bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Humoral Immuno-Inflammatory Pathways Associated with Respiratory Failure in COVID-19 Patients
Authors: Regolo Matteo , Sorce Alessandra , Vaccaro Mauro , Colaci Michele , Stancanelli Benedetta , Natoli Giuseppe , Motta Massimo , Isaia Ivan , Castelletti Federica , Giangreco Federica , Fichera Daniela , Aparo Paola , Lanzafame Alessandra , Russo Mario , Santangelo Nicola , Noto Paola , Malatino Lorenzo
Published: June 2023

All severe cases of SARS-CoV-2 infections are characterized by a high risk of disease progression towards ARDS, leading to a bad outcome. Respiratory symptoms in COVID-19 patients often do not correspond to disease’s worsening. In our sample, median age was 74 years (72–75) and 54% were men. The median period of hospitalization was 9 days. Firstly, we observed a significant asynchronous trend of neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) in 764 selected among 963 patients, who were consecutively recruited in two hospitals (Cannizzaro, S. Marco) in Catania, Italy. NLR values in deceased patients showed an increase from baseline over time. By contrast, CRP tended to fall from baseline to median day of hospitalization in all three subgroups, but steeply increased at the end of hospitalization only in ICU-admitted patients. Then, we evaluated the relationships between NLR and CRP as continuous variables with PaO2/FiO2 ratio (P/F). NLR was an independent predictor of mortality (HR: 1.77, p < 0.0001), while ICU admission was more significantly associated with CRP (HR: 1.70, p < 0.0001). Finally, age, neutrophils, CRP, and lymphocytes are significantly and directly linked to P/F, while the influence of inflammation on P/F, reflected by CRP, was also mediated by neutrophils.
The Correlation of Sleep Disturbance and Location of Glioma Tumors: A Narrative Review
Authors: Allgood JuliAnne E. , Roe Avery , Sparks Bridger B. , Castillo Mercedes , Cruz Angel , Brooks Amanda E. , Brooks Benjamin D.
Published: June 2023

Sleep disturbance can occur when sleep centers of the brain, regions that are responsible for coordinating and generating healthy amounts of sleep, are disrupted by glioma growth or surgical resection. Several disorders cause disruptions to the average duration, quality, or patterns of sleep, resulting in sleep disturbance. It is unknown whether specific sleep disorders can be reliably correlated with glioma growth, but there are sufficient numbers of case reports to suggest that a connection is possible. In this manuscript, these case reports and retrospective chart reviews are considered in the context of the current primary literature on sleep disturbance and glioma diagnosis to identify a new and useful connection which warrants further systematic and scientific examination in preclinical animal models. Confirmation of the relationship between disruption of the sleep centers in the brain and glioma location could have significant implications for diagnostics, treatment, monitoring of metastasis/recurrence, and end-of-life considerations.
Serum and Bronchoalveolar Lavage Fluid Levels of Cytokines in Patients with Lung Cancer and Chronic Lung Disease: A Prospective Comparative Study
Authors: Hogea Patricia , Tudorache Emanuela , Fira-Mladinescu Ovidiu , Marc Monica , Velescu Diana , Manolescu Diana , Bratosin Felix , Rosca Ovidiu , Mavrea Adelina , Oancea Cristian
Published: June 2023

The role of chronic inflammation in the initiation and progression of carcinogenesis has been well-established in previous studies, particularly in the stages of malignant conversion, invasion, and metastasis. This study aimed to explore the potential correlation between the levels of cytokines in serum and bronchoalveolar lavage fluid (BALF) by comparing their levels between patients with lung cancer and those with benign lung diseases. The study measured the concentration of IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-10, and IL-12p70, in venous blood and BALF of a total of 33 patients with lung cancer and 33 patients with benign lung diseases. Significant differences were found between the two groups in various clinical parameters. The cytokine levels were significantly higher among patients with malignant disease, while the BALF analysis revealed higher cytokine levels compared with serum analysis. It was discovered that the levels of cancer-specific cytokines in the lavage fluid increased significantly sooner and were present at a greater concentration than those in the peripheral blood. After one month of treatment, the serum markers decreased significantly but slower in the lavage fluid. The differences between serum and BALF markers remained significant. It was observed that the highest correlation was among IL-6 (serum) and IL-6 (lavage), with a coefficient of 0.774 (p-value < 0.001), and IL-1 (serum) and IL-1β (lavage), with a coefficient value of 0.610 (p-value < 0.001). Other significant correlations among serum and lavage cytokines were observed between IL-6 (lavage) and IL-1 (serum) (rho = 0.631, p-value < 0.001) and CRP (rho = 0.428, p-value = 0.001), respectively. This study revealed significant differences and correlations in clinical parameters, serum markers, and BALF inflammatory markers between patients with lung cancer and those with benign lung pathologies. The results highlight the importance of understanding the inflammatory profiles of these conditions and could contribute to the development of targeted therapies or diagnostic approaches in the future. Further research is needed to validate these findings, explore their implications for clinical practice, and determine the diagnostic and prognostic value of these cytokines for lung cancer.
Creation and Evaluation of a Severity Classification of Hyperkyphosis and Hypolordosis for Exercise Therapy
Authors: Kaps David , Siebers Hannah , Betz Ulrich , Pfirrmann Daniel , Eschweiler Jörg , Hildebrand Frank , Betsch Marcel , Huthwelker Janine , Wolf Claudia , Drees Philipp , Konradi Jürgen
Published: June 2023

