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How variations in carbon supply affect wood formation remains poorly understood in particular in mature forest trees. To elucidate how carbon supply affects carbon allocation and wood formation, we attempted to manipulate carbon supply to the cambial region by phloem girdling and compression during the mid‐ and late‐growing season and measured effects on structural development, CO2 efflux and nonstructural carbon reserves in stems of mature white pines. Wood formation and stem CO2 efflux varied with a location relative to treatment (i.e., above or below the restriction). We observed up to twice as many tracheids formed above versus below the treatment after the phloem transport manipulation, whereas the cell‐wall area decreased only slightly below the treatments, and cell size did not change relative to the control. Nonstructural carbon reserves in the xylem, needles and roots were largely unaffected by the treatments. Our results suggest that low and high carbon supply affects wood formation, primarily through a strong effect on cell proliferation, and respiration, but local nonstructural carbon concentrations appear to be maintained homeostatically. This contrasts with reports of decoupling of source activity and wood formation at the whole‐tree or ecosystem level, highlighting the need to better understand organ‐specific responses, within‐tree feedbacks, as well as phenological and ontogenetic effects on sink‐source dynamics. Wood formation and carbon allocation in mature forest trees are two important processes of the terrestrial carbon cycle, which both lack a mechanistic understanding. By girdling and temporarily compressing the phloem of mature white pine at Harvard Forest, we found that carbon supply variation due to these restrictions in phloem transport affected wood formation and stem respiration without substantially changing local nonstructural carbon reserves. We also observed large changes in the number of cells formed, correlating strongly with the presumed carbon supply gradient. In contrast, changes in cell‐wall thickness along the presumed carbon supply gradient were relatively small and cell size was not detectably affected. The presented carbon sensitivity of cambial cell division, cell elongation and cell‐wall thickening, as well as the effects on stem CO2 efflux and local nonstructural carbon reserves present significant advances in our understanding of wood formation and carbon allocation in forest trees with repercussions on the debate of source‐ versus sink‐limitation of growth in trees. [ABSTRACT FROM AUTHOR]

A systematic procedure for the determination of purity values of amino acid reference materials was developed by use of mass balance method where four categories of impurities (related structure impurities (RSIs), water, organic solvent residue (OSR), and non-volatile residue (NVR)) were quantified separately. The amount of RSIs was determined using a combination of three quantification methods. To ensure metrological traceability in the determination of RSIs, at least one such impurity in each candidate amino acid reference material was quantified using liquid chromatography–isotope dilution tandem mass spectrometry (LC-IDMS/MS). Other RSIs were determined using external calibration liquid chromatography–tandem mass spectrometry (LC-MS/MS) or o-phthaldialdehyde (OPA) derivatization, followed by liquid chromatography–ultraviolet (LC-UV) measurement. As the UV absorption of most RSIs came basically from the same chromophore after OPA derivatization, a relative peak area approach was used in the LC-UV method to quantify the amount of RSIs by comparing their peak areas with that of a reference RSI. The reference RSI was pre-selected and the amount determined by LC-IDMS/MS separately. The absence of D-amino acids was confirmed using Marfey's reagent derivatization, followed by LC-UV analysis. The amounts of water, OSR, and NVR were measured using Karl Fischer coulometry, gas chromatography–mass spectrometry (GC-MS) and thermogravimetry, respectively. By using this procedure, four amino acid (L-valine, L-leucine, L-isoleucine, and L-phenylalanine) certified reference materials (CRMs) were developed from the candidate materials. The homogeneity and stability of the CRMs were demonstrated by use of LC-IDMS/MS or OPA-LC-UV method, following the principles in ISO 17034 and ISO Guide 35. Graphical abstract [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke is a serious cardiovascular disease with high morbidity and mortality rates that affects millions of people worldwide.Currently, the only therapy with proven efficacy for acute ischemic stroke is alteplase, however, it still has many shortcomings and limitations. Therefore,we screen new compounds from traditional Chinese medicine to explore their efficacy against ischemic reperfusion injury. Procyanidins, a natural productextracted from grapes seed, which have been shown can ameliorate cerebral ischemic injury. However, the underlying mechanism is still not very clear. Theaim of this study was to investigate the effect of procyanidins on middle cerebral artery occlusion/reperfusion (MCAO/R)-mediated cerebral ischemic injuryand its underlying possible mechanisms. Methods: SD rats were used to evaluate the effect of procyanidins on MCAO/R induced cerebral ischemic injury in vivo. Histological analysis was used toassess neuronal apoptosis. Cell signaling was assayed by Western blot. Results: In this study, we found that procyanidins can significantly ameliorate the middle cerebral artery occlusion/reperfusion (MCAO/R)-mediatedneurological deficits, and relieved brain edema, cerebral infarction volume, histopathological damage and apoptosis in rats. In addition, procyanidins canalso markedly inhibit MCAO/R and oxygen-glucose deprivation/reoxygenation (OGD/R)-mediated activation of TLR4-p38-NF-κB-NLRP3 signalingpathway in vitro and in vivo. Moreover, procyanidins can inhibit MCAO/R and OGD/R-induced the production of inflammatory cytokines such asinterleukin-1β (IL-1β) in vitro and in vivo. Besides, treatment with TLR4 inhibitor (Cli-095) in BV2 cell also shows the same effect. Conclusion: Altogether, these data suggested that procyanidins exerted a potential neuroprotective effect may by inhibit the TLR4-p38-NF-κB-NLRP3signaling pathway in the brain in MCAO/R rats. [ABSTRACT FROM AUTHOR]

[Display omitted] • A NIR fluorogenic probe Cy-PITC with mitochondrially-targeted ability has been elaborately developed by the novel analyte-replacement strategy. • NIR probe Cy-PITC showed excellent performances for ClO−/HClO including ultrafast response time (within 5 s) and ultralow LOD (2.28 nM). • NIR probe Cy-PITC was triumphantly applied in the fluorescence imaging of exogenous/endogenous mitochondrial ClO−/HClO inside living cells. • NIR probe Cy-PITC was successfully employed for early diagnosis of ClO−/HClO-related rheumatoid arthritis joint tissues. [ABSTRACT FROM AUTHOR]

