Prognosis of pediatric BCP-ALL with IKZF1 deletions and impact of intensive chemotherapy: Results of SCCLG-2016 study.

BACKGROUND: IKZF1 deletion (IKZF1del) is associated with poor prognosis in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). But the prognosis of IKZF1del combined with other prognostic stratification factors remains unclear. Whether intensified treatment improves BCP-ALL prognosis has not been determined. METHODS: A retrospective analysis was performed on 1291 pediatric patients diagnosed with BCP-ALL and treated with the South China Children's Leukemia 2016 protocol. Patients were stratified based on IKZF1 status for comparison of characteristics and outcome. Additionally, IKZF1del patients were further divided based on chemotherapy intensity for outcome assessments. RESULTS: The BCP-ALL pediatric patients with IKZF1del in south China showed poorer early response. Notably, the DFS and OS for IKZF1del patients were markedly lower than IKZF1wt group (3-year DFS: 88.7% [95% CI: 83.4%-94.0%] vs. 93.5% [95% CI: 92.0%-94.9%], P = .021; 3-year OS: 90.7% [95% CI: 85.8% to 95.6%] vs. 96.1% [95% CI: 95% to 97.2%, P = .003]), with a concurrent increase in 3-year TRM (6.4% [95% CI: 2.3%-10.5%] vs. 2.9% [95% CI: 1.9%-3.8%], P = .025). However, the 3-year CIR was comparable between the two groups (5.7% [95% CI: 1.8%-9.5%] vs. 3.7% [95% CI: 2.6%-4.7%], P = .138). Subgroup analyses reveal no factor significantly influenced the prognosis of the IKZF1del cohort. Noteworthy, intensive chemotherapy improved DFS from 85.7% ± 4.1% to 94.1% ± 0.7% in IKZF1del group (P = .084). Particularly in BCR::ABL positive subgroup, the 3-year DFS was remarkably improved from 53.6% ± 20.1% with non-intensive chemotherapy to 100% with intensive chemotherapy (P = .026). CONCLUSIONS: Pediatric BCP-ALL patients with IKZF1del in South China manifest poor outcomes without independent prognostic significance. While no factor substantially alters the prognosis in the IKZF1del group. Intensified chemotherapy may reduce relapse rates and improve DFS in patients with IKZF1del subset, particularly in IKZFdel patients with BCR::ABL positive.

[Essential oil of Cinnamomum camphora mitigates depression-like behavior in mice by regulating Nrf2/HO-1 pathway and inhibiting inflammatory cytokines].

This study aims to investigate the essential oil(EOL) of Cinnamomum camphora regarding its anti-depression effect and mechanism in regulating inflammatory cytokines and the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway. A mouse model of depression was established by intraperitoneal injection of lipopolysaccharide(LPS). Open field, elevated plus maze, and forced swimming tests were carried out to examine mouse behaviors. Western blot and qRT-PCR were employed to determine the expression of proteins and genes in the Nrf2/HO-1 pathway in the hippocampus. The levels of tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1ß in the serum were measured by enzyme-linked immunosorbent assay(ELISA). The changes of apoptosis in mouse brain were detected by Tunel staining. Compared with the blank control group, the model group showed shortened distance travelled and time spent in the central zone and reduced number of entries in the central zone in the open field test. In the elevated plus maze test, the model group showed reduced open arm time(OT%) and open arm entries(OE%). In the force swimming test, the model group showed extended duration of immobility compared with the blank control group. Compared with the model group, the treatment with EOL significantly increased the distance travelled and time spent in the central zone and increased the number of entries in the central zone in the open field test. In addition, EOL significantly increased the OT% and OE% in the elevated plus maze and shor-tened the immobility duration in the forced swimming test. The model group showed lower expression levels of Nrf2 and HO-1 and hig-her levels of TNF-α, IL-6, and IL-1ß than the blank control group. Compared with the model group, the treatment with EOL up-regulated the expression levels of Nrf2 and HO-1 and lowered the levels of TNF-α, IL-6, and IL-1ß. The Tunel staining results showed that the apoptosis rate in the brain tissue of mice decreased significantly after the treatment with EOL. To sum up, EOL can mitigate the depression-like behaviors of mice by up-regulating the expression of Nrf2 and HO-1 and preventing hippocampal inflammatory damage. The findings provide empirical support for the application of EOL and aromatherapy in the treatment of depression.

