A multi-classifier system integrated by clinico-histology-genomic analysis for predicting recurrence of papillary renal cell carcinoma.

Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I-III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p < 0.05). The RFS in our multi-classifier-defined high-risk stage I/II and grade 1/2 groups is significantly worse than in the low-risk stage III and grade 3/4 groups (p < 0.05). Our multi-classifier system is a practical and reliable predictor for recurrence of localized pRCC after surgery that can be used with the current staging system to more accurately predict disease course and inform strategies for individualized adjuvant therapy.

Genetic Landscape and Its Prognostic Impact in Children With Langerhans Cell Histiocytosis.

CONTEXT.­: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm that predominantly affects young children. OBJECTIVE.­: To investigate genetic alterations and their correlation with clinical characteristics and prognosis in pediatric LCH. DESIGN.­: We performed targeted sequencing to detect mutations in LCH lesions from pediatric patients. RESULTS.­: A total of 30 genomic alterations in 5 genes of the MAPK pathway were identified in 187 of 223 patients (83.9%). BRAF V600E (B-Raf proto-oncogene, serine/threonine kinase) was the most common mutation (51.6%), followed by MAP2K1 (mitogen-activated protein kinase kinase 1) alterations (17.0%) and other BRAF mutations (13.0%). ARAF (A-Raf proto-oncogene, serine/threonine kinase) and KRAS (KRAS proto-oncogene, GTPase) mutations were relatively rare (2.2% and 0.9%, respectively). Additionally, FNBP1 (formin-binding protein 1)::BRAF fusion and MAP3K10 (mitogen-activated protein kinase kinase 10) mutations A17T and R823C were identified in 1 case each, with possible constitutive activation of ERK1/2 phosphorylation. BRAF V600E was more frequent in patients with risk organ involvement, while MAP2K1 mutation was more prevalent in patients with single-system LCH (P = .001). BRAF V600E was associated with craniofacial bone, skin, liver, spleen, and ear involvement (all P < .05). Patients with other BRAF mutations had a higher proportion of spinal column involvement (P = .006). Univariate analysis showed a significant difference in progression-free survival among the 4 molecular subgroups for patients treated with first-line therapy (P = .02). According to multivariate analysis, risk organ involvement was the strongest independent adverse prognostic factor (hazard ratio, 8.854; P < .001); BRAF or MAP2K1 mutation was not an independent prognostic factor. CONCLUSIONS.­: Most pediatric patients with LCH carry somatic mutations involving the MAPK pathway, correlating with clinical characteristics and outcomes for first-line chemotherapy.

A Six-Surface System to Describe Anatomy of Anterior Clinoid Process and Its Application in Anterior Clinoidectomy and Resection of Paraclinoid Meningioma.

OBJECTIVE: The anterior clinoid process (ACP) is surrounded by nerves and vessels that, together, constitute an intricate anatomical structure with variations that challenges the performance of individualized anterior clinoidectomy in treating lesions with different extents of invasion. In the present study, we established a 6-surface system for the ACP based on anatomical landmarks and analyzed its value in guiding ACP drilling and resection of paraclinoid meningiomas. METHODS: Using the anatomical characteristics of 10 dry skull specimens, we set 9 anatomical landmarks to delineate the ACP into 6 surfaces. Guided by our 6-surface system and eggshell technique, 5 colored silicone-injected anatomical specimens were dissected via a frontotemporal craniotomy to perform anterior clinoidectomy. Next, 3 typical cases of paraclinoid meningioma were selected to determine the value of using our 6-surface system in tumor resection. RESULTS: Nine points (A-H and T) were proposed to delineate the ACP surface into frontal, temporal, optic nerve, internal carotid artery, cranial nerve III, and optic strut surfaces according to the adjacent tissues. Either intradurally or extradurally, the frontal and temporal surfaces could be identified and drilled into depth, followed by skeletonization of the optic nerve, cranial nerve III, internal carotid artery, and optic strut surfaces. After the residual bone was removed, the ACP was drilled off. In surgery of paraclinoid meningiomas, our 6-surface system provided great benefit in locating the dura, nerves, and vessels, thus, increasing the safety of opening the optic canal and relaxing the oculomotor or optic nerves and allowing for individualized ACP drilling for meningioma removal. CONCLUSIONS: Our 6-surface system adds much anatomical information to the classic Dolenc triangle and can help neurosurgeons, especially junior ones, to increase their understanding of the paraclinoid spatial structure and accomplish individualized surgical procedures with high safety and minimal invasiveness.

