bluuebunny/crossref_metadata_2025 huggingface dataset:
Pure total flavonoids from citrus improve nonalcoholic steatohepatitis liver inflammatory responses by regulating the CCL2/CCR2‐PI3K‐Akt signal transduction pathway
Authors: Wu Liyan , Lu Zengsheng , He Beihui , Yu Jianshun , Yan Maoxiang , Jiang Jianping , Chen Zhiyun
Published: December 2022

Background and Aim

Nonalcoholic steatohepatitis (NASH) is a critical stage in the prognosis of nonalcoholic fatty liver disease (NAFLD). Pure total flavonoids from circus (PTFC) play essential roles in the improvement of NASH symptoms, but the underlying regulatory mechanism remains elusive. Our previous high‐throughput omics screening results indicate that the CCL2/CCR2‐PI3K‐Akt signaling pathway is a key pathway that regulates the liver inflammatory response. PTFC may regulate the CCL2/CCR2‐PI3K‐Akt signaling pathway to improve the liver inflammatory response.

Methods

A mice model of NASH was established by a high‐fat diet, and PTFC was used as treatment. Hematoxylin‐eosin and oil red O staining were used to observe the pathological changes in the liver tissue. Western blotting and real‐time PCR were used to measure the mRNA and protein levels in the liver. The expression of proinflammatory cytokines in the peripheral blood and liver tissues was measured by liquid suspension array. An automatic biochemical method was used to examine serum transaminases and lipids levels, as well as liver lipids.

Results

Compared with the mice in the high‐fat diet group, mice in the HFD + PTFC group showed significantly improved liver histopathology, and levels of serum transaminase and lipids, liver lipids and serum proinflammatory cytokines. Moreover, the mRNA and protein expression and phosphorylation levels of key signaling molecules in the CCL2/CCR2‐PI3K‐Akt signal transduction pathway were obviously reduced by PTFC treatment.

Conclusive Remarks

PTFC can ameliorate NASH symptoms, and the mechanism may be related to regulating the CCL2/CCR2‐PI3K‐Akt signal transduction pathway to reduce the liver inflammatory response.
Synthesis and antitumoral evaluation of natural product‐like compounds based on tropolone and benzotropolone derivatives
Authors: Eugui Macarena , Lucero Valeria , do Carmo Hugo , Cabrera Mauricio , Moyna Guillermo
Published: December 2022

We present the preparation of a series of novel natural product‐like homobarrelenones, norcaranes, and dihydrofluorenones through a diversity‐oriented synthetic (DOS) strategy that combines Diels–Alder reactions and phototransformations, as well as their biological evaluation against MCF‐7, HT‐29, and NCI‐H460 human tumor cells. Six of these demonstrated activities in the micromolar range against the three cell lines, and none were predicted as cytotoxic against human nontumor cells according to in silico studies. In addition, within the set of active derivatives, three exhibited low unspecific cytotoxicity in a sperm motility assay. The rich functionality of the new compounds makes them ideal candidates for exhaustive structure–activity relationship studies.
Synthesis of Picramide Using Nitration and Ammonolysis in Continuous Flow
Authors: Kumar Mittal Ankit , Prakash Gaurav , Pathak Pramod , Maiti Debabrata
Published: December 2022

This paper describes a safer, scalable and continuous process for synthesis of picramide. The process consists of two steps: step‐1. nitration of p‐nitroanisole (PNAN) to 2,4,6‐trinitrianisole (TNAN); step‐2. ammonolysis of TNAN to picramide. Both the steps were optimized in flow, with yield of 90% and 98% in step‐1 and step‐2 respectively. Picramide with HPLC purity greater than 99% was obtained. When compared with batch, in step‐1, flow process provided significant advantage in selectivity and yield. The optimized flow process was scaled to 25 g/hr production rate in a laboratory flow reactor. The method can be considered fit for the safe production of picramide at commercial scale.
Interchangeability and Disorder in the Solid‐State Structures of “Two Wall” Calix[4]pyrroles Equipped with Iodine and Ethynyl para‐Substituents
Authors: Rivoli Andrea , Gomila Rosa M. , Frontera Antonio , Ballester Pablo
Published: December 2022

Herein, the synthesis and X‐ray structures of three α,β “two wall” aryl‐extended calix[4]pyrroles having either identical (symmetrically substituted) or different (non‐symmetrically substituted) meso‐aryl substituents (aryl=4‐ethynylphenyl and 4‐iodophenyl) are reported. The X‐ray structure of the co‐crystal formed by the two symmetrically substituted calix[4]pyrroles is also described. In the solid state, all studied α,β‐calix[4]pyrroles exhibit a 1,3‐alternate conformation with two co‐crystallized acetonitrile solvent molecules H‐bonded to adjacent cis‐pyrrole rings. Remarkably, the 1,3‐conformer of the non‐symmetrically substituted iodophenyl/ethynylphenyl compound is intrinsically chiral. The two enantiomers are present in the average asymmetric unit in a 65 : 35 occupancy ratio displaying a head‐to‐tail directional disorder. This is due to the functional complementarity and the isosteric and isoelectronic properties of the para‐substituents: iodo and ethynyl. That is, the negative belt of iodine is similar to the negative π‐system of the C≡C triple bond and the σ‐hole in the iodine atom is similar to the positive proton at the C≡C−H group.
Fear and promise of the unknown: How losses discourage and promote exploration
Authors: Chin Alycia , Hagmann David , Loewenstein George
Published: December 2022

