bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep Reinforcement Learning for Dynamic Stock Option Hedging: A Review
Authors: Pickard Reilly , Lawryshyn Yuri
Published: December 2023

This paper reviews 17 studies addressing dynamic option hedging in frictional markets through Deep Reinforcement Learning (DRL). Specifically, this work analyzes the DRL models, state and action spaces, reward formulations, data generation processes and results for each study. It is found that policy methods such as DDPG are more commonly employed due to their suitability for continuous action spaces. Despite diverse state space definitions, a lack of consensus exists on variable inclusion, prompting a call for thorough sensitivity analyses. Mean-variance metrics prevail in reward formulations, with episodic return, VaR and CvaR also yielding comparable results. Geometric Brownian motion is the primary data generation process, supplemented by stochastic volatility models like SABR (stochastic alpha, beta, rho) and the Heston model. RL agents, particularly those monitoring transaction costs, consistently outperform the Black–Scholes Delta method in frictional environments. Although consistent results emerge under constant and stochastic volatility scenarios, variations arise when employing real data. The lack of a standardized testing dataset or universal benchmark in the RL hedging space makes it difficult to compare results across different studies. A recommended future direction for this work is an implementation of DRL for hedging American options and an investigation of how DRL performs compared to other numerical American option hedging methods.
Constant Sum Group Flows of Graphs
Authors: Wang Tao-Ming
Published: December 2023

As an analogous concept of a nowhere-zero flow for directed graphs, zero-sum flows and constant-sum flows are defined and studied in the literature. For an undirected graph, a zero-sum flow (constant-sum flow resp.) is an assignment of nonzero integers to the edges such that the sum of the values of all edges incident with each vertex is zero (constant h resp.), and we call it a zero-sum k-flow (h-sum k-flow resp.) if the values of the edges are less than k. We extend these concepts to general constant-sum A-flow, where A is an Abelian group, and consider the case A=Zk the additive Abelian cyclic group of integer congruences modulo k with identity 0. In the literature, a graph is alternatively called Zk-magic if it admits a constant-sum Zk-flow, where the constant sum is called a magic sum or an index for short. We define the set of all possible magic sums such that G admits a constant-sum Zk-flow to be Ik(G) and call it the magic sum spectrum, or for short, the index set of G with respect to Zk. In this article, we study the general properties of the magic sum spectrum of graphs. We determine the magic sum spectrum of complete bipartite graphs Km,n for m≥n≥2 as the additive cyclic subgroups of Zk generated by kd, where d=gcd(m−n,k). Also, we show that every regular graph G with a perfect matching has a full magic sum spectrum, namely, Ik(G)=Zk for all k≥3. We characterize a 3-regular graph so that it admits a perfect matching if and only if it has a full magic sum spectrum, while an example is given for a 3-regular graph without a perfect matching which has no full magic sum spectrum. Another example is given for a 5-regular graph without a perfect matching, which, however, has a full magic sum spectrum. In particular, we completely determine the magic sum spectra for all regular graphs of even degree. As a byproduct, we verify a conjecture raised by Akbari et al., which claims that every connected 4k-regular graph of even order admits a 1-sum 4-flow. More open problems are included.
High Structural Diversity of Aeruginosins in Bloom-Forming Cyanobacteria of the Genus Planktothrix as a Consequence of Multiple Recombination Events
Authors: Entfellner Elisabeth , Baumann Kathrin B. L. , Edwards Christine , Kurmayer Rainer
Published: December 2023

Many compounds produced by cyanobacteria act as serine protease inhibitors, such as the tetrapeptides aeruginosins (Aer), which are found widely distributed. The structural diversity of Aer is intriguingly high. However, the genetic basis of this remains elusive. In this study, we explored the genetic basis of Aer synthesis among the filamentous cyanobacteria Planktothrix spp. In total, 124 strains, isolated from diverse freshwater waterbodies, have been compared regarding variability within Aer biosynthesis genes and the consequences for structural diversity. The high structural variability could be explained by various recombination processes affecting Aer synthesis, above all, the acquisition of accessory enzymes involved in post synthesis modification of the Aer peptide (e.g., halogenases, glycosyltransferases, sulfotransferases) as well as a large-range recombination of Aer biosynthesis genes, probably transferred from the bloom-forming cyanobacterium Microcystis. The Aer structural composition differed between evolutionary Planktothrix lineages, adapted to either shallow or deep waterbodies of the temperate climatic zone. Thus, for the first time among bloom-forming cyanobacteria, chemical diversification of a peptide family related to eco-evolutionary diversification has been described. It is concluded that various Aer peptides resulting from the recombination event act in chemical defense, possibly as a replacement for microcystins.
Determination of the Effect of Heat Input during Laser Welding on the Magnitude of Residual Stresses in the Refurbishment of Al Alloy Casting
Authors: Viňáš Ján , Brezinová Janette , Pástor Miroslav , Šarga Patrik , Džupon Miroslav , Brezina Jakub
Published: December 2023