Observation of Chiral Channels in Helical Covalent Organic Frameworks.

Unraveling the mechanism of chirality transfer across length scales is crucial to the rational development of functional materials with hierarchical chirality. The key obstacle is the lack of structural information, especially at the mesoscopic level. We report herein the structural identification of helical covalent organic frameworks (heliCOFs) with hierarchical chirality, which integrate molecular chirality, channel chirality, and morphology chirality into one crystalline entity. Specifically, benefiting from the highly ordered structure of heliCOFs, the existence of chiral channels at the mesoscopic level has been confirmed by electron crystallography, and the handedness of these chiral channels has been directly determined through the stereopair imaging technique. Accordingly, the chirality transfer in heliCOFs from microscopic to macroscopic levels could be rationalized with a layer-rotating model that has been supported by both crystal structure analysis and theoretical calculations. Observation of chiral channels in heliCOFs not only provides unprecedented data for the understanding of the chirality transfer process but also sheds new light on the rational construction of highly ordered polymeric materials with hierarchical chirality.

Immunotherapy of microsatellite stable colorectal cancer: resistance mechanisms and treatment strategies.

In recent years, immunotherapy strategies based on immune checkpoint inhibitors have yielded good efficacy in colorectal cancer (CRC)especially in colorectal cancer with microsatellite instability-high. However, microsatellite-stable (MSS) CRCs account for about 85% of CRCs and are resistant to immunotherapy. Previous studies have shown that compared with MSS CRC, high microsatellite instability CRC possesses a higher frequency of mutations and can generate more neoantigens. Therefore, improving the sensitivity of immunotherapy to MSS CRC is a hot topic which is crucial for the treatment of MSS CRC. This review aims to discuss the factors contributing to MSS CRC insensitivity to immunotherapy and explored potential solutions to overcome immunotherapy resistance.

Diprotin A TFA Exerts Neurovascular Protection in Ischemic Cerebral Stroke.

Background: It has been established that the dipeptidyl peptidase-4 (DPP-4) inhibitor Diprotin A TFA can reduce vascular endothelial (VE)-cadherin disruption by inhibiting the increase in cleaved ß-catenin in response to hypoxia, thereby protecting the vascular barrier of human umbilical vein endothelial cells. In this study, we sought to investigate the possible effect of Diprotin A TFA on the VE barrier after cerebral ischemic stroke in mice. Methods: C57BL/6J mice were divided into five groups, namely, (1) sham, (2) stroke, (3) stroke + dimethyl sulfoxide (DMSO), (4) stroke + Diprotin A TFA, and (5) stroke + Diprotin A TFA + XAV-939. First, the cerebral ischemia model was established by photothrombotic ischemia, followed by intraperitoneal injection with Diprotin A TFA and XAV-939 at doses of 70 µg/kg and 40 mg/kg 30 min once in the morning and once in the evening for 3 days. Immunofluorescence staining and Western blot methods were used to analyze the expression of vascular and blood-brain barrier (BBB)-associated molecular markers in the peri-infarct area. Results: Compared with the vehicle control group, we found that mice injected with Diprotin A TFA exhibited reduced cerebral infarction volume, increased vascular area and length around the brain injury, increased pericyte and basement membrane coverage, upregulated expression of BBB tight junction proteins, and improved their BBB permeability, whereas the group injected with both drug and inhibitor exhibited significantly aggravated vascular injury and BBB permeability. Conclusion: Diprotin A TFA can reduce VE-cadherin disruption by inhibiting ischemia-hypoxia-induced ß-catenin cleavage to protect blood vessels.