Many situations involving exploration, such as businesses expanding into new products or locations, expose the explorer to the potential for subjective losses. How does the potential to experience losses during the course of a search affect individuals' appetite for exploration? In three incentivized studies, we manipulate search outcomes by presenting participants either with a gain‐only environment or a gain‐loss environment. The two environments offer objectively identical incentives for exploration: Using a framing manipulation, we decrease gain‐loss payoffs and provide participants an initial endowment to offset the difference. Participants decide how to explore a one‐dimensional space, receiving payoffs based on their location each period. We predict and find that participants are motivated to avoid losses, which increases exploration when they are incurring losses but decreases exploration when they face the potential for losses. We conclude that exploration is driven by hope of potential gains, constrained by fear of potential losses, and motivated by avoidance of experienced losses.
Retrospective, real‐life study of venetoclax plus azacitidine or low‐dose cytarabine in French patients with acute myeloid leukemia ineligible for intensive chemotherapy
Authors: Laloi Louise , Billotey Natacha Chaumard , Dumas Pierre‐Yves , Paul Franciane , Villate Alban , Simand Célestine , Fornecker Luc , Puisset Florent , Bertoli Sarah , Simonet Marion Boissard , Laribi Kamel , Houyou Dyhia , Santagostino Alberto , Michel Claire , Guepin Gabrielle Roth , Guerineau Elodie , Tabrizi Reza , Hunault Mathilde , Giltat Aurélien , Kaphan Eléonore , Bulabois Claude , Cartet Elodie , Rocher Clément , Lachenal Florence , Morisset Stéphane , Récher Christian , Pigneux Arnaud , Belhabri Amine , Michallet Mauricette , Michallet Anne‐Sophie
Published: December 2022

Background

Recently, the combination of venetoclax plus a hypomethylating agent (HMA; azacitidine ordecitabine) or low‐dose cytarabine (LDAC) showed promise in Phase III trials in previously untreated AML. In France at the time of this study, venetoclax was not yet approved for AML and there were therefore no formal usage recommendations. Here we report the first study in a French cohort that assessed venetoclax in combination with existing treatments for AML under real‐life conditions.

Method

This retrospective, real‐life study collected data on venetoclax use and management in a French cohort with acute myeloid leukemia (AML) ineligible for intensive chemotherapy.

Result

Of 118 patients, 81 were in second line/beyond (71.6% also hypomethylating agent [HMA]; 23.5% lowdose cytarabine [LDAC]) and 37 in first line. For venetoclax initiation, 57.3% underwent ramp up and 74.6% were hospitalized. Median venetoclax duration was 2.5 months (range 0.03‐16.2). With all treatment lines and regimens, most common grade 3/4 adverse events were hematologic (overall 96.4% of patients) and infections (57.1%). Dosage adjustments for drug interactions and safety varied between centers. In second‐line/beyond, median progression‐free survival was 4.0 months (95% confidence interval [CI] 2.7‐12.8) with venetoclax‐HMA and 3.4 months (1.3‐8.9) with venetoclax‐LDAC; overall response rate was 51.9% and 41.2%, respectively. Thus, we showed that venetoclax‐based treatment yields promising findings in patients with AML, but to address treatment complexity, practice harmonization is needed.
The Antinociceptive Effect of a Hydroalcoholic Extract of Polygala altomontana and Its Chemical Profile Using UPLC‐ESI‐QTOF‐HR‐MS
Authors: Pradi Lucas , Andrade Tassiane E. S. , Lacerda Jhuly W. F. , Karvat Jhenifer , Beppler Larissa M. , Tizziani Tiago , Santos Adair R. S. , Sandjo Louis P.
Published: December 2022

The hydroalcoholic extract of Polygala altomontana (30, 100, and 300 mg/kg, i.g.) showed a dose‐dependent antinociceptive action during the inflammatory phase of the formalin test. In addition, the preparation (30 and 300 mg/kg, i.g.) showed anti‐hyperalgesic action when tested on a mechanical nociception model. UPLC‐ESI‐QTOF‐MS data indicated the active extract contained phenylpropanoid sucrose esters, glycosylated quercetin derivatives, styrylpyrones, and coumarins. Some identified compounds, including styrylpyrones and coumarins, have previously demonstrated antinociceptive action. The results also show that P. altomontana shows potential for developing pain‐relieving herbal remedies and drugs.
Analyzing the Impact of Ramalina digitellata, R. fastigiata, R. fraxinea, and R. polymorpha's Usnic Acid Concentration on Antioxidant, DNA‐Protective, Antimicrobial, and Cytotoxic Properties
Authors: Kiliç Yayla Serpil , Kocakaya Zekiye , Karatoprak Gökçe Şeker , İlgün Selen , Ceylan Ahmet
Published: December 2022

