Unveiling a novel serpinB2-tripeptidyl peptidase II signaling axis during senescence.

Tripeptidyl peptidase II (TPPII or TPP2) degrades N-terminal tripeptides from proteins and peptides. Studies in both humans and mice have shown that TPPII deficiency is linked to cellular immune-senescence, lifespan regulation and the aging process. However, the mechanism of how TPPII participates in these processes is less clear. In this study, we established a chemical probe-based assay and found that although the mRNA and protein levels of TPPII were not altered during senescence, its enzymatic activity was reduced in senescent human fibroblasts. We also showed that elevation of the levels of the serine protease inhibitor serpinB2 reduced TPPII activity in senescent cells. Moreover, suppression of TPPII led to elevation in the amount of lysosomal contents as in well as TPPI (TPP1) and ß-galactosidase activities, suggesting that lysosome biogenesis is induced to compensate for the reduction of TPPII activity in senescent cells. Together, this study discloses a critical role of the serpinB2-TPPII signaling pathway in proteostasis during senescence. Since serpinB2 levels can be increased by a variety of cellular stresses, reduction of TPPII activity through activation of serpinB2 might represent a common pathway for cells to respond to different stress conditions. This article has an associated First Person interview with the first author of the paper.

Speech intelligibility changes the temporal evolution of neural speech tracking.

Listening to speech with poor signal quality is challenging. Neural speech tracking of degraded speech has been used to advance the understanding of how brain processes and speech intelligibility are interrelated. However, the temporal dynamics of neural speech tracking and their relation to speech intelligibility are not clear. In the present MEG study, we exploited temporal response functions (TRFs), which has been used to describe the time course of speech tracking on a gradient from intelligible to unintelligible degraded speech. In addition, we used inter-related facets of neural speech tracking (e.g., speech envelope reconstruction, speech-brain coherence, and components of broadband coherence spectra) to endorse our findings in TRFs. Our TRF analysis yielded marked temporally differential effects of vocoding: ∼50-110 ms (M50TRF), ∼175-230 ms (M200TRF), and ∼315-380 ms (M350TRF). Reduction of intelligibility went along with large increases of early peak responses M50TRF, but strongly reduced responses in M200TRF. In the late responses M350TRF, the maximum response occurred for degraded speech that was still comprehensible then declined with reduced intelligibility. Furthermore, we related the TRF components to our other neural "tracking" measures and found that M50TRF and M200TRF play a differential role in the shifting center frequency of the broadband coherence spectra. Overall, our study highlights the importance of time-resolved computation of neural speech tracking and decomposition of coherence spectra and provides a better understanding of degraded speech processing.

Neural speech tracking shifts from the syllabic to the modulation rate of speech as intelligibility decreases.

The most prominent acoustic features in speech are intensity modulations, represented by the amplitude envelope of speech. Synchronization of neural activity with these modulations supports speech comprehension. As the acoustic modulation of speech is related to the production of syllables, investigations of neural speech tracking commonly do not distinguish between lower-level acoustic (envelope modulation) and higher-level linguistic (syllable rate) information. Here we manipulated speech intelligibility using noise-vocoded speech and investigated the spectral dynamics of neural speech processing, across two studies at cortical and subcortical levels of the auditory hierarchy, using magnetoencephalography. Overall, cortical regions mostly track the syllable rate, whereas subcortical regions track the acoustic envelope. Furthermore, with less intelligible speech, tracking of the modulation rate becomes more dominant. Our study highlights the importance of distinguishing between envelope modulation and syllable rate and provides novel possibilities to better understand differences between auditory processing and speech/language processing disorders.

Relationship between ankle pain, range of motion, strength and balance in individuals with functional ankle instability: a cross-sectional study.

