Labeled Interleaving Distance for Reeb Graphs

Merge trees, contour trees, and Reeb graphs are graph-based topological descriptors that capture topological changes of (sub)level sets of scalar fields. Comparing scalar fields using their topological descriptors has many applications in topological data analysis and visualization of scientific data. Recently, Munch and Stefanou introduced a labeled interleaving distance for comparing two labeled merge trees, which enjoys a number of theoretical and algorithmic properties. In particular, the labeled interleaving distance between merge trees can be computed in polynomial time. In this work, we define the labeled interleaving distance for labeled Reeb graphs. We then prove that the (ordinary) interleaving distance between Reeb graphs equals the minimum of the labeled interleaving distance over all labelings. We also provide an efficient algorithm for computing the labeled interleaving distance between two labeled contour trees (which are special types of Reeb graphs that arise from simply-connected domains). In the case of merge trees, the notion of the labeled interleaving distance was used by Gasparovic et al. to prove that the (ordinary) interleaving distance on the set of (unlabeled) merge trees is intrinsic. As our final contribution, we present counterexamples showing that, on the contrary, the (ordinary) interleaving distance on (unlabeled) Reeb graphs (and contour trees) is not intrinsic. It turns out that, under mild conditions on the labelings, the labeled interleaving distance is a metric on isomorphism classes of Reeb graphs, analogous to the ordinary interleaving distance. This provides new metrics on large classes of Reeb graphs

Resistance imparted by vitamin C, vitamin e and vitamin B12 to the acute hepatic glycogen change in rats caused by noise.

The effects of vitamin C, vitamin E and vitamin B12 on the noise-induced acute change in hepatic glycogen content in rats were investigated. The exposure of rats to 95 dB and 110 dB of noise acutely reduced their hepatic glycogens. Vitamin C (ascorbic acid) and vitamin E (alpha -tocopherol) attenuated the noise-inducedacute reduction in the hepatic glycogen contents. This result suggests that antioxidants could reduce the change via reactive oxygen species. Vitamin B12 (cobalamin) delayed the noiseinduced change, a finding that suggests that vitamin B12 could postpone the acute change via compensating for vitamin B12 deficiency

Covalently immobilized lipase on a thermoresponsive polymer with an upper critical solution temperature as an efficient and recyclable asymmetric catalyst in aqueous media

This work was financially supported by the National Natural Science Foundation of China (Grant No. 21203102), the Tianjin Municipal Natural Science Foundation (Grant No. 14JCQNJC06000), China Scholarship Council (Grant No. 201606200087), MOE (IRT13R30) and 111 Project (B12015).A thermoresponsive lipase catalyst with an upper critical solution temperature (UCST) of about 26 °C was exploited by covalent immobilization of an enzyme, Pseudomonas cepacia lipase (PSL), onto poly(acrylamide-co-acrylonitrile) via glutaraldehyde coupling. The experimental conditions for the PSL immobilization were optimized. The immobilized PSL was much more stable for wide ranges of temperature and pH than the free PSL. The material was also evaluated as an asymmetric catalyst in the kinetic resolution of racemic α-methylbenzyl butyrate at 55 °C in an aqueous medium and exhibited high catalytic performance and stability. Up to 50% conversion and 99.5% product enantiomeric excess were achieved, thus providing highly pure enantiomers. More importantly, this biocatalyst could be easily recovered by simple decantation for reuse based on temperature-induced precipitation. It showed good reusability and retained 80.5% of its original activity with a well reserved enantioselectivity in the 6th cycle. This work would shed light on the future development of new UCST-type enzyme catalysts.PostprintPeer reviewe

Extrauterine growth restriction in preterm infants: Postnatal growth pattern and physical development outcomes at age 3–6 years