Enhanced Visible-Photocatalytic Activities in Strong Acids and Strong Alkalis of Flexible Iron-SrTiO3 Nanofibrous Membranes.

Traditional SrTiO3 (STO) materials have high brittleness and poor deformation resistance. In this work, macroscopically flexible iron-doped SrTiO3 (SFTO) nanofibrous membranes were prepared by electrospinning and calcination, which can be easily isolated and can maintain integrity to recycle as photocatalysts. Moreover, the SFTO nanofibrous membranes showed enhanced photocatalytic performance under strong acids (pH = 2) and strong alkalis (pH = 12). The SFTO nanofibrous membranes increased the catalytic rate of Congo red (CR) dye by about 10 times in visible light. The mechanism of photocatalytic activity enhancement was discussed by the combined effects of hydroxyl radicals and superoxide radicals. The successful preparation of SFTO nanofibrous membranes has offered a simple and economical approach to photocatalysis as well as environmental remediation.

Efficacy of ruxolitinib for HAVCR2 mutation-associated hemophagocytic lymphohistiocytosis and panniculitis manifestations in children.

Frequent germline mutations of HAVCR2, recently identified in subcutaneous panniculitis-like T-cell lymphoma (SPTCL), are associated with an increased risk of hemophagocytic lymphohistiocytosis (HLH). However, SPTCL-HLH represents a challenge because of the difficulties in treatment with poor survival. Its malignant nature, specifically harbouring HAVCR2 mutations, has also been questioned. To better understand its pathology and treatment, we analysed the clinical data of six patients diagnosed at our centre. The median age at onset was 10.5 years (range, 0.8-12.4). Five patients presented with skin lesions of subcutaneous nodules/plaques and/or ulceration. All patients developed HLH; notably, one infant only had HLH without skin involvement. Histopathologically, only two patients were diagnosed with SPTCL and three were reported as panniculitis with no sufficient evidence of lymphoma. Genetically, germline homozygous mutation of HAVCR2 (p.Y82C) was identified in all patients, with a median diagnosis time of 4.6 months. All patients initially received corticosteroids, immunosuppressants or chemotherapy, achieving unfavourable responses. Strikingly, they responded well to ruxolitinib targeting inflammatory cytokines, allowing rapid disease resolution and/or long-term maintenance of remission. The excellent efficacy of ruxolitinib highlights this disease as an inflammatory condition instead of neoplastic nature and indicates novel agents targeting key inflammatory pathways as an encouraging approach for this disease entity.

Acid and alkali-resistant fabric-based triboelectric nanogenerator for self-powered intelligent monitoring of protective clothing in highly corrosive environments.

The corrosion of materials severely limits the application scenarios of triboelectric nanogenerators (TENGs), especially in laboratories, chemical plants and other fields where leakage of chemically corrosive solutions is common. Here, we demonstrate a chemical-resistant triboelectric nanogenerator (CR-TENG) based on polysulfonamide (PSA) and polytetrafluoroethylene (PTFE) non-woven fabrics. The CR-TENG can stably harvest biological motion energy and perform intelligent safety protection monitoring in a strong corrosive environment. After treatment with strong acid and alkali solution for 7 days, the fabric morphology, diameter, tensile properties and output of CR-TENG are not affected, showing high reliability. CR-TENG integrated into protective equipment can detect the working status of protective equipment in real time, monitor whether it is damaged, and provide protection for wearers working in high-risk situations. In addition, the nonwoven-based CR-TENG has better wearing comfort and is promising for self-powered sensing in harsh environments.

Superhydrophobic aerogel blanket with magnetic and solar heating effect enables efficient continuous cleanup of highly viscous crude oil.

