVECs connected by TNTs occurred quickly (<100 ms) and effectively promoted nitric oxide (NO) production in the recipient HUVECs. The kinetic profile of NO release exhibited remarkable similarity in stimulated and recipient HUVECs. But the production of NO in the recipient cell is significantly attenuated (16.3%) compared to that in the stimulated cell, indicating a transfer efficiency of approximately 16.3% for TNTs. This study unveils insights into the TNT-mediated intercellular communication of mechanotransduction.

Taxonomic, Phylogenomic and Bioactivity Profiling of Novel Phycosphere Bacterium from Model Cyanobacterium Synechococcus elongatus PCC 7942.

Phycosphere niches host rich microbial consortia that harbor dynamic algae-bacteria interactions with fundamental significance in varied natural ecosystems. Hence, culturing the uncultured microbial majority of the phycosphere microbiota is vital for deep understanding of the intricate mechanisms governing the dynamic interactions, and also to provide novel and rich microbial resources, and to discover new natural bioactive metabolites. Synechococcus elongatus PCC 7942 is a robust model cyanobacterium widely used in environment, synthesis biology, and biotechnology research. To expand the number of novel phycosphere species that were brought into culture and to discover the natural bioactivities, we presented a new yellow-pigmented bacterium named ABI-127-1, which was recovered from the phycosphere of PCC 7942, using an optimized bacterial isolation procedure. Combined polyphasic taxonomic and phylogenomic characterization was performed to confidently identify the new isolate as a potential novel species belonging to the genus Qipengyuania. The observed bioactivity of strain ABI-127-1 with promoting potential towards the growth and CO2 fixation efficiency of the host microalgae was measured. Additionally, the bacterial production of active bioflocculant exopolysaccharides was evaluated after culture optimization. Thus, these findings revealed the potential environmental and biotechnological implications of this new microalgae growth-promoting bacterium isolated from the phycosphere microenvironment.

Sensitive quantitation of ultra-trace toxic aconitines in complex matrices by perfusion nano-electrospray ionization mass spectrometry combined with gas-liquid microextraction.

The accurate analysis of ultra-trace (e.g. <10-4 ng/mL) substances in complex matrices is a burdensome but vital problem in pharmaceutical analysis, with important implications for precise quality control of drugs, discovery of innovative medicines and elucidation of pharmacological mechanisms. Herein, an innovative constant-flow perfusion nano-electrospray ionization (PnESI) technique was developed firstly features significant quantitative advantages in high-sensitivity ambient MS analysis of complex matrix sample. More importantly, double-labeled addition enrichment quantitation strategies of gas-liquid microextraction (GLME) were proposed for the first time, allowing highly selective extraction and enrichment of specific target analytes in a green and ultra-efficient (>1000-fold) manner. Using complex processed Aconitum herbs as example, PnESI-MS directly enabled the qualitative and absolute quantitative analysis of the processed Aconitum extracts and characterized the target toxic diester alkaloids with high sensitivity, high stability, wide linearity range, and strong resistance to matrix interference. Further, GLME device was applied to obtain the highly specific enrichment of the target diester alkaloids more than 1000-fold, and accurate absolute quantitation of trace aconitine, mesaconitine, and hypaconitine in the extracts of Heishunpian, Zhichuanwu and Zhicaowu was accomplished (e.g., 0.098 pg/mL and 0.143 pg/mL), with the quantitation results well below the LODs of aconitines from any analytical instruments available. This study built a systematic strategy for accurate quantitation of ultra-trace substances in complex matrix sample and expected to provide a technological revolution in many fields of pharmaceutical research.

United States Life Tables, 2021.