The rise in the occurrence of musculoskeletal disorders, such as thoracic hyperkyphosis (THK) or lumbar hypolordosis (LHL), is a result of demographic changes. Exercise therapy is an effective approach that can reduce related disabilities and costs. To ensure successful therapy, an individualized exercise program adapted to the severity of the disorder is expedient. Nevertheless, appropriate classification systems are scarce. This project aimed to develop and evaluate a severity classification focused on exercise therapy for patients with THK or LHL. A multilevel severity classification was developed and evaluated by means of an online survey. Reference limits of spinal shape angles were established by data from video rasterstereography of 201 healthy participants. A mean kyphosis angle of 50.03° and an average lordosis angle of 40.72° were calculated as healthy references. The strength of the multilevel classification consisting of the combination of subjective pain and objective spinal shape factors was confirmed by the survey (70% agreement). In particular, the included pain parameters were considered relevant by 78% of the experts. Even though the results of the survey provide important evidence for further analyses and optimization options of the classification system, the current version is still acceptable as therapeutic support.
Pharmacological Properties of Chemically Characterized Extracts from Mastic Tree: In Vitro and In Silico Assays
Authors: Ouahabi Safae , Loukili El Hassania , Elbouzidi Amine , Taibi Mohamed , Bouslamti Mohammed , Nafidi Hiba-Allah , Salamatullah Ahmad Mohammad , Saidi Nezha , Bellaouchi Reda , Addi Mohamed , Ramdani Mohamed , Bourhia Mohammed , Hammouti Belkheir
Published: June 2023

The mastic tree, scientifically known as Pistacia lentiscus, which belongs to the Anacardiaceae family, was used in this study. The aim of this research was to analyze the chemical composition of this plant and assess its antioxidant and antibacterial properties using both laboratory experiments and computer simulations through molecular docking, a method that predicts the binding strength of a small molecule to a protein. The soxhlet method (SE) was employed to extract substances from the leaves of P. lentiscus found in the eastern region of Morocco. Hexane and methanol were the solvents used for the extraction process. The n-hexane extract was subjected to gas chromatography-mass spectrometry (GC/MS) to identify its fatty acid content. The methanolic extract underwent high-performance liquid chromatography with a diode-array detector (HPLC-DAD) to determine the presence of phenolic compounds. Antioxidant activity was assessed using the DPPH spectrophotometric test. The findings revealed that the main components in the n-hexane extract were linoleic acid (40.97 ± 0.33%), oleic acid (23.69 ± 0.12%), and palmitic acid (22.83 ± 0.10%). Catechin (37.05 ± 0.15%) was identified as the predominant compound in the methanolic extract through HPLC analysis. The methanolic extract exhibited significant DPPH radical scavenging, with an IC50 value of 0.26 ± 0.14 mg/mL. The antibacterial activity was tested against Staphylococcus aureus, Listeria innocua, and Escherichia coli, while the antifungal activity was evaluated against Geotrichum candidum and Rhodotorula glutinis. The P. lentiscus extract demonstrated notable antimicrobial effects. Additionally, apart from molecular docking, other important factors, such as drug similarity, drug metabolism and distribution within the body, potential adverse effects, and impact on bodily systems, were considered for the substances derived from P. lentiscus. Scientific algorithms, such as Prediction of Activity Spectra for Substances (PASS), Absorption, Distribution, Metabolism, Excretion (ADME), and Pro-Tox II, were utilized for this assessment. The results obtained from this research support the traditional medicinal usage of P. lentiscus and suggest its potential for drug development.
rSO2 Measurement Using NIRS for Lower-Limb Blood Flow Monitoring and Estimation of Safe Balloon Occlusion/Deflation Time in Patients with PAS Who Underwent PBOA during CS
Authors: Tokue Hiroyuki , Tokue Azusa , Tsushima Yoshito
Published: June 2023

We examined the utility of regional oxygen saturation (rSO2) measurement using near-infrared spectroscopy (NIRS) for monitoring lower-limb blood flow and estimate the safe balloon occlusion/deflation time in patients with PAS who underwent prophylactic balloon occlusion of the abdominal artery (PBOA) during cesarean section (CS). During CS, the NIRS probes were positioned on either of the anterior tibial muscles. rSO2 was measured continuously during balloon occlusion/deflation. A cycle consisted of inflating the aortic balloon for 30 min and deflating it for 5 min. The rSO2 before/during balloon occlusion and after 5 min of balloon deflation were evaluated. Sixty-two lower limbs (fifteen women and data from 31 sessions of balloon inflation/deflation) were evaluated. rSO2 during balloon occlusion was significantly lower than rSO2 before balloon occlusion (57.9% ± 9.6% vs. 80.3% ± 6.0%; p < 0.01). There were no significant differences between rSO2 before balloon occlusion and rSO2 after 5 min of balloon deflation (80.3% ± 6.0% vs. 78.7% ± 6.6%; p = 0.07). Postoperatively, the lower limbs showed no ischemic symptoms. NIRS can assess lower-limb rSO2 during PBOA for PAS in real time to determine ischemia severity, duration, and recovery capacity.
Dual-Band and Wideband Bandpass Filters Using Coupled Lines and Tri-Stepped Impedance Stubs
Authors: Alazemi Abdullah J.
Published: June 2023

