bluuebunny/crossref_metadata_2025 huggingface dataset:
Somatostatin and Somatostatin Receptors in Tumour Biology
Authors: Kumar Ujendra
Published: December 2023

Somatostatin (SST), a growth hormone inhibitory peptide, is expressed in endocrine and non-endocrine tissues, immune cells and the central nervous system (CNS). Post-release from secretory or immune cells, the first most appreciated role that SST exhibits is the antiproliferative effect in target tissue that served as a potential therapeutic intervention in various tumours of different origins. The SST-mediated in vivo and/or in vitro antiproliferative effect in the tumour is considered direct via activation of five different somatostatin receptor subtypes (SSTR1-5), which are well expressed in most tumours and often more than one receptor in a single cell. Second, the indirect effect is associated with the regulation of growth factors. SSTR subtypes are crucial in tumour diagnosis and prognosis. In this review, with the recent development of new SST analogues and receptor-specific agonists with emerging functional consequences of signaling pathways are promising therapeutic avenues in tumours of different origins that are discussed.
Increasing the Activity of the High-Fidelity SpyCas9 Form in Yeast by Directed Mutagenesis of the PAM-Interacting Domain
Authors: Davletshin Artem I. , Matveeva Anna A. , Bachurin Stanislav S. , Karpov Dmitry S. , Garbuz David G.
Published: December 2023

CRISPR/Cas systems are used for genome editing, both in basic science and in biotechnology. However, CRISPR/Cas editors have several limitations, including insufficient specificity leading to “off-targets” and the dependence of activity on chromatin state. A number of highly specific Cas9 variants have now been obtained, but most of them are characterized by reduced activity on eukaryotic chromatin. We identified a spatial cluster of amino acid residues in the PAM-recognizing domain of Streptococcus pyogenes Cas9, whose mutations restore the activity of one of the highly specific forms of SpyCas9 without reducing its activity in Saccharomyces cerevisiae. In addition, one of these new mutations also increases the efficiency of SpyCas9-mediated editing of a site localized on the stable nucleosome. The improved Cas9 variants we obtained, which are capable of editing hard-to-reach regions of the yeast genome, may help in both basic research and yeast biotechnological applications.
Antibody Response to HERV-K and HERV-W Envelope Epitopes in Patients with Myasthenia Gravis
Authors: Simula Elena Rita , Zarbo Ignazio Roberto , Arru Giannina , Sechi Elia , Meloni Rossella , Deiana Giovanni Andrea , Solla Paolo , Sechi Leonardo Antonio
Published: December 2023

Myasthenia gravis is an antibody-mediated autoimmune neurological disorder characterized by impaired neuromuscular junction transmission, resulting in muscle weakness. Recently, the involvement of Human Endogenous Retroviruses (HERVs) in the pathophysiology of different immune-mediated and neurodegenerative diseases, such as multiple sclerosis, has been demonstrated. We aimed to investigate potential immune system involvement related to humoral responses targeting specific epitopes of HERV-K and HERV-W envelope proteins in myasthenia gravis. Myasthenia gravis patients were recruited in the Neurology Unit, while healthy controls were selected from the Blood Transfusion Center, both affiliated with AOU Sassari. Highly immunogenic antigens of HERV-K and HERV-W envelope proteins were identified using the Immune Epitope Database (IEDB) online tool. These epitopes were utilized in enzyme-linked immunosorbent assays (ELISA) to detect autoantibodies in serum directed against these sequences. The study involved 39 Healthy Donors and 47 MG patients, further categorized into subgroups based on the presence of autoantibodies: MG-AchR Ab+ (n = 17), MG-MuSK Ab+ (n = 7), double seronegative patients (MG-DSN, n = 18), MG-LRP4 Ab + (n = 4), and one patient with no antibodies data (n = 1). Our findings revealed high levels of autoantibodies in myasthenia gravis patients directed against the HERV-K-env-su(19–37), HERV-K-env-su(109–126), HERV-K-env-su(164–186), HERV-W-env(93–108), HERV-W-env(129–14), and HERV-W-env(248–262) epitopes. Notably, these results remained highly significant even when patients were subdivided into MG-AchR Ab+ and MG-DSN subgroups. Correlation analysis further revealed significant positive associations between the antibody levels against HERV-K and HERV-W families in patients, suggesting a synergistic action of the two HERVs in the pathology context since this correlation is absent in the control group. This study marks the first identification of a specific humoral response directed against defined epitopes of HERV-K and HERV-W envelope proteins in myasthenia gravis patients. These findings lay the foundation for future investigations aimed at elucidating the molecular mechanisms driving this immune response. The detection of these autoantibodies suggests the potential for novel biomarkers, especially within the MG-DSN patient subgroup, addressing the need for new biomarkers in this population.
The Effect of Municipal Biosolids on the Growth, Physiology and Synthesis of Phenolic Compounds in Ocimum basilicum L.
Authors: Lobiuc Andrei , Stoleru Vasile , Gheorghiţă Roxana , Burducea Marian
Published: December 2023