Rapid cleanup of highly-viscous oil spills the sea is eagerly desired while still remains a great challenge. Hydrophobic and lipophilic adsorbents are regarded as ideal candidate for oil spill remediation. However, traditional adsorbents are not suitable for viscous crude oil, which would block the porous structure and lead to poor adsorption efficiency. In this work, a non-contact responsive superhydrophobic SiO2 aerogel blankets (SAB) with excellent magnetic and solar heating effect for efficient removal of viscosity oils under harsh environments was developed, via assembled MXene and Fe3O4/polydimethylsiloxane layer-by-layer along the SAB skeleton (Fe3O4/MXene@SAB). The Fe3O4/MXene@SAB exhibited excellent compression tolerance (compression stress 70.69 kPa), superhydrophobic performance (water contact angle 166°), and corrosion resistance (weak acid/strong base). Due to high water repellency and stable porous structure, the Fe3O4/MXene@SAB could successfully separate oil-water mixture, while with remarkable separation flux (1.50-3.19 × 104 L m-2 h-1), and separation efficiency (99.91-99.98 %). Furthermore, the responsive Fe3O4/MXene@SAB also showed outstanding magnetic-heating and solar-heating conversion efficiency, which could continuously separate high viscosity crude oil from seawater by pump even under relatively low magnetic fields and mild sun. The superhydrophobic blankets hold great promise for efficient treatment of heavy oil spills.

Circulating succinate-modifying metabolites accurately classify and reflect the status of fumarate hydratase-deficient renal cell carcinoma.

Germline or somatic loss-of-function mutations of fumarate hydratase (FH) predispose patients to an aggressive form of renal cell carcinoma (RCC). Since other than tumor resection there is no effective therapy for metastatic FH-deficient RCC, an accurate method for early diagnosis is needed. Although MRI or CT scans are offered, they cannot differentiate FH-deficient tumors from other RCCs. Therefore, finding noninvasive plasma biomarkers suitable for rapid diagnosis, screening, and surveillance would improve clinical outcomes. Taking advantage of the robust metabolic rewiring that occurs in FH-deficient cells, we performed plasma metabolomics analysis and identified 2 tumor-derived metabolites, succinyl-adenosine and succinic-cysteine, as excellent plasma biomarkers for early diagnosis. These 2 molecules reliably reflected the FH mutation status and tumor mass. We further identified the enzymatic cooperativity by which these biomarkers are produced within the tumor microenvironment. Longitudinal monitoring of patients demonstrated that these circulating biomarkers can be used for reporting on treatment efficacy and identifying recurrent or metastatic tumors.

Stretchable, flexible and breathable polylactic acid/polyvinyl pyrrolidone bandage based on Kirigami for wounds monitoring and treatment.

Chronic wounds are slow to recover. During treatment, the dressing needs to be removed to check the recovery status, a process that often results in wound tears. Traditional dressings lack stretching and flexing properties and are not suitable using on wounds in joints, which require movement from time to time. In this study, we present a stretchable, flexible and breathable bandage consisting of three layers, including Mxene coating on the top, the polylactic acid/polyvinyl pyrrolidone (PLA/PVP) layer designed as Kirigami in the middle, and the f-sensor at the bottom. By the way, the f-sensor is in contact with the wound sensing real-time microenvironmental changes due to infection. When the infection intensifies, the Mxene coating at the top is utilized to enable anti-infection treatment. And Kirigami structure of PLA/PVP ensures that this bandage has stretchability, bendability, and breathability. The stretch of the smart bandage increases to 831 % compared to the original structure, and the modulus reduces to 0.04 %, which adapts extremely well to the movement of the joints and relieves the pressure on the wound. This monitoring-treatment closed-loop working mode, eliminating the need to remove dressings and avoid tissue tearing, shows a promising capability in the field of surgical wound care.

Formation of low-density electrospun fibrous network integrated mesenchymal stem cell sheet.

Cell sheets combined with electrospun fibrous mats represent an attractive approach for the repair and regeneration of injured tissues. However, the conventional dense electrospun mats as supportive substrates in forming "cell sheet on fiber mat" complexes suffer from problems of limiting the cellular function and eliciting a host response upon implantation. To give full play to the role of electrospun biomimicking fibers in forming quality cell sheets, this study proposed to develop a cell-fiber integrated sheet (CFIS) featuring a spatially homogeneous distribution of cells within the fiber structure by using a low-density fibrous network for cell sheet formation. A low-density electrospun polycaprolactone (PCL) fibrous network at a density of 103.8 ± 16.3 µg cm-2 was produced by controlling the fiber deposition for a short period of 1 min and subsequently transferred onto polydimethylsiloxane rings for facilitating cell sheet formation, in which rat bone marrow-derived mesenchymal cells were used. Using a dense electrospun PCL fibrous mat (481.5 ± 7.5 µg cm-2) as the control, it was found that cells on the low-density fibrous network (L-G) exhibited improved capacities in spreading, proliferation, stemness maintenance and matrix-remodeling during the process of CFIS formation. Structurally, the CFIS constructs revealed strong integration between the cells and the fibrous network, thus providing excellent cohesion and physical integrity to enable strengthening of the formed cell sheet. By contrast, the cell sheet formed on the dense fibrous mat (D-G) showed a two-layer (biphasic) structure due to the limitation of cellular invasion. Moreover, such engineered CFIS was identified with enhanced immunomodulatory effects by promoting LPS-stimulated macrophages towards an M2 phenotype in vitro. Our results suggest that the CFIS may be used as a native tissue equivalent "cell sheet" for improving the efficacy of the tissue engineering approach for the repair and regeneration of impaired tissues.