The paper presents the results of research on the evaluation of the quality of coating layers made by a laser. The base material, which was Dievar steel (1.2343), was coated with a single layer using additional materials in the form of a wire with a diameter of ø 1.0 mm. As additional material, wires with chemistry corresponding to steels 1.2343 and 1.6356 were used. The primary objective was to verify the possibilities of innovative use of additive materials based on maraging steels, which were chosen from the production of two manufacturers with slightly different chemical compositions. The experiment verified the influence of the cladding parameters on the residual stress values around the fabricated maraging layers. Metallographic analysis by light microscopy was carried out in order to identify the individual structures as well as to assess the occurrence of internal defects in the coatings. The effect of the mixing of the coating metal with the base material was also assessed by means of a low-load hardness assessment, which was carried out in accordance with EN ISO 4063-2. Based on the results, it can be concluded that, in terms of residual stresses, the measured values were approximately the same for all the additive materials used; however, due to the desired mechanical properties of the additively formed layers, it is possible to recommend additive materials based on medium- and high-alloy steels for additive manufacturing.
A Study on the Influence of Zr on the Strengthening of the Al-10% Al2O3 Composite Obtained by Mechanical Alloying
Authors: Prosviryakov Alexey S. , Bazlov Andrey I. , Churyumov Alexander Yu. , Mikhaylovskaya Anastasia V.
Published: December 2023

Al2O3 is a traditional strengthening phase in aluminum matrix composites due to its high hardness and melting point. At the same time, zirconium is an important alloying element for heat-resistant aluminum alloys. However, its effect on the structure and properties of Al-Al2O3 composites remains unexplored at present. In this work, the effect of the addition of Zr (5 wt%) on the microstructure and strengthening of the Al-10 vol% Al2O3 composite was investigated for the first time. Composite materials with and without Zr addition were obtained through mechanical alloying as a result of ball milling for 20 h followed by multi-directional forging (MDF) at a temperature of 400 °C. OM, SEM and XRD were used to study the microstructure and its parameters. The work showed that the use of mechanical alloying and MDF contributes to the formation of dense composite samples with a nanocrystalline microstructure and a uniform distribution of alumina particles. The addition of Zr contributes to a 1.4-fold increase in the microhardness and yield strength of a compact sample at room temperature due to the formation of Al3Zr (L12) dispersoids. It was been shown that the largest contribution to the strength of both materials comes from grain boundary strengthening, which is at least 50% of the yield strength. The resulting composites exhibit high heat resistance. For example, their compressive yield strength at 350 °C is approximately 220 MPa.
An Accurate Electro-Thermal Coupling Model of a GaAs HBT Device under Floating Heat Source Disturbances
Authors: Sun Xiaohong , Yang Yijun , Zhang Chaoran , Zhang Xiaodong , Tian Ting
Published: December 2023

Taking into consideration the inaccurate temperature predictions in traditional thermal models of power devices, we undertook a study on the temperature rise characteristics of heterojunction bipolar transistors (HBTs) with a two-dimensional cross-sectional structure including a sub-collector region. We developed a current-adjusted polynomial electro-thermal coupling model based on investigating floating heat sources. This model was developed using precise simulation data acquired from SILVACO (Santa Clara, CA, USA). Additionally, we utilized COMSOL software (version 5.6) to simulate the temperature distribution within parallel power cells, examining further impacts resulting from thermal coupling. The research findings indicate that the rise in current induces modifications in the local carrier concentration, thereby prompting variations in the local electric field, including changes in the heat source’s peak location and intensity. The device’s peak temperature exhibits a non-linear trend regulated by the current, revealing an error margin of less than 1.5% in the proposed current-corrected model. At higher current levels, the drift of the heat source leads to an increase in the heat dissipation path and reduces the coupling strength between parallel devices. Experiments were performed on 64 GaAs (gallium arsenide) HBT-based power cells using a QFI infrared imaging system. Compared to the traditional temperature calculation model, the proposed model increased the accuracy by 6.84%, allowing for more precise predictions of transistor peak temperatures in high-power applications.
LiOtBu-Promoted Intramolecular 1,3-Dipolar Cycloaddition of the 2′-Alkynyl-biaryl-2-aldehyde N-Tosylhydrazones Approach to 3-Substituted 1H-Dibenzo[e,g]indazoles
Authors: Lv Jiaying , Hua Ruimao
Published: December 2023

A two-step, one-pot synthesis of 3-substituted 1H-dibenzo[e,g]indazoles in good to high yields via a LiOtBu-promoted intramolecular 1,3-dipolar cyclization of 2′-alkynyl-biaryl-2-aldehyde N-tosylhydrazones was developed. The N-Ts-hydrazones used were prepared in situ via the reactions of 2′-alkynyl-biaryl-2-aldehydes and TsNHNH2 (p-methylbenzenesulfonohydrazide). Two types of signals related to the hydrogen bonds, forming in several products, were observed in the 1H NMR spectra recorded in DMSO-d6, assigned to N-H bonds in their dimeric species of product and tautomer.
Novel Janus Kinase Inhibitors in the Treatment of Dermatologic Conditions
Authors: Ryguła Izabella , Pikiewicz Wojciech , Kaminiów Konrad
Published: December 2023