BACKGROUND: About 15-60% of individuals with ankle sprains may develop functional ankle instability (FAI), which is characterised by ankle pain, decreased muscle strength, limited range of motion, and impaired balance, causing a decline in social activity and quality of life. However, the relationship between those characters is still unclear. This study aimed to investigate whether a relationship existed between ankle pain, active range of motion (AROM), strength and balance and if ankle pain, AROM and strength can predict balance in individuals with FAI. METHODS: Seventy-seven subjects (46 males; 31 females) with unilateral FAI participated in this study. Ankle pain was measured by the visual analogue scale (VAS), ankle AROM was measured using a universal goniometer, ankle strength was measured using a handheld dynamometer, the static balance was measured by the Time in Balance Test (TBT) and the dynamic balance was measured by the modified Star Excursion Balance Test (mSEBT). Pearson product-moment correlations were used to determine the correlations between ankle pain, AROM, strength and balance. Multiple linear regressions were used to investigate if ankle pain, AROM and strength can predict balance in individuals with FAI. RESULTS: VAS and AROM-plantarflexion predicted 25.6% of the TBT (f2 = 0.344, P < 0.001). AROM-dorsiflexion predicted 24.6% of the mSEBT-anterior reach (f2 = 0.326, P < 0.001). VAS, AROM-plantarflexion and strength-plantarflexion predicted 33.5% of the mSEBT-posteromedial reach (f2 = 0.504, P < 0.001). AROM-plantarflexion and strength-plantarflexion predicted 28.2% of the mSEBT-posterolateral reach (f2 = 0.393, P < 0.001). CONCLUSION: This study shows that ankle plantarflexion strength, AROM of dorsiflexion and plantarflexion and pain are predictors of balance in individuals with FAI. These factors could be considered in the rehabilitation of FAI. TRIAL REGISTRATION: Trial registration number: ChiCTR2200063532.

A Rare Case of Abnormal Hemoglobin Variant Hb Mizuho: [HBB: c.206T > C ß 68(E12) Leu-Pro]: A First Report in the Chinese Population.

A 6-month-old female infant presented with unexplained hemolytic anemia, showing no abnormalities by capillary electrophoresis and genetic testing for α- and ß-thalassemia mutations that are commonly seen in the Chinese population. A rare Hb Mizuho: [HBB: c.206T > C ß 68(E12) Leu- Pro] variant was identified by next-generation sequencing (NGS) and verified by Sanger sequencing. Hb Mizuho: [HBB: c.206T > C ß 68(E12) Leu- Pro] is not easily detectable because it is extremely unstable, and the correct diagnosis is usually made via DNA sequencing. This is the first report of this variant in the Chinese population.

Degradation levels of continuous speech affect neural speech tracking and alpha power differently.

Making sense of a poor auditory signal can pose a challenge. Previous attempts to quantify speech intelligibility in neural terms have usually focused on one of two measures, namely low-frequency speech-brain synchronization or alpha power modulations. However, reports have been mixed concerning the modulation of these measures, an issue aggravated by the fact that they have normally been studied separately. We present two MEG studies analyzing both measures. In study 1, participants listened to unimodal auditory speech with three different levels of degradation (original, 7-channel and 3-channel vocoding). Intelligibility declined with declining clarity, but speech was still intelligible to some extent even for the lowest clarity level (3-channel vocoding). Low-frequency (1-7 Hz) speech tracking suggested a U-shaped relationship with strongest effects for the medium-degraded speech (7-channel) in bilateral auditory and left frontal regions. To follow up on this finding, we implemented three additional vocoding levels (5-channel, 2-channel and 1-channel) in a second MEG study. Using this wider range of degradation, the speech-brain synchronization showed a similar pattern as in study 1, but further showed that when speech becomes unintelligible, synchronization declines again. The relationship differed for alpha power, which continued to decrease across vocoding levels reaching a floor effect for 5-channel vocoding. Predicting subjective intelligibility based on models either combining both measures or each measure alone showed superiority of the combined model. Our findings underline that speech tracking and alpha power are modified differently by the degree of degradation of continuous speech but together contribute to the subjective speech understanding.

Phylogeny and biogeography of the northern temperate genus Dracocephalum s.l. (Lamiaceae).