Chlorogenic acid improves food allergy through the AMPK/ACC/CPT-1 pathway.

Chlorogenic acid (CGA) is a polyphenol prevalent in daily food and plants. Food allergy (FA) can lead to metabolic disorders of the immune system. The objective of this study was to investigate CGA therapeutic effect on FA and regulatory mechanism through shrimp food allergy in mice models. Here, 24 female BALB/C mice were randomly allocated into the (I) Control group, (II) Food allergy group, (III) Chlorogenic acid low (50 mg/kg), and (IV) high group (200 mg/kg). Enzyme-linked immunosorbent assay revealed that CGA decreased levels of IgE and IgG induced by food allergy significantly. Real-time PCR demonstrated that high-dose chlorogenic acid significantly reduced Acetyl-CoA carboxylase (ACC) mRNA expression and increased Carnitine palmitoyltransferase-1 (CPT-1) mRNA expression. Western blot indicated that CGA promoted a noticeable increase at the levels of AMP-activated protein kinase (AMPK) and ACC phosphorylation, resulting in a significant activation in AMPK and inhibition in ACC, and increased CPT-1 expression. Consequently, CGA improves FA by the regulation of the AMPK/ACC/CPT-1 signaling pathway in the spleen. PRACTICAL APPLICATIONS: Chlorogenic acid is a water-soluble polyphenolic substance that is widely distributed in natural plants that show a variety of pharmacological effects. At present, CGA has been developed as a weigh-reducing tonic in western countries. As one of the most widely found and most easily obtained phenolic acids from food, the diverse physiological effects of CGA (such as anti-inflammatory, antioxidant, metabolic regulation, intestinal microbial regulation, etc.) imply its potential for application in functional foods, food additives, and clinical medicine. However, the basic molecular mechanisms of its effects have not been elucidated. In this study, CGA reduced allergy in a mouse model, likely by interacting with the AMPK/ACC/CPT-1 pathway.

A New Practical Method Based on MRI to Individually Localize the Transverse-Sigmoid Sinus Junction in Retrosigmoid Craniotomy: A Retrospective Before-After Study.

Background: Although the asterion has long been used as a skeletal surface marker of the transverse-sigmoid sinuses junction (TSSJ) point in the retrosigmoid approach, abundant evidence shows that the relationship between asterion and TSSJ point varies greatly. In recent years, new technologies have been developed, such as neuronavigation and three-dimensional volume rendering imaging, that can guide in exposing the TSSJ point individually. However, they are not only expensive but also difficult to apply in emergency surgery. Objective: To introduce a quick, practical, and low-cost new method for locating the TSSJ point precisely. Methods: In this retrospective before-after study, the test group located the TSSJ point with our new method during a 6-month period, while the control group used asterion as a surface landmark to estimate the TSSJ during the preceding 6 months. The primary outcome is the immediate exposure rate of the TSSJ point by the initial burr hole. Results: There were 60 patients in both control and test groups as no significant difference in the general clinical characteristics of both groups were observed. The new three-step method significantly increased the TSSJ exposure rate by initial burr hole compared with the control group (96.67% vs. 53.33%, P = 0.0002). Moreover, the total bone loss and craniotomy duration were significantly reduced by the new method. Incidence of sinus injury (10% vs. 6.6%), post-operation infection (3.33% vs. 3.33%), and CSF leakage (3.33% vs. 0%) were similar. Conclusions: The novel three-step approach accurately locates TSSJ points in retrosigmoid craniotomy, reduces bone defects, saves time, and does not increase the risk of sinus injury, infection, and CSF leakage.