The continuous development of drinking water networks is leading to the production of increasing amounts of waste water and sewage sludge. Secondary-treated sewage sludge is called biosolids and can be used as fertilizers in agriculture due to its rich nutrient content. The aim of this study was to evaluate the effects of biosolids mixed with an eroded soil on the morphology, physiology and synthesis of bioactive compounds in basil. The study was performed in pots under laboratory-controlled conditions. In total, four substrates were tested: S1 biosolids 100%, S2 biosolids 15% + eroded soil 85%, S3 eroded soil 100% and S4 control (commercial growing substrate). At the morphological level, a significant increase in plant height, number of branches, fresh biomass and dry biomass was found in the S2 variant. At the physiological level, photosynthesis and chlorophyll content did not vary significantly, but the quantum yield of PSII (ΦPSII) was significantly higher at S1 and S2. The oxidative status evaluated by determining the activity of SOD, POD and CAT enzymes was better in S2 and S3 compared to S3. Regarding the synthesis of bioactive compounds (rosmarinic acid, caffeic acid and gallic acid), it was stimulated in S1 and S2. In conclusion, biosolids application stimulated the stress response mechanisms in basil plants by increasing the quantum yield chlorophyll fluorescence and catalase activity, alleviating the negative effects of eroded soil.
An Integrated Access and Backhaul Approach to Sustainable Dense Small Cell Network Planning
Authors: Zhang Jie , Wang Qiao , Mitchell Paul , Ahmadi Hamed
Published: December 2023

Integrated access and backhaul (IAB) networks offer transformative benefits, primarily their deployment flexibility in locations where fixed backhaul faces logistical or financial challenges. This flexibility is further enhanced by IAB’s inherent ability for adaptive network expansion. However, existing IAB network planning models, which are grounded in the facility location problem and are predominantly addressed through linear programming, tend to neglect crucial geographical constraints. These constraints arise from the specific deployment constraints related to the positioning of IAB donors to the core network, and the geographic specificity required for IAB-node placements. These aspects expose an evident research void. To bridge this, our research introduces a geographically aware optimization methodology tailored for IAB deployments. In this paper, we detail strategies for both single-hop and multi-hop situations, concentrating on IAB donors distribution and geographical constraints. Uniquely in this study, we employ the inherent data rate limitations of network nodes to determine the maximum feasible hops, differing from traditional fixed maximum hop count methods. We devise two optimization schemes for single-hop and multi-hop settings and introduce a greedy algorithm to effectively address the non-convex multi-hop challenge. Extensive simulations across various conditions (such as diverse donor numbers and node separations) were undertaken, with the outcomes assessed against the benchmark of the single-hop scenario’s optimal solution. Our findings reveal that the introduced algorithm delivers efficient performance for geographically constrained network planning.
Age- and Density-Dependent Parasitism Rate and Development Time of the Generalist Egg-Parasitoid Ooencyrtus telenomicida (Hymenoptera: Encyrtidae) on Eggs of the Brown Marmorated Stink Bug, Halyomorpha halys
Authors: Koutsogeorgiou Eleni I. , Moysiadis Theodoros , Fifis Georgios T. , Gogolashvili Nikoloz E. , Chatzimpalasis Dimitrios , Andreadis Stefanos S.
Published: December 2023

Halyomorpha halys (Hemiptera: Pentatomidae) is an invasive pest species that was imported into Greece in 2011 and since then, has caused severe qualitative and quantitative damage to economically important crops. Its management relies mainly on the use of broad-spectrum insecticides, with little to no information available concerning the potential use of native parasitoids in terms of classical biological control. Our study aimed to assess the parasitism rate and development time of the gregarious egg parasitoid Ooencyrtus telenomicida (Hymenoptera: Encyrtidae) on H. halys egg-masses, depending on several factors such as: (i) age of parasitoids, (ii) density of parasitoids, (iii) age of host eggs, and (iv) oviposition experience of parasitoids. According to our results, the younger the host eggs and the more parasitoids, the higher the parasitism rate achieved by adults of O. telenomicida, with the maximum mean value of the parasitism rate observed with 1-day-old host eggs and 4 parasitoid pairs (57.3%). On the contrary, the lowest mean value of the parasitism rate was observed with 4-day-old host eggs and 1 parasitoid pair (6.5%). Similarly, the age of parasitoids significantly affected parasitisation. The older the parasitoids were, the higher the parasitism rate achieved by adults of O. telenomicida, with a three-fold higher parasitism rate observed at 3–4 and 5–6-day-old O. telenomicida, compared to 1–2-day-old (31.8, 32.4, and 12.1%, respectively). Individuals that developed in younger host eggs displayed a shorter development time, and the shortest development time was observed for O. telenomicida laid by 2 parasitoid pairs. Parasitoid age did not affect the development time of O. telenomicida, although there was a tendency for individuals laid by younger female parasitoids to exhibit a shorter development time. Our findings provide valuable information on the potential use of O. telenomicida as a biocontrol agent of H. halys.
Estimation of Topical Glaucoma Medication Over-Prescription and Its Associated Factors
Authors: Takao Eri , Ichitani Aona , Tanito Masaki
Published: December 2023

This study aims to report the disparity between the ideal and actual quantities of eyedrops prescribed to individual glaucoma patients. This retrospective observational study included 676 patients receiving treatment with antiglaucoma topical medication(s) in at least one eye. These patients had follow-up appointments scheduled at mean intervals of 3.4 ± 1.4 months and were actively using antiglaucoma medication. The mean age was 70.4 ± 11.9 years, with 372 (55%) being male. The over-prescription volume was 1.4 ± 1.7 bottles per month for each medication when prescribed for both eyes. Multiple regression analysis revealed that older age (p = 0.03), hyperopic refractive error (p < 0.0001), and the use of multiple medications (p = 0.03) were associated with a larger over-prescription volume, while the use of unit-dose medication only (p < 0.0001) was associated with a smaller over-prescription volume. Factors such as sex, Mini-Cog cognitive function score, best-corrected visual acuity, intraocular pressure, glaucoma type, and a history of cataract surgery were not significantly associated. This study revealed a significant over-prescription of eyedrops for glaucoma patients, with actual prescriptions often exceeding the theoretically ideal amount by 2.4 times, influenced by factors like age and the format of prescriptions, where unit-dose eyedrops show promise in reducing excess.
Is There Any Effect of Change in Pre-Wash and Post-Wash Semen Parameters on the Success of Intrauterine Insemination?
Authors: Yavuzcan Ali , Yurtçu Engin , Keyif Betül , Osmanlıoğlu Şeyma
Published: December 2023