In this paper, two bandpass filters—one with a dual-band response and the other with a wideband response—were designed, implemented, and experimented with. The filters are based on the novel combination of series coupled lines and tri-stepped impedance stubs. However, coupled lines along with tri-stepped impedance open stubs (TSIOSs) give a third-order dual passband response. The advantage of dual-band filters using coupled lines and TSIOSs is that they have wide passbands that are close together and separated by a single transmission zero. In contrast, the inclusion of tri-stepped impedance short-circuited stubs (TSISSs) instead of TSIOSs provides a fifth-order wide passband response. The advantage of wideband bandpass filters using coupled lines and TSISSs is that they have a very good selectivity factor. Theoretical analysis was carried out to validate both filter configurations. The tested bandpass filter using coupled lines and TSIOS units had two close wide passbands operating at 0.92 and 1.52 GHz center frequencies, respectively. The dual-band bandpass filter was implemented to operate in GSM and GPS applications. The first passband had a 3 dB fractional bandwidth (FBW) of 38.04%, while the second passband had a 3 dB FBW of 22.36%. The experimental result of the wideband bandpass filter (with coupled lines and TSISS units) had a center frequency of 1.51 GHz with a 3 dB fractional bandwidth of 62.91% and a selectivity factor of 0.90. A good congruence was demonstrated between the full-wave simulated and tested results for both filters.
Three-Dimensional Integrated Fan-Out Wafer-Level Package Micro-Bump Electromigration Study
Authors: Tian Wenchao , Gao Ran , Gu Lin , Ji Haoyue , Zhou Liming
Published: June 2023

To meet the demands for miniaturization and multi-functional and high-performance electronics applications, the semiconductor industry has shifted its packaging approach to multi-chip vertical stacking. Among the advanced packaging technologies for high-density interconnects, the most persistent factor affecting their reliability is the electromigration (EM) problem on the micro-bump. The operating temperature and the operating current density are the main factors affecting the EM phenomenon. Therefore, when a micro-bump structure is in the electrothermal environment, the EM failure mechanism of the high-density integrated packaging structure must be studied. To investigate the relationship between loading conditions and EM failure time in micro-bump structures, this study established an equivalent model of the vertical stacking structure of fan-out wafer-level packages. Then, the electrothermal interaction theory was used to carry out numerical simulations in an electrothermal environment. Finally, the MTTF equation was invoked, with Sn63Pb37 as the bump material, and the relationship between the operating environment and EM lifetime was investigated. The results showed that the current aggregation was the location where the bump structure was most susceptible to EM failure. The accelerating effect of the temperature on the EM failure time was more obvious at a current density of 3.5 A/cm2, which was 27.51% shorter than 4.5 A/cm2 at the same temperature difference. When the current density exceeded 4.5 A/cm2, the change in the failure time was not obvious, and the maximum critical value of the micro-bump failure was 4 A/cm2~4.5 A/cm2.
Sodium Storage Properties of Carbonaceous Flowers
Authors: Sun Xiaolei , Luo Feng
Published: June 2023

As a promising energy storage system, sodium-ion batteries face challenges related to the stability and high-rate capability of their electrode materials, especially carbon, which is the most studied anode. Previous studies have demonstrated that three-dimensional architectures composed of porous carbon materials with high electrical conductivity have the potential to enhance the storage performance of sodium-ion batteries. Here, high-level N/O heteroatoms-doped carbonaceous flowers with hierarchical pore architecture are synthesized through the direct pyrolysis of homemade bipyridine-coordinated polymers. The carbonaceous flowers could provide effective transport pathways for electrons/ions, thus allowing for extraordinary storage properties in sodium-ion batteries. As a consequence, sodium-ion battery anodes made of carbonaceous flowers exhibit outstanding electrochemical features, such as high reversible capacity (329 mAh g−1 at 30 mA g−1), superior rate capability (94 mAh g−1 at 5000 mA g−1), and ultralong cycle lifetimes (capacity retention rate of 89.4% after 1300 cycles at 200 mA g−1). To better investigate the sodium insertion/extraction-related electrochemical processes, the cycled anodes are experimentally analyzed with scanning electron microscopy and transmission electron microscopy. The feasibility of the carbonaceous flowers as anode materials was further investigated using a commercial Na3V2(PO4)3 cathode for sodium-ion full batteries. All these findings indicate that carbonaceous flowers may possess great potential as advanced materials for next-generation energy storage applications.
Peripheralization Strategies Applied to Morphinans and Implications for Improved Treatment of Pain
Authors: Schmidhammer Helmut , Al-Khrasani Mahmoud , Fürst Susanna , Spetea Mariana
Published: June 2023

Opioids are considered the most effective analgesics for the treatment of moderate to severe acute and chronic pain. However, the inadequate benefit/risk ratio of currently available opioids, together with the current ‘opioid crisis’, warrant consideration on new opioid analgesic discovery strategies. Targeting peripheral opioid receptors as effective means of treating pain and avoiding the centrally mediated side effects represents a research area of substantial and continuous attention. Among clinically used analgesics, opioids from the class of morphinans (i.e., morphine and structurally related analogues) are of utmost clinical importance as analgesic drugs activating the mu-opioid receptor. In this review, we focus on peripheralization strategies applied to N-methylmorphinans to limit their ability to cross the blood–brain barrier, thus minimizing central exposure and the associated undesired side effects. Chemical modifications to the morphinan scaffold to increase hydrophilicity of known and new opioids, and nanocarrier-based approaches to selectively deliver opioids, such as morphine, to the peripheral tissue are discussed. The preclinical and clinical research activities have allowed for the characterization of a variety of compounds that show low central nervous system penetration, and therefore an improved side effect profile, yet maintaining the desired opioid-related antinociceptive activity. Such peripheral opioid analgesics may represent alternatives to presently available drugs for an efficient and safer pain therapy.
The Residue and Dietary Risk Assessment of Spirotetramat and Its Four Metabolites in Cabbage Using Ultra-High-Performance Liquid Chromatography–Tandem Mass Spectrometry
Authors: Cao Junli , Li Jindong , Ren Pengcheng , Qi Yanli , Qin Shu
Published: June 2023