Inhibitory effect and mechanism of action of juniper essential oil on gray mold in cherry tomatoes.

Juniper essential oil (JEO), which is mostly known as an immune system booster and effective detoxifier, has substantial antimicrobial activity. A comparison of the inhibitory effects of three plant essential oils from juniper (Juniperus rigida), cedarwood (Juniperus virginiana), and cypress (Crupressus sempervirens) on four plant pathogenic fungi indicated that JEO was the most effective at inhibiting the growth of gray mold (Botrytis cinerea). Additional studies were subsequently conducted to explore the in vivo and in vitro antifungal activity and possible mechanism of JEO against B. cinerea. The results show that JEO inhibited the germination of spores and mycelial growth of B. cinerea in a concentration-dependent manner and exhibited strong inhibition when its concentration exceeded 10 µL/mL. JEO also significantly inhibited the incidence of disease and diameters of gray mold lesions on cherry tomato fruit (Solanum lycopersicum). After 12 h of treatment with JEO, the extracellular conductivity, and the contents of soluble protein, malondialdehyde, and hydrogen peroxide were 3.1, 1.2, 7.2, and 4.7 folds higher than those of the control group, respectively (P < 0.05), which indicated that JEO can damage membranes. Scanning electron microscopy observations revealed that JEO affected the morphology of mycelia, causing them to shrivel, twist and distort. Furthermore, JEO significantly improved the activities of the antioxidant-related enzymes superoxide dismutase and catalase but reduced the pathogenicity-related enzymes polygalacturonase (PG), pectin lyase and endoglucanase of B. cinerea (P < 0.05). In particular, PG was reduced by 93% after treatment with JEO for 12 h. Moreover, the 18 constituents of JEO were identified by gas chromatography/mass spectrometry (GC-MS) analysis, mainly limonene (15.17%), γ-terpinene (8.3%), ß-myrcene (4.56%), terpinen-4-ol (24.26%), linalool (8.73%), α-terpineol (1.03%), o-cymene (8.35%) and other substances with antimicrobial activity. Therefore, JEO can be an effective alternative to prevent and control gray mold on cherry tomato fruit.

Enantioselective nickel-catalyzed dicarbofunctionalization of 3,3,3-trifluoropropene.

Despite paramount applications of chiral trifluoromethylated compounds in medicinal chemistry and materials science, limited strategies have been developed for catalytic asymmetric synthesis of such valuable fluorinated structures. Here, we report a nickel catalyzed enantioselective dicarbofunctionalization of inexpensive industrial chemical 3,3,3-trifluoropropene (TFP) with readily available tertiary alkyl and aryl iodides. The reaction overcomes the ß-F elimination side reaction of TFP, and proceeds efficiently under mild reaction conditions. The protocol possesses advantages, such as synthetic convenience, high enantioselectivity, and excellent functional group tolerance, providing rapid and straightforward access to chiral trifluoromethylated compounds of medicinal interest.

Superhydrophobic nanofibrous sponge with hierarchically layered structure for efficient harsh environmental oil-water separation.

Oil leakage has posed serious threat to the environment, but still remain a great challenge to be solved especially for harsh environmental conditions. Herein, robust superhydrophobic nickel hydroxide grown by hydrothermal method and stearic acid modification on a blow-spun polyacrylonitrile (PAN)/Al2O3 nanofibrous sponge was proposed, so that the nickel hydroxide-modified polyacrylonitrile sponge (NPAS) was successfully obtained for efficient oil-water separation. The porous NPAS with a distinctive hierarchically layered structure, which exhibited excellent separation efficiency and mechanical elasticity. Due to its superhydrophobic and high porosity, the absorption capacity of NPAS could reach as high as 45 g g-1. It could not only separate a series of oil-water mixture with a high steady flux of 12,413 L m-2 h-1 (dichloromethane-water), but also separate stabilized emulsions with a superior flux 2032 L m-2 h-1 (water-in-dichloromethane) under gravity, all of that with above 99.92% separation efficiencies, which was higher than that of the most reported sponges. Most importantly, its strong acid/alkali resistance enable it is suitable for hazardous materials treatment applications in harsh environmental conditions. This novel NPAS via facile large-scale blow-spinning provide an efficient strategy for oil-containing wastewater treatment and environmental protection.