(1) Background: We aimed to investigate the effect of change in pre-wash and post-wash semen parameters on intrauterine insemination (IUI) success in a homogenous study group. (2) Methods: IUI cycles conducted at an infertility clinic were included in this study. Patient records were examined retrospectively. Δ sperm count (per mL) was calculated as [pre-wash sperm count (per mL)–post-wash sperm count (per mL)]. Δ Total progressive motile sperm count (TPMSC) was also calculated as (post-wash TPMSC-pre-wash TPMSC). (3) Results: No statistically significant difference was detected in terms of Δ sperm count (p = 0.38), and Δ TPMSC (p = 0.76) regarding the clinical pregnancy rate (CPR). There was no statistically significant difference between CPR (+) and CPR (−) groups in terms of post-wash sperm count, TPMSC, TPMSC ≥ 10 × 10⁶, TPMSC ≥ 5 × 10⁶ (p = 0.65, p = 0.79, p = 0.49, p = 0.49, respectively). The live birth rate (LBR) showed no statistically significant differences except for a pre-wash TPMSC ≥ 10 × 10⁶ (p = 0.02). Through the performed ROC analysis, no statistically significant cutoff value could be set for the pre-wash TPMSC. (4) Conclusions: There is only a pre-wash TPMSC ≥ 10 × 10⁶ that showed a significant role in the success of IUI, even when considering all other pre-wash and post-wash semen parameters. Δ sperm count and Δ are not useful markers for IUI success.
Urban Morphology and Forms of the Territory: Between Urban and Landscape Design
Authors: Neglia Giulia Annalinda
Published: December 2023

This paper explores the relationship between territory and urban space, discussing the joint development processes of urban and territorial morphologies. The paper argues that territorial structure is a precursor to urban design. It also discusses how landscape architecture can respond to the morphological needs of contemporary urban design as the boundaries between city and territory merge. The introduction and framework review section examines various approaches to studying the relationship between urban morphology and interstitial spaces or unbuilt geographies, which are often still considered empty spaces, physically incorporated but excluded from urban design. It also briefly discusses the role that green spaces and territorial morphologies have played, or not played, in defining urban form from antiquity to modernity. The paper then focuses on the role of hydromorphologies in shaping the urban form of Rome, Boston and Bari. These cities are analyzed as case studies to discuss 20th-century approaches to urban planning in relation to territorial layout. Finally, this study analyzes a marginal area of the metropolitan city of Bari in order to propose possible landscape morphologies of reconnection for the resulting interstitial areas.
Incep-FrictionNet-Based Pavement Texture Friction Level Classification Prediction Method
Authors: Xu Guomin , Lin Xiuquan , Wang Shifa , Zhan You , Liu Jing , Huang He
Published: December 2023

Pavement skid resistance is crucial for driving safety, and pavement texture significantly impacts skid resistance performance. To realize the application of pavement texture data in assessing pavement skid resistance performance, this paper proposes a convolutional neural network model based on the InceptionV4 module to predict the pavement friction level from the pavement texture dataset. The surface texture data of indoor test-rutted slabs were collected using a portable laser scanner. The surface friction coefficient of rutted slabs was measured using a pendulum tribometer. After data pre-processing, a total of nine types of texture data that are in the range of 0.4 to 0.8 skid resistance levels are selected at an interval of 0.05 for training, validation, and testing of the network model. The same dataset and training parameters were also used to train a conventional convolutional network model for comparison. The results showed that the proposed network model achieved 97.89% classification accuracy on the test set, which was 11.94 percentage points higher than the comparison model. This demonstrates that the proposed model in this paper can evaluate pavement friction levels by non-contact scanning of textures and has higher evaluation accuracy.
OSMAC-Based Discovery and Biosynthetic Gene Clusters Analysis of Secondary Metabolites from Marine-Derived Streptomyces globisporus SCSIO LCY30
Authors: Li Yanqing , Gong Naying , Zhou Le , Yang Zhijie , Zhang Hua , Gu Yucheng , Ma Junying , Ju Jianhua
Published: December 2023

The one strain many compounds (OSMAC) strategy is an effective method for activating silent gene clusters by cultivating microorganisms under various conditions. The whole genome sequence of the marine-derived strain Streptomyces globisporus SCSIO LCY30 revealed that it contains 30 biosynthetic gene clusters (BGCs). By using the OSMAC strategy, three types of secondary metabolites were activated and identified, including three angucyclines, mayamycin A (1), mayamycin B (2), and rabolemycin (3); two streptophenazines (streptophenazin O (4) and M (5)); and a macrolide dimeric dinactin (6), respectively. The biosynthetic pathways of the secondary metabolites in these three families were proposed based on the gene function prediction and structural information. The bioactivity assays showed that angucycline compounds 1–3 exhibited potent antitumor activities against 11 human cancer cell lines and antibacterial activities against a series of Gram-positive bacteria. Mayamycin (1) selectively exhibited potent cytotoxicity activity against triple-negative breast cancer (TNBC) cell lines such as MDA-MB-231, MDA-MB-468, and Bt-549, with IC50 values of 0.60–2.22 μM.
Increased Absorption and Inhibitory Activity against Candida spp. of Imidazole Derivatives in Synergistic Association with a Surface Active Agent
Authors: Aonofriesei Florin
Published: December 2023