Reference measurement procedures are essential for the accurate measurement of urea in human serum. The widely used gas chromatography-isotope dilution mass spectrometry (GC–IDMS) involves tedious derivatization processes. We developed and validated a simple liquid chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS) method for the measurement of urea in human serum. In this method, 13 C, 15 N 2 -urea was spiked into serum samples as the internal standard, and pure urea certified reference material (CRM) was used as the calibration standard to ensure the traceability of the measurements to the International System of Units (SI). The sample cleanup procedure involved a simple protein precipitation step, followed by centrifugation and filtration. The developed LC-IDMS/MS method was found to be accurate and highly reproducible. The coefficient of variation (CV) was generally below 1%. Good accuracy was demonstrated by measuring serum CRMs from two National Metrology Institutes (NMIs) with relative deviations from the certified values being close to or below 1%, and measurement uncertainties of 2.0%–2.8%. The method was used to assign the reference values of serum urea in ten cycles of an external quality assessment (EQA) program for clinical laboratories over a period of four years. The robust mean of the reported results from clinical laboratories using automated analyzers were close to the assigned values from LC-IDMS/MS method. With good accuracy and precision, as well as simple sample cleanup procedure, the developed LC-IDMS/MS method can be used as a reference measurement procedure for the measurement of urea in human serum. [ABSTRACT FROM AUTHOR]

Understanding how terrestrial ecosystems would respond to future climate change can substantially contribute to scientific evaluation of the interactions between vegetation and climate. To reveal the future climate impacts might on the nature and magnitude of global vegetation, the spatiotemporal distribution and net primary productivity (NPP) of global terrestrial biomes and their dynamics in this century were quantitatively simulated and compared by using the improved Comprehensive and Sequential Classification System and the segmentation model. The 33 general circulation models under the four scenarios of Representative Concentration Pathways (RCPs) were utilized to simulate the future climate change. The multi-model ensemble results showed that at the global scale, the distribution of forests and deserts would expand by more than 2% and 4% over this century, respectively. By contrast, more than 11% of grassland regions would shrink. Despite the considerable differences in the simulated responses of the biomes, the poleward movement or expansion of temperate forest were prominent features across all the scenarios. Meanwhile, the terrestrial NPP was projected to increase by 7.44, 9.51, 9.46, and 12.02 Pg DW·a − 1 in 2070s relative to 1970s in the RCP2.6, RCP4.5, RCP6.0, and RCP8.5, respectively. The largest NPP decrease would occur in tundra & alpine steppe. NPP in the Tropical Zone, the North Temperate Zone, and the North Frigid Zone was estimated to increase in this century, whereas NPP in the South Temperate Zone was projected to decrease slightly across all scenarios. Overall, ecosystems in the mid-/high latitudes would be more vulnerable to future climate change in terms of distribution ranges and primary productivity despite the existing uncertainties. Some vegetation would benefit from the warmer and wetter climate. However, most of these plants would suffer and experience irreversible changes, particularly in the northern hemisphere. [ABSTRACT FROM AUTHOR]

Facile and scalable approaches for preparing fluorescent microspheres are indispensable tools in material science due to their immense potential for reducing the tedious conditional trial-and-error experiments for every single material. In this study, we propose a microfluidic method based on oscillating electric field (OEF)-induced electrojetting to fabricate size-controllable fluorescent microspheres embedded with various fluorescent substances. Briefly, an oscillating electric field is used to manipulate the size and productivity of highly uniform droplets; the size of droplets can be adjusted by simply varying the intensity and frequency of the electric field over a range of near three orders of magnitude. Subsequently, ultraviolet (UV) irradiation is used to solidify the droplets to fabricate fluorescent microspheres. To demonstrate the universality of the proposed method in different types of fluorescent substances, we use fluorescein sodium (FS), green fluorescent protein (GFP), and CdTe quantum dots (QDs) to synthesize fluorescent microspheres. The prepared microspheres show narrow size distribution (average coefficient of variation below 2.1%) and intense fluorescence emission. Overall, the proposed method is a novel and facile approach for synthesizing fluorescent microspheres, showing great promise for the preparation of polymer, functionalized and other materials with potential applications in various fields of biomaterials and biochemical assays. [Display omitted] • A facile and scalable method to fabricate size-controllable fluorescent microspheres is proposed. • A microfluidic emulsification system based on an OEFIE is firstly established. • The size of droplets can be adjusted within a range of near three orders of magnitude. • The prepared fluorescent microspheres exhibit an ultra-narrow size distribution. • The universality of the proposed method was demonstrated by applying it to various fluorescent substrates. [ABSTRACT FROM AUTHOR]

• FfWCC affects the colony morphology but not its growth rate in Flammulina filiformis. • FfWCC positively regulates the number and the length of the mushroom fruiting body. • FfWCC regulates the morphogenesis by acting on the cell wall-related enzyme genes. Light is a common environmental factor in nature, which was often used in Flammulina filiformis industrialized cultivation. In this study, we identified white collar photoreceptor (FfWc1 and FfWc2) with conserved PAS domain in F. filiformis. The results of the overall light treatment showed that the transcription levels of FfWc1 and FfWc2 reached the peak under the blue light with 3 μmol·m−2·s−1 intensity, and increased by 3.3-fold and 10.1-fold, respectively, at 3 h after the blue light irradiation. During the fruiting body development of F. filiformis, FfWc1 and FfWc2 were significantly up-regulated with the formation of primordia and the rapid elongation of the stipe (around day 8 after primordia formation). Further, we performed the knockdown and overexpression of FfWc1 / FfWc2 , the results showed that aerial mycelia became denser, the number of fruiting body increased, and the length of the stipe increased in the FfWc1 / FfWc2 overexpression strains, while the opposite results were found in the FfWc1 / FfWc2 knockdown strains. In addition, total nine genes encoding cell wall-related enzymes, including exo-β-1, 3-glucanase, β-1, 6-glucan synthase and chitinase, were up-regulated with varying degrees in FfWc1 / FfWc2 overexpression strains, seven of them (except for two chitinases) were down-regulated in FfWc1 / FfWc2 knockdown strains. It suggested that WC may regulate the growth morphology of mycelia and the elongation rate of fruiting body by acting on these cell wall-related enzyme genes, and then affect the morphological development of F. filiformis. The results clearly demonstrate the significant changes in the fruiting body morphology of F. filiformis under the partial loss or increase of WC function, and have guiding significance for scientific use of blue light to regulate the commodity characters of mushroom. [ABSTRACT FROM AUTHOR]

Transforming growth factor-β (TGF-β) is a multifunctional regulatory cytokine that maintains tolerance in the immune system by regulating the proliferation, differentiation and survival of lymphocytes. TGF-β blockade therapy for cancer has achieved some results but shows limited efficacy and side effects because these drugs are not selective and act on various types of cells throughout the body. We demonstrate here that dominant negative TGF-β receptor type II specifically targeting T cells decreases tumor load in tumor-bearing mice. In addition, the dominant negative TGF-β receptor type II promotes the proliferation and differentiation of T cells and increases the expression of T-bet, which in turn promotes the secretion of granzyme A, granzyme B, perforin and IFN-γ secreted by T cells, and enhances the cytotoxicity and anti-tumor effects of T cells. Moreover, we also found that dominant negative TGF-β receptor type II reduces the proportion of regulatory T cells (Tregs) in tumor tissue and spleen of tumor-bearing mice. Co-culture experiments with T cells and tumor cells revealed that dominant negative TGF-β receptor type II inhibited tumor cell proliferation and increased apoptosis. Our results indicate that specifically inhibiting TGF-β receptor type II in T cells increases anti-tumor immunity and has a strong therapeutic potential. [Display omitted] • dnTGF-βRII promotes the differentiation of T cells into effector T cells. • dnTGF-βRII reduces the proportion of Tregs in tumor tissue and spleen. • dnTGF-βRII induces the expression of CTL multiple effector molecules by removal of TGF-β signal from inhibiting T-bet. [ABSTRACT FROM AUTHOR]