Janus kinase inhibitors, also known as JAK inhibitors, JAKinibs or JAKi, are a new group of disease-modifying drugs. They work by inhibiting enzymes involved in the transmission of information from receptors located in the cell membrane to the cell interior, specifically to the cell nucleus, thus disrupting the JAK-STAT pathway. This pathway plays a role in key cellular processes such as the immune response and cell growth. This feature is used in the treatment of patients with rheumatological, gastroenterological and hematological diseases. Recently, it has been discovered that JAK-STAT pathway inhibitors also show therapeutic potential against dermatological diseases such as atopic dermatitis, psoriasis, alopecia areata and acquired vitiligo. Studies are underway to use them in the treatment of several other dermatoses. Janus kinase inhibitors represent a promising class of drugs for the treatment of skin diseases refractory to conventional therapy. The purpose of this review is to summarize the latest knowledge on the use of JAKi in dermatological treatment.
Solid-State 13C Nuclear Magnetic Resonance Study of Soluble and Insoluble β-Glucans Extracted from Candida lusitaniae
Authors: Bikmurzin Ruslan , Maršalka Arūnas , Kalėdienė Lilija
Published: December 2023

β-glucans are widely known for their biological activities. However, the choice of extraction method can significantly influence their structural characteristics, thereby potentially impacting their biological functions. In this paper, three fractions of β-glucans were obtained from Candida lusitaniae yeast via alkali and hot-water extraction methods and were analyzed using solid-state 13C nuclear magnetic resonance (NMR) spectroscopy. Solid-state NMR spectroscopy was used as a nondestructive technique that preserves the structure of the analyzed molecules. The results suggest that differences in the β-glucan structure are affected by the choice of extraction method. The main difference occurred in the 82–92 ppm region with signal presence suggesting that β-glucans have a linear structure when hot-water-extracted, which is absent in alkali-extracted fractions resulting in the acquisition of β-glucans with an ordered, possibly helical structure. A hot-water extracted water-insoluble (HWN) fraction consists of linear β-1,3-glucans with other signals indicating the presence of β-1,6-linked side chains, chitin and small amounts of α-glucan impurities. For those that are alkali-extracted, alkali-insoluble (AN) and water-soluble (AWS) fractions are structurally similar and consist of an ordered β-1,3-glucan structure with β-1,6-linked side chains and a significant amount of α-glucan and chitin in both fractions.
Effects of Transglutaminase Concentration and Drying Method on Encapsulation of Lactobacillus plantarum in Gelatin-Based Hydrogel
Authors: Chen Junliang , Liu Zhiqin , Ma Shuhua , Chen Xin , Li Linlin , Liu Wenchao , Ren Guangyue , Duan Xu , Cao Weiwei , Xu Yunfeng , Xie Qinggang
Published: December 2023

Lactobacillus plantarum is a kind of probiotic that benefits the host by regulating the gut microbiota, but it is easily damaged when passing through the gastrointestinal tract, hindering its ability to reach the destination and reducing its utilization value. Encapsulation is a promising strategy for solving this problem. In this study, transglutaminase (TGase)-crosslinked gelatin (GE)/sodium hexametaphosphate (SHMP) hydrogels were used to encapsulate L. plantarum. The effects of TGase concentration and drying method on the physiochemical properties of the hydrogels were determined. The results showed that at a TGase concentration of 9 U/gGE, the hardness, chewiness, energy storage modulus, and apparent viscosity of the hydrogel encapsulation system were maximized. This concentration produced more high-energy isopeptide bonds, strengthening the interactions between molecules, forming a more stable three-dimensional network structure. The survival rate under the simulated gastrointestinal conditions and storage stability of L. plantarum were improved at this concentration. The thermal stability of the encapsulation system dried via microwave vacuum freeze drying (MFD) was slightly higher than that when dried via freeze drying (FD). The gel structure was more stable, and the activity of L. plantarum decreased more slowly during the storage period when dried using MFD. This research provides a theoretical basis for the development of encapsulation technology of probiotics.
Marine-Derived Compounds as Potential Inhibitors of Hsp90 for Anticancer and Antimicrobial Drug Development: A Comprehensive In Silico Study
Authors: Ouassaf Mebarka , Bourougaa Lotfi , Al-Mijalli Samiah Hamad , Abdallah Emad M. , Bhat Ajmal R. , A. Kawsar Sarkar M.
Published: December 2023

Marine compounds constitute a diverse and invaluable resource for the discovery of bioactive substances with promising applications in the pharmaceutical development of anti-inflammatory and antibacterial agents. In this study, a comprehensive methodology was employed, encompassing pharmacophore modeling, virtual screening, in silico ADMET assessment (encompassing aspects of absorption, distribution, metabolism, excretion, and toxicity), and molecular dynamics simulations. These methods were applied to identify new inhibitors targeting the Hsp90 protein (heat shock protein 90), commencing with a diverse assembly of compounds sourced from marine origins. During the virtual screening phase, an extensive exploration was conducted on a dataset comprising 31,488 compounds sourced from the CMNPD database, characterized by a wide array of molecular structures. The principal objective was the development of structure-based pharmacophore models, a valuable approach when the pool of known ligands is limited. The pharmacophore model DDRRR was successfully constructed within the active sites of the Hsp90 crystal structure. Subsequent docking studies led to the identification of six compounds (CMNPD 22591, 9335, 10015, 360799, 15115, and 20988) demonstrating substantial binding affinities, each with values below −8.3 kcal/mol. In the realm of in silico ADMET predictions, five of these compounds exhibited favorable pharmacokinetic properties. Furthermore, molecular dynamics simulations and total binding energy calculations using MM-PBSA indicated that these marine-derived compounds formed exceptionally stable complexes with the Hsp90 receptor over a 100-nanosecond simulation period. These findings underscore the considerable potential of these novel marine compounds as promising candidates for anticancer and antimicrobial drug development.
Antibiotics and Antibiotic Resistance—Mur Ligases as an Antibacterial Target
Authors: Hervin Vincent , Roy Vincent , Agrofoglio Luigi A.
Published: December 2023