Spirotetramat is a potential tetronic acid pesticide for controlling various pests with piercing–sucking mouthparts. To clarify its dietary risk on cabbage, we established an ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method and then investigated the residual levels of spirotetramat and its four metabolites in cabbage collected from field experiments under good agricultural practices (GAPs). The average recoveries of spirotetramat and its metabolites in cabbage were 74~110%, while the relative standard deviation (RSD) was 1~6%, and the limit of quantitation (LOQ) was 0.01 mg kg−1. The terminal residue of spirotetramat was in the range of <0.05~0.33 mg kg−1, the chronic dietary risk (RQc) was 17.56%, and the acute dietary risk (RQa) was 0.025~0.049%, which means an acceptable dietary intake risk. This study provides data to guide on the use of spirotetramat and to establish the maximum residue limits (MRLs) of spirotetramat on cabbage.
Identification Mechanism of BACE1 on Inhibitors Probed by Using Multiple Separate Molecular Dynamics Simulations and Comparative Calculations of Binding Free Energies
Authors: Wang Yiwen , Yang Fen , Yan Dongliang , Zeng Yalin , Wei Benzheng , Chen Jianzhong , He Weikai
Published: June 2023

β-amyloid cleaving enzyme 1 (BACE1) is regarded as an important target of drug design toward the treatment of Alzheimer’s disease (AD). In this study, three separate molecular dynamics (MD) simulations and calculations of binding free energies were carried out to comparatively determine the identification mechanism of BACE1 for three inhibitors, 60W, 954 and 60X. The analyses of MD trajectories indicated that the presence of three inhibitors influences the structural stability, flexibility and internal dynamics of BACE1. Binding free energies calculated by using solvated interaction energy (SIE) and molecular mechanics generalized Born surface area (MM-GBSA) methods reveal that the hydrophobic interactions provide decisive forces for inhibitor–BACE1 binding. The calculations of residue-based free energy decomposition suggest that the sidechains of residues L91, D93, S96, V130, Q134, W137, F169 and I179 play key roles in inhibitor–BACE1 binding, which provides a direction for future drug design toward the treatment of AD.
Synthesis of a Cyclooctapeptide, Cyclopurpuracin, and Evaluation of Its Antimicrobial Activity
Authors: Maharani Rani , Yayat Hasna Noer Agus , Hidayat Ace Tatang , Al Anshori Jamaludin , Sumiarsa Dadan , Farabi Kindi , Mayanti Tri , Nurlelasari  , Harneti Desi , Supratman Unang
Published: June 2023

Cyclopurpuracin is a cyclooctapeptide isolated from the methanol extract of Annona purpurea seeds with a sequence of cyclo-Gly-Phe-Ile-Gly-Ser-Pro-Val-Pro. In our previous study, the cyclisation of linear cyclopurpuracin was problematic; however, the reversed version was successfully cyclised even though the NMR spectra revealed the presence of a mixture of conformers. Herein, we report the successful synthesis of cyclopurpuracin using a combination of solid- and solution-phase synthetic methods. Initially, two precursors of cyclopurpuracin were prepared, precursor linear A (NH2-Gly-Phe-Ile-Gly-Ser(t-Bu)-Pro-Val-Pro-OH) and precursor linear B (NH-Pro-Gly-Phe-Ile-Gly-Ser(t-Bu)-Pro-Val-OH, and various coupling reagents and solvents were trialled to achieve successful synthesis. The final product was obtained when precursors A and B were cyclised using the PyBOP/NaCl method, resulting in a cyclic product with overall yields of 3.2% and 3.6%, respectively. The synthetic products were characterised by HR-ToF-MS, 1H-NMR, and 13C-NMR, showing similar NMR profiles to the isolated product from nature and no conformer mixture. The antimicrobial activity of cyclopurpuracin was also evaluated for the first time against S. aureus, E. coli, and C. albicans, showing weak activity with MIC values of 1000 µg/mL for both synthetic products, whereas the reversed cyclopurpuracin was more effective with an MIC of 500 µg/mL.
Variation in the Main Health-Promoting Compounds and Antioxidant Capacity of Three Leafy Vegetables in Southwest China
Authors: Zhang Yi , Huang Wenli , Zhang Chenlu , Huang Huanhuan , Yang Shihan , Wang Yiqing , Huang Zhi , Tang Yi , Li Xiaomei , Lian Huashan , Li Huanxiu , Zhang Fen , Sun Bo
Published: June 2023

Malabar spinach (Basella alba), amaranth (Amaranthus tricolor), and sweet potato (Ipomoea batatas) are leafy vegetables found in Southwest China. The variation of chlorophyll, carotenoids, ascorbic acid, total flavonoids, phenolic compounds, and antioxidant capacity was studied in the leaves and stems of the three vegetables. The content of main health-promoting compounds and the antioxidant capacity in the leaves were higher than that in the stems, indicating that the leaves of the three vegetables possess greater nutritional value. The trend of total flavonoids in all three vegetables was similar to the trend of antioxidant capacity, suggesting that the total flavonoids may be the major antioxidants wihin these vegetables. Eight individual phenolic compounds were detected in three different vegetables. The most abundant levels of individual phenolic compounds in the leaves and stems of malabar spinach, amaranth, and sweet potato were 6′-O-feruloyl-d-sucrose (9.04 and 2.03 mg g−1 DW), hydroxyferulic acid (10.14 and 0.73 mg g−1 DW), and isorhamnetin-7-O-glucoside (34.93 and 6.76 mg g−1 DW), respectively. Sweet potato exhibited a higher total and individual phenolic compound content compared to malabar spinach and amaranth. Overall, the results demonstrate that the three leafy vegetables possess high nutritional value, and could be used not only for consumption but also in various other fields, including medicine and chemistry.
Differential Mobility Spectrometry-Tandem Mass Spectrometry with Multiple Ion Monitoring Coupled with in Source-Collision Induced Dissociation: A New Strategy for the Quantitative Analysis of Pharmaceutical Polymer Excipients in Rat Plasma
Authors: Zhang Yuyao , Zhang Zhi , Liu Yingze , Cai Deqi , Gu Jingkai , Sun Dong
Published: June 2023