Development and application of an LC-MS/MS method for pharmacokinetic study of ruxolitinib in children with hemophagocytic lymphohistiocytosis.

Ruxolitinib (RUX), a small molecule inhibitor of JAK1/JAK2, has been identified as the possible novel targeted agent for the treatment of hemophagocytic lymphohistiocytosis (HLH). However, due to the lack of randomized clinical trials (RCTs), it is extremely difficult to determine the effective therapeutic dose for RUX in HLH patients, especially in pediatric patients. At the same time, the clinical response of pediatric patients to RUX varies greatly among individuals according to several case reports. Therefore, it is imperative to investigate the pharmacokinetic and pharmacodynamic characteristics of RUX in HLH children, and this must be based on a satisfactory method to determine the concentration of RUX. Owing to several limits of published analytical methods, herein, we describe a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method for monitoring RUX in children's plasma samples. The protein precipitation method using methanol was used for sample cleanup. The analytes were separated by gradient elution in which 2.0 mM ammonium acetate in distilled water and acetonitrile were used as mobile phases. In the positive electrospray ionization (ESI+) mode, the m/z 307.1 → 186.0 and 316.1 → 185.9 ion pair transitions of RUX and RUX-d9 were used for the qualitative and quantitative analysis, respectively. The calibration curves of RUX were linear in the concentration range from 0.5 to 400 ng mL-1. The intra- and inter-batch precision, accuracy, recovery, dilution completeness, and stability of this method were all within acceptable standards, and no matrix effects or residues were found. This method was successfully applied to the clinical pharmacokinetic study of RUX in 32 children with HLH. The pharmacokinetic parameters of HLH children after a single dose of RUX and the steady state plasma concentration after multiple administrations were proposed through this method. Most importantly, it was found that the age and serum creatinine (SCr) of children with HLH had a significant and complex impact on the in vivo process of RUX after the single as well as multiple administrations of RUX.

A study of ruxolitinib response-based stratified treatment for pediatric hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a lethal disorder characterized by hyperinflammation. Recently, ruxolitinib (RUX), targeting key cytokines in HLH, has shown promise for HLH treatment. However, there is a lack of robust clinical trials evaluating its efficacy, especially its utility as a frontline therapy. In this study (www.chictr.org.cn, ChiCTR2000031702), we designed ruxolitinib as a first-line agent for pediatric HLH and stratified the treatment based on its early response. Fifty-two newly diagnosed patients were enrolled. The overall response rate (ORR) of ruxolitinib monotherapy (day 28) was 69.2% (36/52), with 42.3% (22/52) achieving sustained complete remission (CR). All responders achieved their first response to ruxolitinib within 3 days. The response to ruxolitinib was significantly associated with the underlying etiology at enrollment (P = .009). Epstein-Barr virus (EBV)-HLH patients were most sensitive to ruxolitinib, with an ORR of 87.5% (58.3% in CR). After ruxolitinib therapy, 57.7% (30/52) of the patients entered intensive therapy with additional chemotherapy. Among them, 53.3% (16/30) patients achieved CR, and 46.7% (14/30) patients dominated by chronic active EBV infection-associated HLH (CAEBV-HLH) developed refractory HLH by week 8. The median interval to additional treatment since the first ruxolitinib administration was 6 days (range, 3-25 days). Altogether, 73.1% (38/52) of the enrolled patients achieved CR after treatment overall. The 12-month overall survival (OS) for all patients was 86.4% (95% confidence interval [CI], 77.1% to 95.7%). Ruxolitinib had low toxicity and was well tolerated compared with intensive chemotherapy. Our study provides clinical evidence for ruxolitinib as a frontline agent for pediatric HLH. The efficacy was particularly exemplified with stratified regimens based on the early differential response to ruxolitinib. This study was registered in the Chinese Clinical Trials Registry Platform (http://www.chictr.org.cn/) as ChiCTR2000031702.

The High Flux of Superhydrophilic-Superhydrophobic Janus Membrane of cPVA-PVDF/PMMA/GO by Layer-by-Layer Electrospinning for High Efficiency Oil-Water Separation.