Objectives-This report presents complete period life tables for the United States by Hispanic origin and race and sex, based on age-specific death rates in 2021. Methods-Data used to prepare the 2021 life tables are 2021 final mortality statistics; July 1, 2021, population estimates based on the Blended Base population estimates produced by the U.S. Census Bureau; and 2021 Medicare data for people ages 66-99. The methodology used to estimate life tables for the Hispanic population remains unchanged from that developed for the publication of life tables by Hispanic origin for data year 2006. The same methodology is used to estimate life tables for the American Indian and Alaska Native non-Hispanic and Asian non-Hispanic populations. The methodology used to estimate the 2021 life tables for all other groups was first implemented with data year 2008. Results-In 2021, the overall expectation of life at birth was 76.4 years, decreasing 0.6 year from 77.0 in 2020. From 2020 to 2021, life expectancy at birth decreased by 0.7 year for males (from 74.2 to 73.5) and by 0.6 year for females (79.9 to 79.3). Between 2020 and 2021, life expectancy decreased by 1.5 years for the American Indian and Alaska Native non-Hispanic population (67.1 to 65.6), 0.7 year for the White non-Hispanic population (77.4 to 76.7), 0.3 year for the Black non-Hispanic population (71.5 to 71.2), 0.1 year for the Hispanic population (77.9 to 77.8), and 0.1 year for the Asian non-Hispanic population (83.6 to 83.5).

Deaths: Final Data for 2020.

Objective-This report presents final 2020 data on U.S. deaths, death rates, life expectancy, infant and maternal mortality, and trends by selected characteristics such as age, sex, Hispanic origin and race, state of residence, and cause of death. Methods-Information reported on death certificates is presented in descriptive tabulations. The original records are filed in state registration offices. Statistical information is compiled in a national database through the Vital Statistics Cooperative Program of the National Center for Health Statistics. Causes of death are processed according to the International Classification of Diseases, 10th Revision. Beginning in 2018, all states and the District of Columbia were using the 2003 revised certificate of death for the entire year, which includes the 1997 Office of Management and Budget revised standards for race. Data based on these revised standards are not completely comparable to previous years. Results-In 2020, a total of 3,383,729 deaths were reported in the United States. The age-adjusted death rate was 835.4 deaths per 100,000 U.S. standard population, an increase of 16.8% from the 2019 rate. Life expectancy at birth was 77.0 years, a decrease of 1.8 years from 2019. Age-specific death rates increased from 2019 to 2020 for age groups 15 years and over and decreased for age group under 1 year. Many of the 15 leading causes of death in 2020 changed from 2019. COVID-19, a new cause of death in 2020, became the third leading cause in 2020. The infant mortality rate decreased 2.9% to a historic low of 5.42 infant deaths per 1,000 live births in 2020. Conclusions-In 2020, the age-adjusted death rate increased and life expectancy at birth decreased for the total, male, and female populations, primarily due to the influence of deaths from COVID-19.

Combination of Internal Extractive Electrospray Ionization Mass Spectrometry and Statistical Analysis for High-Throughput Molecular Differentiation of Rehmannia glutinosa Samples.

Rehmannia glutinosa (Gaert.) Libosch. ex Fisch. et Mey. is a perennial herb of the Scrophulariaceae family, which has long enjoyed a good reputation in China, and has a wide range of pharmacological effects and clinical applications. The place of origin is an important factor affecting the chemical composition of R. glutinosa, resulting in different pharmacological effects. Herein, internal extractive electrospray ionization mass spectrometry (iEESI-MS) combined with statistical techniques was established for high-throughput molecular differentiation of different R. glutinosa samples. Dried and processed R. glutinosa samples from four different places of origin were analyzed by iEESI-MS with high throughput (>200 peaks) and rapidness (<2 min/sample) without sample pretreatment. Clear separation models created by OPLS-DA were then established for distinguishing the places of origin of dried and processed R. glutinosa by using the obtained MS data. In addition, the molecular differences between the pharmacological effects of dried and processed R. glutinosa were also investigated by OPLS-DA, and 31 different components were screened out. This work provides a promising method for evaluating the quality of traditional Chinese medicines and studying the biochemical mechanism of processing.

Provisional Mortality Data - United States, 2022.

The National Center for Health Statistics' (NCHS) National Vital Statistics System (NVSS) collects and reports annual mortality statistics using U.S. death certificate data. Because of the time needed to investigate certain causes of death and to process and review death data, final annual mortality data for a given year are typically released 11 months after the end of the calendar year. Provisional data, which are based on the current flow of death certificate data to NCHS, provide an early estimate of deaths, before the release of final data. NVSS routinely releases provisional mortality data for all causes of death and for deaths associated with COVID-19.* This report is an overview of provisional U.S. mortality data for 2022, including a comparison with 2021 death rates. In 2022, approximately 3,273,705 deaths† occurred in the United States. The estimated 2022 age-adjusted death rate decreased by 5.3%, from 879.7 per 100,000 persons in 2021 to 832.8. COVID-19 was reported as the underlying cause or a contributing cause in an estimated 244,986 (7.5%) of those deaths (61.3 deaths per 100,000). The highest overall death rates by age, race and ethnicity, and sex occurred among persons who were aged ≥85 years, non-Hispanic American Indian or Alaska Native (AI/AN), non-Hispanic Black or African American (Black), and male. In 2022, the four leading causes of death were heart disease, cancer, unintentional injuries, and COVID-19. Provisional death estimates provide an early indication of shifts in mortality trends and can guide public health policies and interventions aimed at reducing mortality, including deaths directly or indirectly associated with the COVID-19 pandemic.