The northern temperate genus Dracocephalum consists of approximately 70 species mainly distributed in the steppe-desert biomes of Central and West Asia and the alpine region of the Qinghai-Tibetan Plateau (QTP). Previous work has shown that Dracocephalum is not monophyletic and might include Hyssopus and Lallemantia. This study attempts to clarify the phylogenetic relationships, diversification patterns, and the biogeographical history of the three genera (defined as Dracocephalum s.l.). Based on a sampling of 66 taxa comprising more than 80% from extant species of Dracocephalum s.l., morphological, phylogenetic (maximum parsimony, likelihood, and Bayesian inference based on nuclear ITS and ETS, plastid rpl32-trnL, trnL-trnF, ycf1, and ycf1-rps15, and two low-copy nuclear markers AT3G09060 and AT1G09680), molecular dating, diversification, and ancestral range estimation analyses were carried out. Our results demonstrate that both Hyssopus and Lallemantia are embedded within Dracocephalum and nine well-supported clades can be recognized within Dracocephalum s.l. Analyses of divergence times suggest that the genus experienced an early rapid radiation during the middle to late Miocene with major lineages diversifying within a relatively narrow timescale. Ancestral area reconstruction analyses indicate that Dracocephalum s.l. originated in Central and West Asia and southern Siberia, and dispersed from Central and West Asia into the QTP and adjacent areas twice independently during the Pliocene. The aridification of the Asian interior possibly promoted the rapid radiation of Dracocephalum within this region, and the uplift of the QTP appears to have triggered the dispersal and recent rapid diversification of the genus in the QTP and adjacent regions. Combining molecular phylogenetic and morphological evidence, a revised infrageneric classification of Dracocephalum s.l. is proposed, which recognizes nine sections within the genus.

Polydatin alleviates DSS- and TNBS-induced colitis by suppressing Th17 cell differentiation via directly inhibiting STAT3.

Inflammatory bowel disease (IBD) is a non-specific chronic intestinal inflammatory disease, often presenting with abdominal pain, diarrhea, bloody stool, anorexia, and body loss. It is difficult to cure completely and a promising treatment is urgently needed. Natural compounds can offer promising chemical agents for treatment of diseases. Polydatin is a natural ingredient extracted from the dried rhizome of Polygonum cuspidatum, which has anti-inflammatory, anti-tumor, and dementia protection activities. The purpose of this study was to evaluate the therapeutic effect of polydatin on IBD and explore its possible mechanism. We found that polydatin could effectively suppress the differentiation of Th17 cells in vitro, but had no effect on the differentiation of Treg cells. Polydatin significantly alleviated colitis induced by dextran sulfate sodium (DSS) and 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) in mice, and dramatically decreased the proportion of Th17 cells in spleen and mesenteric lymph nodes. Mechanism investigations revealed that polydatin specifically inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation by directly binding to STAT3, leading to Th17 cell reduction and thereby alleviating colitis. These findings provide novel insights into the anti-colitis effect of polydatin, which may be a promising drug candidate for the treatment of IBD.

An updated tribal classification of Lamiaceae based on plastome phylogenomics.

BACKGROUND: A robust molecular phylogeny is fundamental for developing a stable classification and providing a solid framework to understand patterns of diversification, historical biogeography, and character evolution. As the sixth largest angiosperm family, Lamiaceae, or the mint family, consitutes a major source of aromatic oil, wood, ornamentals, and culinary and medicinal herbs, making it an exceptionally important group ecologically, ethnobotanically, and floristically. The lack of a reliable phylogenetic framework for this family has thus far hindered broad-scale biogeographic studies and our comprehension of diversification. Although significant progress has been made towards clarifying Lamiaceae relationships during the past three decades, the resolution of a phylogenetic backbone at the tribal level has remained one of the greatest challenges due to limited availability of genetic data. RESULTS: We performed phylogenetic analyses of Lamiaceae to infer relationships at the tribal level using 79 protein-coding plastid genes from 175 accessions representing 170 taxa, 79 genera, and all 12 subfamilies. Both maximum likelihood and Bayesian analyses yielded a more robust phylogenetic hypothesis relative to previous studies and supported the monophyly of all 12 subfamilies, and a classification for 22 tribes, three of which are newly recognized in this study. As a consequence, we propose an updated phylogenetically informed tribal classification for Lamiaceae that is supplemented with a detailed summary of taxonomic history, generic and species diversity, morphology, synapomorphies, and distribution for each subfamily and tribe. CONCLUSIONS: Increased taxon sampling conjoined with phylogenetic analyses based on plastome sequences has provided robust support at both deep and shallow nodes and offers new insights into the phylogenetic relationships among tribes and subfamilies of Lamiaceae. This robust phylogenetic backbone of Lamiaceae will serve as a framework for future studies on mint classification, biogeography, character evolution, and diversification.

Outcome of young adult patients with very-high-risk acute lymphoblastic leukemia treated with pediatric-type chemotherapy - a single institute experience.