Fused-Ring-Linked Covalent Organic Frameworks.

The development of linkage chemistry in the research area of covalent organic frameworks (COFs) is fundamentally important for creating robust structures with high crystallinity and diversified functionality. We reach herein a new level of complexity and controllability in linkage chemistry by achieving the first synthesis of fused-ring-linked COFs. A series of bicyclic pyrano[4,3-b]pyridine COFs have been constructed via a cascade protocol involving Schiff-base condensation, intramolecular [4 + 2] cycloaddition, and dehydroaromatization. With a broad scope of Brønsted or Lewis acids as the catalyst, the designed monomers, that is, O-propargylic salicylaldehydes and multitopic anilines, were converted into the fused-ring-linked frameworks in a one-pot fashion. The obtained COFs exhibited excellence in terms of purity, stability, and crystallinity, as comprehensively characterized by solid-state nuclear magnetic resonance (NMR) spectroscopy, powder X-ray diffraction, high-resolution transmission electron microscopy, and so on. Specifically, the highly selective formation (>94%) of pyrano[4,3-b]pyridine linkage was verified by quantitative NMR measurements combined with 13C-labeling synthesis. Moreover, the fused-ring linkage possesses fully locked conformation, which benefits to the high crystallinity observed for these COFs. Advancing the linkage chemistry from the formation of solo bonds or single rings to that of fused rings, this study has opened up new possibilities for the concise construction of sophisticated COF structures with high controllability.

Apple polyphenols delay postharvest senescence and quality deterioration of 'Jinshayou' pummelo fruit during storage.

Introduction: Apple polyphenols (AP), derived from the peel of mature-green apples, are widely used as natural plant-derived preservatives in the postharvest preservation of numerous horticultural products. Methods: The goal of this research was to investigate how AP (at 0.5% and 1.0%) influences senescence-related physiological parameters and antioxidant capacity of 'Jinshayou' pummelo fruits stored at 20°C for 90 d. Results: The treating pummelo fruit with AP could effectively retard the loss of green color and internal nutritional quality, resulting in higher levels of total soluble solid (TSS) content, titratable acidity (TA) content and pericarp firmness, thus maintaining the overall quality. Concurrently, AP treatment promoted the increases in ascorbic acid, reduced glutathione, total phenols (TP) and total flavonoids (TF) contents, increased the scavenging rates of 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and hydroxyl radical (•OH), and enhanced the activities of superoxide dismutase (SOD), catalase, peroxidase, ascorbate peroxidase (APX), and glutathione reductase (GR) as well as their encoding genes expression (CmSOD, CmCAT, CmPOD, CmAPX, and CmGR), reducing the increases in electrolyte leakage, malondialdehyde content and hydrogen peroxide level, resulting in lower fruit decay rate and weight loss rate. The storage quality of 'Jinshayou' pummelo fruit was found to be maintained best with a 1.0% AP concentration. Conclusion: AP treatment can be regarded as a promising and effective preservative of delaying quality deterioration and improving antioxidant capacity of 'Jinshayou' pummelo fruit during storage at room temperature.

Tianxiangdan Improves Coronary Microvascular Dysfunction in Rats by Inhibiting Microvascular Inflammation via Nrf2 Activation.