The emergence of Multidrug Resistance (MDR) strains of bacteria has accelerated the search for new antibacterials. The specific bacterial peptidoglycan biosynthetic pathway represents opportunities for the development of novel antibacterial agents. Among the enzymes involved, Mur ligases, described herein, and especially the amide ligases MurC-F are key targets for the discovery of multi-inhibitors, as they share common active sites and structural features.
Authoring Moving Parts of Objects in AR, VR and the Desktop
Authors: Vargas González Andrés N. , Williamson Brian , LaViola Joseph J.
Published: December 2023

Creating digital twins of real objects is becoming more popular, with smartphones providing 3D scanning capabilities. Adding semantics to the reconstructed virtual objects is important to possibly reproduce training scenarios that otherwise could demand significant resources or happen in dangerous scenarios in some cases. The aim of this work is to evaluate the usability of authoring object component behaviors in immersive and non-immersive approaches. Therefore, we present an evaluation of the perceived ease of use to author moving parts of objects under three different conditions: desktop, augmented reality (AR) and virtual reality (VR). This paper provides insights into the perceived benefits and issues that domain experts might encounter when authoring geometrical component behaviors across each interface. A within-subject study is the major contribution of this work, from which is presented an analysis based on the usability, workload and user interface preferences of participants in the study. To reduce confounding variables in the study, we ensured that the virtual objects and the environment used for the evaluation were digital twins of the real objects and the environment that the experiment took place in. Results show that the desktop interface was perceived as more efficient and easier to use based on usability and workload measures. The desktop was preferred for performing component selection but no difference was found in the preference for defining a behavior and visualizing it. Based on these results, a set of recommendations and future directions are provided to achieve a more usable, immersive authoring experience.
Synthesis, Characterization and Potential Antimicrobial Activity of Selenium Nanoparticles Stabilized with Cetyltrimethylammonium Chloride
Authors: Blinova Anastasiya , Blinov Andrey , Kravtsov Alexander , Nagdalian Andrey , Rekhman Zafar , Gvozdenko Alexey , Kolodkin Maksim , Filippov Dionis , Askerova Alina , Golik Alexey , Serov Alexander , Shariati Mohammad Ali , Alharbi Naiyf S. , Kadaikunnan Shine , Thiruvengadam Muthu
Published: December 2023

Selenium nanoparticles (Se NPs) have a number of unique properties that determine the use of the resulting nanomaterials in various fields. The focus of this paper is the stabilization of Se NPs with cetyltrimethylammonium chloride (CTAC). Se NPs were obtained by chemical reduction in an aqueous medium. The influence of the concentration of precursors and synthesis conditions on the size of Se NPs and the process of micelle formation was established. Transmission electron microscopy was used to study the morphology of Se NPs. The influence of the pH of the medium and the concentration of ions in the sol on the stability of Se micelles was studied. According to the results of this study, the concentration of positively charged ions has a greater effect on the particle size in the positive Se NPs sol than in the negative Se NPs sol. The potential antibacterial and fungicidal properties of the samples were studied on Escherichia coli, Micrococcus luteus and Mucor. Concentrations of Se NPs stabilized with CTAC with potential bactericidal and fungicidal effects were discovered. Considering the revealed potential antimicrobial activity, the synthesized Se NPs-CTAC molecular complex can be further studied and applied in the development of veterinary drugs, pharmaceuticals, and cosmetics.
The Burden of Gastric Cancer Attributable to High Sodium Intake: A Longitudinal Study from 1990 to 2019 in China
Authors: Jiang Liying , Wang Anqi , Yang Shuo , Fang Haiqin , Wang Qihe , Li Huzhong , Liu Sana , Liu Aidong
Published: December 2023

Backgrounds: Excessive intake of sodium is a crucial risk factor of gastric cancer. However, it is still unclear whether the profile of gastric cancer burden is attributable to high sodium intake in China. This study aims to evaluate the levels and trends of gastric cancer burden attributable to high sodium intake across China from 1990 to 2019. Methods: We acquired data from the GBD (Global Burden of Disease Study) 2019 via the Global Health Data Exchange query tool. The details of regions from 1 January 1990 to 31 December 2019 from the China National Center for Food Safety Risk Assessment were also used. We conducted an integrated analysis on the gastric cancer burden attributable to high sodium intake among Chinese residents. The gastric cancer-related deaths, disability-adjusted life years (DALYs), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR), all being calculated to be attributable to sodium intake, were reckoned as separated by age, sex, SDI, and regions. Then, the estimated annual percentage change (EAPC) was regarded as the secular trends of gastric cancer’s ASMR and ASDR due to high sodium intake from 1990 to 2019. We further explored the associations between SDI (Socio-demographic index) and the ASMR and ASDR. The rates were calculated per 100,000 population as age-standardized rates. Results: Briefly, the number of gastric cancer-related deaths and DALYs being attributed to high sodium intake were 37,131.48 (95% UI: 833.14 to 138,478.72) and 873,813.19 (95% UI: 19,283.13 to 3,220,231.82) in 2019; both have increased by a third since 1990. However, the ASMR decreased with an EAPC of −1.72% (95% CI: −2.11% to −1.33%), while ASDR increased with an EAPC of 0.36% (95% CI: 0.08% to 0.68%), respectively. The age-specific numbers and rates of deaths, as well as DALYs of gastric cancer being attributed to high sodium intake, elevated gradually with age. And, they were higher in males than in females. The gastric cancer burden being attributed to high sodium intake in 2019 and its temporal trends from 1990 to 2019 varied greatly by SDI quintile and geographic locations. There was a strong negative association between the EAPC in ASMR and SDI in 2019 (ρ = −0.642, p < 0.001). The EAPC in ASDR and SDI also exhibited a negative connection in 2019 (ρ = −0.538, p = 0.0012). Conclusions: Overall, using a longitudinal sample from different regions, the study presented that gastric cancer burden attributed to high sodium intake still exists seriously and varies remarkably by regions, sex, and age across China. The disparity of socioeconomic status on disease burden also exists. Integrated and precise approaches for gastric cancer prevention are anticipated in the future.
Is Dietary (Food) Supplement Intake Reported in European National Nutrition Surveys?
Authors: Papatesta Eleni Maria , Kanellou Anastasia , Peppa Eleni , Trichopoulou Antonia
Published: December 2023