ObjectivesTo investigate the postnatal growth trajectories of preterm infants and evaluate the association between extrauterine growth restriction (EUGR) at discharge and adverse physical growth outcomes at age 3–6 years.MethodsPremature infants admitted to Shanghai Children’s Medical Center within 24 h after birth from 1 January 2016 to 31 December 2018 were enrolled. Neonatal complications, nutrition support, and anthropometric data were collected and analyzed to diagnose EUGR on different definitions at discharge. The weight and the height of each subject were collected by telephone investigation from 1 September 2021 to 31 November 2021 to access the incidences of overweight/obesity, short stature, and thinness at age 3–6 years.ResultsA total of 527 preterm infants were included in the final sample. The overall mean weight and height Z-scores were –0.37 ± 0.97 SD and –0.29 ± 1.18 SD at birth, and increased to –0.03 ± 1.11 SD and 0.13 ± 1.2 SD at follow-up, respectively. The logistic regression analysis indicated longitudinal EUGR on head circumference as the risk factor of overweight or obesity, cross-sectional EUGR on height as the risk factor of short stature, and delayed EN as the risk factor of thinness.ConclusionThe growth trajectories of the preterm newborns tended toward the normal direction. Longitudinal EUGR on the head circumference and cross-sectional EUGR on height at discharge were associated with adverse physical growth outcomes at age 3–6 years

T Cell Receptor (TCR)-Induced PLC-γ1 Sumoylation via PIASxβ and PIAS3 SUMO E3 Ligases Regulates the Microcluster Assembly and Physiological Function of PLC-γ1

The SUMO modification system plays an important role in T cell activation, yet how sumoylation regulates TCR-proximal signaling remains largely unknown. We show here that Phospholipase C-γ1 (PLC-γ1) is conjugated by SUMO1 at K54 and K987 upon TCR stimulation and that K54 sumoylation is pivotal for PLC-γ1-mediated T cell activation. We further demonstrate that TCR-induced K54 sumoylation of PLC-γ1 significantly promotes the formation of PLC-γ1 microclusters and the association of PLC-γ1 with the adaptor proteins SLP76 and Gads, but only slightly affects the phosphorylation of PLC-γ1 on Y783, which determines the enzyme catalytic activity. Moreover, upon TCR stimulation, the SUMO E3 ligases PIASxβ and PIAS3 both interact with PLC-γ1 and cooperate to sumoylate PLC-γ1, facilitating the assembly of PLC-γ1 microclusters. Together, our findings reveal a critical role of PLC-γ1 K54 sumoylation in PLC-γ1 microcluster assembly that controls PLC-γ1-mediated T cell activation, suggesting that sumoylation may have an important role in the microcluster assembly of TCR-proximal signaling proteins

Chinese herbal injections in combination with radiotherapy for advanced pancreatic cancer: A systematic review and network meta-analysis.

Advanced pancreatic cancer (APC) is a fatal disease with limited treatment options. This study aims to evaluate the effectiveness and safety of different Chinese herbal injections (CHIs) as adjuvants for radiotherapy (RT) in APC and compare their treatment potentials using network meta-analysis. We systematically searched three English and four Chinese databases for randomized controlled trials (RCTs) from inception to July 25, 2023. The primary outcome was the objective response rate (ORR). Secondary outcomes included Karnofsky performance status (KPS) score, overall survival (OS), and adverse events (AEs). The treatment potentials of different CHIs were ranked using the surface under the cumulative ranking curve (SUCRA). The Cochrane RoB 2 tool and CINeMA were used for quality assessment and evidence grading. Eighteen RCTs involving 1199 patients were included. Five CHIs were evaluated. Compound Kushen injection (CKI) combined with RT significantly improved ORR compared to RT alone (RR 1.49, 95 % CrI 1.21-1.86). Kanglaite (KLT) plus RT (RR 1.58, 95 % CrI 1.20-2.16) and CKI plus RT (RR 1.49, 95 % CrI 1.16-1.95) were associated with improved KPS score compared to radiation monotherapy, with KLT+RT being the highest rank (SUCRA 72.28 %). Regarding AEs, CKI plus RT was the most favorable in reducing the incidence of leukopenia (SUCRA 90.37 %) and nausea/vomiting (SUCRA 85.79 %). CKI may be the optimal choice of CHIs to combine with RT for APC as it may improve clinical response, quality of life, and reduce AEs. High-quality trials are necessary to establish a robust body of evidence. PROSPERO, CRD42023396828. [Abstract copyright: © 2023 Korea Institute of Oriental Medicine. Published by Elsevier B.V.