BACKGROUND: Tianxiangdan (TXD) is used in traditional Chinese medicine because of its therapeutic and preventive effects in the treatment of coronary heart disease. However, the underlying mechanism of TXD in coronary microvascular disease (CMD) remains unclear. METHODS: A rat model of CMD was developed to study the mechanism of TXD activity. Sodium laurate was injected into the left ventricle of Sprague-Dawley rats to induce CMD. The rats were divided into six groups: a sham-operated (sham) group, an untreated CMD group, a low-dose TXD group (0.81 g·kg-1·d-1), a mid-dose TXD (TXD-M) group (1.62 g·kg-1·d-1), a high-dose TXD (TXD-H) group (3.24 g·kg-1·d-1), and a nicorandil (NCR) group (1.35 mg·kg-1·d-1). The effect of TXD on rats with CMD was observed after four weeks, and the mechanism of TXD in lipopolysaccharide (LPS)-induced cardiac microvascular endothelial cells (CMECs) was explored through treatment with 50 µg/mL TXD. RESULTS: Compared with the rats in the untreated CMD group, rats in the TXD-M and TXD-H groups showed higher left ventricular ejection fraction values, improved pathological structures, decreased expressions of interleukin (IL)-1ß, tumor necrosis factor-alpha (TNF-α), phosphorylated nuclear factor-κB inhibitor α (IκBα) and phosphorylated p65, and increased expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (P < 0.05). These effects were more pronounced in the TXD-H group than in the TXD-M group. In vitro experiments showed that TXD treatment increased the viability of LPS-induced CMECs and decreased the expression of IL-1ß, TNF-α, phosphorylated IκBα, and phosphorylated p65 (P < 0.05). However, the effects of TXD on CMECs were markedly reversed upon treatment with ML385 (Nrf2 inhibitor). CONCLUSION: The results showed that TXD exerts a protective effect on rats with CMD and related inflammatory injuries, and its anti-inflammatory mechanism is related to the activation of Nrf2 signalling.

[Comparative study between electroacupuncture at Neima point and Neiguan (PC 6) and epidural nerve block for preemptive analgesia in patients undergoing thoracic surgery].

OBJECTIVE: To compare the clinical effect between electroacupuncture (EA) at Neima point and Neiguan (PC 6) and epidural nerve block for preemptive analgesia in patients undergoing thoracic surgery. METHODS: Sixty patients with elective radical esophagectomy were randomly divided into a group A, a group B and a control group, 20 cases in each group. The patients in the group A were treated with injection of 20 mL 0.375% ropivacaine at epidural space 30 min before anesthesia induction, followed by normal anesthesia during operation; the patients in the group B were treated with 30 min EA at bilateral Neima point and Neiguan (PC 6) before anesthesia induction, followed by normal anesthesia during operation; the patients in the control group were treated with general anesthesia alone. Patient-controlled intravenous analgesia was applied for all the patients. The mean arterial pressure (MAP) and heart rate (HR) were recorded at the following time points: before acupuncture/epidural puncture (T0), skin incision (T1), extubation (T2) and 2 h after operation (T3); the dosage of anesthetics and extubation time were recorded; the plasma levels of ß-endorphin (ß-EP), 5-hydroxytryptamine (5-HT) and prostaglandin E2 (PGE2) were measured at the following time points: T0, T3, 12 h after operation (T4), 24 h after operation (T5) and 48 h after operation (T6). Visual analogue scale (VAS) was used to evaluate the analgesic effect. RESULTS: The MAP at T1 and T2 in the group A was lower than that in group B and control group (P<0.05), and HR at T1 and T2 was lower than that in control group (P<0.05). The MAP and HR at T1 and T2 in the group B were lower than those in the control group (P<0.05). The dosage of remifentanil in the group A and group B was lower than that in the control group (P<0.05), and extubation time was earlier than that in the control group (P<0.05). The content of ß-EP at T4, T5 and T6 in the group B was higher than that in the group A and control group (P<0.05); the contents of 5-HT and PGE2 at T3, T4 and T5 in the group A and group B were lower than those in the control group (P<0.05). The VAS scores at T3, T4 and T5 in the group A and group were lower than those in the control group (P<0.05). CONCLUSION: The preemptive analgesia of EA at Neima point and Neiguan (PC 6) and epidural nerve block could both provide effective perioperative analgesia for thoracic surgery. The EA could better maintain intraoperative hemodynamics and has less physiological disturbance.

Photoacoustic-Based Miniature Device with Smartphone Readout for Point-of-Care Testing of Uric Acid.