This paper’s purpose was to evaluate the interaction between three imidazole derivatives, (2-methyl-1H-imidazol-1-yl)methanol (SAM3), 1,1′-methanediylbis(1H-benzimidazole (AM5) and (1H-benzo[d]imidazol-1-yl)methanol 1-hydroxymethylbenzimidazole (SAM5) on the one hand, and sodium dodecyl sulphate (SDS) on the other, as antifungal combinations against Candida spp. Inhibitory activity was assessed using the agar diffusion method and Minimal Inhibitory Concentration (MIC) and showed moderate inhibitory activity of single imidazole derivatives against Candida spp. The mean value of MIC ranged from 200 µg/mL (SAM3) to 312.5 µg/mL (SAM3), while for SDS the MIC was around 1000 µg/mL. When used in combination with SDS, the imidazole derivatives demonstrated an improvement in their antifungal activity. Their MIC decreased over five times for AM5 and over seven times for SAM3 and SAM5, respectively, and ranged from 26.56 µg/mL (SAM3) to 53.90 µg/mL (AM5). Most combinations displayed an additive effect while a clear synergistic effect was recorded in only a few cases. Thus, the FIC Index (FICI) with values between 0.311 and 0.375 showed a synergistic effect against Candida spp. when SDS was associated with SAM3 (three strains), SAM5 (two strains) and AM5 (one strain). The association of imidazole derivatives with SDS led to the increased release of cellular material as well as the intracellular influx of crystal violet (CV), which indicated an alteration of the membrane permeability of Candida spp. cells. This favored the synergistic effect via increasing the intracellular influx of imidazoles.
Diamonds Discovered in the Forearc Harzburgites Hint at the Deep Mantle Source of the Skenderbeu Massif, Western Mirdita Ophiolite
Authors: Wu Weiwei , Yang Jingsui , Yang Yu , Milushi Ibrahim , Wang Yun
Published: December 2023

The ultra-deep genesis of ophiolitic peridotite has reshaped our perception of the genesis of the oceanic mantle. Although ultra-high pressure (UHP) mineral assemblages have been unearthed in dozens of ophiolites in different orogenic belts around the world, the vast majority of them have been limited to podiform chromitites formed in suprasubduction zone (SSZ) settings, leaving uncertainty about whether such UHP minerals are intrinsic to the oceanic mantle or influenced by a specific mantle rock type. Here, we report on the occurrence of diamonds recovered from the harzburgites within the Skenderbeu massif, Mirdita ophiolite. The whole-rock, mineralogical major and trace element compositions, and redox states of the harzburgites align with modern abyssal harzburgites. Trace element modeling of clinopyroxene indicates that harzburgites have endured varying degrees of garnet-facies melting (~2%–5%) before progressing to spinel-facies melting (~10%–12%). Mineralogical characteristics further support that the Skenderbeu harzburgites underwent late-period MORB-like melt metasomatism in a forearc spreading center. An unusual mineral assemblage of diamonds has been separated from the studied harzburgites. The first occurrence of ophiolite-hosted diamonds discovered in the forearc harzburgites, together with previous similar discoveries in the SSZ ophiolitic chromitites, suggest that the ophiolite-hosted diamonds are not specific to certain mantle rocks.
New Quinoid Bio-Inspired Materials Using Para-Azaquinodimethane Moiety
Authors: Zwaihed Walaa , Maurel François , Kobeissi Marwan , Schmaltz Bruno
Published: December 2023

Quinoid single molecules are regarded as promising materials for electronic applications due to their tunable chemical structure-driven properties. A series of three single bio-inspired quinoid materials containing para-azaquinodimethane (p-AQM) moiety were designed, synthesized and characterized. AQM1, AQM2 and AQM3, prepared using aldehydes derived from almonds, corncobs and cinnamon, respectively, were studied as promising quinoid materials for optoelectronic applications. The significance of facile synthetic procedures is highlighted through a straightforward two-step synthesis, using Knoevenagel condensation. The synthesized molecules showed molar extinction coefficients of 22,000, 32,000 and 61,000 L mol−1 cm−1, respectively, for AQM1, AQM2 and AQM3. The HOMO-LUMO energy gaps were calculated experimentally, theoretically showing the same trends: AQM3 < AQM2 < AQM1. The role of the aryl substituent was studied and showed an impact on the electronic properties. DFT calculations show planar structures with quinoidal bond length alternation, in agreement with the experimental results. Finally, these bio-based materials showed high thermal stabilities between 290 °C and 340 °C and a glassy behavior after the first heating–cooling scan. These results highlight these bio-based single molecules as potential candidates for electronic or biomedical applications.
Polymeric Materials in Speciation Analysis Based on Solid-Phase Extraction
Authors: Dakova Ivanka , Yordanova Tanya , Karadjova Irina
Published: December 2023