COVID-19 Mortality Update - United States, 2022.

The National Center for Health Statistics' (NCHS) National Vital Statistics System (NVSS) collects and reports annual mortality statistics using U.S. death certificate data. Provisional data, which are based on the current flow of death certificate data to NCHS, provide an early estimate of deaths before the release of final data.* This report summarizes provisional U.S. COVID-19 death data for 2022. In 2022, COVID-19 was the underlying (primary) or contributing cause in the chain of events leading to 244,986 deaths† that occurred in the United States. During 2021-2022, the estimated age-adjusted COVID-19-associated death rate decreased 47%, from 115.6 to 61.3 per 100,000 persons. COVID-19 death rates were highest among persons aged ≥85 years, non-Hispanic American Indian or Alaska Native (AI/AN) populations, and males. In 76% of deaths with COVID-19 listed on the death certificate, COVID-19 was listed as the underlying cause of death. In the remaining 24% of COVID-19 deaths, COVID-19 was a contributing cause. As in 2020 and 2021, during 2022, the most common location of COVID-19 deaths was a hospital inpatient setting (59%). However, an increasing percentage occurred in the decedent's home (15%), or a nursing home or long-term care facility (14%).§ Provisional COVID-19 death estimates provide an early indication of shifts in mortality trends and can help guide public health policies and interventions aimed at reducing COVID-19-associated mortality.

Metabolite Fingerprinting for Identification of Panax ginseng Metabolites Using Internal Extractive Electrospray Ionization Mass Spectrometry.

Ginseng, a kind of functional food and medicine with high nutritional value, contains various pharmacological metabolites that influence human metabolic functions. Therefore, it is very important to analyze the composition and metabolites of ginseng. However, the analysis of active metabolites in ginseng samples usually involves various experimental steps, such as extraction, chromatographic separation, and characterization, which may be time-consuming and laborious. In this study, an internal extractive electrospray ionization mass spectrometry (iEESI-MS) method was developed to analyze active metabolites in ginseng samples with sequential sampling and no pretreatment. A total of 44 metabolites, with 32 ginsenosides, 6 sugars, and 6 organic acids, were identified in the ginseng samples. The orthogonal partial least-squares discriminant analysis (OPLS-DA) score plot showed a clear separation of ginseng samples from different origins, indicating that metabolic changes occurred under different growing conditions. This study demonstrated that different cultivation conditions of ginseng can be successfully discriminated when using iEESI-MS-based metabolite fingerprints, which provide an alternative solution for the quality identification of plant drugs.

Online Sequential Determination of Organic/Inorganic Lead Speciation in PM2.5 Using Electrochemical Mass Spectrometry.

The information regarding the occurrence and abundance of lead (Pb) in PM2.5 is useful for the evaluation of air pollution status and tracing the pollution source. Herein, electrochemical mass spectrometry (EC-MS) for sequential determination of Pb species in PM2.5 samples without sample pretreatment has been developed using the combination of online sequential extraction with mass spectrometry (MS) detection. Four kinds of Pb species including water-soluble Pb compounds, fat-soluble Pb compounds, water/fat-insoluble Pb compounds, and a water/fat-insoluble Pb element were sequentially extracted from PM2.5 samples, in which water-soluble Pb compounds, fat-soluble Pb compounds, and water/fat-insoluble Pb compounds were extracted sequentially by elution using H2O, CH3OH, and EDTA-2Na as the eluent respectively, while the water/fat-insoluble Pb element was extracted by electrolysis using EDTA-2Na as the electrolyte. The extracted water-soluble Pb compounds, water/fat-insoluble Pb compounds, and water/fat-insoluble Pb element were transformed into EDTA-Pb in real time for online electrospray ionization mass spectrometry analysis, while the extracted fat-soluble Pb compounds were directly detected by electrospray ionization mass spectrometry. The advantages of the reported method include the obviation of sample pretreatment, high speed of analysis (<60 min/sample), low detection limit (0.16 pg), low sample consumption (30 µg), and high accuracy (>90%), which indicates the potential of this method for the rapid quantitative species detection of metals in environmental particulate matter samples.