Objectives: T helper 9 (Th9) cells are recognised for their characteristic expression of the transcription factor PU.1 and production of interleukin-9 (IL-9), which has been implicated in various autoimmune diseases. However, its precise relationship with rheumatoid arthritis (RA) pathogenesis needs to be further clarified., Methods: The expression levels of PU.1 and IL-9 in patients with RA were determined by ELISA, western blotting (WB) and immunohistochemical staining. PU.1-T cell-conditional knockout (KO) mice, IL-9 KO and IL-9R KO mice were used to establish collagen antibody-induced arthritis (CAIA), respectively. The inhibitor of PU.1 and IL-9 blocking antibody was used in collagen-induced arthritis (CIA). In an in vitro study, the effects of IL-9 were investigated using siRNAs and IL-9 recombinant proteins. Finally, the underlying mechanisms were further investigated by luciferase reporter analysis, WB and Chip-qPCR., Results: The upregulation of IL-9 expression in patients with RA exhibited a positive correlation with clinical markers. Using CAIA and CIA model, we demonstrated that interventions targeting PU.1 and IL-9 substantially mitigated the inflammatory phenotype. Furthermore, in vitro assays provided the proinflammatory role of IL-9, particularly in the hyperactivation of macrophages and fibroblast-like synoviocytes. Mechanistically, we uncovered that PU.1 and IL-9 form a positive feedback loop in RA: (1) PU.1 directly binds to the IL-9 promoter, activating its transcription and (2) Th9-derived IL-9 induces PU.1 via the IL-9R-JAK1/STAT3 pathway., Conclusions: These results support that the PU.1-IL-9 axis forms a positive loop in Th9 dysregulation of RA. Targeting this signalling axis presents a potential target approach for treating RA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Ovarian cancer (OC) is a common gynecological tumor with high mortality, which is difficult to control its progression with conventional treatments and is prone to recurrence. Recent studies have identified OC as an immunogenic tumor that can be recognized by the host immune system. Immunotherapy for OC is being evaluated, but approaches such as immune checkpoint inhibitors have limited efficacy, adoptive cell therapy is an alternative therapy, in which CAR(chimeric antigen receptor)-T therapy has been applied to the clinical treatment of hematological malignancies. In addition, CAR-NK and CAR-macrophage (CAR-M) have also shown great potential in the treatment of solid tumors. Here, we discuss recent advances in preclinical and clinical studies of CAR-T for OC treatment, introduce the efforts made by researchers to modify the structure of CAR in order to achieve effective OC immunotherapy, as well as the research status of CAR-NK and CAR-M, and highlight emerging therapeutic opportunities that can be utilized to improve the survival of patients with OC using CAR-based adoptive cell therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Thioredoxin-reductase 2 (Txnrd2) belongs to the thioredoxin-reductase family of selenoproteins and is a key antioxidant enzyme in mammalian cells to regulate redox homeostasis. Here, we reported that Txnrd2 exerted a major influence in brain damage caused by Intracerebral hemorrhage (ICH) by suppressing endoplasmic reticulum (ER) stress oxidative stress and via Trx2/Prx3 pathway. Furthermore, we demonstrated that pharmacological selenium (Se) rescued the brain damage after ICH by enhancing Txnrd2 expression. Primarily, expression and localization of Txnrd2, Trx2 and Prx3 were determined in collagenase IV-induced ICH model. Txnrd2 was then knocked down using siRNA interference in rats which were found to develop more severe encephaledema and neurological deficits. Mechanistically, we observed that loss of Txnrd2 leads to increased lipid peroxidation levels and ER stress protein expression in neurons and astrocytes. Additionally, it was revealed that Se effectively restored the expression of Txnrd2 in brain and inhibited both the activity of ER stress protein activity and the generation of reactive oxygen species (ROS) by promoting Trx2/Prx3 kilter when administrating sodium selenite in lateral ventricle. This study shed light on the effect of Txnrd2 in regulating oxidative stress and ER stress via Trx2/Prx3 pathway upon ICH and its promising potential as an ICH therapeutic target., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Cardiovascular diseases (CVDs) remain a global health concern, and body mass index (BMI) is known to be associated with an increased risk of CVD, but the exact mechanisms underlying this relationship remain unclear. This study employs Mendelian randomization (MR) to investigate the causal association between BMI and electrocardiogram (ECG) indices, providing insights into potential pathways linking obesity to CVD., Methods: We conducted a comprehensive MR study utilizing large-scale genetic and ECG data from diverse populations. Instrumental variables were selected from genome-wide association studies, ensuring their relevance to BMI. Causal relationships between BMI and ECG indices, including P wave duration, PR interval, QRS duration, and QT interval, were assessed using various MR methods, with inverse variance weighted (IVW) considered as the primary analysis., Results: Our MR analysis revealed a significant positive causal association between higher BMI and P wave duration (β = 8.078, 95% CI: 5.322 to 10.833, p < 0.001), suggesting a potential mechanism through which higher BMI may contribute to arrhythmogenic risks. However, no significant causal associations were observed between BMI and PR interval, QRS duration, or QT interval (all p > 0.005). In addition, our study also found that there is no horizontal pleiotropy between BMI and P wave duration, PR interval, QRS duration, and QT interval, suggesting that the conclusions of this study are robust., Conclusion: This study supports a causal relationship between elevated BMI and prolonged P wave duration, a marker of increased atrial arrhythmogenic risk. Further investigations are still needed to elucidate the underlying mechanisms., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Transfected stem cells and T cells are promising in personalized cell therapy and immunotherapy against various diseases. However, existing transfection techniques face a fundamental trade-off between transfection efficiency and cell viability; achieving both simultaneously remains a substantial challenge. This study presents an acoustothermal transfection method that leverages acoustic and thermal effects on cells to enhance the permeability of both the cell membrane and nuclear envelope to achieve safe, efficient, and high-throughput transfection of primary T cells and stem cells. With this method, two types of plasmids were simultaneously delivered into the nuclei of mesenchymal stem cells (MSCs) with efficiencies of 89.6 ± 1.2%. CXCR4-transfected MSCs could efficiently target cerebral ischemia sites in vivo and reduce the infarct volume in mice. Our acoustothermal transfection method addresses a key bottleneck in balancing the transfection efficiency and cell viability, which can become a powerful tool in the future for cellular and gene therapies.