Polylactic acids (PLAs) are synthetic polymers composed of repeating lactic acid subunits. For their good biocompatibility, PLAs have been approved and widely applied as pharmaceutical excipients and scaffold materials. Liquid chromatography-tandem mass spectrometry is a powerful analytical tool not only for pharmaceutical ingredients but also for pharmaceutical excipients. However, the characterization of PLAs presents particular problems for mass spectrometry techniques. In addition to their high molecular weights and wide polydispersity, multiple charging and various adductions are intrinsic features of electrospray ionization. In the present study, a strategy combining of differential mobility spectrometry (DMS), multiple ion monitoring (MIM) and in-source collision-induced dissociation (in source-CID) has been developed and applied to the characterization and quantitation of PLAs in rat plasma. First, PLAs will be fragmented into characteristic fragment ions under high declustering potential in the ionization source. The specific fragment ions are then screened twice by quadrupoles to ensure a high signal intensity and low interference for mass spectrometry detection. Subsequently, DMS technique has been applied to further reduce the background noise. The appropriately chosen surrogate specific precursor ions could be utilized for the qualitative and quantitative analysis of PLAs, which provided results with the advantages of low endogenous interference, sufficient sensitivity and selectivity for bioassay. The linearity of the method was evaluated over the concentration range 3–100 μg/mL (r2 = 0.996) for PLA 20,000. The LC-DMS-MIM coupled with in source-CID strategy may contribute to the pharmaceutical studies of PLAs and the possible prospects of other pharmaceutical excipients.
Comparative Study of Thermal and Plasma-Enhanced Atomic Layer Deposition of Iron Oxide Using Bis(N,N′-di-butylacetamidinato)iron(II)
Authors: Choi Boyun , Park Gun-Woo , Jeong Jong-Ryul , Jeon Nari
Published: June 2023

Only a few iron precursors that can be used in the atomic layer deposition (ALD) of iron oxides have been examined thus far. This study aimed to compare the various properties of FeOx thin films deposited using thermal ALD and plasma-enhanced ALD (PEALD) and to evaluate the advantages and disadvantages of using bis(N,N′-di-butylacetamidinato)iron(II) as an Fe precursor in FeOx ALD. The PEALD of FeOx films using iron bisamidinate has not yet been reported. Compared with thermal ALD films, PEALD films exhibited improved properties in terms of surface roughness, film density, and crystallinity after they were annealed in air at 500 °C. The annealed films, which had thicknesses exceeding ~ 9 nm, exhibited hematite crystal structures. Additionally, the conformality of the ALD-grown films was examined using trench-structured wafers with different aspect ratios.
Constructing Randomly Lamellar HKUST–1@Clinoptilolite through Polyethylene Glycol—Assisted Hydrothermal Method and Coordinated Complexation for Enhanced Adsorptive Separation for CO2 and CH4
Authors: Zhang Mingxuan , Zhou Jiawei , Wan Chunlei , Liu Ming , Wu Xia , Sun Jihong
Published: June 2023

Clinoptilolite (CP) was successfully synthesized via a hydrothermal route in the presence of polyethylene glycol (PEG), and it was then delaminated by washing using Zn2+ containing acid. HKUST-1, as one kind of the Cu-based MOFs, showed a high CO2 adsorption capacity owing to its large pore volume and specific surface area. In the present work, we selected one of the most efficient ways for preparing the HKUST-1@CP compounds via coordination between exchanged Cu2+ and ligand (trimesic acid). Their structural and textural properties were characterized by XRD, SAXS, N2 sorption isotherms, SEM, and TG-DSC profiles. Particularly, the effect of the additive PEG (average molecular weight of 600) on the induction (nucleation) periods and growth behaviors were detailed and investigated in the hydrothermal crystallization procedures of synthetic CPs. The corresponding activation energies of induction (En) and growth (Eg) periods during crystallization intervals were calculated. Meanwhile, the pore size of the inter-particles of HKUST-1@CP was 14.16 nm, and the BET specific area and pore volume were 55.2 m2/g and 0.20 cm3/g, respectively. Their CO2 and CH4 adsorption capacities and selectivity were preliminarily explored, showing 0.93 mmol/g for HKUST-1@CP at 298 K with the highest selective factor of 5.87 for CO2/CH4, and the dynamic separation performance was evaluated in column breakthrough experiments. These results suggested an efficient way of preparing zeolites and MOFs composites that is conducive to being a promising adsorbent for applications in gas separation.
Fermented Lettuce Extract Induces Immune Responses through Polarization of Macrophages into the Pro-Inflammatory M1-Subtype
Authors: Kim Bo-Young , Ryu Ji Hyeon , Park Jisu , Ji Byeongjun , Chun Hyun Soo , Kim Min Sun , Shin Yong-Il
Published: June 2023