Purification of quantum dot-based bioprobes with a salting out strategy.

A salting out strategy is reported for purification of IgG-conjugated QD (IgG-QD) bioprobes. Adding NaCl can precipitate free IgG selectively, while the IgG-QD maintains good colloidal stability. The dynamic light scattering technique reveals that this is due to the relatively positive zeta potential of free IgG than that of the IgG-QD.

U.S. State Life Tables, 2020.

Objectives-This report presents complete period life tables for each of the 50 states and the District of Columbia (D.C.) by sex based on age-specific death rates in 2020.

United States Life Tables, 2020.

Objectives-This report presents complete period life tables for the United States by Hispanic origin, race, and sex, based on age-specific death rates in 2020.

Polarity-Specific Profiling of Metabolites in Single Cells by Probe Electrophoresis Mass Spectrometry.

Sensitive analysis of metabolites in a single cell is of fundamental significance for the better understanding of biological variability, differential susceptibility in disease therapy, and cell-to-cell heterogeneity as well. Herein, polarity-specific profiling of metabolites in a single cell was implemented by probe electrophoresis mass spectrometry (PEMS), which combined electrophoresis sampling of metabolites from a single cell and nanoelectrospray ionization-mass spectrometry (nanoESI-MS) analysis of the sampled metabolites. Enhanced extraction of either negatively or positively charged metabolites from a single cell was achieved by applying a DC voltage offset of +2.0 and -2.0 V to the probe, respectively. The experimental data demonstrated that PEMS features high throughput (≥200 peaks) and high sensitivity (≥10-times signal enhancement for [Choline + H]+, [Glutamine + H]+, [Arginine + H]+, etc.) in comparison with direct nanoESI-MS analysis. The biological effects of CdSe quantum dots (QDs) and γ-radiation on Allium cepa cells were investigated by PEMS, which revealed that CdSe QDs lead to the increase of intracellular amines while γ-radiation causes the decrease of intracellular acids. Therefore, this work provides an alternative platform to probe novel insights of cells by sensitive analysis of polarity-specific metabolites in a single cell.

United States Life Tables, 2019.

This report presents complete period life tables for the United States by Hispanic origin, race, and sex, based on age-specific death rates in 2019. Starting with the 2019 data year, this report adds life tables for the non-Hispanic American Indian or Alaska Native (AIAN) and non-Hispanic Asian populations.

Combination of Electrochemistry and Mass Spectrometry to Study Nitric Oxide Metabolism and Its Modulation by Compound K in Breast Cancer Cells.

The levels of l-arginine and asymmetric dimethylarginine (ADMA) and the amount of the nitric oxide (NO) production have recently been linked to breast cancer and pharmaceutical effect evaluation. Herein, a method combining electrochemistry and high-resolution mass spectrometry (HRMS) was established and used to study NO metabolism and its modulation by ginsenoside compound K (CK) in breast cancer cells. Platinum nanoparticles-decorated fluorine tin oxide was employed as an electrochemical sensor for in situ detection of NO release, while HRMS was used for the analysis of the NO-related metabolites. Through the combination of the electrochemical and HRMS results, decreases in arginine and NO and increases in ADMA and ornithine were observed after modulation by CK, and two highly correlated metabolic pathways including arginine and proline metabolism and vascular smooth muscle contraction were found. This method offers a new strategy for fast evaluation of pharmaceutical efficacy based on NO metabolism.

Molecular differentiation of Panax notoginseng grown under different conditions by internal extractive electrospray ionization mass spectrometry and multivariate analysis.