Hydroxychloroquine attenuates autoimmune hepatitis by suppressing the interaction of GRK2 with PI3K in T lymphocytes

Hydroxychloroquine (HCQ) is derivative of the heterocyclic aromatic compound quinoline, which has been used for the treatment of autoimmune diseases. The central purpose of this study was to investigate therapeutic effects and inflammatory immunological molecular mechanism of HCQ in experimental autoimmune hepatitis (AIH). Treatment with HCQ ameliorated hepatic pathologic damage, inflammatory infiltration, while promoted regulatory T cell (Treg) and down-regulated CD8+T cell differentiation in AIH mice induced by S-100 antigen. In vitro, HCQ also suppressed pro-inflammatory cytokine (IFN-γ, TNF-α, and IL-12) secretion, promoted anti-inflammatory cytokine (TGF-β1) secretion. HCQ mainly impaired T cell lipid metabolism but not glycolysis to promote Treg differentiation and function. Mechanistically, HCQ down-regulated GRK2 membrane translocation in T cells, inhibited GRK2-PI3K interaction to reduce the PI3K recruiting to the membrane, followed by suppressing the phosphorylation of PI3K-AKT-mTOR signal. Pretreating T cells with paroxetine, a GRK2 inhibitor, disturbed HCQ effect to T cells. HCQ also reversed the activation of the PI3K-AKT axis by 740 Y-P (PI3K agonist). Meanwhile, HCQ inhibited the PI3K-AKT-mTOR, JAK2-STAT3-SOCS3 and increased the AMPK signals in the liver and T cells of AIH mice. In conclusion, HCQ exhibited specific and potent therapeutic effects on AIH and attendant liver injury, which was attributed to HCQ acted on GRK2 translocation, inhibited metabolism-related PI3K-AKT and inflammation-related JAK2-STAT3 signal in T lymphocytes, thereby modulating lipid metabolism of T cell function to regulate Treg differentiation and function

Prospektywne, trwające 6 miesięcy badanie poświęcone ocenie skuteczności i bezpieczeństwa stosowania walproinianu o przedłużonym uwalnianiu oraz jakości życia chorych na padaczkę stosujących ten lek

Celem tego prospektywnego, wieloośrodkowego badania, przeprowadzonego metodą otwartej próby, była ocena skuteczności i bezpieczeństwa stosowania walproinianu o przedłużonym uwalnianiu(ER, extender-release) oraz jego wpływu na jakość życia u chorych na padaczkę. Do badania włączono osoby z potwierdzonym rozpoznaniem padaczki. Uczestnikom przez 6 miesięcy podawano walproinian ER jako pierwszy lek w monoterapii lub w połączeniu z dotychczas stosowanym lekiem. Ocenę skuteczności i bezpieczeństwa leczenia przeprowadzono po 1 (V1), 3 (V3) i 6 miesiącach (V6) od rozpoczęcia badania. Do oceny jakości życia przed terapią i po 6 miesiącach leczenia użyto kwestionariusza QOLIE-31. W analizie uwzględniono 958 chorych na padaczkę. Wyjściowa częstość napadów padaczkowych wynosiła 8,56 na miesiąc. Średnia dawka podtrzymująca walproinianu ER wynosiła 750 mg na dobę. Liczba napadów padaczkowych w miesiącu, oszacowana podczas ostatniej wizyty, zmniejszyła się o 88,3% w stosunku do wartości wyjściowych. Nastąpiła poprawa jakości życia w zakresie następujących kategorii: &#8222;obawa przed napadami&#8221; (p = 0,000), &#8222;ogólna jakość życia&#8221; (p = 0,000), &#8222;funkcjonowanie społeczne&#8221; (p < 0,01) i &#8222;pytanie 31.&#8221; (ocena ogólnego stanu zdrowia) (p = 0,000). Odnotowano pogorszenie w zakresie aktywności życiowej (p = 0,000). We wczesnej fazie leczenia najczęstszymi działaniami niepożądanymi były suchość w jamie ustnej, zawroty głowy i jadłowstręt. Po 6 miesiącach pacjenci najczęściej skarżyli się na zwiększenie masy ciała, łysienie plackowate i drżenie. Wyniki badania dowodzą, że stosowanie walproinianu ER w monoterapii lub w terapii skojarzonej przez 6 miesięcy wiąże się z istotnie większym procentowym ograniczeniem częstości wszystkich rodzajów napadów w stosunku do wartości wyjściowych i z istotnie większym odsetkiem odpowiedzi na leczenie oraz odsetkiem chorych bez napadów. Ponadto terapia była dobrze tolerowana przez chorych i powodowała poprawę jakości życia. Polski Przegląd Neurologiczny 2010; 6 (4): 212&#8211;21