Chimeric antigen receptor (CAR)-immune cell therapy has revolutionized the anti-tumor field, achieving efficient and precise tumor clearance by directly guiding immune cell activity to target tumors. In addition, the use of CAR-immune cells to influence the composition and function of the immune system and ultimately achieve virus clearance and immune system homeostasis has attracted the interest of researchers. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered a global pandemic of coronavirus disease 2019 (COVID-19). To date, the rapidly mutating SARS-CoV-2 continues to challenge existing therapies and has raised public concerns regarding reinfection. In patients with COVID-19, the interaction of SARS-CoV-2 with the immune system influences the course of the disease, and the coexistence of over-activated immune system components, such as macrophages, and severely compromised immune system components, such as natural killer cells, reveals a dysregulated immune system. Dysregulated immune-induced inflammation may impair viral clearance and T-cell responses, causing cytokine storms and ultimately leading to patient death. Here, we summarize the research progress on the use of CAR-immune cells against SARS-CoV-2 infection. Furthermore, we discuss the feasibility, challenges and prospect of CAR-immune cells as a new immune candidate therapy against SARS-CoV-2., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Nonlinear frequency division multiplexing (NFDM) systems, especially the eigenvalue communications have the potential to overcome the nonlinear Shannon capacity limit. However, the baud rate of eigenvalue communications is typically restricted to a few GBaud, making it challenging to mitigate laser frequency impairments such as the phase noise and frequency offset (FO) using digital signal processing (DSP) algorithms in intradyne detections (IDs). Therefore, we introduce the polarization division multiplexing-self-homodyne detection (PDM-SHD) into the NFDM link, which could overcome the impact of phase noise and FO by transmitting a pilot carrier originating from the transmitter laser to the receiver through the orthogonal polarization state of signal. To separate the signal from the carrier at the receiver, a carrier to signal power ratio (CSPR) unrestricted adaptive polarization controlling strategy is proposed and implemented by exploiting the optical intensity fluctuation of the light in a particular polarization rather than its direct optical power as the feedback. Optical injection locking (OIL) is used subsequently to amplify optical power of pilot carrier and mitigate the impact of signal-signal beat interference (SSBI). Additionally, the effects of cross-polarization modulation (XPolM) and modulation instability (MI) in long haul transmission are explored and inhibited. The results show that the tolerable FO range is about 3.5 GHz, which is 17 times larger than the ID one. When 16-amplitude phase shift keying (APSK) or 64-APSK constellations are used, identical Q-factor performance can be obtained by using distributed feedback (DFB, ∼10 MHz) laser, external cavity laser (ECL, ∼100kHz), or fiber laser (FL, ∼100 Hz), respectively, which demonstrates that our proposed PDM-SHD eigenvalue communication structure is insensitive to the laser linewidth. Under the impact of cycle slip, the Q-factor difference of 16-APSK signal between the ECL-ID system and ECL-SHD system can be up to 8.73 dB after 1500 km transmission.

Enabling communication networks with sensing functionality has attracted significant interest lately. The digital subcarrier multiplexing (DSCM) technology is widely promoted in short-reach scenarios for its inherent flexibility of fine-tuning the spectrum. Its compatibility with large-scale as-deployed coherent architectures makes it particularly suited for cost-sensitive integrated sensing and communication applications. In this paper, we propose a scheme of spectrally integrating the digital linear frequency modulated sensing signal into DSCM signals to achieve simultaneous sensing and communication through shared transmitter. Consequently, this cost-effective scheme has been demonstrated to achieve 100-Gb/s dual-polarization quadrature phase-shift keying (DP-QPSK) and 200-Gb/s dual-polarization 16-ary quadrature amplitude modulation (DP-16QAM) transmission with a distributed acoustic sensing sensitivity of 69 p ε /Hz and 88 p ε /Hz respectively, at a spatial resolution of 4 m.

Background: The chimeric antigen receptor (CAR)-T therapy has a limited therapeutic effect on solid tumors owing to the limited CAR-T cell infiltration into solid tumors and the inactivation of CAR-T cells by the immunosuppressive tumor microenvironment. Macrophage is an important component of the innate and adaptive immunity, and its unique phagocytic function has been explored to construct CAR macrophages (CAR-Ms) against solid tumors. This study aimed to investigate the therapeutic application of CAR-Ms in ovarian cancer., Methods: In this study, we constructed novel CAR structures, which consisted of humanized anti-HER2 or CD47 scFv, CD8 hinge region and transmembrane domains, as well as the 4-1BB and CD3ζ intracellular domains. We examined the phagocytosis of HER2 CAR-M and CD47 CAR-M on ovarian cancer cells and the promotion of adaptive immunity. Two syngeneic tumor models were used to estimate the in vivo antitumor activity of HER2 CAR-M and CD47 CAR-M., Results: We constructed CAR-Ms targeting HER2 and CD47 and verified their phagocytic ability to ovarian cancer cells in vivo and in vitro. The constructed CAR-Ms showed antigen-specific phagocytosis of ovarian cancer cells in vitro and could activate CD8 + cytotoxic T lymphocyte (CTL) to secrete various anti-tumor factors. For the in vivo model, mice with human-like immune systems were used. We found that CAR-Ms enhanced CD8 + T cell activation, affected tumor-associated macrophage (TAM) phenotype, and led to tumor regression., Conclusions: We demonstrated the inhibition effect of our constructed novel HER2 CAR-M and CD47 CAR-M on target antigen-positive ovarian cancer in vitro and in vivo, and preliminarily verified that this inhibitory effect is due to phagocytosis, promotion of adaptive immunity and effect on tumor microenvironment., (© 2023. BioMed Central Ltd., part of Springer Nature.)

This Letter demonstrates the high compatibility of the self-homodyne coherent detection (SHCD) transmission system with the Brillouin optical time-domain analyzer (BOTDA). By fully utilizing the remote delivered local oscillator (LO) light of the transmission system, the first, to the best of our knowledge, endogenously integrated BOTDA subsystem is achieved. The remote delivery of the homologous laser source in the SHCD system ensures the frequency match between the probe light and the pump light of the BOTDA. Furthermore, an injection-locked distributed feedback (DFB) laser is employed to amplify the LO and eliminate the impact induced by the Brillouin gain. The experiment demonstrates that a 16-km distributed temperature sensing based on BOTDA can be insensibly emerged into a 50-Gbaud DP-16QAM SHCD transmission system (400 Gbps/λ/core), achieving a spatial resolution of 3 meters and a temperature accuracy of 1°C. Remarkably, the auxiliary sensing module has negligible impact on the transmission.