Dietary (food) supplements (DSs) have seen a sharp increase in use and popularity in recent years. Information on DS consumption is vital for national nutrition monitoring. The objective of this study was to investigate whether DS intake was reported in the National Nutrition Surveys (NNSs) in all European countries. NNSs reporting DS use were retrieved via literature review (i.e., PubMed, Google Scholar, Scopus), scientific and organizational publications (EFSA), or open-published government and other official reports. Included were the European NNSs referring to adults, published in English, French, or German, post-2000. Out of the 53 European countries, 30 recorded DS intake. Among them, related findings on the percentage of DS intake were published in 21 cases, 5 of them written in the local language. DS use varied by nation, with Finland and Denmark having the greatest (over 50%) and Italy having the lowest percentage (5%). In terms of comprehensive reported data on DS consumption in Europe and the investigation of the contribution of DSs to total nutrient intake, there is a need for improvement. Common DS categories should be defined upon agreement among the involved scientific parties to allow for comparable data and estimations between surveys.
Nutritional Strategies for the Management of Type 2 Diabetes Mellitus: A Narrative Review
Authors: Minari Tatiana Palotta , Tácito Lúcia Helena Bonalume , Yugar Louise Buonalumi Tácito , Ferreira-Melo Sílvia Elaine , Manzano Carolina Freitas , Pires Antônio Carlos , Moreno Heitor , Vilela-Martin José Fernando , Cosenso-Martin Luciana Neves , Yugar-Toledo Juan Carlos
Published: December 2023

Background: Thinking about greater adherence to dietary planning, it is extremely important to be aware of all nutritional strategies and dietary prescriptions available in the literature, and of which of them is the most efficient for the management of T2DM. Methods: A search was carried out in 2023 for randomized clinical trials, systematic reviews, meta-analyses, and guidelines in the following databases: Pubmed, Scielo, Web of Science, CrossRef and Google Scholar. In total, 202 articles were collected and analyzed. The period of publications was 1983–2023. Results: There is still no consensus on what the best nutritional strategy or ideal dietary prescription is, and individuality is necessary. In any case, these references suggest that Mediterranean Diet may of greater interest for the management of T2DM, with the following recommended dietary prescription: 40–50% carbohydrates; 15–25% proteins; 25–35% fats (<7% saturated, 10% polyunsaturated, and 10% monounsaturated); at least 14 g of fiber for every 1000 kcal consumed; and <2300 mg sodium. Conclusions: Individuality is the gold standard for dietary prescriptions, however, the Mediterranean diet with low levels of carbohydrates and fats seems to be the most promising strategy for the management of T2DM.
Nutrition Interventions for Pediatric Obesity Prevention: An Umbrella Review of Systematic Reviews
Authors: Rozga Mary , Handu Deepa
Published: December 2023

Nutrition interventions to prevent pediatric obesity can help to establish healthy habits to improve current and future health. The objective of this umbrella review of systematic reviews (SRs) is to examine the impact of obesity prevention interventions with a nutrition component on body mass index measures, overweight/obesity prevalence, and cost-effectiveness in participants 2–17 years old. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods were used, and this umbrella review was registered on PROSPERO (CRD42023443033). Included SRs were required to search ≥2 databases and to assess the risk of bias (RoB) of primary studies, and they were published 2017–June 2023. Database searches identified 4776 articles, and 31 SRs were included. In all age groups combined, interventions with both nutrition and physical activity were effective and cost-effective in all settings combined, and in the community setting specifically. In children ≤5 years old, interventions in the home and family, community, and healthcare settings demonstrated some efficacy, whereas in children 6–12 years old, school interventions were most effective. Evidence with individuals 13–17 years was limited. The certainty of evidence was generally low due to RoB in included studies, inconsistency, and imprecision. Pediatric obesity prevention interventions with nutrition should be tailored to the developmental stage to ensure appropriateness and efficacy.
The Effects of ESC/ESH-Based Written Generic Lifestyle Advice and a Nutraceutical on 24-Hour Blood Pressure in Patients with High–Normal Office Blood Pressure and Low–Moderate Cardiovascular Risk
Authors: Landolfo Matteo , Spannella Francesco , Poliseno Chiara , Massacesi Adriano , Giulietti Federico , Festa Roberto , Cavazzin Enrico , Sasso Giulio , Mazza Alberto , Sarzani Riccardo
Published: December 2023

