Online Monitoring of Lactate Efflux by Multi-Channel Microfluidic Chip-Mass Spectrometry for Rapid Drug Evaluation

An online multichannel microfluidic chip-mass spectrometry (MS) platform was developed for cell metabolism studies. Paper-spray ionization was employed for microsampling from different microchannels and, at the same time, the interface for direct MS analysis without any sample pretreatment. Near-real-time MS sensing of lactate in different microfluidic channels could be achieved in a preprogrammed and automatic manner. Influences of hypoxia on lactate efflux from normal cells and cancer cells, as well as the differential inhibitory effects and dose–response information on α-cyano-4-hydroxycinnamate on cancer cells of different types were exhibited. The potential of further coupling MS, complementary to optical and electrochemical techniques, to microfluidic devices for cell studies was thus demonstrated

Table_1_Diet of the earliest modern humans in East Asia.DOCX

Reconstructing diet can offer an improved understanding toward the origin and evolution of modern humans. However, the diet of early modern humans in East Asia is poorly understood. Starch analysis of dental calculus is harmless to precious fossil hominins and provides the most direct evidence of plant food sources in early modern human dietary records. In this paper, we examined the starch grains in dental calculus from Fuyan Cave hominins in Daoxian (South China), which were the earliest modern humans in East Asia. Our results reveal the earliest direct evidence of a hominin diet made of acorns, roots, tubers, grass seeds, and other yet-unidentified plants in marine isotope stage 5 between 120 and 80 ka. Our study also provides the earliest evidence that acorns may have played an important role in subsistence strategies. There may have been a long-lasting tradition of using these plants during the Late Pleistocene in China. Plant foods would have been a plentiful source of carbohydrates that greatly increased energy availability to human tissues with high glucose demands. Our study provides the earliest direct consumption of carbohydrates-rich plant resources from modern humans in China for the first time. In addition, it also helps elucidate the evolutionary advantages of early modern humans in the late Middle and early Upper Pleistocene.</p

DataSheet1_Dapagliflozin promotes angiogenesis in hindlimb ischemia mice by inducing M2 macrophage polarization.docx

Critical limb ischemia (CLI) is associated with a higher risk of limb amputation and cardiovascular death. Dapagliflozin has shown great potential in the treatment of cardiovascular disease. However, the effects of dapagliflozin on CLI and the underlying mechanisms have not been fully elucidated. We evaluated the effect of dapagliflozin on recovery from limb ischemia using a mouse model of hindlimb ischemia. The flow of perfusion was evaluated using a laser Doppler system. Tissue response was assessed by analyzing capillary density, arterial density, and the degree of fibrosis in the gastrocnemius muscle. Immunofluorescence and Western blot were used to detect the expression of macrophage polarization markers and inflammatory factors. Our findings demonstrate the significant impact of dapagliflozin on the acceleration of blood flow recovery in a hindlimb ischemia mouse model, concomitant with a notable reduction in limb necrosis. Histological analysis revealed that dapagliflozin administration augmented the expression of key angiogenic markers, specifically CD31 and α-SMA, while concurrently mitigating muscle fibrosis. Furthermore, our investigation unveiled dapagliflozin’s ability to induce a phenotypic shift of macrophages from M1 to M2, thereby diminishing the expression of inflammatory factors, including IL-1β, IL-6, and TNF-α. These effects were partially mediated through modulation of the NF-κB signaling pathway. Lastly, we observed that endothelial cell proliferation, migration, and tube-forming function are enhanced in vitro by utilizing a macrophage-conditioned medium derived from dapagliflozin treatment. Taken together, our study provides evidence that dapagliflozin holds potential as an efficacious therapeutic intervention in managing CLI by stimulating angiogenesis, thereby offering a novel option for clinical CLI treatment.</p

Additional file 1 of A rare case of anti-DPPX encephalitis combined with neuroleptospirosis

Supplementary Material

Profiling DNA Cargos in Single Extracellular Vesicles via Hydrogel-Based Droplet Digital Multiple Displacement Amplification