The present study is focused on the antimicrobial, antioxidant, cytotoxic, and DNA protective effects of methanol extract obtained from R. digitellata, R. fastigiata, R. fraxinea, and R. polymorpha species that are distributed in Turkey. The highest total phenol content was determined in R. digitellata (144.6 mgGAE/gextract), and the highest total amount of flavonoids was found in R. fastigiata (20.40 mgGAE/gextract). The content of usnic acid was determined by High‐Performance Liquid Chromatography (HPLC) and the highest amount was found in R. digitellata. DPPH (1,1‐diphenyl‐2‐picrylhydrazyl) and ABTS [2,2’‐azinobis(3‐ethylbenzathiazoline‐6‐sulfonic acid)] radical scavenging methods were used for antioxidant activity. R. fraxinea showed the highest DPPH⋅ and ABTS+⋅ scavenging activity. In addition, the DNA protective effect was investigated using pBR322 plasmid DNA, and; all studied species were found to have DNA protective effects. The antibacterial activity was investigated using the disc diffusion method, and the R. digitellata methanol extract showed the best results with a 12.35 mm zone on Proteus mirabilis. On the human lung cancer (A549) and breast cancer (MDA‐MB‐231) cell lines, cytotoxic activity was assessed using an MTT assay. All lichen extracts were found to have a significant cytotoxic effect on both cancer cell lines at 1000 μg/mL concentration. These results suggest that Ramalina species may be potential candidates for developing new phytopharmaceuticals and functional components.
Spatio‐temporal metabolokinetics and therapeutic effect of CD106+ mesenchymal stem/stromal cells upon mice with acute lung injury
Authors: Zhang Leisheng , Zhuo Yi , Yu Hao
Published: December 2022

Longitudinal investigations have revealed the unique attributes of mesenchymal stem/stromal cells (MSCs) in regenerative medicine. However, the spatio‐temporal metabolokinetics and efficacy of MSCs with vascular cell adhesion molecule 1 (also known as CD106) expression in phenotypes and therapeutic effect upon acute lung injury (ALI) mice are largely obscure. For the purpose, we took advantage of the “3IL”‐based strategy and Lentivirus‐mediated green fluorescent protein (GFP) delivery for the generation of the CD106+ subset (denote as CD106+‐MSCs) from umbilical cord‐derived MSCs (denote as NT‐MSCs). Therewith, the cellular phenotypes of CD106+‐MSCs including immunophenotypes, multilineage differentiation potential towards adipocytes and osteoblasts were confirmed by flow cytometry and qRT‐PCR assay. Meanwhile, multifaceted characteristics of transcriptomic features were analyzed by utilizing the RNA‐SEQ and bioinformatics. Furthermore, to compare the therapeutic effects and spatio‐temporal dynamics of CD106+‐MSCs, we conducted in vivo fluorescent tracer, hematoxylin and eosin staining, blood smear, blood routine and cytokine detection in mice. Herein, we generated CD106+‐MSCs with GFP expression and confirmed the conservative property of phenotypes. Compared to NT‐MSCs with minimal CD106 expression, CD106+‐MSCs manifested consistent distribution and metabolokinetics in vivo but with preferable ameliorative effect upon the pathological appearance and proinflammatory cytokine secretion in ALI mice. Collectively, our data indicated the preferable therapeutic effects of CD106+‐MSCs upon ALI mice, which would benefit the further exploration of the CD106+ subset for pulmonary diseases and investigational new drug application purposes.
Reproductive rights and adolescent mental health
Authors: Sappenfield C.A. , Nugent N.R.
Published: December 2022

In the United States, September marks the return to school, the start of fall, and National Suicide Prevention Awareness Month. Throughout the month, there is a public health push for dissemination of suicide prevention strategies for adolescents, as it is well‐established that suicide is one of the leading causes of death in young people. Experts highlight the importance of safe‐handling protocols for lethal means like gun locks and prescription blister packs, accessible health insurance plans that provide mental health care, increased support for national suicide prevention lifelines and text lines, calls for the overhauls of the juvenile justice and foster care systems… the list goes on. Yet, one topic that we may forget about when talking about suicide and adolescent mental health is access to reproductive and family planning services, including abortions.
Comparison of radiation exposure associated with transradial and transfemoral access: An updated meta‐analysis
Authors: Saqib Najam , Pir Muhammad S. , Rajagopalan Sharath , Patel Tejas M. , Pancholy Samir B.
Published: December 2022

Objectives

To assess differences in radiation exposure between transradial access (TRA) and transfemoral access (TFA) for coronary procedures.

Background

TRA is associated with increased radiation exposure as compared to TFA. We compared radiation exposure between the two access sites.

Methods

Databases were searched from June 2014 to August 2021 for randomized controlled trials (RCTs) reporting coprimary outcomes of fluoroscopy time (FT) and/or dose area product (DAP) comparing TRA with TFA. Meta‐regression was performed to assess the behavior of weighted mean difference (WMD) in FT from 1995 to 2021. Observational study data was used for corroborative evidence.

Results

Data from 8 RCTs (11,611 patients) showed the WMD of FT was 0.62 min (37 s) (95% confidence interval [CI]: [0.08−1.17], p = 0.023) in favor of TFA, WMD in DAP (9169 patients) was 1.94 Gy.cm2 (95% CI: [−2.1 to 5.9], p = 0.35) showing no significant difference. Pooled data from OBS and RCTs (83,990 patients) showed a similar trend. Studies from outside US between 1995 and 2021 showed WMD of FT between TRA and TFA of 0.88 min (52 s) (95% CI: [0.67−1.09], p = 0.005) versus 2.1 min (126 s) (95% CI: [1.38−2.8], p = 0.005) for US in favor of TFA. Meta‐regression showed a declining WMD of FT between TRA and TFA from 1.6 min (96 s) in 1996 to 0.5 min (30 s) in 2020 with the lower limit of CI crossing the zero line in 2019.