(1) Background: Lifestyle changes, eventually coupled with a nutraceutical, are recommended strategies for managing high–normal blood pressure (BP) patients with low–moderate cardiovascular (CV) risk. In a real-life clinical setting, we evaluated the effects of generic written lifestyle advice, extrapolated from the 2018 ESC/ESH guidelines, and a beetroot-based nutraceutical on 24 h BP in a population with a high–normal office BP and low–moderate CV risk. (2) Methods: A longitudinal observational study was conducted in two ESH Hypertension Excellence Centres on 43 consecutive subjects with high–normal BP according to repeated office BP (OBP) measurements and a low–moderate CV risk based on SCORE2/SCORE2-OP. Additionally, 24 h ambulatory BP monitoring (ABPM) was carried out at baseline and three months after lifestyle changes, according to generic written advice from the 2018 ESC/ESH guidelines, coupled with a nutraceutical containing 500 mg of dry beetroot extract. (3) Results: The mean age was 50 ± 11 years, with male prevalence (54%). The prevalence of overweight/obesity was 58%. The mean OBP was 135 ± 3/85 ± 3 mmHg. At baseline, the mean 24 h BP, daytime BP, and night-time BP were 127 ± 7/80 ± 6 mmHg, 131 ± 8/83 ± 6 mmHg, and 118 ± 8/70 ± 5 mmHg, respectively, BP profiles compatible with hypertension status in some subjects. After a median follow-up of 98 (92–121) days, all BPs, except night-time diastolic BP, were significantly decreased: −3 ± 6/−2 ± 4 mmHg for 24 h BP, −3.9 ± 6.0/−3.0 ± 4.0 mmHg for daytime BP, and −3.3 ± 7.4/−1.3 ± 4.7 mmHg for night-time BP, respectively. No significant clinical changes in body weight were detected. BP decreased independently of baseline BP levels, sex, smoking status, and body mass index, while a more substantial BP decrease was observed in older patients. (4) Conclusions: Our exploratory study shows, for the first time, that written generic lifestyle advice taken from the ESC/ESH hypertension guidelines coupled with a beetroot-based nutraceutical may represent a valid initial non-pharmacological approach in subjects with a high–normal office BP and low–moderate CV risk, even without personalized diet interventions.
Differential Immune Responses and Underlying Mechanisms of Metabolic Reprogramming in Smooth and Rough Variants of Mycobacterium peregrinum Infections
Authors: Lee Ji Won , Kim Ho Won , Yu A-Reum , Yoon Hoe Sun , Kang Minji , Park Hwan-Woo , Lee Sung Ki , Whang Jake , Kim Jong-Seok
Published: December 2023

Mycobacterium peregrinum (Mpgm) is a rapidly growing mycobacteria that is classified as a nontuberculous mycobacterium (NTM) and is commonly found in environmental sources such as soil, water, and animals. Mpgm is considered an opportunistic pathogen that causes infection in immunocompromised individuals or those with underlying medical conditions. Although there have been clinical reports on Mpgm, reports of the immune response and metabolic reprogramming have not been published. Thus, we studied standard Mpgm-ATCC and two clinical strains (Mpgm-S and Mpgm-R) using macrophages and mouse bone marrow-derived cells. Mpgm has two types of colony morphologies: smooth and rough. We grew all strains on the 7H10 agar medium to visually validate the morphology. Cytokine levels were measured via ELISA and real-time PCR. The changes in mitochondrial function and glycolysis in Mpgm-infected macrophages were measured using an extracellular flux analyzer. Mpgm-S-infected macrophages showed elevated levels of inflammatory cytokines, including interleukin (IL)-6, IL-12p40, and tumor necrosis factor (TNF)-α, compared to Mpgm-ATCC- and Mpgm-R-infected macrophages. Additionally, our findings revealed metabolic changes in Mpgm-ATCC and two clinical strains (Mpgm-S and Mpgm-R) during infection; significant changes were observed in the mitochondrial respiration, extracellular acidification, and the oxygen consumption of BMDMs upon Mpgm-S infection. In summary, within the strains examined, Mpgm-S displayed greater virulence, triggered a heightened immune response, and induced more profound shifts in bioenergetic metabolism than Mpgm-ATCC and Mpgm-R. This study is the first to document distinct immune responses and metabolic reorganization following Mpgm infection. These findings lay a crucial foundation for further investigations into the pathogenesis of Mpgm.
Unveiling the Pain Relief Potential: Harnessing Analgesic Peptides from Animal Venoms
Authors: Pereira Ana Flávia Marques , Cavalcante Joeliton S. , Angstmam Davi Gomes , Almeida Cayo , Soares Gean S. , Pucca Manuela B. , Ferreira Junior Rui Seabra
Published: December 2023