Glioma is the most common tumor of the primary central nervous system, and its malignant phenotype has been shown to be closely related to glioma stem cells (GSCs). Although temozolomide has significantly improved the therapeutic outcome of glioma with a high penetration rate of the blood-brain barrier, resistance is often present in patients. Moreover, evidence has shown that the crosstalk between GSCs and tumor-associated microglia/macrophages (TAMs) affect the clinical occurrence, growth, and multi-tolerance of chemoradiotherapy in gliomas. Here, we highlight its vital roles in the maintenance of the stemness of GSCs and the ability of GSCs to recruit TAMs to the tumor microenvironment and promote their polarization into tumor-promoting macrophages, hence providing groundwork for future research into new treatment strategies of cancer., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Intracerebral hemorrhage (ICH) induces high mortality and disability. Neuronal death is the principal factor to unfavourable prognosis in ICH. However, the mechanisms underlying this association remain unclear. In this study, we investigated the molecular mechanisms by which neuronal ferroptosis occurs after ICH and whether the use of corresponding modulators can inhibit neuronal death and improve early outcomes in a rat ICH model. Our findings indicated that Nox4 and TF/TfR were upregulated in the perihematomal tissues of ICH rats. Oxidative stress and iron overload induced by Nox4 and TF/TfR promoted neuronal ferroptosis post-ICH. In contrast, application of Nox4-siRNA and the deferoxamine (DFO) attenuated peroxidation and iron deposition in the hemorrhagic brain, alleviated neuronal ferroptosis, and improved sensorimotor function in ICH rats. Additionally, our findings indicated that the post-ICH neuronal reduced glutathione (GSH) depletion were not related to dysfunctional glutamine delivery in astrocytes but rather to downregulation of EAAT3 due to lipid peroxidation-induced dysfunction in the neuronal membrane. These findings indicate that ferroptosis is involved in neuronal death in model rats with collagenase-induced ICH. Oxidative stress and iron overload induced by Nox4 and TF/TfR exacerbate ferroptosis after ICH, while Nox4 downregulation and iron chelation exert neuroprotective effects. The present results highlight the cysteine importer EAAT3 as a potential biomarker of ferroptosis and provide insight into the neuronal death process that occurs following ICH, which may aid in the development of translational treatment strategies for ICH., Competing Interests: Declaration of competing interest The authors have declared that no conflict of interest exists., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to summarize the clinical application experience of video-assisted thoracic surgery (VATS) combined with three-dimensional computed tomography-bronchography and angiography (3D-CTBA) in anatomical basal segmentectomy., Methods: Clinical data of 42 patients who underwent bilateral lower sub-basal segmentectomy by VATS combined with 3D-CTBA in our hospital from January 2020 to June 2022 were retrospectively analyzed; the patients included 20 males and 22 females, with a median age of 48 (30-65) years. Combined with the preoperative enhanced CT and 3D-CTBA techniques to identify the altered bronchi, arteries, and veins during the operation, the anatomical resection of each basal segment of both lower lungs was completed through the fissure approach or inferior pulmonary vein approach., Results: All operations were successfully completed without conversion to thoracotomy or lobectomy. The median operation time was 125 (90-176) min, the median intraoperative blood loss was 15 (10-50) mL, the median postoperative thoracic drainage time was 3 (2-17) days, and the median postoperative hospital stay was 5 (3-20) days. The median number of resected lymph nodes was 6 (5-8). There was no in-hospital death. Postoperative pulmonary infection occurred in 1 case, lower extremity deep vein thrombosis (DVT) in 3 cases, pulmonary embolism in 1 case, and persistent air leakage in the chest in 5 cases, all of which were improved by conservative treatment. Two cases of pleural effusion after discharge were improved after ultrasound guided drainage. Postoperative pathology showed 31 cases of minimally invasive adenocarcinoma, 6 cases of adenocarcinoma in situ (AIS), 3 cases of severe atypical adenomatous hyperplasia (AAH), and 2 cases of other benign nodules. All cases were lymph node-negative., Conclusion: VATS combined with 3D-CTBA is safe and feasible in anatomical basal segmentectomy; consequently, this approach should be promoted and applied in clinical work., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor HL declared a shared parent affiliation with the authors at the time of review., (Copyright © 2023 Zhang, Wang, Feng, Chen, Feng, Qin and Han.)

Owing to the random birefringence of optical fibers, the recovery of the state of polarization (SOP) is urgently needed, especially in the nonlinear spectrum division multiplexing transmissions. Based on the variance of the polarization power ratio among symbols as the cost function, we propose a novel algorithm for the blind SOP recovery of eigenvalue communications. In the single eigenvalue transmissions with phase-shift keying or 16-ary amplitude and phase-shift keying constellations, at least 25.3 dB polarization extinction ratio can be achieved by using a block length of 30, even under 7 dB OSNR condition. It also shows that the proposed algorithm can be employed in multi-eigenvalue NFDM transmissions and full-spectrum modulated NFDM system. In the experiment, our proposed algorithm performs the same as the training symbol based method in back-to-back and less than 3000 km fiber link conditions; a maximum performance gain of 1.6 dB was obtained in ultra-long-haul condition (4300 km). It also shows that the impact of the polarization mode dispersion of a single-mode fiber on the algorithm is negligible.