Conclusion

Radiation exposure between TRA and TFA continues to decrease overtime and is becoming clinically nonsignificant.
Stability and Acidity of Sites at the External Surface and at Point Defects of Faujasite
Authors: Jarrin Thomas , de Bruin Theodorus , Chizallet Céline
Published: December 2022

Faujasite is one of the most industrially employed zeolite for its catalytic properties. The strong Brønsted bulk bridging Al−OH−Si sites are often thought to be the main origin of the Brønsted acidity of faujasite. However, many reactions also take place at the surface of the material and of its mesopores, where other types of acid sites exist. This study aims at unraveling the nature and strength of faujasite bulk and surface acid sites. Using Density Functional Theory (DFT), we rank the faujasite acid sites based on their stability, investigate their dehydration properties, and study their Brønsted and Lewis acidity via the adsorption of pyridine. Calculations are performed on cells with high (47 for bulk cells and about 300 for surface slabs) and low Si/Al ratio (about 3) and on cells containing defects under the form of silanol nests. These environments generate Brønsted acid sites of various strengths, and strong Lewis acid sites, even in the absence of extra‐framework species.
Cover crop termination timings and methods effect on cotton (Gossypium hirsutum L.) development and yield
Authors: Denton Savana , Raper Tyson , Stewart Scott , Dodds Darrin
Published: December 2022

Cover crops have been promoted for use in agricultural systems due to both environmental and economic opportunities. Cotton (Gossypium hirsutum L.) growers in West Tennessee faced challenges in 2015 and 2016 with cover crop termination management which resulted in failed cotton stands. The objective of this experiment was to determine effects of cover crop termination timing and method on cotton emergence, development, and yield. Field experiments were conducted from 2018 to 2020 in both small plot and on‐farm scenarios across West Tennessee. Cover crop termination timings consisted of an at‐planting termination, 3 weeks prior to planting, and both a broadcast and furrow‐strip termination 6 weeks prior to planting. The cover crop termination methods consisted of chemical termination, mechanical termination, and chemical + mechanical termination. At‐planting termination reduced emergence by 25% and delayed maturity of 65% of the stand relative to a 6‐week broadcast termination. Mechanical termination reduced emergence by 26% and delayed maturity of 26% of the stand relative to the chemical and chemical plus mechanical termination treatments. Thrips injury ratings were greater in cotton following a chemical + mechanical termination of the cover crop. Damage from three‐cornered alfalfa hoppers (Sissistilus festinus) was less prevalent in cotton following cover crops terminated 6 weeks prior to planting in a broadcast method compared to other timings. While early season effects were observed, end‐of‐season yield differences were not noted. Still, producers in short season environments should be aware of the higher level of risk associated with at‐planting terminations or terminations.
Quinoid Conjugated Polymer Nanoparticles with NIR‐II Absorption Peak Toward Efficient Photothermal Therapy**
Authors: Li Meng , Li Zheng , Yu Danni , Wang Ming , Wang Dong , Wang Bing
Published: December 2022

Recently, extensive efforts have been devoted to the development of the second near‐infrared bio‐window (NIR‐II, 1000–1700 nm) theranostic agents owing to the excellent tissue‐penetration capability of NIR‐II light. The exploration of organic NIR‐II photothermal therapy materials, especially those with absorption peak over 1000 nm, is an appealing yet significantly challenging task. Herein, we have designed conjugated polymer nanoparticles (PIS NPs) with NIR‐II absorption peak at 1026 nm through a combined strategy of introducing quinoid donor‐acceptor (D–A) structures, constructing intramolecular “conformational locks” and extending the conjugation area to narrow the band gap. Irradiated at 1064 nm, PIS NPs showed remarkable photothermal conversion performance for efficient photothermal ablation of tumor cells in vitro and in vivo. This study provides useful insights into the rational design of organic NIR‐II photothermal agents based on multiple strategies.
Activity Sensing of Coagulation and Fibrinolytic Proteases
Authors: Sondag Daan , Verhoeven Stijn , Löwik Dennis W. P. M. , van Geffen Mark , Veer Cornelis van't , van Heerde Waander L. , Boltje Thomas J. , Rutjes Floris P. J. T.
Published: December 2022

The blood coagulation cascade is a complex physiological process involving the action of multiple coupled enzymes, cofactors, and substrates, ultimately leading to clot formation. Serine proteases have a crucial role, and aberrations in their activity can lead to life‐threatening bleeding disorders and thrombosis. This review summarizes the essential proteases involved in blood coagulation and fibrinolysis, the endogenous peptide sequences they recognize and hydrolyze, and synthetic peptide probes based on these sequences to measure their activity. The information in this review can contribute to developing novel anticoagulant therapies and specific substrates for point‐of‐care diagnosis of coagulation pathologies.
From Lactose to Alkyl Galactoside Fatty Acid Esters as Non‐Ionic Biosurfactants: A Two‐Step Enzymatic Approach to Cheese Whey Valorization
Authors: Semproli Riccardo , Simona Robescu Marina , Sangiorgio Sara , Pargoletti Eleonora , Bavaro Teodora , Rabuffetti Marco , Cappelletti Giuseppe , Speranza Giovanna , Ubiali Daniela
Published: December 2022