BACKGROUND/PURPOSE: Adult patients of acute lymphoblastic leukemia (ALL) with very high-risk (VHR) characteristics have an inferior outcome, and allogeneic hematopoietic stem cell transplantation (HSCT) is usually performed. In contrast, VHR pediatric patients can be treated effectively with minimal residual disease (MRD)-guided pediatric protocols and HSCT are not always needed. METHODS: We retrospectively reviewed young adult ALL VHR patients treated with the pediatric-type (TPOG-ALL-2002 VHR) regimen in our institute from 2008 to 2019 and compared the event-free survival (EFS) with patients treated with an adult-type regimen (Hyper-CVAD alternating with high dose methotrexate and cytarabine). RESULTS: We identified 16 patients treated with the TPOG and 11 treated with the Hyper-CVAD regimen. Philadelphia chromosome-positive (n = 10) and T-cell immunophenotype (n = 11) are the most common VHR features. Compared with the Hyper-CVAD group, patients treated with the TPOG regimen showed a trend toward better EFS with a hazard ratio (HR) of 0.42 (p = 0.16). Compared with untransplanted patients, HSCT showed a positive trend in the Hyper-CVAD (HR 0.22, p = 0.12) but not in the TPOG group (p = 0.37). Untransplanted patients treated initially with the hyper-CVAD regimen had a significantly worse outcome than the TPOG regimen (HR 4.19, p < 0.05). In the TPOG group, patients with negative MRD at the end of consolidation had a significantly better outcome (HR 0.12, p = 0.03). CONCLUSION: Young adult VHR patients can be effectively treated with the TPOG-ALL-2002 protocol, and those who achieved MRD negativity before the end of consolidation have a good outcome without allogeneic HSCT.

Human IL12p80 Promotes Murine Oligodendrocyte Differentiation to Repair Nerve Injury.

Nerve injury of the central nervous system and the peripheral nervous system still poses a major challenge in modern clinics. Understanding the roles of neurotrophic factors and their molecular mechanisms on neuro-regeneration will not only benefit patients with neural damage but could potentially treat neurodegenerative disorders, such as amyotrophic lateral sclerosis. In this study, we showed that human IL12 p40-p40 homodimer (hIL12p80) within PLA and PLGA conduits improved sciatic nerve regeneration in mice. As such, the group of conduits with NSCs and hIL12p80 (CNI) showed the best recovery among the groups in the sciatic functional index (SFI), compound muscle action potential (CMAP), and Rotarod performance analyses. In addition, the CNI group had a faster recovery and outperformed the other groups in SFI and Rotarod performance tests beginning in the fourth week post-surgery. Immunohistochemistry showed that the CNI group increased the diameter of the newly regenerated nerve by two-fold (p < 0.01). In vitro studies showed that hIL12p80 stimulated differentiation of mouse NSCs to oligodendrocyte lineages through phosphorylation of Stat3 at Y705 and S727. Furthermore, implantation using PLGA conduits (C2.0 and C2.1) showed better recovery in the Rotarod test and CMAP than using PLA conduits in FVB mice. In B6 mice, the group with C2.1 + NSCs + hIL12p80 (C2.1NI) not only promoted sciatic functional recovery but also reduced the rate of experimental autotomy. These results suggested that hIL12p80, combined with NSCs, enhanced the functional recovery and accelerated the regeneration of damaged nerves in the sciatic nerve injury mice. Our findings could further shed light on IL12's application not only in damaged nerves but also in rectifying the oligodendrocytes' defects in neurodegenerative diseases, such as amyotrophic lateral sclerosis and multiple sclerosis.

[Efficacy and mechanism of low glycoside from Epimedii Folium flavonoids on retinoic acid-induced osteoporosis in rats].

In this study, the secondary osteoporosis model was induced by oral administration of retinoic acid for two weeks in SD male rats. The efficacy and mechanism of LG on secondary osteoporosis in rats were explored through the bone morphogenetic protein 2(BMP-2)/Runt-related transcription factor 2(Runx2)/Osterix signaling pathway. With Xianling Gubao Capsules(XLGB) as the positive control, three dose groups of low glycoside from Epimedii Folium flavonoids(LG), i.e., low-dose group(LG-L), medium-dose group(LG-M), and high-dose group(LG-H), were set up. After modeling, the rats in each group were treated correspondingly by gavage for eight weeks. The action target of LG in the treatment of secondary osteoporosis in rats was analyzed by measuring the body weight and the organ indexes of rats including heart index and testis index. The efficacy of LG was characterized by the pathological changes of the femur, the microstructural parameters of the trabecular bone, and the biomechanical properties of femoral tissues in rats. The mechanism of LG was explored by measuring the relevant biochemical indexes and the changes in BMP-2, Runx2, and Osterix content in rats with secondary osteoporosis. The results showed that the action target of LG in the treatment of secondary osteoporosis in rats was the testis. LG can improve the bone loss of the femur, increase the number and thickness of the trabecular bone, reduce the porosity and separation of the trabecular bone, potentiate the resistance of bone to deformation and destruction, up-regulate the serum content of Ca, P, aminoterminal propeptide of type Ⅰ procollagen(PINP), and osteocalcin(OC), promote bone matrix calcification and the expression of BMP-2, Runx2, and Osterix proteins, and accelerate bone formation, thereby reducing the risk of fractures, and ultimately exerting anti-secondary osteoporosis efficacy.