It has been reported that lettuce and its bioactive compounds enhance the host immune system by acting as immune modulators. This study aimed to identify the immunological effect of fermented lettuce extract (FLE) on macrophages. To evaluate the efficacy of FLE in enhancing macrophage function, we measured and compared the levels of macrophage activation-related markers in FLE- and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Treatment with FLE activated RAW 264.7 macrophages, increased their phagocytic ability, and increased the production of nitric oxide (NO) and pro-inflammatory cytokine levels—similar to LPS. The effects of FLE on M1/M2 macrophage polarization were investigated by determining M1 and M2 macrophage transcript markers in mouse peritoneal macrophages. The FLE-related treatment of peritoneal macrophages enhanced the expression of M1 markers but reduced IL-4 treatment-induced M2 markers. After the generation of tumor-associated macrophages (TAMs), alterations in the levels of M1 and M2 macrophage markers were measured after treatment with FLE. The FLE-related treatment of TAMs increased the expression and production of pro-inflammatory cytokines and also led to the enhanced apoptosis of pancreatic cancer cells. These findings suggest that FLE may be useful for macrophage-targeted cancer therapy because of its ability to regulate the activation and polarization of macrophages in the tumor microenvironment.
Long-Tailed Food Classification
Authors: He Jiangpeng , Lin Luotao , Eicher-Miller Heather , Zhu Fengqing
Published: June 2023

Food classification serves as the basic step of image-based dietary assessment to predict the types of foods in each input image. However, foods in real-world scenarios are typically long-tail distributed, where a small number of food types are consumed more frequently than others, which causes a severe class imbalance issue and hinders the overall performance. In addition, none of the existing long-tailed classification methods focus on food data, which can be more challenging due to the inter-class similarity and intra-class diversity between food images. In this work, two new benchmark datasets for long-tailed food classification are introduced, including Food101-LT and VFN-LT, where the number of samples in VFN-LT exhibits real-world long-tailed food distribution. Then, a novel two-phase framework is proposed to address the problem of class imbalance by (1) undersampling the head classes to remove redundant samples along with maintaining the learned information through knowledge distillation and (2) oversampling the tail classes by performing visually aware data augmentation. By comparing our method with existing state-of-the-art long-tailed classification methods, we show the effectiveness of the proposed framework, which obtains the best performance on both Food101-LT and VFN-LT datasets. The results demonstrate the potential to apply the proposed method to related real-life applications.
Oligomalt, a New Slowly Digestible Carbohydrate, Is Well Tolerated in Healthy Young Men and Women at Intakes Up to 180 Gram per Day: A Randomized, Double-Blind, Crossover Trial
Authors: Johansen Odd Erik , Curti Delphine , von Eynatten Maximilian , Rytz Andreas , Lahiry Anirban , Delodder Frederik , Ufheil Gerhard , D’Urzo Carmine , Orengo Audrey , Thorne Kate , Lerea-Antes Jaclyn S.
Published: June 2023

In this randomized, double-blind triple-crossover study (NCT05142137), the digestive tolerance and safety of a novel, slowly digestible carbohydrate (SDC), oligomalt, an α-1,3/α-1,6-glucan α-glucose-based polymer, was assessed in healthy adults over three separate 7-day periods, comparing a high dose of oligomalt (180 g/day) or a moderate dose of oligomalt (80 g/day in combination with 100 g maltodextrin/day) with maltodextrin (180 g/day), provided as four daily servings in 300 mL of water with a meal. Each period was followed by a one-week washout. A total of 24 subjects (15 females, age 34 years, BMI 22.2 kg/m2, fasting blood glucose 4.9 mmol/L) were recruited, of whom 22 completed the course. The effects on the primary endpoint (the Gastrointestinal Symptom Rating Score (GSRS)) showed a statistically significant dose dependency, albeit of limited clinical relevance, between a high dose of oligomalt and maltodextrin (mean (95% CI) 2.29 [2.04, 2.54] vs. 1.59 [1.34, 1.83], respectively; difference: [−1.01, −0.4], p < 0.0001), driven by the GSRS-subdomains “Indigestion” and “Abdominal pain”. The GSRS difference ameliorated with product exposure, and the GSRS in those who received high-dose oligomalt as their third intervention period was similar to pre-intervention (mean ± standard deviation: 1.6 ± 0.4 and 1.4 ± 0.3, respectively). Oligomalt did not have a clinically meaningful impact on the Bristol Stool Scale, and it did not cause serious adverse events. These results support the use of oligomalt across various doses as an SDC in healthy, normal weight, young adults.
Discovery of a New Chalcone-Trimethoxycinnamide Hybrid with Antimitotic Effect: Design, Synthesis, and Structure—Activity Relationship Studies
Authors: Moreira Joana , Silva Patrícia M. A. , Barros Matilde , Saraiva Lucília , Pinto Madalena , Bousbaa Hassan , Cidade Honorina
Published: June 2023

In this work, the design and synthesis of a new chalcone-trimethoxycinnamide hybrid (7) based on the combination of subunits of two promising antiproliferative compounds (CM-M345 (1) and BP-M345 (2)), previously obtained by our research group, are reported. In order to expand the structure–activity relationship (SAR) knowledge, a new series of 7-analogues was also designed and synthetized. All the compounds were evaluated for their antitumor activity against melanoma (A375-C5), breast adenocarcinoma (MCF-7), and colorectal carcinoma (HCT116) cell lines, as well as non-tumor HPAEpiC cells. Three of the newly synthesized compounds (6, 7, and 13) exhibited potent antiproliferative activity, mainly on colorectal tumor cells (GI50 = 2.66–3.26 μM), showing hybrid 7 selectivity for tumor cells. We performed molecular mechanism studies to evaluate the potential interference of compounds with the p53 pathway, namely, p53–MDM2 interaction and mitosis in HCT116 cells. The antiproliferative activities of compounds were shown to be p53-independent. Compound 7 emerged as an antimitotic agent by inducing the mitotic arrest of colorectal tumor cells, and subsequently, cell death.
Nanotechnology-Based Topical Delivery of Natural Products for the Management of Atopic Dermatitis
Authors: Marques Mário Pedro , Varela Carla , Mendonça Laura , Cabral Célia
Published: June 2023