Speciation analysis is a relevant topic since the (eco)toxicity, bioavailability, bio (geo)chemical cycles, and mobility of a given element depend on its chemical forms (oxidation state, organic ligands, etc.). The reliability of analytical results for chemical species of elements depends mostly on the maintaining of their stability during the sample pretreatment step and on the selectivity of further separation step. Solid-phase extraction (SPE) is a matter of choice as the most suitable and widely used procedure for both enrichment of chemical species of elements and their separation. The features of sorbent material are of great importance to ensure extraction efficiency from one side and selectivity from the other side of the SPE procedure. This review presents an update on the application of polymeric materials in solid-phase extraction used in nonchromatographic methods for speciation analysis.
Microfluidic Preparation of pH-Responsive Microsphere Fibers and Their Controlled Drug Release Properties
Authors: Wang Ning , Wei Yixuan , Hu Yanrong , Sun Xiaoting , Wang Xiaohong
Published: December 2023

In this study, a capillary microfluidic device was constructed, and sodium alginate solution and a pH-sensitive hydrophobic polymer (p(BMA-co-DAMA-co-MMA)) solution were introduced into the device for the preparation of hydrogel fibers loaded with polymer microspheres. The structure of the microsphere fiber, including the size and spacing of the microspheres, could be controlled by flow rate, and the microspheres were able to degrade and release cargo responding to acidic pH conditions. By modification with carboxymethylcellulose (CMC), alginate hydrogel exhibited enhanced pH sensitivity (shrunk in acidic while swollen in basic condition). This led to an impact on the diffusion rate of the molecules released from the inner microspheres. The microsphere fiber showed dramatic and negligible degradation and drug release in tumor cell (i.e., A431 and A549 cells) and normal cell environments, respectively. These results indicated that the microsphere fiber prepared in this study showed selective drug release in acidic environments, such as tumor and inflammation sites, which could be applied as a smart surgical dressing with normal tissue protective properties.
Thermoelectric Properties of Mg3(Bi,Sb)2 under Finite Temperatures and Pressures: A First-Principles Study
Authors: Peng Qing , Ma Xinjie , Yang Xiaoyu , Yuan Xiaoze , Chen Xiao-Jia
Published: December 2023

Mg3Bi2−vSbv (0 ≤ v ≤ 2) is a class of promising thermoelectric materials that have a high thermoelectric performance around room temperatures, whereas their thermoelectric properties under pressures and temperatures are still illusive. In this study, we examined the influence of pressure, temperature, and carrier concentration on the thermoelectric properties of Mg3Bi2−vSbv using first-principle calculations accompanied with Boltzmann transport equations method. There is a decrease in the lattice thermal conductivity of Mg3Sb2 (i.e., v = 2) with increasing pressure. For a general Mg3Bi2−vSbv system, power factors are more effectively improved by n-type doping where electrons are the primary carriers over holes in n-type doping, and can be further enhanced by applied pressure. The figure of merit (zT) exhibits a positive correlation with temperature. A high zT value of 1.53 can be achieved by synergistically tuning the temperature, pressure, and carrier concentration in Mg3Sb2. This study offers valuable insights into the tailoring and optimization of the thermoelectric properties of Mg3Bi2−vSbv.
Longitudinal Neuropsychological Assessment of Symptomatic Edema after Subthalamic Nucleus Deep Brain Stimulation Surgery: A Case Series Study
Authors: De Ieso Silvia , Di Rauso Giulia , Cavallieri Francesco , Beltrami Daniela , Marti Alessandro , Napoli Manuela , Pascarella Rosario , Feletti Alberto , Fioravanti Valentina , Toschi Giulia , Rispoli Vittorio , Antonelli Francesca , Puzzolante Annette , Pavesi Giacomo , Gasparini Federico , Valzania Franco
Published: December 2023

Severe non-infectious or non-haemorrhagic brain edema surrounding the electrode represents a rare complication of subthalamic nucleus deep brain stimulation (STN-DBS) surgery. The aim of this study is to report three patients with advanced Parkinson’s Disease (PD) who developed symptomatic brain edema after STN-DBS surgery treated with intravenous steroids with a specific profile of reversible cognitive alterations. Patients were both assessed with a comprehensive neuropsychological battery including attention, memory, visuo-spatial and executive tasks. They were also briefly assessed for emotional and behavioural alterations, and for possible limitations in the activities of daily living. Normative data for an Italian population were available for all neuropsychological tests. The patients were firstly assessed before the surgery (baseline) as soon as they became symptomatic for the post-surgery edema and a few more times in follow-up up to ten months. In all patients we observed the resolution of cognitive deficits within six months after surgery with the corresponding reabsorption of edema at brain CT scans. The appearance of post-DBS edema is a fairly frequent and clinically benign event. However, in some rare cases it can be very marked and lead to important clinical—albeit transient—disturbances. These events can compromise, at least from a psychological point of view, the delicate path of patients who undergo DBS and can prolong the post-operative hospital stay. In this setting it could be helpful to perform a brain CT scan in 2–3 days with the aim of detecting the early appearance of edema and treating it before it can constitute a relevant clinical problem.
Diet-Wide Association Study for the Incidence of Type 2 Diabetes Mellitus in Community-Dwelling Adults Using the UK Biobank Data
Authors: Liu Jiahao , Shang Xianwen , Chen Yutong , Tang Wentao , Yusufu Mayinuer , Chen Ziqi , Chen Ruiye , Hu Wenyi , Jan Catherine , Li Li , He Mingguang , Zhu Zhuoting , Zhang Lei
Published: December 2023