Epstein-Barr virus latent membrane protein-1 upregulates autophagy and promotes viability in Hodgkin lymphoma: Implications for targeted therapy.

Hodgkin lymphoma (HL) is composed of neoplastic Hodgkin and Reed-Sternberg cells in an inflammatory background. The neoplastic cells are derived from germinal center B cells that, in most cases, are infected by Epstein-Barr virus (EBV), which may play a role in tumorigenesis. Given that EBV-latent membrane protein 1 (LMP1) regulates autophagy in B cells, we explored the role of autophagy mediated by EBV or LMP1 in HL. We found that EBV-LMP1 transfection in HL cells induced a modest increase in autophagy signals, attenuated starvation-induced autophagic stress, and alleviated autophagy inhibition- or doxorubicin-induced cell death. LMP1 knockdown leads to decreased autophagy LC3 signals. A xenograft mouse model further showed that EBV infection significantly increased expression of the autophagy marker LC3 in HL cells. Clinically, LC3 was expressed in 15% (19/127) of HL samples, but was absent in all cases of nodular lymphocyte-predominant and lymphocyte-rich classic HL cases. Although expression of LC3 was not correlated with EBV status or clinical outcome, autophagic blockade effectively eradicated LMP1-positive HL xenografts with better efficacy than LMP1-negative HL xenografts. Collectively, these results suggest that EBV-LMP1 enhances autophagy and promotes the viability of HL cells. Autophagic inhibition may be a potential therapeutic strategy for treating patients with HL, especially EBV-positive cases.

Pretreatment with Propofol Reduces Pulmonary Injury in a Pig Model of Intestinal Ischemia-Reperfusion via Suppressing the High-Mobility Group Box 1 Protein (HMGB1)/Toll-Like Receptor 4 (TLR4)/Protein Kinase R (PKR) Signaling Pathway.

BACKGROUND Propofol improves rodent pulmonary injury after intestinal ischemia-reperfusion (IIR). However, its effect and underlying mechanisms in large animals remain unclear. Here, we examined whether pretreatment with propofol could relieve lung injury during IIR in pigs, then investigated the underlying mechanism. MATERIAL AND METHODS A porcine model of IIR-induced lung injury was built by clamping the super mesenteric artery for 2 h and loosening the clamp for 4 h. Randomized grouping was used, and pigs were assigned to a sham-operated group, an IIR with saline pretreatment group, and an IIR with propofol pretreatment group. Pulmonary histopathologic changes, permeability, and oxygenation were assessed to evaluate the effect of propofol. We assessed levels of methane dicarboxylic aldehyde (MDA), superoxide dismutase (SOD), myeloperoxidase (MPO), high-mobility group box 1 protein (HMGB1), Toll-like receptor 4 (TLR4), and double-stranded RNA activated protein kinase R (PKR) to investigate the underlying mechanism. RESULTS IIR caused severe lung damage, including morphological changes, high permeability, airway resistance, low static compliance, hypoxemia, and acidemia. Pulmonary and plasma MDA content and MPO activity increased, whereas SOD activity decreased. The HMGB1/TLR4/PKR signaling pathway was activated following IIR. Pretreatment with propofol markedly attenuated lung injury (such as reducing the lung edema and permeability), increased MDA content and MPO activity, and restored SOD activity induced by IIR, accompanied by inhibiting the effect of the HMGB1/TLR4/PKR signaling pathway. CONCLUSIONS IIR caused acute lung injury in pigs. Pretreatment with propofol alleviated the lung injury, which was related to its suppression of the HMGB1/TLR4/PKR signaling pathway.