Real-time and rapid detection of various biomarkers in body fluids has important significance for early disease diagnosis, efficient monitoring of treatment, and evaluation of prognosis. However, traditional detection methods not only require bulky and costly instruments but also are not suitable for the analysis of heterogeneous samples (e.g., serum and urine), limiting their applications in point-of-care testing (POCT). Herein, an integrated photoacoustic (PA) device with a smartphone as the acoustic signal readout has been constructed, greatly reducing the volume and cost of the instrument, and providing a potential miniature platform for POCT of clinical samples. By exploiting the electron transfer product of 3,3',5,5'-tetramethylbenzidine (TMB) (i.e., TMB++) as the PA probe and hemin-graphene oxide (H-GO) complex as the peroxidase, quantitative analysis of uric acid was successfully performed by using only 30 µL of a sample solution. Due to the favorable stability of artificial enzymes, reaction reagents could be effectively embedded in agar gel to make a portable "test strip". Therefore, operators just need to drop clinical samples on the "test strip" for PA analysis, which is user friendly without requiring complex sample preparation steps. In addition, since the acoustic change mainly comes from the PA effect, it has a lower background signal than UV-vis and fluorescence analysis, greatly improving the analytical performance. The simplicity, low cost, and broad adaptability make this miniature PA device attractive for on-site detection, particularly in resource-limited settings.

In Situ Generation of Prussian Blue by MIL-53 (Fe) for Point-of-Care Testing of Butyrylcholinesterase Activity Using a Portable High-Throughput Photothermal Device.

Butyrylcholinesterase (BuChE), the primary source of serum cholinesterase activity, is an indispensable biochemical marker for clinical diagnosis of liver function and organophosphorus poisoning. The requirement for bulky and expensive instruments represents a huge hindrance for point-of-care testing (POCT) of BuChE, especially in resource-limited settings. Herein, an easy-operated, economic, and portable photothermal (PT) biosensing platform for high-throughput BuChE detection was rationally designed. BuChE could "light up" the PT signal through in situ generation of Prussian blue (PB) by MIL-53 (Fe), which allowed us to translate biological signals into temperature signals. Such temperature change signals could be monitored at high throughput (six samples for a single measurement) by a miniature self-made integrated PT device via combining separable 96-well plates, a three-dimensional (3D) printed sample bracket, 808 nm lasers, and thermometers, satisfying the requirement for rapid on-site detection in a large batch with low cost. In addition, the large specific surface area, 3D network structure, and high porosity of MIL-53 (Fe) offered a beneficial platform for its reaction with enzymatic hydrolysate, resulting in high sensing sensitivity and low detection limit (0.3 U L-1), which was at least 20 000 times lower than the normal human serum BuChE activity. This facile, affordable, and broad applicability PT sensing platform provides a beneficial reference for the rational design of other disease diagnostic approaches suitable for POCT.

COVID-19 and early-stage lung cancer both featuring ground-glass opacities: a propensity score-matched study.

BACKGROUND: Radiological manifestations of coronavirus disease 2019 (COVID-19) featured ground-glass opacities (GGOs), especially in the early stage, which might create confusion in differential diagnosis with early lung cancer. We aimed to specify the radiological characteristics of COVID-19 and early lung cancer and to unveil the discrepancy between them. METHODS: One hundred and fifty-seven COVID-19 patients and 374 early lung cancer patients from four hospitals in China were retrospectively enrolled. Epidemiological, clinical, radiological, and pathological characteristics were compared between the two groups using propensity score-matched (PSM) analysis. RESULTS: COVID-19 patients had more distinct symptoms, tended to be younger (P<0.0001), male (P<0.0001), and had a higher body mass index (P=0.014). After 1:1 PSM, 121 matched pairs were identified. Regarding radiological characteristics, patients with a single lesion accounted for 17% in COVID-19 and 89% in lung cancer (P<0.0001). Most lesions were peripherally found in both groups. Lesions in COVID-19 involved more lobes (median 3.5 vs. 1; P<0.0001) and segments (median 6 vs. 1; P<0.0001) and tended to have multiple types (67%) with patchy form (54%). Early lung cancer was more likely to have a single type (92%) with oval form (66%). Also, COVID-19 and early lung cancer either had some distinctive features on computed tomography (CT) images. CONCLUSIONS: Both COVID-19 and early lung cancers showed GGOs, with similar but independent features. The imaging characteristics should be fully understood and combined with epidemiological history, pathogen detection, laboratory tests, short-term CT reexamination, and pathological results to aid differential diagnosis.