Due to the substantial heterogeneity among extracellular vesicle (EV) subpopulations, single-EV analysis has the potential to elucidate the mechanisms behind EV biogenesis and shed light on the myriad functions, leading to the development of novel diagnostics and therapeutics. While many studies have been devoted to reveal between-EV variations in surface proteins and RNAs, DNA cargos (EV-DNA) have received little attention. Here, we report a hydrogel-based droplet digital multiple displacement amplification approach for the comprehensive analysis of EV-DNA at the single-EV level. Single EVs are dispersed in thousands of hydrogel droplets and lysed for DNA amplification and identification. The droplet microfluidics strategy empowers the assay with single-molecule sensitivity and capability for absolute quantification of DNA-containing EVs. In particular, our findings indicate that 5–40% EVs are associated with DNA, depending on the cell of origin. Large EVs exhibit a higher proportion of DNA-containing EVs and a more substantial presence of intraluminal DNA, compared to small EVs. These DNA-containing EVs carry multiple DNA fragments on average. Furthermore, both double-stranded DNA and single-stranded DNA were able to be detected at the single-EV level. Utilizing this method, the abundance, distribution, and biophysical properties of EV-DNA in various EV populations are evaluated. The DNA level within EVs provides insight into the status of the originating cells and offers valuable information on the outcomes of anticancer treatments. The utilization of single-EV analysis for EV-DNA holds significant promise for early cancer detection and treatment response monitoring

Brain MRI changes and CDMS conversion.

<p>UON, unilateral optic neuritis; n, number; DIS, dissemination of the lesion in space; DIT, dissemination of the lesion over time.</p><p>Brain MRI changes and CDMS conversion.</p

Comparison of systematically relevant traits in MLDG 1678¹.

<p>¹Abbreviations: LPHO = Lower Pleistocene <i>Homo</i>; MPHO = Middle Pleistocene <i>Homo</i>; NEAN = Neanderthals; MPMH = Middle Pleistocene Modern Humans; EULU = Early Upper-Late Upper Palaeolithic humans. ST = subtrochanteric region; MS = mid-shaft region; AP = anteroposterior diameter; ML = mediolateral diameter.</p><p>Sample compositions, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143332#pone.0143332.s004" target="_blank">S1 Table</a>.</p><p>Comparison of systematically relevant traits in MLDG 1678<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143332#t002fn001" target="_blank">¹</a>.</p

Patient demographic characteristics.

<p>n, number; SON, severe optic neuritis (visual acuity ≤10/100).</p><p>Patient demographic characteristics.</p

Metric data for the Maludong femur (MLDG 1678).

<p>¹Calculated by dividing the relevant area by reconstructed body mass, after Ref [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143332#pone.0143332.ref034" target="_blank">34</a>].</p><p>Metric data for the Maludong femur (MLDG 1678).</p

A Hominin Femur with Archaic Affinities from the Late Pleistocene of Southwest China - Fig 3

<p>Scatterplots comparing sample medians for mid-shaft (MS) variables, size-adjusted variables and mid-shaft/subtrochanteric area index: (A) Anteroposterior (AP) diameter (mm). (B) Mediolateral (ML) diameter (mm). (C) Total area (TA: mm²). (D) Cortical area (CA: mm²). (E) %-Cortical area (%-CA). (F) Size-adjusted total area. (G) Size-adjusted cortical area. (H) Pilastric index (%). (I) Mid-shaft/subtrochanteric (MS/ST) area index (%). (Error bars = 95% confidence interval of median [dark] and 1.5 x interquartile range [light]; Abbreviations: LPHO = Lower Pleistocene <i>Homo</i>; MPHO = Middle Pleistocene <i>Homo</i>; NEAN = Neanderthals; MPMH = Middle Pleistocene Modern Humans; EULU = Early Upper-Late Upper Palaeolithic humans [see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143332#pone.0143332.s004" target="_blank">S1 Table</a>]).</p