Objectives: To uncover the function and underlying mechanism of an essential transcriptional factor, PU.1, in the development of rheumatoid arthritis (RA)., Methods: The expression and localisation of PU.1 and its potential target, FMS-like tyrosine kinase 3 (FLT3), in the synovium of patients with RA were determined by western blot and immunohistochemical (IHC) staining. UREΔ (with PU.1 knockdown) and FLT3-ITD (with FLT3 activation) mice were used to establish collagen antibody-induced arthritis (CAIA). For the in vitro study, the effects of PU.1 and FLT3 on primary macrophages and fibroblast-like synoviocytes (FLS) were investigated using siRNAs. Mechanistically, luciferase reporter assays, western blotting, FACS and IHC were conducted to show the direct regulation of PU.1 on the transcription of FLT3 in macrophages and FLS. Finally, a small molecular inhibitor of PU.1, DB2313, was used to further illustrate the therapeutic effects of DB2313 on arthritis using two in vivo models, CAIA and collagen-induced arthritis (CIA)., Results: The expression of PU.1 was induced in the synovium of patients with RA when compared with that in osteoarthritis patients and normal controls. FLT3 and p-FLT3 showed opposite expression patterns compared with PU.1 in RA. The CAIA model showed that PU.1 was an activator, whereas FLT3 was a repressor, of the development of arthritis in vivo. Moreover, results from in vitro assays were consistent with the in vivo results: PU.1 promoted hyperactivation and inflammatory status of macrophages and FLS, whereas FLT3 had the opposite effects. In addition, PU.1 inhibited the transcription of FLT3 by directly binding to its promoter region. The PU.1 inhibitor DB2313 clearly alleviated the effects on arthritis development in the CAIA and CIA models., Conclusions: These results support the role of PU.1 in RA and may have therapeutic implications by directly repressing FLT3. Therefore, targeting PU.1 might be a potential therapeutic approach for RA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In recent years, the self-homodyne coherent (SHC) system and the constellation shaping (CS) technique have drawn considerable attention due to their abilities to further improve the transmission capacity for various scenarios. From the security point of view, the CS technique and the SHC infrastructure also provide new dimensions for encryption. We propose a high-security and reliable SHC system based on the CS technique and the digital chaos. With a four-dimensional hyperchaotic system, chaotic sequences are generated and used for the exclusive or operation, chaotic constant composition distribution matching, phase disturbance, and optical-layer time-delay disturbance. Moreover, 64-ary circular quadrature amplitude modulation (64CQAM) format is adopted for transmission due to its advantages of sensitivity to phase noise, immunity to conventional digital signal processing, and ability of time-mismatch masking, which is verified by simulation in a SHC system. Last, we conduct an experimental verification in a 20GBaud probabilistically shaped 64CQAM SHC system. Consequently, with a large-linewidth laser source, optical-layer security can be protected by time mismatches of tens of picoseconds. And the digital-layer security is protected by an enormous key space of 10 127 . The proposed scheme can provide reliable real-time encryption for the optical fiber transmission, serving as a potential candidate for the future high-capacity inter/intra-datacenter security interconnect.

Whether sources or sinks control wood growth remains debated with a paucity of evidence from mature trees in natural settings. Here, we altered carbon supply rate in stems of mature red maples (Acer rubrum) within the growing season by restricting phloem transport using stem chilling; thereby increasing carbon supply above and decreasing carbon supply below the restrictions, respectively. Chilling successfully altered nonstructural carbon (NSC) concentrations in the phloem without detectable repercussions on bulk NSC in stems and roots. Ring width responded strongly to local variations in carbon supply with up to seven-fold differences along the stem of chilled trees; however, concurrent changes in the structural carbon were inconclusive at high carbon supply due to large local variability of wood growth. Above chilling-induced bottlenecks, we also observed higher leaf NSC concentrations, reduced photosynthetic capacity, and earlier leaf coloration and fall. Our results indicate that the cambial sink is affected by carbon supply, but within-tree feedbacks can downregulate source activity, when carbon supply exceeds demand. Such feedbacks have only been hypothesized in mature trees. Consequently, these findings constitute an important advance in understanding source-sink dynamics, suggesting that mature red maples operate close to both source- and sink-limitation in the early growing season., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.)

We experimentally demonstrate a 4 × 10 Gb/s cost-effective coherent ultra-dense wavelength division multiplexing passive optical network (UDWDM-PON) by the use of unequally-spaced 4-level pulse-amplitude modulation (UES-PAM-4) signaling. Because of the advantages of simple architecture and low cost, the simplified coherent receiver (SCR) based on the transmitted signal diversity (TS-D) has been reported, but its receiver sensitivity is constrained by the severe noise arising in the higher level of conventional PAM-4 signals. Here, we first experimentally demonstrate the UES-PAM-4 signaling for the SCR based on the TS-D, by altering the PAM-4 level spacing and the decision threshold through the gradient descent algorithm (GDA). Consequently, we can experimentally achieve -30.1 dBm RS for single wavelength at the bit-error ratio (BER) of 3.8 × 10 -3 . Compared with the conventional equally-spaced PAM-4 (ES-PAM-4) signaling, 1.3 dB RS enhancement can be secured after the 20-km standard single-mode fiber (SSMF) transmission. Meanwhile, the UES-PAM-4 signaling is experimentally verified for 4 × 10 Gb/s UDWDM-PON. An average RS of -29.6 dBm and 32.6 dB power budget are obtained after the 20-km SSMF transmission. The proposed UES-PAM-4 signaling with the RS enhancement is a promising candidate for the UDWDM-PON by utilizing the existing optical distribution network (ODN).

Wood formation determines major long-term carbon (C) accumulation in trees and therefore provides a crucial ecosystem service in mitigating climate change. Nevertheless, we lack understanding of how species with contrasting wood anatomical types differ with respect to phenology and environmental controls on wood formation. In this study, we investigated the seasonality and rates of radial growth and their relationships with climatic factors, and the seasonal variations of stem nonstructural carbohydrates (NSC) in three species with contrasting wood anatomical types (red oak: ring-porous; red maple: diffuse-porous; white pine: coniferous) in a temperate mixed forest during 2017-2019. We found that the high ring width variability observed in both red oak and red maple was caused more by changes in growth duration than growth rate. Seasonal radial growth patterns did not vary following transient environmental factors for all three species. Both angiosperm species showed higher concentrations and lower inter-annual fluctuations of NSC than the coniferous species. Inter-annual variability of ring width varied by species with contrasting wood anatomical types. Due to the high dependence of annual ring width on growth duration, our study highlights the critical importance of xylem formation phenology for understanding and modelling the dynamics of wood formation., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation.)

In this Letter, we analytically model the impact of polarization crosstalk in the polarization-multiplexed carrier self-homodyne (PMC-SH) system with adaptive polarization control technology. When the optical paths of the signal and local oscillator (LO) are matched well, it is found that the polarization crosstalk results in a nonlinear shift on the constellation. Thus, we further propose a compensation scheme based on a low-complexity polynomial nonlinear equalizer (PNLE). Both simulation and experimental results validate our theoretical analysis. Moreover, the proposed PNLE-based compensation scheme achieves up to 1.23 dB tolerance improvement with respect to polarization crosstalk for 20 Gbaud 64QAM in the experiment.

For space division multiplexing self-homodyne coherent systems, we propose a novel digital in-service relative time delay (RTD) estimation method without any additional optoelectronic device. Taking advantage of the frequency-domain periodicity of the colored frequency modulation noise, we manage to find the peak with location reflecting the RTD in its autocorrelation function (ACF). The peak to average ratio is further enhanced by leveraging a low-pass differential finite impulse response filter for robust identification. By simulations, the method is validated to be feasible for various linewidths, formats (16QAM, 32QAM and 64QAM), and links up to 80 km. Particularly, it is proved to be inherently compatible with large-linewidth low-cost lasers for the 10-km link. Also, for a low-complexity implementation, we discuss the way to reduce the number of points used to calculate the ACF while maintaining the same dynamic range. Furthermore, we demonstrate a 50-GBaud 16-QAM experiment to investigate its performances. With received optical power varying from -11 dBm to -17 dBm, 2 16 points are sufficient to provide an estimation accuracy of standard deviation (STD) less than 0.089 ns for the RTD range of [2.6, 491.0 ns]. The STD can be lowered to 0.036 ns by adopting 2 18 points. Especially, at -11-dBm ROP, the highest performance has been achieved with an accuracy smaller than the symbol period (0.018-ns STD) and a RTD range of [1.5, 491.0 ns].