Phytoactinopolyspora mesophila sp. nov., isolated from a saline-alkaline soil.

A novel moderately halophilic, filamentous actinobacterium, designated as XMNu-373T, was isolated from a saline-alkaline soil sample collected from the Mongolia Plateau, Dongwu County, Inner Mongolia Autonomous Region, PR China. The isolate grew optimally at 28‒37 °C, pH 7.0‒8.0 and with 2-5 % (w/v) NaCl. The substrate mycelia fragmented into rod-like elements, and the white aerial mycelia formed spore chains at maturity. The predominant menaquinone was MK-9(H4). The polar lipids were diphosphatidylglycerol, three unidentified phosphoglycolipids, an unidentified aminophospholipid, two phosphatidylinositol mannosides, four unidentified phospholipids, phosphatidylglycerol and two unidentified lipids. The major cellular fatty acids were iso-C16 : 0, anteiso-C17 : 0 and anteiso-C15 : 0. The genomic DNA G+C content was 66.2 mol%. It shared high 16S rRNA gene sequence similarities to Phytoactinopolyspora halotolerans YIM 96448T (96.1 %) and Phytoactinopolyspora endophytica EGI 60009T (96.0 %). Phylogenetic trees based on 16S rRNA gene sequences revealed that strain XMNu-373T resided in the clade of family Jiangellaceae, and it formed a monophyletic branch distinct from four other recognized type species in the subclade of the genus Phytoactinopolyspora. On the basis of polyphasic taxonomic evidence, strain XMNu-373T represents a novel species of the genus Phytoactinopolyspora, for which the name Phytoactinopolyspora mesophila sp. nov. is proposed. The type strain is XMNu-373T (=JCM 33740T=CGMCC 4.7654T).

Targeted mutagenesis in Arabidopsis thaliana using CRISPR-Cas12b/C2c1.

Cas12b/C2c1 is a newly identified class 2 CRISPR endonuclease that was recently engineered for targeted genome editing in mammals and rice. To explore the potential applications of the CRISPR-Cas12b system in the dicot Arabidopsis thaliana, we selected BvCas12b and BhCas12b v4 for analysis. We successfully used both endonucleases to induce mutations, perform multiplex genome editing, and create large deletions at multiple loci. No significant mutations were detected at potential off-target sites. Analysis of the insertion/deletion frequencies and patterns of mutants generated via targeted gene mutagenesis highlighted the potential utility of CRISPR-Cas12b systems for genome editing in Arabidopsis.

Sevoflurane modulates the cancer stem cell-like properties and mitochondrial membrane potential of glioma via Ca2+-dependent CaMKII/JNK cascade.