A library of alkyl galactosides was synthesized to provide the “polar head” of sugar fatty acid esters to be tested as non‐ionic surfactants. The enzymatic transglycosylation of lactose resulted in alkyl β‐D‐galactopyranosides, whereas the Fischer glycosylation of galactose afforded isomeric mixtures of α‐ and β‐galactopyranosides and α‐ and β‐galactofuranosides. n‐Butyl galactosides from either routes were enzymatically esterified with palmitic acid, used as the fatty acid “tail” of the surfactant, giving the corresponding n‐butyl 6‐O‐palmitoyl‐galactosides. Measurements of interfacial tension and emulsifying properties of n‐butyl 6‐O‐palmitoyl‐galactosides revealed that the esters of galactopyranosides are superior to those of galactofuranosides, and that the enantiopure n‐butyl 6‐O‐palmitoyl‐β‐D‐galactoside, prepared by the fully enzymatic route, leads to the most stable emulsion. These results pave the way to the use of lactose‐rich cheese whey as raw material for the obtainment of bio‐based surfactants.
Towards the Reduction of Pt Loading in High Temperature Proton Exchange Membrane Fuel Cells – Effect of Fe−N−C in Pt‐Alloy Cathodes
Authors: Müller‐Hülstede Julia , Uhlig Lisa M. , Schmies Henrike , Schonvogel Dana , Meyer Quentin , Nie Yan , Zhao Chuan , Vidakovic Jurica , Wagner Peter
Published: December 2022

Pt poisoning by phosphate in high temperature proton exchange membrane fuel cells (HT‐PEMFC) leads to loadings up to 1 mgPt cm−2 per electrode of costly materials. While cheaper Fe−N−C catalysts are unaffected by phosphate deactivation and contribute to the catalysis of the oxygen reduction reaction, their volumetric activity is substantially lower. In this study, the effect of Pt‐loading reduced hybrid cathodes for HT‐PEMFC is investigated using commercial Celtec®‐P‐based assembling. A promising effect of Fe−N−C incorporation in terms of acid attraction and activity retention is found. A longer activation (230 h, 0.3 A cm−2) for the hybrid membrane electrode assembly (MEA) is necessary, due to the slower acid distribution within Fe−N−Cs. This study shows the potential of Pt‐content reduction by up to 25 % compared to standard MEA using hybrid electrodes. Moreover, important insights for future strategies of cell activation are revealed for these hybrid MEAs.
Catalyst‐Free Synthesis of Covalent Adaptable Network (CAN) Polyurethanes from Lignin with Editable Shape Memory Properties
Authors: Ma Xiaozhen , Li Shuqi , Wang Fan , Wu Jialong , Chao Yeyan , Chen Xun , Chen Peng , Zhu Jin , Yan Ning , Chen Jing
Published: December 2022

Here a new strategy of catalyst‐free direct synthesis of covalent adaptable network polyurethanes (LPUs) from lignin with editable shape memory effect is reported. Using unmodified lignin, PEG, and isocyanate under the condition of the isocyanate index less than 1.0 (NCO/OH<1.0), a variety of LPUs are obtained. When NCO/OH=0.8, a stable cross‐linked network can be formed (ex. the gel content of LPU50‐0.8 was 98±0.3 %). The activation energy (Ea) value of LPUs is similar to that of polyhydroxyurethanes (PHUs), at around 110 kJ mol−1. With an increase of lignin content, the LPUs show a transition from ductile fracture to brittle fracture mode. And the mechanical properties of LPUs are significantly enhanced after extrusion processing, with the maximum modulus reaching 649±26 MPa and the maximum toughness up to 9927±111 kJ m−3. The improvement in mechanical properties is due to the homogenization of complex cross‐linked network under the powerful external force of the extruder and the lignin that originally was free in the system participated in the exchange reactions. Moreover, LPUs can also be prepared continuously in one step by using an extruder as the reactor. In addition, LPU50‐0.8 has an editable shape memory effect. This study develops a novel method for the synthesis of LPU from lignin with NCO/OH<1.0, showcasing new possibilities for value‐added utilization of lignin, and expands the bio‐based products portfolio from biomass feedstock to help meet future green manufacturing demands.
Differential effects of proton pump inhibitors and vonoprazan on vascular endothelial growth factor expression in cancer cells
Authors: Ando‐Matsuoka Rie , Yagi Kenta , Takaoka Mayu , Sakajiri Yuko , Shibata Tomokazu , Sawada Ryusuke , Maruo Akinori , Miyata Koji , Aizawa Fuka , Hamano Hirofumi , Niimura Takahiro , Izawa‐Ishizawa Yuki , Goda Mitsuhiro , Sakaguchi Satoshi , Zamami Yoshito , Yamanishi Yoshihiro , Ishizawa Keisuke
Published: December 2022

Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion, used as first‐line agents in treating peptic ulcers. However, we have previously reported that PPIs may diminish the therapeutic effect of anti‐vascular endothelial growth factor (VEGF) drugs in patients with cancer. In this study, we explored the effects of vonoprazan, a novel gastric acid secretion inhibitor used for the treatment of peptic ulcers, on the secretion of VEGF in cancer cells and attempted to propose it as an alternative PPI for cancer chemotherapy. The effects of PPI and vonoprazan on VEGF expression in cancer cells were compared by real‐time reverse transcription‐polymerase chain reaction and ELISA. The interaction of vonoprazan and PPIs with transcriptional regulators by docking simulation analysis. In various cancer cell lines, including the human colorectal cancer cell line (LS174T), PPI increased VEGF messenger RNA expression and VEGF protein secretion, while this effect was not observed with vonoprazan. Molecular docking simulation analysis showed that vonoprazan had a lower binding affinity for estrogen receptor alpha (ER‐α), one of the transcriptional regulators of VEGF, compared to PPI. Although the PPI‐induced increase in VEGF expression was counteracted by pharmacological ER‐α inhibition, the effect of vonoprazan on VEGF expression was unchanged. Vonoprazan does not affect VEGF expression in cancer cells, which suggests that vonoprazan might be an alternative to PPIs, with no interference with the therapeutic effects of anti‐VEGF cancer chemotherapy.
Biomarkers and clinical indicators of disease activity in vitiligo
Authors: Delbaere Liesbeth , Speeckaert Reinhart , Herbelet Sandrine , Belpaire Arno , Duponselle Jolien , van Geel Nanja
Published: December 2022

Background: The management of vitiligo is guided by the assessment of disease activity. However, this assessment is hampered by the absence of a highly feasible and reliable single marker to evaluate activity. Furthermore, the need for an objective, easy, preferably noninvasive marker is further stressed by the increased amount of research performed on new treatment strategies for vitiligo.

Objectives: In this review, the available research on clinical signs linked to disease activity, and biomarkers in tissues and blood are summarized.

Results: In the group of clinical signs, the Koebner phenomenon has the strongest evidence of an association with disease activity, while confetti‐like depigmentation is gaining importance and seems to outweigh this role. For the tissue markers, the most evidence is available for histopathological findings, such as epidermal spongiosis with vacuolar degeneration in the basal cells and inflammatory infiltrate. Circulating biomarkers such as interleukin‐1β (IL‐1β), IL‐17, interferon‐γ, tumor growth factor‐β, soluble cluster of differentiation 25, autoantibodies, and oxidative stress markers show the most promising results. Nevertheless, none of them are currently regarded as the gold standard.

Discussion: In conclusion, we encourage researchers to investigate various biomarkers and clinical signs in their trials in a standardized manner to get insight into their exact value, so they can be used to optimize treatment selection, gain insight into the disease, and predict future disease progression.
A genetic warning system for a hierarchically structured wildlife monitoring framework
Authors: Zimmerman Shawna J. , Aldridge Cameron L. , O'Donnell Michael S. , Edmunds David R. , Coates Peter S. , Prochazka Brian G. , Fike Jennifer A. , Cross Todd B. , Fedy Bradley C. , Oyler‐McCance Sara J.
Published: December 2022

Genetic variation is a well‐known indicator of population fitness yet is not typically included in monitoring programs for sensitive species. Additionally, most programs monitor populations at one scale, which can lead to potential mismatches with ecological processes critical to species' conservation. Recently developed methods generating hierarchically nested population units (i.e., clusters of varying scales) for greater sage‐grouse (Centrocercus urophasianus) have identified population trend declines across spatiotemporal scales to help managers target areas for conservation. The same clusters used as a proxy for spatial scale can alert managers to local units (i.e., neighborhood‐scale) with low genetic diversity, further facilitating identification of management targets. We developed a genetic warning system utilizing previously developed hierarchical population units to identify management‐relevant areas with low genetic diversity within the greater sage‐grouse range. Within this warning system we characterized conservation concern thresholds based on values of genetic diversity and developed a statistical model for microsatellite data to robustly estimate these values for hierarchically nested populations. We found that 41 of 224 neighborhood‐scale clusters had low genetic diversity, 23 of which were coupled with documented local population trend decline. We also found evidence of cross‐scale low genetic diversity in the small and isolated Washington population, unlikely to be reversed through typical local management actions alone. The combination of low genetic diversity and a declining population suggests relatively high conservation concern. Our findings could further facilitate conservation action prioritization in combination with population trend assessments and (or) local information, and act as a base‐line of genetic diversity for future comparison. Importantly, the approach we used is broadly applicable across taxa.
Lost reproductive value reveals a high burden of juvenile road mortality in a long‐lived species
Authors: Keevil Matthew G. , Noble Natasha , Boyle Sean P. , Lesbarrères David , Brooks Ronald J. , Litzgus Jacqueline D.
Published: December 2022

Adult mortality is often the most sensitive vital rate affecting at‐risk wildlife populations. Therefore, road ecology studies often focus on adult mortality despite the possibility for roads to be hazardous to juvenile individuals during natal dispersal. Failure to quantify concurrent variation in mortality risk and population sensitivity across demographic states can mislead the efforts to understand and mitigate the effects of population threats. To compare relative population impacts from road mortality among demographic classes, we weighted mortality observations by applying reproductive value analysis to quantify expected stage‐specific contributions to population growth. We demonstrate this approach for snapping turtles (Chelydra serpentina) observed on roads at two focal sites in Ontario, Canada, where we collected data for both live and dead individuals observed on roads. We estimated reproductive values using stage‐classified matrix models to compare relative population‐level impacts of adult and juvenile mortality. Reproductive value analysis is a tractable approach to assessing demographically variable effects for applications covering large spatial scales, nondiscrete populations, or where abundance data are lacking. For one site with long‐term life‐history data, we compared demographic frequency on roads to expected general population frequencies predicted by the matrix model. Our application of reproductive value is sex specific but, as juvenile snapping turtles lack external secondary sex characters, we estimated the sex ratio of road‐crossing juveniles after dissecting and sexing carcasses collected on roads at five sites across central Ontario, Canada. Juveniles were more abundant on roads than expected, suggesting a substantial dispersal contribution, and the road‐killed juvenile sex ratio approached 1:1. A higher proportion of juveniles were also found dead compared with adults, and cumulative juvenile mortality had similar population‐level importance as adult mortality. This suggests that the impact of roads needs to be considered across all life stages, even in wildlife species with slow life histories, such as snapping turtles, that are particularly sensitive to adult mortality.
Nutrient enrichment promotes invasion success of alien plants via increased growth and suppression of chemical defenses
Authors: Shan Liping , Oduor Ayub M. O. , Huang Wei , Liu Yanjie
Published: December 2022