The concept of pain encompasses a complex interplay of sensory and emotional experiences associated with actual or potential tissue damage. Accurately describing and localizing pain, whether acute or chronic, mild or severe, poses a challenge due to its diverse manifestations. Understanding the underlying origins and mechanisms of these pain variations is crucial for effective management and pharmacological interventions. Derived from a wide spectrum of species, including snakes, arthropods, mollusks, and vertebrates, animal venoms have emerged as abundant repositories of potential biomolecules exhibiting analgesic properties across a broad spectrum of pain models. This review focuses on highlighting the most promising venom-derived toxins investigated as potential prototypes for analgesic drugs. The discussion further encompasses research prospects, challenges in advancing analgesics, and the practical application of venom-derived toxins. As the field continues its evolution, tapping into the latent potential of these natural bioactive compounds holds the key to pioneering approaches in pain management and treatment. Therefore, animal toxins present countless possibilities for treating pain caused by different diseases. The development of new analgesic drugs from toxins is one of the directions that therapy must follow, and it seems to be moving forward by recommending the composition of multimodal therapy to combat pain.
Microneedle-Mediated Transdermal Delivery of Genetic Materials, Stem Cells, and Secretome: An Update and Progression
Authors: Nainggolan Avelia Devina Calista , Anjani Qonita Kurnia , Hartrianti Pietradewi , Donnelly Ryan F. , Kurniawan Arief , Ramadon Delly
Published: December 2023

Medical practitioners commonly use oral and parenteral dosage forms to administer drugs to patients. However, these forms have certain drawbacks, particularly concerning patients’ comfort and compliance. Transdermal drug delivery presents a promising solution to address these issues. Nevertheless, the stratum corneum, as the outermost skin layer, can impede drug permeation, especially for macromolecules, genetic materials, stem cells, and secretome. Microneedles, a dosage form for transdermal delivery, offer an alternative approach, particularly for biopharmaceutical products. In this review, the authors will examine the latest research on microneedle formulations designed to deliver genetic materials, stem cells, and their derivatives. Numerous studies have explored different types of microneedles and evaluated their ability to deliver these products using preclinical models. Some of these investigations have compared microneedles with conventional dosage forms, demonstrating their significant potential for advancing the development of biotherapeutics in the future.
Cell Membrane Biomimetic Nano-Delivery Systems for Cancer Therapy
Authors: Xia Zhenxing , Mu Weiwei , Yuan Shijun , Fu Shunli , Liu Yongjun , Zhang Na
Published: December 2023

Nano-delivery systems have demonstrated great promise in the therapy of cancer. However, the therapeutic efficacy of conventional nanomedicines is hindered by the clearance of the blood circulation system and the physiological barriers surrounding the tumor. Inspired by the unique capabilities of cells within the body, such as immune evasion, prolonged circulation, and tumor-targeting, there has been a growing interest in developing cell membrane biomimetic nanomedicine delivery systems. Cell membrane modification on nanoparticle surfaces can prolong circulation time, activate tumor-targeting, and ultimately improve the efficacy of cancer treatment. It shows excellent development potential. This review will focus on the advancements in various cell membrane nano-drug delivery systems for cancer therapy and the obstacles encountered during clinical implementation. It is hoped that such discussions will inspire the development of cell membrane biomimetic nanomedical systems.
IDF-11774 Induces Cell Cycle Arrest and Apoptosis by Inhibiting HIF-1α in Gastric Cancer
Authors: Kim Won-Ho , Kim Min-Jee , Jin Jun-O , Lee Peter C. W.
Published: December 2023

Hypoxia-inducible factor-1 alpha (HIF-1α) is a regulatory factor of intracellular oxygen supersession. The expression or increased activity of HIF-1α is closely related to various human cancers. Previously, IDF-11774 was demonstrated to inhibit HSP70 chaperone activity and suppress the accumulation of HIF-1α. In this study, we aimed to determine the effects of IDF-11774 on gastric cancer cell lines. Treatment with IDF-11774 was found to markedly decrease the proliferation, migration, and invasion of the gastric cancer cell lines. Furthermore, the phosphorylation levels of extracellular signal-regulated kinase 1/2, p38, and Jun N-terminal kinase in the mitogen-activated protein kinase signaling pathways were markedly increased in a dose-dependent manner, ultimately promoting apoptosis via the induction of cell cycle arrest. Our findings indicate that HIF-1α inhibitors are potent drugs for the treatment of gastric cancer.
The Efficacy and Safety of Intranasal Formulations of Ketamine and Esketamine for the Treatment of Major Depressive Disorder: A Systematic Review
Authors: Boudieu Ludivine , Mennetrier Myriam , Llorca Pierre-Michel , Samalin Ludovic
Published: December 2023

Ketamine and its enantiomers represent an innovative glutamatergic agent as a treatment for individuals with treatment-resistant depression (TRD) and major depressive disorder (MDD) with suicidal ideation and behavior. Intranasal (IN) formulations could allow for quick onset of action on depressive symptoms as well as a reduction in side effects by bypassing the blood–brain barrier compared with administration via the intravenous route. The aim of this review was to provide an up-to-date analysis of the data on the efficacy and safety of IN ketamine and IN esketamine for the treatment of MDD. A systematic review following PRISMA guidelines was conducted. Databases (PubMed, Embase, MEDLINE, PsycINFO, and Google Scholar) were searched to capture articles about IN ketamine or IN esketamine for MDD. This systematic review highlighted the interest in IN routes of ketamine and esketamine for MDD patients with TRD or active suicidal ideation. They provide a rapid onset of antidepressant action within the first hours after administration. Nevertheless, the evidence of efficacy is stronger for IN esketamine than for IN ketamine in MDD patients. The safety profile appears to be acceptable for IN esketamine but requires further studies, and a more accurate IN delivery device is required for ketamine.
Fusarium Wilt Invasion Results in a Strong Impact on Strawberry Microbiomes
Authors: Yang Hongjun , Zhang Xu , Qiu Xiaohong , Chen Jiajia , Wang Yuanhua , Zhang Geng , Jia Sizhen , Shen Xiangqi , Ye Wenwu , Yan Zhiming
Published: December 2023