AIMS: Gliomas are responsible for the majority of deaths from primary brain tumours. Sevoflurane showed inhibition effects on the tumor progression in vitro. However, whether sevoflurane could affect the stemness of glioma stem cells (GSCs) and the potential molecular mechanism have not been well elucidated. MAIN METHODS: Effects of sevoflurane on cell viability, proliferation and invasion ability of glioma cells as well as tumor growth in vivo were assessed. Sphere formation assay was performed to evaluate the effect of sevoflurane on the stemness of GSCs. Effects of sevoflurane on mitochondrial function was evaluated by intracellular/mitochondrial reactive oxygen species (ROS) level and mitochondrial membrane potential. Expression levels of proliferation-related proteins, stemness markers and proteins in CaMKII/JNK cascade were measured by Western blot. KEY FINDINGS: Sevoflurane inhibited the viability, proliferation and invasion ability of glioma cells (U87MG and U373MG). Western blot showed that sevoflurane decreased the expression levels of proliferation and invasion-related proteins. Sphere formation ability of GSCs, expression levels of stemness markers and mitochondrial function were significantly suppressed by sevoflurane. Moreover, sevoflurane treatment significantly increased the Ca2+ concentration and stimulated phosphorylation of CaMKII, JNK and IRS1. Ca2+ chelator BAPTA-AM combined with sevoflurane synergistically inhibited colony forming ability and the expression levels of proliferation-related proteins and stemness markers. In addition, the in vivo study further confirmed that sevoflurane inhibited tumor growth via Ca2+-dependent CaMKII/JNK cascade. SIGNIFICANCE: The present study demonstrated that sevoflurane inhibited glioma tumorigenesis and modulated the cancer stem cell-like properties and mitochondrial membrane potential via activation of Ca2+-dependent CaMKII/JNK cascade.

Immune-enhancement effects of oligosaccharides from Codonopsis pilosula on cyclophosphamide induced immunosuppression in mice.

As an important edible traditional Chinese medicine, Codonopsis pilosula has good immunomodulation effects. This study focuses on C. pilosula oligosaccharides (CPO), which are the sweetness components of C. pilosula. CPO were obtained through systematic separation and purification (the yield is 14.3%), and the effect of CPO on the immunological activities of immunocompromised mice induced by cyclophosphamide (CTX) was evaluated. The results showed that CPO could increase immune organ indices, phagocytic index and immunoglobulin contents, stimulate the proliferation of splenic lymphocytes (coordinating with ConA and LPS), enhance the earlap swelling of the DTH reaction, promote the production of NO and cytokines (IL-2 and IFN-γ) and upregulate the expression of the corresponding mRNA. In addition, CPO upregulated the protein expression of phosphorylated p38, phosphorylated ERK1/2 and phosphorylated JNK, which indicated that CPO might exert immunomodulatory effects through the MAPK signaling pathway. These findings indicated that CPO are important immunomodulatory components in C. pilosula and could be developed as immunomodulators in medicine or functional food areas.

Baseline Brain Gray Matter Volume as a Predictor of Acupuncture Outcome in Treating Migraine.

Background: The present study aimed to investigate the use of imaging biomarkers to predict the outcome of acupuncture in patients with migraine without aura (MwoA). Methods: Forty-one patients with MwoA received 4 weeks of acupuncture treatment and two brain imaging sessions at the Beijing Traditional Chinese Medicine Hospital affiliated with Capital Medical University. Patients kept a headache diary for 4 weeks before treatment and during acupuncture treatment. Responders were defined as those with at least a 50% reduction in the number of migraine days. The machine learning method was used to distinguish responders from non-responders based on pre-treatment brain gray matter (GM) volume. Longitudinal changes in GM predictive regions were also analyzed. Results: After 4 weeks of acupuncture, 19 patients were classified as responders. Based on 10-fold cross-validation for the selection of GM features, the linear support vector machine produced a classification model with 73% sensitivity, 85% specificity, and 83% accuracy. The area under the receiver operating characteristic curve was 0.7871. This classification model included 10 GM areas that were mainly distributed in the frontal, temporal, parietal, precuneus, and cuneus gyri. The reduction in the number of migraine days was correlated with baseline GM volume in the cuneus, parietal, and frontal gyri in all patients. Moreover, the left cuneus showed a longitudinal increase in GM volume in responders. Conclusion: The results suggest that pre-treatment brain structure could be a novel predictor of the outcome of acupuncture in the treatment of MwoA. Imaging features could be a useful tool for the prediction of acupuncture efficacy, which would enable the development of a personalized medicine strategy.