Atopic dermatitis (AD) is a chronic eczematous inflammatory disease that may arise from environmental, genetic, and immunological factors. Despite the efficacy of current treatment options such as corticosteroids, such approaches are mainly focused on symptom relief and may present certain undesirable side effects. In recent years, isolated natural compounds, oils, mixtures, and/or extracts have gained scientific attention because of their high efficiency and moderate to low toxicity. Despite their promising therapeutic effects, the applicability of such natural healthcare solutions is somewhat limited by their instability, poor solubility, and low bioavailability. Therefore, novel nanoformulation-based systems have been designed to overcome these limitations, thus enhancing the therapeutic potential, by promoting the capacity of these natural drugs to properly exert their action in AD-like skin lesions. To the best of our knowledge, this is the first literature review that has focused on summarizing recent nanoformulation-based solutions loaded with natural ingredients, specifically for the management of AD. We suggest that future studies should focus on robust clinical trials that may confirm the safety and effectiveness of such natural-based nanosystems, thus paving the way for more reliable AD treatments.
T-705-Derived Prodrugs Show High Antiviral Efficacies against a Broad Range of Influenza A Viruses with Synergistic Effects When Combined with Oseltamivir
Authors: Ganter Benedikt , Zickler Martin , Huchting Johanna , Winkler Matthias , Lüttjohann Anna , Meier Chris , Gabriel Gülsah , Beck Sebastian
Published: June 2023

Emerging influenza A viruses (IAV) bear the potential to cause pandemics with unpredictable consequences for global human health. In particular, the WHO has declared avian H5 and H7 subtypes as high-risk candidates, and continuous surveillance of these viruses as well as the development of novel, broadly acting antivirals, are key for pandemic preparedness. In this study, we sought to design T-705 (Favipiravir) related inhibitors that target the RNA-dependent RNA polymerase and evaluate their antiviral efficacies against a broad range of IAVs. Therefore, we synthesized a library of derivatives of T-705 ribonucleoside analogues (called T-1106 pronucleotides) and tested their ability to inhibit both seasonal and highly pathogenic avian influenza viruses in vitro. We further showed that diphosphate (DP) prodrugs of T-1106 are potent inhibitors of H1N1, H3N2, H5N1, and H7N9 IAV replication. Importantly, in comparison to T-705, these DP derivatives achieved 5- to 10-fold higher antiviral activity and were non-cytotoxic at the therapeutically active concentrations. Moreover, our lead DP prodrug candidate showed drug synergy with the neuraminidase inhibitor oseltamivir, thus opening up another avenue for combinational antiviral therapy against IAV infections. Our findings may serve as a basis for further pre-clinical development of T-1106 prodrugs as an effective countermeasure against emerging IAVs with pandemic potential.
Extracellular Vesicles and Infection: From Hijacked Machinery to Therapeutic Tools
Authors: Gonçalves Diogo , Pinto Sandra N. , Fernandes Fábio
Published: June 2023

Extracellular vesicles (EVs) comprise a broad range of secreted cell-derived membrane vesicles. Beyond their more well-characterized role in cell communication, in recent years, EVs have also been shown to play important roles during infection. Viruses can hijack the biogenesis of exosomes (which are small EVs) to promote viral spreading. Additionally, these exosomes are also important mediators in inflammation and immune responses during both bacterial and viral infections. This review summarizes these mechanisms while also describing the impact of bacterial EVs in regulating immune responses. Finally, the review also focuses on the potential and challenges of using EVs, in particular, to tackle infectious diseases.
The Foliar Anatomy and Micromorphology of Cyphostemma hypoleucum (Vitaceae)
Authors: Rambau Unarine , Naidoo Yougasphree , Sadashiva Channangihalli Thimmegowda , Baijnath Himansu , Dewir Yaser Hassan , Magyar-Tábori Katalin
Published: June 2023

Cyphostemma hypoleucum (Harv.) Desc. ex Wild & R.B. Drumm is a perennial climber, indigenous to Southern Africa, and belongs to the Vitaceae. Although there have been many studies of Vitaceae micromorphology, only a few taxa have been described in detail. This study aimed to characterize the micro-morphology of the leaf indumentum and determining its possible functions. Stereo microscope, scanning electron microscope (SEM), and transmission electron microscope (TEM) were used to produce images. Micrographs of stereomicroscopy and SEM showed the presence of non-glandular trichomes. In addition, pearl glands were observed on the abaxial surface using a stereo microscope and SEM. These were characterized by a short stalk and a spherical- shaped head. The density of trichomes decreased on both surfaces of leaves as the leaf expanded. Idioblasts that contained raphide crystals were also detected in tissues. The results obtained from various microscopy techniques confirmed that non-glandular trichomes serve as the main external appendages of the leaves. Additionally, their functions may include serving as a mechanical barrier against environmental factors such as low humidity, intense light, elevated temperatures, as well as herbivory and insect oviposition. Our results may also be added to the existing body of knowledge with regard to microscopic research and taxonomic applications.
Molecular Aggregation Strategy for Pore Generation in SiOC Ceramics Induced by the Conjugation Force of Phenyl
Authors: Yi Gang , Yu Yuxi
Published: June 2023