A simple and novel strategy of superhydrophilic-superhydrophobic Janus membrane was provided here to deal with the increasingly serious oil-water separation problem, which has a very bad impact on environmental pollution and resource recycling. The Janus membrane of cPVA-PVDF/PMMA/GO with opposite hydrophilic and hydrophobic properties was prepared by layer-by-layer electrospinning. The structure of the Janus membrane is as follows: firstly, the mixed solution of polyvinylidene fluoride (PVDF), polymethylmethacrylate (PMMA) and graphene oxide (GO) was electrospun to form a hydrophobic layer, then polyvinyl alcohol (PVA) nanofiber was coated onto the hydrophobic membrane by layer-by-layer electrospinning to form a composite membrane, and finally, the composite membrane was crosslinked to obtain a Janus membrane. The addition of GO can significantly improve the hydrophobicity, mechanical strength and stability of the Janus membrane. In addition, the prepared Janus membrane still maintained good oil-water separation performance and its separation efficiency almost did not decrease after many oil-water separation experiments. The flux in the process of oil-water separation can reach 1909.9 L m-2 h-1, and the separation efficiency can reach 99.9%. This not only proves the separation effect of the nanocomposite membrane, but also shows its high stability and recyclability. The asymmetric Janus membrane shows good oil-water selectivity, which gives Janus membrane broad application prospects in many fields.

Transcriptomic analysis of interactions between Lymantria dispar larvae and carvacrol.

Due to its biological activity, carvacrol (CAR) is widely used in medicine, agriculture, and forestry. Our previous studies showed that in Lymantria dispar larvae, CAR treatment can induce the production of antifeedants and lead to growth inhibition and death of larvae. However, the effect CAR exerts on RNA levels in L. dispar larvae remains unclear. In this study, the Illumina HiSeq4000 sequencing platform was used to sequence the total RNA of L. dispar larvae. A total of six cDNA libraries (three treatments and three controls) were established and 39,807 genes were generated. Compared with the control group, 296 differentially expressed genes (DEGs) (142 up-regulated and 154 down-regulated) were identified after CAR treatment. GO and KEGG enrichment analyses showed that these DEGs mainly clustered in the metabolism of xenobiotics, carbohydrates, and lipids. Furthermore, 12 DEGs were found to be involved in detoxification, including six cytochrome P450s, two esterases, one glutathione peroxidase, one UDP-glycosyltransferase gene, and two genes encoding heat shock proteins. The expression levels of detoxification genes changed under CAR treatment (especially P450s), which further yielded candidate genes for explorations of the insecticidal mechanism of CAR. The reliability of transcriptome data was verified by qRT-PCR. The enzyme activities of CYP450 and acid phosphatase significantly increased (by 38.52 U/mg·prot and 0.12 µmol/min·mg, respectively) 72 h after CAR treatment. However, the activity of alkaline phosphatase did not change significantly. These changes in enzyme activity corroborated the reliability of the transcriptome data at the protein level. The results of GO enrichment analysis of DEGs indicated that CAR influenced the oxidation-reduction process in L. dispar larvae. Furthermore, CAR can cause oxidative stress in L. dispar larvae, identified through the determination of peroxidase and polyphenol oxidase activities, total antioxidant capacity, and hydrogen peroxide content. This study provides useful insight into the insecticidal mechanism of CAR.

Significance of serum Th1/Th2 cytokine levels in underlying disease classification of childhood HLH.

OBJECT: Goal of this research was to investigate values of serum cytokines in childhood HLH with different triggers, with the expectation to find secretion spectrum of 5 main types of underlying diseases. METHOD: 118 newly diagnosed HLH were included, and serum concentrations of 6 cytokines were tested before treatment began. Absolute cytokine levels and ratios between them were then studied in the HLH groups collectively and separately RESULTS: In general, IFN-γ, IL-10 and IL-6 showed differences among 5 HLH groups. Specifically, relative levels of these three cytokines to each other were meaningful in distinguishing 4 types of HLH. Level of IL-6 was higher than those of IFN-γ or IL-10 in HLH driven by Systemic auto-inflammatory disorders (SAIDs) or Langerhans Cell Histiocytosis (LCH), while primary HLH and EBV-HLH shared elevated ratio of IL-10 to IL-6. Although more than one distinctive ratios were found in 3 HLH groups, combination of these parameters didn't offer optimal balance between sensitivity and specificity. CONCLUSION: As a group of easily gained laboratory findings, cytokine levels were reliable in the procedure of roughly classifying HLH cases with the help of patients' clinical phenotype. However, adequate data is still needed to explore the significance of these indicators in identifying one particular underlying disease accurately.