Plant-endophytic microbes affect plant growth, development, nutrition, and resistance to pathogens. However, how endophytic microbial communities change in different strawberry plant compartments after Fusarium pathogen infection has remained elusive. In this study, 16S and internal transcribed spacer rRNA amplicon sequencing were used to systematically investigate changes in the bacterial and fungal diversity and composition in the endophytic compartments (roots, stems, and leaves) of healthy strawberries and strawberries with Fusarium wilt, respectively. The analysis of the diversity, structure, and composition of the bacterial and fungal communities revealed a strong effect of pathogen invasion on the endophytic communities. The bacterial and fungal community diversity was lower in the Fusarium-infected endophytic compartments than in the healthy samples. The relative abundance of certain bacterial and fungal genera also changed after Fusarium wilt infection. The relative abundance of the beneficial bacterial genera Bacillus, Bradyrhizobium, Methylophilus, Sphingobium, Lactobacillus, and Streptomyces, as well as fungal genera Acremonium, Penicillium, Talaromyces, and Trichoderma, were higher in the healthy samples than in the Fusarium wilt samples. The relative abundance of Fusarium in the infected samples was significantly higher than that in the healthy samples, consistent with the field observations and culture isolation results for strawberry wilt. Our findings provide a theoretical basis for the isolation, identification, and control of strawberry wilt disease.
Ag2O-Containing Biocidal Interpolyelectrolyte Complexes on Glass Surfaces—Adhesive Properties of the Coatings
Authors: Pigareva Vladislava A. , Paltsev Oleg S. , Marina Valeria I. , Lukianov Dmitrii A. , Moiseenko Andrei V. , Shchelkunov Nikita M. , Fedyanin Andrey A. , Sybachin Andrey V.
Published: December 2023

Biocidal coatings are of great interest to the healthcare system. In this work, the biocidal activity of coatings based on a complex biocide containing polymer and inorganic active antibacterial components was studied. Silver oxide was distributed in a matrix of a positively charged interpolyelectrolyte complex (IPEC) of polydiallyldimethylammonium chloride (PDADMAC) and sodium polystyrene sulfonate (PSS) using ultrasonic dispersion, forming nanoparticles with an average size of 5–6 nm. The formed nanoparticles in the matrix are not subject to agglomeration and changes in morphology during storage. It was found that the inclusion of silver oxide in a positively charged IPEC allows a more than 4-fold increase in the effectiveness of the complex biocide against E. coli K12 in comparison with the biocidal effect of PDADMAC and IPEC. Polycation, IPEC, and the IPEC/Ag2O ternary complex form coatings on the glass surface due to electrostatic adsorption. Adhesive and cohesive forces in the resulting coatings were studied with micron-scale coatings using dynamometry. It was found that the stability of the coating is determined primarily by adhesive interactions. At the macro level, it is not possible to reliably identify the role of IPEC formation in adhesion. On the other hand, use of the optical tweezers method makes it possible to analyze macromolecules at the submicron scale and to evaluate the multiple increase in adhesive forces when forming a coating from IPEC compared to coatings from PDADMAC. Thus, the application of ternary IPEC/Ag2O complexes makes it possible to obtain coatings with increased antibacterial action and improved adhesive characteristics.
Conversion of Waste Expanded Polystyrene into Blue-Emitting Polymer Film for Light-Emitting Diode Applications
Authors: Su Huanyou , Lin Hua , Li Pengfei , Li Bowen , Xu Xiaodong , Li Jiacheng , Wu Yuanquan , Hui Jiaqi , Liu Dan
Published: December 2023

The wide range of applications and continuous demand for plastics is causing serious global environmental problems. Massive discharges of expanded polystyrene (EPS) are thought to be primarily responsible for the increased white pollution. Waste EPS has received wide attention in the development of innovative products. White light-emitting diodes pumped by a near-UV chip (n-UV WLEDs) are regarded as a very promising solid-state lighting. The performance of the n-UV WLED is largely determined by the properties of the tricolor luminescence materials. In this work, a blue-emitting polymer film for n-UV WLED applications was developed from waste EPS. First, using waste EPS as a raw material, benzimidazole groups were bonded to PS benzene rings by chemical reactions to obtain modified PS (PS-PBI). Then, a film based on PS-PBI was prepared by a simple solution drop-casting method. The PS-PBI film can emit intense blue light when irradiated with 365 nm light. An n-UV WLED pumped by a 365 nm UV chip was fabricated using PS-PBI film as the blue-emitting layer. The fabricated n-UV WLED shows excellent luminescence properties, such as a bright white light with color coordinates of (0.337, 0.331), a relatively low color temperature (CCT, 5270 K), and an especially high color rendering index (CRI, 93.6). The results prove that the blue-emitting PS-PBI film prepared from waste EPS is a very promising candidate for n-UV WLED applications. The strategy of converting waste EPS into a high-value-added blue-emitting film in this work provides a convenient and feasible approach for upcycling waste EPS, achieving significant environmental and economic benefits.