Porous silicon oxycarbide (SiOC) ceramics with tailorable microstructure and porosity were fabricated using phenyl-substituted cyclosiloxane (C-Ph) as a molecular-scale porogen are analyzed in this study. A gelated precursor was synthesized via the hydrosilylation of hydrogenated and vinyl-functionalized cyclosiloxanes (CSOs), followed by pyrolysis at 800–1400 °C in flowing N2 gas. Tailored morphologies, such as closed-pore and particle-packing structures, with porosities in the range 20.2–68.2% were achieved by utilizing the high boiling point of C-Ph and the molecular aggregation in the precursor gel induced by the conjugation force of phenyl. Moreover, some of the C-Ph participated in pyrolysis as a carbon source, which was confirmed by the carbon content and thermogravimetric analysis (TGA) data. This was further confirmed by the presence of graphite crystals derived from C-Ph, as determined by high-resolution transmission electron microscopy (HRTEM). In addition, the proportion of C-Ph involved in the ceramic process and its mechanism were investigated. The molecular aggregation strategy for phase separation was demonstrated to be facile and efficient, which may promote further research on porous materials. Moreover, the obtained low thermal conductivity of 27.4 mW m−1 K−1 may contribute to the development of thermal insulation materials.
Evaluation of the Interface Strength in the Abaca-Fiber-Reinforced Bio-Polyethylene Composites
Authors: Seculi Faust , Espinach Francesc X. , Julián Fernando , Delgado-Aguilar Marc , Mutjé Pere , Tarrés Quim
Published: June 2023

Bio-based polymers, with any of their constituents based on nonrenewable sources, can answer the demands of society and regulations regarding minimizing the environmental impact. The more similar such biocomposites are to oil-based composites, the easier the transition, especially for companies that do not like the uncertainty. A BioPE matrix, with a structure similar to that of a high-density polyethylene (HDPE), was used to obtain abaca-fiber-reinforced composites. The tensile properties of these composites are displayed and compared with commercial glass-fiber-reinforced HDPE. Since the strength of the interface between the reinforcements and the matrix is responsible for the exploitation of the strengthening abilities of the reinforcements, several micromechanical models were used to obtain an estimation of the strength of the interface and the intrinsic tensile strength of the reinforcements. Biocomposites require the use of a coupling agent to strengthen their interface, and once an 8 wt.% of such coupling agent was added to the composites, these materials returned tensile properties in line with commercial glass-fiber-reinforced HDPE composites.
A Regression Approach to Model Refractive Index Measurements of Novel 3D Printable Photocurable Resins for Micro-Optofluidic Applications
Authors: Saitta Lorena , Cutuli Emanuela , Celano Giovanni , Tosto Claudio , Stella Giovanna , Cicala Gianluca , Bucolo Maide
Published: June 2023

In this work, a quadratic polynomial regression model was developed to aid practitioners in the determination of the refractive index value of transparent 3D printable photocurable resins usable for micro-optofluidic applications. The model was experimentally determined by correlating empirical optical transmission measurements (the dependent variable) to known refractive index values (the independent variable) of photocurable materials used in optics, thus obtaining a related regression equation. In detail, a novel, simple, and cost-effective experimental setup is proposed in this study for the first time for collecting the transmission measurements of smooth 3D printed samples (roughness ranging between 0.04 and 2 μm). The model was further used to determine the unknown refractive index value of novel photocurable resins applicable in vat photopolymerization (VP) 3D printing techniques for manufacturing micro-optofluidic (MoF) devices. In the end, this study proved how knowledge of this parameter allowed us to compare and interpret collected empirical optical data from microfluidic devices made of more traditional materials, i.e., Poly(dimethylsiloxane) (PDMS), up to novel 3D printable photocurable resins suitable for biological and biomedical applications. Thus, the developed model also provides a quick method to evaluate the suitability of novel 3D printable resins for MoF device fabrication within a well-defined range of refractive index values (1.56; 1.70).
The Siddha with a Thousand Faces: Non-Tantric and Tantric Elements in the Construction of the Buddhist Siddha in *Jñānākara’s Commentary to the Introduction to the [Path of] Mantra
Authors: Wenta Aleksandra
Published: June 2023

This paper is a continuation of an earlier study published by the current author dedicated to the virtually unexplored tantric Buddhist scholar of the phyi dar period, *Jñānākara (11th century), through the textual analysis of his masterpiece, the Introduction to the [Path of] Mantra (Skt. *Mantrāvatāra), now available only in the Tibetan translation as Gsang sngags ‘jug pa. In the previous paper, I have discussed the broader historical framework of the eleventh-century Indo-Tibetan world and *Jñānākara’s role in establishing, what I called, the “orthodoxy of tantric practice”. I have also provided a critical edition of the root text, the *Mantrāvatāra, accompanied by an English translation. While the previous study focused mainly on the debatable and highly controversial issue of tantric sexual initiations adopted by the monastics and hermeneutical tools employed by *Jñānākara to refute the literal interpretation of tantric scriptures, the current paper will concentrate on the exposition of tantric practice understood as the accumulation of causes and conditions (hetu-pratyaya) leading to the status of the siddha. This paper will trace tantric and non-tantric elements in *Jñānākara’s construction of the Buddhist siddha that integrated the kāya doctrine of the Yogācāra. My analysis will be based on *Jñānākara’s auto-commentary to his root text, the Commentary to the Introduction to the [Path of] Mantra (Skt. *Mantrāvatāravṛtti, Tib. Gsang sngags ‘jug pa ‘grel pa) which has not received any scholarly attention so far. Special attention will be paid to the intertextual dimension of his discourse that integrates the Mahāyāna models of the bodhisattva path.