Intracerebral hemorrhage (ICH) can induce intensively oxidative stress, neuroinflammation, and brain cell apoptosis. However, currently, there is no highly effective treatment available. Puerarin (PUE) possesses excellent neuroprotective effects by suppressing the NF-κB pathway and activating the PI3K/Akt signal, but its role and related mechanisms in ICH-induced early brain injury (EBI) remain unclear. In this study, we intended to observe the effects of PUE and molecular mechanisms on ICH-induced EBI. ICH was induced in rats by collagenase IV injection. PUE was intraperitoneally administrated alone or with simultaneously intracerebroventricular injection of LY294002 (a specific inhibitor of the PI3K/Akt signal). Neurological deficiency, histological impairment, brain edema, hematoma volume, blood-brain barrier destruction, and brain cell apoptosis were evaluated. Western blot, immunohistochemistry staining, reactive oxygen species (ROS) measurement, and enzyme-linked immunosorbent assay were performed. PUE administration at 50 mg/kg and 100 mg/kg could significantly reduce ICH-induced neurological deficits and EBI. Moreover, PUE could notably restrain ICH-induced upregulation of the NF-κB pathway, pro-inflammatory cytokines, ROS level, and apoptotic pathway and activate the PI3K/Akt signal. However, LY294002 delivery could efficaciously weaken these neuroprotective effects of PUE. Overall, PUE could attenuate ICH-induced behavioral defects and EBI possibly by PI3K/Akt signal stimulation-mediated inhibition of the NF-κB pathway, and this made PUE a potential candidate as a promising therapeutic option for ICH-induced EBI., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

We experimentally demonstrated a geometric shaped (GS) 64-ary amplitude phase shift keying (64-APSK) eigenvalue transmission. The signal is modulated on the scatter coefficient of a single eigenvalue and linear minimum mean square error (LMMSE) estimator is used to reduce the noise. The channel response is estimated by transmitting a normally distributed 64-APSK constellation through a communication link. Based on the polar coordinates distribution of the received constellation, the diameter distributions for each circle can be obtained so that circles with larger noise can obtain larger judgment width. After optimization, the experimental results show that the Q-factor gain is 1.13 dB under 22 dB received optical signal to noise ratio (OSNR) configuration and 0.88 dB after 900 km transmission compared with normally distributed APSK configuration.

Chimeric antigen receptor (CAR)-T cell therapy has been shown to be an effective treatment for hematological tumors, but the treatment of solid tumors still lacks effectiveness. In the tumor microenvironment, macrophages are the innate immune cells with the highest infiltration rate. Tumor-associated macrophages (TAMs) stimulate angiogenesis, increase tumor invasion, and mediate immunosuppression. Because macrophages can infiltrate solid tumor tissue and interact with almost all cellular components in the tumor microenvironment (including tumor cells, immune cells such as T-cells, NK cells, DCs, and other resident non-immune cells), researchers are trying to use macrophages modified with CAR (CAR-M) against solid tumors. This review describes recent reports of CAR-M-based tumor treatments and summarizes their shortcomings and future applications., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Testosterone in human serum is commonly tested in clinical laboratories using immunoassay methods as well as liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. To standardize and ensure the accuracy of the measurement results, reference procedures with higher metrological order are required. A simple measurement procedure based on one-step liquid-liquid extraction (LLE) and liquid chromatography-isotope dilution tandem mass spectrometry (LC-IDMS/MS) was developed for total testosterone in human serum. The procedure involved serum spiked with 13 C 3 -testosterone, equilibration for 2 h, and extraction with an organic solvent. Testosterone certified reference material (CRM) was used as the calibration standard to ensure the traceability to the International System of Units (SI). Testosterone in serum CRMs from the National Institute for Standards and Technology (NIST) and LGC were used to validate the accuracy of the newly developed method. The deviations of the obtained values from the NIST and LGC certified values ranged from -0.55% to 0.45%. Similarly, the coefficient of variations (CVs) of the replicate measurements were in the range of 0.55% and 0.78%, respectively. The relative expanded uncertainties were comparable with those of the certified materials. The newly developed LC-IDMS/MS procedure demonstrated adequate trueness and precision, and was simple to perform. The method can be used for value assignment of testosterone in external quality assessment (EQA) materials as well as certification of CRMs in the future. Graphical abstract.

Background: Free glycerol in human serum is measured in clinical laboratories using enzymatic methods, which can be affected by interferences from biological samples. These methods are not applicable when stable isotopic tracers are used to determine lipid kinetics. Hence, a reference measurement procedure for free glycerol in human serum is needed., Methods: A reference measurement procedure based on two-step gas chromatography-isotope dilution mass spectrometry (GC-IDMS) was developed for the measurement of free glycerol in human serum. This procedure involved spiking with (13)C3-glycerol, protein precipitation and cation exchange SPE, followed by two-step derivatization with 1-butylboronic acid and N-methyl-N-trimethylsilyltrifluoroacetamide. Tripalmitin certified reference material (CRM) was used as the calibration standard to ensure metrological traceability., Results: Good precision and accuracy were obtained as demonstrated by relative standard deviation (RSD) of 1.51%-3.33%, with average recoveries over 98%. The relative measurement uncertainty was below 3% with major contributions from the concentration of glycerol calibration solution, choice of ion pair, linear regression, and measurement precision., Conclusions: With good accuracy and precision, as well as clear metrological traceability, the developed GC-IDMS procedure is useful in producing traceable and accurate measurement of free glycerol in human serum., (Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

This study is to examine whether the activation of Rho kinase (ROCK) accounts for hemoglobin (Hb)-induced disruption of blood-brain barrier (BBB) after the occurrence of intracerebral hemorrhage. A model of intracerebral injection of Hb was established in rats. Changes in the levels of mRNA of RhoA, ROCK2 and matrix metalloproteinase-9 (MMP-9) were measured using quantitative real-time polymerase chain reaction. Protein expression of RhoA, ROCK2, claudin-5 and MMP-9, as well as ROCK activity, were determined using Western blotting. Immunohistochemical assay was performed to visualize the expression of RhoA, ROCK2, claudin-5 and MMP-9 in endothelial cells. Hb injection produced a significant increase in BBB permeability and water content in the brain. Significant reduction of claudin-5 expression was detected by Western blotting and immunofluorescence in Hb group. The levels of RhoA and ROCK2 were significantly up-regulated from 6 h to 12 h after Hb injection and were concomitant with the increase in ROCK activity. Immunofluorescence double staining showed enhanced p-myosin light chain immunoreactivity but diminished claudin-5 staining in endothelial cells. Significant up-regulation of MMP-9 expression was detected after Hb injection, and statistical analyses further confirmed a positive correlation of MMP-9 expression with ROCK activity. The results showed that ROCK was activated in endothelial cells by Hb. This may account for the early disruption of the BBB via up-regulation of p-myosin light chain expression and aggravation of injuries to TJ proteins. The activation of ROCK may also increase MMP-9 expression, thereby leading to further BBB disruption.