This longitudinal study used diet-wide association studies (DWAS) to investigate the association between diverse dietary food and nutrient intakes and the onset of type 2 diabetes mellitus (T2DM). Out of 502,505 participants from the UK Biobank, 119,040 with dietary data free of T2DM at the baseline were included, and 3241 developed T2DM during a median follow-up of 11.7 years. The DWAS analysis, which is based on Cox regression models, was used to analyse the associations between dietary food or nutrient intake factors and T2DM risk. The study found that 10 out of 225 dietary factors were significantly associated with the T2DM risk. Total alcohol (HR = 0.86, 0.85–0.92, p = 1.26 × 10−32), red wine (HR = 0.89, 0.88–0.94, p = 7.95 × 10−19), and fresh tomatoes (HR = 0.92, 0.89–0.94, p = 2.3 × 10−11) showed a negative association with T2DM risk, whereas sliced buttered bread exhibited a positive association. Additionally, 5 out of 21 nutrient intake variables revealed significant associations with the T2DM risk, with iron having the highest protective effect and starch as a risk factor. In conclusion, DWAS is an effective method for discovering novel associations when exploring numerous dietary variables simultaneously and could provide valuable insight into future dietary guidance for T2DM.
Socio-Spatial Segregation of Unhealthy Food Environments across Public Schools in Santiago, Chile
Authors: Kain Juliana , Sandoval Moisés H. , Orellana Yasna , Cruz Natalie , Díez Julia , Weisstaub Gerardo
Published: December 2023

Santiago, Chile is a very segregated city, with higher childhood obesity rates observed in vulnerable areas. We compared the counts and proximity of unhealthy food outlets (UFOs) around a 400 m buffer of 443 public schools (municipal and subsidized) located in socioeconomically diverse neighborhoods in 14 municipalities of Santiago. This was a cross-sectional study in which the socioeconomic status (SES) of the population living inside the buffer was classified as middle-high, middle, and low. We used the Kruskal–Wallis test for comparisons of density and proximity between type of school, SES, and population density. We used a negative binomial model (unadjusted and adjusted by population density) to determine the expected change in counts of UFOs by SES, which was compared to the reference (middle-high). Low SES neighborhoods had significantly more counts of UFOs, and these were located much closer to schools. Low and middle SES neighborhoods had an 88% and 48% higher relative risk of having UFOs compared to middle-high SES areas; (IRR = 1.88; 95% CI 1.59–2.23) and (IRR = 1.48; 95% CI 1.20–1.82), respectively. A socio-spatial segregation of UFOs associated with childhood obesity across public schools was observed in Santiago.
Mechanism of Antitumor Effects of Saffron in Human Prostate Cancer Cells
Authors: Khan Mohammad , Hearn Kaitlyn , Parry Christian , Rashid Mudasir , Brim Hassan , Ashktorab Hassan , Kwabi-Addo Bernard
Published: December 2023

Prostate cancer is the most common cancer and the second leading cause of cancer deaths among men in the USA. Several studies have demonstrated the antitumor properties of saffron in different types of cancers, including prostate cancer. The oral administration of saffron extract has been reported to have antitumor effects on aggressive prostate-cancer-cell-line-derived xenografts in nude male mice. The objective of this study was to carry out in vitro studies of saffron-treated prostate cancer cells to ascertain the effects of saffron on key intermediates in prostate carcinogenesis. Our studies demonstrated the significant inhibition of cell proliferation for androgen-sensitive prostate cancer cell lines via apoptotic pathways. We also demonstrate the statistically significant down-regulation of DNA methyltransferases (COMT, MGMT, EHMT2, and SIRT1 deacetylase) in saffron-treated prostate cancer cells. In addition, saffron-treated prostate cancer cells displayed a statistically significant dysregulation of DNA repair intermediates (WRN, p53, RECQ5, MST1R, and WDR70) in a time-dependent manner. Furthermore, Western blot analysis demonstrated that saffron treatment induced changes in the expression of other key genes (DNMT1, DNMT3b, MBD2, CD44, HDAC3, c-Myc, NF-kB, TNFα, AR, N-RAS, and PTEN) in prostate cancer cells. Collectively, our findings demonstrate the important mechanisms by which saffron mediates anti-tumor properties in prostate cancer. These findings suggest that the use of saffron supplements alongside standard treatment protocols may yield beneficial effects for individuals with prostate cancer.
Relative Recovery of Non-Alcoholic Fatty Liver Disease (NAFLD) in Diet-Induced Obese Rats
Authors: Aboujassoum Hamda M. , Mohamed-Ali Vidya , Abraham David , Clapp Lucie H. , Al-Naemi Hamda A.
Published: December 2023