In support of the prediction of the enemy release hypothesis regarding a growth–defense trade‐off, invasive alien plants often exhibit greater growth and lower anti‐herbivory defenses than native plants. However, it remains unclear how nutrient enrichment of invaded habitats may influence competitive interactions between invasive alien and co‐occurring native plants, as well as production of anti‐herbivore defense compounds, growth‐promoting hormones, and defense‐regulating hormones by the two groups of plants. Here, we tested whether: (i) nutrient enrichment causes invasive alien plants to produce greater biomass and lower concentrations of the defense compounds flavonoids and tannins than native plants; and (ii) invasive alien plants produce lower concentrations of a defense‐regulating hormone jasmonic acid (JA) and higher concentrations of a growth‐promoting hormone gibberellic acid (GA3). In a greenhouse experiment, we grew five congeneric pairs of invasive alien and native plant species under two levels each of nutrient enrichment (low vs. high), simulated herbivory (leaf clipping vs. no‐clipping), and competition (alone vs. competition) in 2.5‐L pots. In the absence of competition, high‐nutrient treatment induced a greater increase in total biomass of invasive alien species than that of native species, whereas the reverse was true under competition as native species benefitted more from nutrient enrichment than invasive alien species. Moreover, high‐nutrient treatment caused a greater increase in total biomass of invasive alien species than that of native species in the presence of simulated herbivory. Competition induced higher production of flavonoids and tannins. Simulated herbivory induced higher flavonoid expression in invasive alien plants under low‐nutrient than high‐nutrient treatments. However, flavonoid concentrations of native plants did not change under nutrient enrichment and simulated herbivory treatments. Invasive alien plants produced higher concentrations of GA3 than native plants. Taken together, these results suggest that impact of nutrient enrichment on growth of invasive alien and co‐occurring native plants may depend on the level of competition that they experience. Moreover, invasive alien plants might adjust their flavonoid‐based defense more efficiently than native plants in response to variation in soil nutrient availability and herbivory pressure. Our findings suggest that large‐scale efforts to reduce nutrient enrichment of invaded habitats may help to control future invasiveness of target alien plant species.
Inferring population connectivity in eastern massasauga rattlesnakes (Sistruruscatenatus) using landscape genetics
Authors: Martin Scott A. , Peterman William E. , Lipps Gregory J. , Gibbs H. Lisle
Published: December 2022

Assessing the environmental factors that influence the ability of a threatened species to move through a landscape can be used to identify conservation actions that connect isolated populations. However, direct observations of species' movement are often limited, making the development of alternate approaches necessary. Here we use landscape genetic analyses to assess the impact of landscape features on the movement of individuals between local populations of a threatened snake, the eastern massasauga rattlesnake (Sistrurus catenatus). We linked connectivity data with habitat information from two landscapes of similar size: a large region of unfragmented habitat and a previously studied fragmented landscape consisting of isolated patches of habitat. We used this analysis to identify features of the landscape where modification or acquisition would enhance population connectivity in the fragmented region. We found evidence that current connectivity was impacted by both contemporary land‐cover features, especially roads, and inherent landscape features such as elevation. Next, we derived estimates of expected movement ability using a recently developed pedigree‐based approach and least‐cost paths through the unfragmented landscape. We then used our pedigree and resistance map to estimate resistance polygons of the potential extent for S. catenatus movement in the fragmented landscape. These polygons identify possible sites for future corridors connecting currently isolated populations in this landscape by linking the impact of future habitat modification or land acquisition to dispersal ability in this species. Overall, our study shows how modeling landscape resistance across differently fragmented landscapes can identify habitat features that affect contemporary movement in threatened species in fragmented landscapes and how this information can be used to guide mitigation actions whose goal is to connect isolated populations.
The ontogenetic dietary shift from non‐dangerous to dangerous prey in predator‐eating predators under capture risk
Authors: Suzuki Yuya , Ikemoto Mito , Yokoi Tomoyuki
Published: December 2022