False-negative frozen section of sentinel nodes in early breast cancer (cT1-2N0) patients.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is the standard approach for the axillary region in early breast cancer patients with clinically negative nodes. The present study investigated patients with false-negative sentinel nodes in intraoperative frozen sections (FNSN) using real-world data. METHODS: A case-control study with a 1:3 ratio was conducted. FNSN was determined when sentinel nodes (SNs) were negative in frozen sections but positive for metastasis in formalin-fixed paraffin-embedded (FFPE) sections. The control was defined as having no metastasis of SNs in both frozen and FFPE sections. RESULTS: A total of 20 FNSN cases and 60 matched controls from 333 SLNB patients were enrolled between April 1, 2005, and November 31, 2009. The demographics and intrinsic subtypes of breast cancer were similar between the FNSN and control groups. The FNSN patients had larger tumor sizes on preoperative mammography (P = 0.033) and more lymphatic tumor emboli on core biopsy (P < 0.001). Four FNSN patients had metastasis in nonrelevant SNs. Another 16 FNSN patients had benign lymphoid hyperplasia of SNs in frozen sections and metastasis in the same SNs from FFPE sections. Micrometastasis was detected in seven of 16 patients, and metastases in nonrelevant SNs were recognized in two patients. All FNSN patients underwent a second operation with axillary lymph node dissection (ALND). After a median follow-up of 143 months, no FNSN patients developed breast cancer recurrence. The disease-free survival, breast cancer-specific survival, and overall survival in FNSN were not inferior to those in controls. CONCLUSIONS: Patients with a larger tumor size and more lymphatic tumor emboli have a higher incidence of FNSN. However, the outcomes of FNSN patients after completing ALND were noninferior to those without SN metastasis. ALND provides a correct staging for patients with metastasis in nonsentinel axillary lymph nodes.

Identification of CD44 as a Cell-Surface Marker for Kit Negative Interstitial Cells of Cajal in Adult Mouse Colon.

Loss of Kit protein expression is proven to influence the plasticity of interstitial cells of Cajal (ICCs) and may contribute to gastrointestinal (GI) dysfunctions. The role and fate of Kit negative ICCs are unclear, and cell-specific markers for the Kit ICCs are unknown. In this study, we treated adult mice with imatinib (a Kit signaling blocker) for 8 or 16 days and investigated whether CD44 is a specific marker for the Kit negative ICCs in the adult mouse colon. We aimed at examining the protein and mRNA level of CD44 and Kit by using Western blot and real-time RT-PCR, respectively. Our results indicated that Kit expression was downregulated for both protein and mRNA levels after imatinib treatment for 8 or 16 days as compared to the vehicle-treated mice. Interestingly, CD44 expression remained unchanged throughout the treatment. Immunostaining on whole-mount preparations for Kit and CD44 showed that CD44 was exclusively co-localized with Kit in the ICCs of the vehicle-treated mouse colon. After imatinib treatment, a number of CD44+/Kit- cells with elaborated processes were observed with an evident decrease of Kit+ cell number within the muscular layers (ICC-IM) and around the myenteric nerve plexus (ICC-MY) as compared to vehicle-treated mice. After discontinuing imatinib for 16 days, Kit+ ICC-MY and ICC-IM were completely co-localized with normalization of CD44 and Kit+ cell numbers. Overall, our results identify CD44 as a cell-specific surface marker for Kit-ICCs and may be useful to understand the role and fate of Kit- ICCs in GI disorders.

[Migration of phenolic active ingredients in Danshen Dizhuye during ultrafiltration of hollow fiber membrane].

Study the suitability of organic film for salvianolic acid in the ultrafiltration process of Danshen Dizhuye. UPLC was used to analyze the migration of nine phenolic active ingredients in Danshen Dizhuye during ultrafiltration of PES hollow fiber membrane and PS hollow fiber membrane. The structural composition of multi-components was analyzed by three different batches of Danshen Dizhuye before and after ultrafiltration of the two membranes. The results showed that 9 phenolic active ingredients in Danshen Dizhuye did not change significantly after ultrafiltration through PES membrane. However, after ultrafiltration through PS membrane, the content of sodium danshensu, protocatechualdehyde, caffeic acid, 3-hydroxy-4-methoxycinnamic acid and rosmarinic acid in Danshen Dizhuye did not change significantly, while salvianolic acid D, salvianolic acid B and lithospermic acid decreased by about 20%, and the content of salvianolic acid A decreased significantly. The final content in equilibrium was only about 20% of the original solution. Therefore, an in-depth study on the migration particularity of salvianolic acid A in ultrafiltration membrane was the focuse. The results showed that the loss of salvianolic acid A was caused by both membranes during ultrafiltration, and salvianolic acid A was lost more in PS membrane. When the membrane was washed and regenerated, it was found that salvianolic acid A was detected in the ethanol washing solution, but not in the washing liquid, indicating that the loss of salvianolic acid A during the ultrafiltration was mainly adsorptive action. The results suggested that the migration of phenolic active ingredients in Danshen Dizhuye during the membrane ultrafiltration process did not completely follow the molecular weight passing rule of the membrane pore size. At the same time, it may be affected by factors, such as the structure of the membrane material, and the interaction between the membrane structure and the structure of components, and exhibit different migration behaviors during the ultrafiltration of the membrane.