Consumption of a high-carbohydrate diet has a critical role in the induction of weight gain and obesity-related pathologies. This study tested the hypothesis that a carbohydrate-rich diet induces weight gain, ectopic fat deposition, associated metabolic risks and development of non-alcoholic fatty liver disease (NAFLD), which are partially reversible following carbohydrate reduction. Sprague Dawley (SD) rats were fed a carbohydrate-enriched cafeteria diet (CAF) or normal chow (NC) ad libitum for 16–18 weeks. In the reversible group (REV), the CAF was replaced with NC for a further 3 weeks (18–21 weeks). Animals fed the CAF diet showed significantly increased body weight compared to those fed NC, accompanied by abnormal changes in their systemic insulin and triglycerides, elevation of hepatic triglyceride and hepatic steatosis. In the REV group, when the CAF diet was stopped, a modest, non-significant weight loss was associated with improvement in systemic insulin and appearance of the liver, with lower gross fatty deposits and hepatic triglyceride. In conclusion, a carbohydrate-enriched diet led to many features of metabolic syndrome, including hyperinsulinemia, while a dietary reduction in this macronutrient, even for a short period, was able to restore normoinsulinemia, and reversed some of the obesity-related hepatic abnormalities, without significant weight loss.
Predictors of Complete Pathological Response with Chemoimmunotherapy in Triple-Negative Breast Cancer: A Meta-Analysis
Authors: Roy Arya Mariam , Chintamaneni Supritha , Alaklabi Sabah , Awada Hassan , Attwood Kristopher , Gandhi Shipra
Published: December 2023

Background: Multiple randomized controlled trials (RCTs) have investigated the impact of adding checkpoint inhibitors to neoadjuvant chemotherapy for triple-negative breast cancer (TNBC) patients. However, there is a lack of biomarkers that can help identify patients who would benefit from combination therapy. Our research identifies response predictors and assesses the effectiveness of adding immunotherapy to neoadjuvant chemotherapy for TNBC patients. Methods: We identified eligible RCTs by searching PubMed, Cochrane CENTRAL, Embase, and oncological meetings. For this meta-analysis, we obtained odds ratios using the standard random effects model. To assess the heterogeneity of the study outcomes, the I2 statistic was obtained. Potential bias was assessed using a funnel plot and the corresponding Egger’s test. Results: In total, 1637 patients with TNBC were included from five RCTs. Neoadjuvant chemoimmunotherapy significantly improved pCR when compared to neoadjuvant chemotherapy alone. In the subgroup analysis, neoadjuvant chemoimmunotherapy showed higher pCR rates in both Programmed death-ligand 1 (PD-L1)-positive and PD-L1-negative TNBC patients. An Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0 correlated with increased pCRs (OR = 1.9, p < 0.001) in neoadjuvant chemoimmunotherapy vs. neoadjuvant chemotherapy, but no benefit was observed for patients with ECOG PS 1. Nodal positivity was significantly associated with pCR (OR = 2.52, p < 0.001), while neoadjuvant chemoimmunotherapy did not benefit patients with negative lymph nodes. Conclusions: Checkpoint inhibition and neoadjuvant chemotherapy significantly increased pCRs in TNBC patients, regardless of their PDL-1 status. Additional checkpoint inhibitors improved pCR rates, mainly for patients with ECOG PS 0 and lymph node-positive disease.
The Effective Synthesis of New Benzoquinoline Derivatives as Small Molecules with Anticancer Activity
Authors: Zbancioc Gheorghita , Mangalagiu Ionel I. , Moldoveanu Costel
Published: December 2023

In this study, some novel benzo[c]quinoline derivatives were synthesized, their structural characteristics were described, and their in vitro anticancer efficacy was investigated. The synthesis involves an initial quaternization of the nitrogen atom from benzo[c]quinoline and then a [3+2] dipolar cycloaddition reaction of the in situ formed ylide. The effectiveness of synthesis using traditional thermal heating (TH) compared to microwave (MW) and ultrasound (US) irradiation was investigated in detail. The setup of a reaction under MW or US irradiation offers a number of additional benefits: higher yields, a reduction in the amount of solvent used compared to TH, a reduction in the reaction time from hours to minutes, and a reduction in the amount of energy consumed. The structure of all the obtained compounds was proved by several spectral techniques (FTIR, HRMS, and NMR). All benzo[c]quinoline derivatives (quaternary salts and cycloadducts) along with ten other benzo[f]quinoline derivatives (quaternary salts and cycloadducts), previously obtained, were tested in an in vitro single-dose anticancer experiment. The results demonstrated that the cycloadducts 5a–c and 6a–c exhibit stronger anticancer activity than quaternary salts 3a–c. The most active compound is compound 5a, with anticancer activity on most of the cell lines studied, while the second most active compound is 6c, showing significant lethality for the SR leukemia cell line (17%). Structure-activity relationship (SAR) correlations are also included in the study.
Core-Shell Microspheres Prepared Using Coaxial Electrostatic Spray for Local Chemotherapy of Solid Tumors
Authors: Zhang Xiaowei , Zhu Rundong , Wang Xingzhi , Wang Hao , Xu Zushun , Wang Yongan , Quan Dongqin , Shen Liao
Published: December 2023

Local chemotherapy is an alternative therapeutic strategy that involves direct delivery of drugs to the tumor site. This approach avoids adverse reactions caused by the systemic distribution of drugs and enhances the tumor-suppressing effect by concentrating the drugs at the tumor site. Drug-loaded microspheres are injectable sustained-release drug carriers that are highly suitable for local chemotherapy. However, a complex preparation process is one of the main technical difficulties limiting the development of microsphere formulations. In this study, core-shell structured microspheres loaded with paclitaxel (PTX; with a core-shell structure, calcium alginate outer layer, and a poly (lactic acid-co-glycolic acid) copolymer inner layer, denoted as PTX-CA/PLGA-MS) were prepared using coaxial electrostatic spray technology and evaluated in vitro and in vivo. PTX-CA/PLGA-MS exhibited a two-stage drug release profile and enhanced anti-tumor effect in animal tumor models. Importantly, the preparation method reported in this study is simple and reduces the amount of organic solvent(s) used substantially.
An Improved In Vitro Blood-Brain Barrier Model for the Evaluation of Drug Permeability Using Transwell with Shear Stress
Authors: Kim Junhyeong , Shin Seong-Ah , Lee Chang Sup , Chung Hye Jin
Published: December 2023