Evaluating the patterns and generality of ontogenetic dietary shifts (ODSs) contributes to understanding prey–predator interactions and food web dynamics. Numerous studies have focused on predators that target distinctively lower trophic‐level organisms. However, the ODS of predators that routinely prey on organisms at similar trophic levels (i.e., predator‐eating predators) have been neglected in ODS research. The ODS patterns of predator eaters may not fit into conventional frameworks owing to constraints of potential capture risk (e.g., deadly counterattack from prey) and body size. We aimed to reveal the ODS patterns of predator eaters and determine whether the patterns were affected by body size and capture risk. Assuming that capture risk is a significant factor in ODS patterns, we expected: (1) juvenile araneophagic spiders to forage on non‐dangerous prey (insects) and capture larger non‐dangerous prey more frequently than dangerous prey (spiders); and (2) as they grow, their prey types will shift from non‐dangerous to dangerous prey because larger predators will be able to capture dangerous prey as the optimal food. As a result of field observations, we revealed that the major ODS pattern in these spiders changed from a mixed (both insect and spider) to a spider‐dominant diet. The model selection approach showed that this diet shift was partly due to predator size, and the relative importance of predator size was higher than the life stage per se and almost equal to species identity. In these spiders, the body size of spider prey tended to be smaller than that of insects when the predators were small, suggesting that capture risk may be a critical factor in determining the ODS patterns of these predators. Therefore, our study adds to the evidence that the capture risk is crucial in comprehensively understanding the mechanisms determining ODS patterns in natural systems.
The influence of weevil herbivory on leaf litter chemistry in dioecious willows
Authors: Ramstack Hobbs Joy M. , Garthwaite Iris J. , Lancaster Logan , Moffett‐Dobbs Jordan A. , Johnson Kelly , Criss Nichole , McConathy Victoria , James C. Andrew , Gipe Alex , Claeson Shannon M. , LeRoy Carri J.
Published: December 2022

Leaf litter inputs can influence the structure and function of both terrestrial and adjacent aquatic ecosystems. Dioecy and herbivory are two factors that together have received little attention, yet have the potential to affect the quantity, quality, and timing of riparian litterfall, litter chemistry, and litter decomposition processes. Here, we explore litter chemistry differences for the dioecious Sitka willow (Salix sitchensis Sanson ex. Bong), which is establishing on primary successional habitats at Mount St. Helens (WA, USA) and is heavily infested with a stem‐boring weevil (Cryptorhynchus lapathi). Weevil‐attacked branches produced summer senesced litter that had significantly higher %N, lower C:N ratios, and lower condensed tannins than litter from branches that were unattacked by the weevil and senesced naturally in the autumn. Weevils more often attack female willows; however, these common litter chemicals did not significantly differ between males and females within the weevil‐attacked and ‐unattacked groups. High‐resolution mass spectrometry was used to isolate compounds in litter from 10 Sitka willow individuals with approximately 1500–1600 individual compounds isolated from each sample. There were differences between weevil‐attacked litter and green leaf samples, but at this level, there was no clustering of male and female samples. However, further exploration of the isolated compounds determined a suite of compounds present only in either males or females. These findings suggest some variation in more complex litter chemistry between the sexes, and that significant differences in weevil‐attacked litter chemistry, coupled with the shift in seasonality of litter inputs to streams, could significantly affect in‐stream ecological processes, such as decomposition and detritivore activity.
Highly‐Selective Construction of Aza‐Fused Pyrrolo Isoquinoline Derivatives
Authors: Zheng Jing , He Yuan , Dong Lin
Published: December 2022

A novel Rh(III)‐catalyzed cascade C−H activation/annulation/nucleophilic attack/Michael addition of 2‐phenyloxazoles with maleimides for highly‐selective construction of pyrroloisoquinoline derivatives through conditions control is reported. In this reaction, oxazoles were used both as the directing group and potential functionalized reagents, H2O was the nucleophile. The notable features of this protocol include atom economy and highly regioselectivity.
Incorporation of awareness programs into a model of the spread of HIV/AIDS among people who inject drugs
Authors: Alsharari Maha , Greenhalgh David
Published: December 2022

Mathematical modeling techniques have been used extensively during the human immunodeficiency virus (HIV) epidemic. Drug injection causes increased HIV spread in most countries globally. The media is crucial in spreading health awareness by changing mixing behavior. The published studies show some of the ways that differential equation models can be employed to explain how media awareness programs influence the spread and containment of disease (Greenhalgh et al. Appl Math Comput. 2015;251:539–563). Here we build a differential equation model which shows how disease awareness programs can alter the HIV prevalence in a group of people who inject drugs (PWIDs). This builds on previous work by Greenhalgh and Hay (1997) and Liang et al. (2016). We have constructed a mathematical model to describe the improved model that reduces the spread of the diseases through the effect of awareness of disease on sharing needles and syringes among the PWID population. The model supposes that PWIDs clean their needles before use rather than after. We carry out a steady state analysis and examine local stability. Our discussion has been focused on two ways of studying the influence of awareness of infection levels in epidemic modeling. The key biological parameter of our model is the basic reproductive number . is a crucial number which determines the behavior of the infection. We find that if is less than one then the disease‐free steady state is the unique steady state and moreover whatever the initial fraction of infected individuals then the disease will die out as time becomes large. If exceeds one there is the disease‐free steady state and a unique steady state with disease present. We also showed that the disease‐free steady state is locally asymptotically stable if is less than one, neutrally stable if is equal to one and unstable if exceeds one. In the last case, when is greater than one the endemic steady state was locally asymptotically stable. Our analytical results are confirmed by using simulation with realistic parameter values. In nontechnical terms, the number is a critical value describing how the disease will spread. If is less than or equal to one then the disease will always die out but if exceeds one and disease is present the disease will sustain itself and moreover the numbers of PWIDs with disease will tend to a unique nonzero value.