A portable photoacoustic device for facile and sensitive detection of serum alkaline phosphatase activity.

It is still a high challenge to develop a simple, sensitive and portable approach for bioassay in strong scattering medium. Herein, a photoacoustic (PA) device is developed for the detection of alkaline phosphatase (ALP) in serum with silver nanoparticles (AgNPs) as signal probe, without any requirements for expensive equipment, professional operation and pre-processing of real samples. ALP as an important disease marker could catalyze the breakdown of sodium L-ascorbyl-2-phosphate (AAP) into ascorbic acid (AA), thereby reducing Ag+ to AgNPs. AgNPs could generate strong PA signal under the irradiation of modulated 638-nm laser due to their localized plasmon resonance, and detected by the self-made portable PA device. Under the optimized experimental conditions, the present PA device exhibits excellent photostability and reproducibility with the relative standard deviation (RSD) of 2.2% at the concentration of 25 U L-1 ALP. Linear calibration graph is obtained within 5-70 U L-1 for ALP, along with a detection limit of 1.1 U L-1. This portable PA device is applied to detect ALP in serum samples, providing satisfactory spiking recoveries and competitive analytical performances with the current techniques. The PA-based analytical strategy obviously opens up a new avenue to the detection of disease-correlated biomarker in practice.

A miniaturized photoacoustic device with laptop readout for point-of-care testing of blood glucose.

Photoacoustic (PA) effect has been widely applied in many fields, e.g., physics, chemistry and biomedicine. Herein, a miniaturized PA device is developed by integrating laser source, photo chopper, PA cell, microphone, and laptop for point-of-care testing in bioassay. With glucose assay as model, a piece of paper strip preloading chitosan, starch-potassium iodide (KI) and glucose oxidase (GOD) as lab-on-paper is employed for loading sample prior to PA detection. In the presence of glucose, the product generated on the paper strip would give rise to a strong PA signal in the PA cell under the irradiation of frequency-modulated laser at 520 nm via laptop readout. With a sample volume of 20 µL, a detection limit of 0.03 mM is obtained for glucose assay, along with a linear range of 0.08-1 mM. The accuracy and practicability of the present PA device is well demonstrated by detecting glucose in whole blood. Differing from the conventional PA instrument, the present PA device is really small in bulk with competitive sensitivity and excellent stability, offering a promising tool for point-of-care testing in bioassay.

Exposure of adult mice to perfluorobutanesulfonate impacts ovarian functions through hypothyroxinemia leading to down-regulation of Akt-mTOR signaling.

Perfluorobutanesulfonate (PFBS), a short-chain perfluoroalkyl substance, is used in many industrial products. Preliminary evidence suggests that exposure to PFBS may increase the risk of infertility. The aim of this study was to investigate the influence of PFBS on ovarian function. Herein, we show that exposure of adult female mice to PFBS (200 mg/kg/day) (PFBS-mice) caused a decrease in the levels of serum total triiodothyronine and thyroxine, which depended on the activation of peroxisome proliferator-activated receptor α (PPARα). The numbers of secondary, early antral and antral follicles were reduced in PFBS-mice with an increase in the atretic follicles, and these changes were recovered by the replacement of L-thyroxinein or the treatment with PPARα antagonist GW6471. PFBS-induced hypothyroxinemia led to a decrease in the levels of Akt, mTOR and p70S6K phosphorylation in ovarian granular cells and cumulus cells, which suppressed the proliferation of these cells and enhanced autophagic death of granular cells and cumulus cells. The levels of serum estradiol and progesterone were reduced in PFBS-mice with a low expression of the steroidogenic genes Star and P450scc in ovarian tissues, which were sensitive to the replacement of L-thyroxinein or the blockade of PPARα. The results indicate that exposure to PFBS (≥200 mg/kg/day) through reducing thyroid hormones causes down-regulation of Akt-mTOR signaling in granular cells and cumulus cells, leading to the deficits in the development of follicles and the biosynthesis of ovarian hormones.