Determination of total thyroxine in human serum using hollow fiber liquid-phase microextraction (HF-LPME) has been accomplished for the first time. HF-LPME serves as an inexpensive sample pretreatment and the cleanup method that is nearly solvent-free. Thyroxine was extracted through a water immiscible organic solvent immobilized in the wall pores of a polypropylene hollow fiber into 20μl of an aqueous acceptor phase inside the lumen of the hollow fiber. This technique produced extracts that had comparable cleanness with those obtained using solid-phase extraction (SPE). Serum samples with endogenous thyroxine were spiked with isotopically-labeled thyroxine and analyzed by liquid chromatography-tandem mass spectrometry after HF-LPME extraction. Extraction parameters including the organic phase, acid/base concentration of acceptor phase, stirring speed and extraction time were optimized. The calibration range was found to be linear over 1-1000ng/g with the limit of detection (LOD) of 0.3 ng/g. For quantification of total thyroxine in human serum, 6 subsamples were prepared and the results indicated very good precision with a relative standard deviation of <1.3%. The difference from the SPE method was less than 1.2%, with independent t-test showing insignificant bias. Two reference materials of human serum were analyzed, and our obtained values were compared with the reference values. The results showed very good precision with RSD around 0.2% and the deviation from the reference values were -3.1% and -2.1%. The newly developed method is precise, accurate, inexpensive, and environmentally friendly., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Purpose: To delineate the pterygoid canal (PC) configuration and its position in relation to surrounding important anatomical landmarks using three-dimensional reconstructive technology based on CT for the Chinese., Methods: The computerized tomography arteriography (CTA) data of 137 patients were retrospectively evaluated using neuroimaging three-dimensional reconstructive software. The morphological parameters of the PC as well as the spatial relationship and distance between the PC relative to internal carotid artery (ICA) and the foramen rotundum were evaluated., Results: 83.9% of the PC can be identified by our neuroimaging three-dimensional reconstructive software. The mean distance from the PC to the ICA was 2.6 ± 1.2 mm. The mean distance between medial aspects of bilateral ICA was 19.6 ± 2.7 mm. The distal vertical and horizontal distances between the PC and foramen rotundum were 5.2 ± 3.2 and 6.1 ± 2.8 mm, respectively. All the proximal end of the PC were inferior-lateral to the ICA. The PC mainly (92.9%) ran posteriorly with a medial to lateral direction. The distance from the PC to ICA was positively correlated with the distance between bilateral ICA and the distal diameter of the PC. The vertical distance between the PC and foramen rotundum was positively correlated with the length of the PC and the horizontal distance between the PC and foramen rotundum., Conclusions: Understanding the configuration and spatial relationship of the PC may be helpful to improve the accuracy and safety of operation during the expanded transnasal endoscopic approaches to skull base. The three-dimensional reconstructive virtual anatomic technology may be a useful tool to delineate the PC configuration and its position to surrounding important anatomical landmarks.

Hemoglobin (Hb) released from extravasated erythrocytes may have a critical role in the process of blood-brain barrier (BBB) disruption and subsequent edema formation after intracerebral hemorrhage (ICH). Excessive nitric oxide (NO) production synthesized by nitric oxide synthase (NOS) has been well documented to contribute to BBB disruption. However, considerably less attention has been focused on the role of NO in Hb-induced BBB disruption. This study was designed to examine the hypothesis that Hb-induced NOS overexpression and excessive NO production may contribute to the changes of tight junction (TJ) proteins and subsequent BBB dysfunction. Hemoglobin was infused with stereotactic guidance into the right caudate nucleus of male Sprague Dawley rats. Then, we investigated the effect of Hb on the BBB permeability, changes of TJ proteins (claudin-5, occludin, zonula occludens-1 (ZO-1), and junctional adhesion molecule-1 (JAM-1)), iron deposition, expression of inducible NOS (iNOS) and endothelial NOS (eNOS), as well as NO production. Hb injection caused a significant increase in BBB permeability. Significant reduction of claudin-5, ZO-1, and JAM-1 was observed after Hb injection as evidenced by PCR and immunofluorescence. After a decrease at early stage, occludin showed a fivefold increase in mRNA level at 7 days. Significant iron deposition was detectable from 48 h to 7 days in a time-dependent manner. The iNOS and eNOS levels dramatically increased after Hb injection concomitantly with large quantities of NO released. Furthermore, enhanced iNOS or eNOS immunoreactivity was co-localized with diffused or diminished claudin-5 staining. We concluded that overexpressed NOS and excessive NO production induced by Hb may contribute to BBB disruption, which may provide an important potential therapeutic target in the treatment of ICH.

Background: An isotope dilution mass spectrometry (IDMS) technique has been developed for high accuracy analysis of glucose in human serum. Currently, all the IDMS methods for glucose analysis are based on gas chromatography-mass spectrometry (GC-MS). In this study, isotope dilution liquid chromatography-tandem mass spectrometry (ID LC-MS/MS) was investigated., Methods: NIST SRM 965b glucose in frozen human serum was analyzed by linear regression IDMS based on both LC-MS/MS and GC-MS. Serum samples were spiked with isotope labeled glucose and deproteinized by acetonitrile. For LC-MS/MS measurement, the supernate was injected directly after filtration and dilution. For GC-MS measurement, the supernate was evaporated to dryness and went through a two-step derivatization before injection., Results: All measurements had good precision with CVs of <1%. Results from GC-MS agreed very well with results from LC-MS/MS, with a difference of <0.7%. The final reporting values in this study, based solely on LC-MS/MS, were within the certified ranges. The relative expanded uncertainties were within the range of 1.37% to 1.69% for the 4 levels of glucose, which were comparable with uncertainties from the certificate., Conclusions: The IDMS method based on LC-MS/MS is precise and accurate. It does not require lengthy derivatization steps and thus, greatly simplifies the sample preparation procedure., (Copyright © 2012 Elsevier B.V. All rights reserved.)