Panax notoginseng is a highly valuable and widely used herb in traditional Chinese medicine. The quality and efficacy of Panax notoginseng grown under different conditions can greatly vary due to the differences in chemical composition. The analysis of chemical composition in Panax notoginseng typically involves various experimental steps including extraction, chromatographic separation and characterization, which can be time- and labor-consuming. Therefore, the efficient quality assessment and control of Panax notoginseng requires the development of more rapid methods for the chemical characterization and classification of Panax notoginseng. In this study, a method based on internal extractive electrospray ionization mass spectrometry (iEESI-MS) was developed to characterize chemical components of Panax notoginseng samples under different growth conditions (e.g., place of origin, soil quality, growth season) at the speed of 0.5 min per sample, without sample pretreatment and chromatographic separation. A total of 35 chemical components, including sugars, saponins, organic acids, etc., were identified in Panax notoginseng samples. Clear separation was observed in the multivariate analysis of the iEESI-MS data from Panax notoginseng samples grown under different conditions. The difference in the content of sucrose, fructose, Rg1, Rf, Rb1, Noto-R1, malonyl-Rb1, malonyl-Rg1, malonyl-Rf, Rd, Re, linoleic acid, palmitic acid and malic acid can be used as key characteristic indicators to discriminate origin, commercial specifications, and cultivation conditions of Panax notoginseng samples. The results of our study indicate the high power of iEESI-MS for the rapid molecular characterization and classification of Panax notoginseng under different growth conditions, which can be used for the quality assessment of traditional herbal medicines as well as in pharmaceutical and clinical analysis.

Mortality in the United States, 2021.

This report presents final 2021 U.S. mortality data on deaths and death rates by demographic and medical characteristics. These data provide information on mortality patterns among U.S. residents by variables such as sex, age, race and Hispanic origin, and cause of death. Life expectancy estimates, ageadjusted death rates, age-specific death rates, the 10 leading causes of death,infant mortality rates, and the 10 leading causes of infant death were analyzed by comparing 2021 and 2020 final data (1).

Mortality Profile of the Non-Hispanic American Indian or Alaska Native Population, 2019.

Objectives-This report presents a mortality profile of the U.S. non-Hispanic American Indian or Alaska Native (AIAN) population for 2019. Standard mortality statistics, adjusted for race and Hispanic-origin misclassification on death certificates, are provided along with comparisons with the three major U.S. populations: non-Hispanic white, non-Hispanic black, and Hispanic.

Online discovery of the molecular mechanism for directionally detoxification of Fuzi using real-time extractive electrospray ionization mass spectrometry.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii Debeaux, a famous traditional medicinal herb for collapse, rheumatic fever, and painful joints, always raises global concerns about its fatal toxicity from toxic alkaloids when improperly processed. Therefore, it is urgent to clarify the internal molecular mechanism of processing detoxification on Aconitum and develop simple and reliable approaches for clinical application, which is also of great significance to the rational medicinal use of Aconitum. AIM OF THE STUDY: The study aimed at developing a complete molecular mechanism exploration strategy in complex medicinal herb decocting system, clarifying the internal molecular mechanism of processing detoxification on Aconitum, and exploring valid approaches for detoxification. MATERIALS AND METHODS: Aconiti Lateralis Radix Praeparata (Fuzi) was selected as the model for exploring the complex Aconitum detoxification mechanism using an advanced online real-time platform based on extractive electrospray ionization mass spectrometry. The methods realized the sensitive capture of dynamic trace intermediates, accurate qualitative and quantitative analysis, and real-time and long-term monitoring of multi-components with satisfactory accuracy and resistance to complex matrices. RESULTS: Components in the complex Aconitum decocting system were real-timely characterized and fat meat was discovered and verified to directionally detoxify Aconitum while reserving the therapy effect. More importantly, the dynamic detoxification mechanism in the chemically complex Aconitum decoction was molecularly profiled. A novel reaction pathway based on nucleophilic substitution reaction mechanism was proposed. As confirmed by the theoretic calculations at DFT B3LYP/6-31G (d) levels, fatty acids (e.g., palmitic acid) acted as a green, cheap, and high-performance catalyst and promote the decomposition of toxic diester alkaloids to non-toxic and active benzoyl-monoester alkaloids through the discovered mechanism. CONCLUSION: The study exposed a novel detoxification molecular mechanism of Aconitum and provided an effective method for the safe use of Aconitum, which could effectively guide the development of traditional processing technology and compatibility regulation of the toxic herb and had great value to the modernization and standardization development of traditional medicine.