Identification and characterization of permissive cells to dengue virus infection in human hematopoietic stem and progenitor cells.

BACKGROUND: Dengue virus (DENV) is a significant threat to public health in tropical and subtropical regions, where the frequency of human migration is increasing. Transmission of DENV from donors to recipients after hematopoietic stem cell transplantation has been steadily described. However, the underlying mechanisms remain unclear. STUDY DESIGN AND METHODS: Freshly isolated bone marrow (BM) was subjected to DENV infection, followed by multicolor fluorescence-activated cell sorting (FACS) analysis. Virus in supernatants was collected and analyzed by plaque assay. RESULTS: DENV-1 to DENV-4 could effectively infect freshly obtained BM and produced infectious virus. DENV infection did not change the quantitative population of hematopoietic stem and progenitor cells (HSPCs), megakaryocytic progenitor cells (MkPs) and megakaryocytes. Additionally, DENV antigen, nonstructural protein 1, was enriched in HSPCs and MkPs of DENV infected marrow cells. CD34+, CD133+, or CD61+ cells sorted out from BM were not only the major contributing targets facilitating the DENV infection directly but also facilitated the spread of DENV into other cells when cocultured. CONCLUSION: Results suggest that DENV can efficiently infect HSPCs, which might jeopardize the recipients if DENV-infected cells were subsequently used. We therefore raise the need for DENV screening for both the donors and recipients of hematopoietic stem cell transplantation, especially for donors exposed to endemic areas, to mitigate DENV infection in immunocompromised recipients.

Intussusception caused by typhlitis: a rare complication in a patient with acute lymphoblastic leukemia after chemotherapy.

INTRODUCTION: Intussusception, which is common in pediatric patients but rare in adults with leukemia, usually presents with an intralumenal lesion as a lead point in adults. CASE REPORT: We herein report the case of a 38-year-old female who developed right lower quadrant abdominal pain and fever on day 16 of chemotherapy. Abdominal computed tomography showed ileocecal intussusception. The patient underwent surgery, and the definitive pathological diagnosis was typhlitis leading to intussusception. Albeit very rare in adults, typhlitis-induced intussusception should be suspected in those with leukemia presenting with abdominal pain.

Aging, cognition, and the brain: effects of age-related variation in white matter integrity on neuropsychological function.

Alterations in brain structure are viewed as neurobiological indicators which are closely tied to cognitive changes in healthy human aging. The current study used diffusion tensor imaging (DTI) tractography to investigate the relationship between age, brain variation in white matter (WM) integrity, and cognitive function. Sixteen younger adults (aged 20-28 years) and 18 healthy older adults (aged 60-75 years) underwent DTI scanning and a standardized battery of neuropsychological measures. Behaviorally, older adults exhibited poorer performance on multiple cognitive measures compared to younger adults. At the neural level, the effects of aging on theWM integrity were evident within interhemispheric (the anterior portion of corpus callosum) and transverse (the right uncinate fasciculus) fibers of the frontal regions, and the cingulum-angular fibers. Our correlation results showed that age-related WM differentially influenced cognitive function, with increased fractional anisotropy values in both the anterior corpus callosum and the right cingulum/angular fibers positively correlated with performance on the visuospatial task in older adults. Moreover, mediation analysis further revealed that the WM tract integrity of the frontal interhemspheric fibers was a significant mediator of age-visuospatial performance relation in older adults, but not in younger adults. These findings support the vulnerability of the frontal WM fibers to normal aging and push forward our understanding of cognitive aging by providing a more integrative view of the neural basis of linkages among aging, cognition, and brain.