The development of drugs targeting the central nervous system (CNS) is challenging because of the presence of the Blood-Brain barrier (BBB). Developing physiologically relevant in vitro BBB models for evaluating drug permeability and predicting the activity of drug candidates is crucial. The transwell model is one of the most widely used in vitro BBB models. However, this model has limitations in mimicking in vivo conditions, particularly in the absence of shear stress. This study aimed to overcome the limitations of the transwell model using immortalized human endothelial cells (hCMEC/D3) by developing a novel dish design for an orbital shaker, providing shear stress. During optimization, we assessed cell layer integrity using trans-endothelial electrical resistance measurements and the % diffusion of lucifer yellow. The efflux transporter activity and mRNA expression of junctional proteins (claudin-5, occludin, and VE-cadherin) in the newly optimized model were verified. Additionally, the permeability of 14 compounds was evaluated and compared with published in vivo data. The cell-layer integrity was substantially increased using the newly designed annular shaking-dish model. The results demonstrate that our model provided robust conditions for evaluating the permeability of CNS drug candidates, potentially improving the reliability of in vitro BBB models in drug development.
Comparative Antioxidant and Antimicrobial Activities of Several Conifer Needles and Bark Extracts
Authors: Popescu (Stegarus) Diana , Frum Adina , Dobrea Carmen , Cristea Ramona , Gligor Felicia , Vicas Laura , Ionete Roxana , Sutan Nicoleta , Georgescu Cecilia
Published: December 2023

Nowadays, an increased concern regarding using natural products for their health benefits can be observed. The aim of this study was to assess and compare several phenolic compounds found in 15- to 60-year-old Douglas fir, silver fir, larch, pine, and spruce needle and bark extracts and to evaluate their antioxidant and antimicrobial activities. Spectrophotometric assays were used to determine the total polyphenol content and the antioxidant activity that was assessed by using the DPPH• radical scavenging assay (RSA), the ferric reducing antioxidant power assay (FRAP), and the ABTS•+ radical cation scavenging assay (ABTS). The phytochemical content was determined by using high-performance liquid chromatography, and the antimicrobial activity was determined by assessing the minimal inhibition concentration (MIC). The results of the study show a total polyphenol content of 62.45–109.80 mg GAE/g d.w. and an antioxidant activity of 91.18–99.32% for RSA, 29.16–35.74 µmol TE/g d.w. for FRAP, and 38.23–53.57 µmol TE/g d.w. for ABTS. The greatest quantity of phenolic compound for most of the extracts was for (+)-catechin, and it had values between 165.79 and 5343.27 µg/g d.w. for these samples. The antimicrobial inhibition for all the extracts was the strongest for Staphylococcus aureus (MIC 62.5–125 µg/mL). The extracts analyzed could be used for their bioactive potential after further investigations.
Genome-Wide Identification and Expression Analysis of the SUT Family from Three Species of Sapindaceae Revealed Their Role in the Accumulation of Sugars in Fruits
Authors: Jiang Sirong , An Pengliang , Xia Chengcai , Ma Wanfeng , Zhao Long , Liang Tiyun , Liu Qi , Xu Rui , Huang Dongyi , Xia Zhiqiang , Zou Meiling
Published: December 2023

Sapindaceae is an economically important family of Sapindales and includes many fruit crops. The dominant transport and storage form of photoassimilates in higher plants is sucrose. Sucrose transporter proteins play an irreplaceable role in the loading, transportation, unloading, and distribution of sucrose. A few SUT (sugar transporter) family genes have been identified and characterized in various plant species. In this study, 15, 15, and 10 genes were identified in litchi, longan, and rambutan, respectively, via genome-wide screening. These genes were divided into four subgroups based on phylogenetics. Gene duplication analysis suggested these genes underwent potent purifying selection and tandem duplications during evolution. The expression levels of SlSut01 and SlSut08 were significantly increased in the fruits of Sapindaceae members. The homologs of these two genes in longan and rambutan were also highly expressed in the fruits. The expression pattern of SUTs in three organs of the two varieties was also explored. Subcellular colocalization experiments revealed that the proteins encoded by both genes were present in the plasma membrane. This report provides data for the functional study of SUTs in litchi and provides a basis for screening sugar accumulation-related genes in fruits of Sapindaceae.
Salt Tolerance in Soybeans: Focus on Screening Methods and Genetics
Authors: Guan Rong-Xia , Guo Xiao-Yang , Qu Yue , Zhang Zheng-Wei , Bao Li-Gao , Ye Rui-Yun , Chang Ru-Zhen , Qiu Li-Juan
Published: December 2023

Salinity greatly affects the production of soybeans in arid and semi-arid lands around the world. The responses of soybeans to salt stress at germination, emergence, and other seedling stages have been evaluated in multitudes of studies over the past decades. Considerable salt-tolerant accessions have been identified. The association between salt tolerance responses during early and later growth stages may not be as significant as expected. Genetic analysis has confirmed that salt tolerance is distinctly tied to specific soybean developmental stages. Our understanding of salt tolerance mechanisms in soybeans is increasing due to the identification of key salt tolerance genes. In this review, we focus on the methods of soybean salt tolerance screening, progress in forward genetics, potential mechanisms involved in salt tolerance, and the importance of translating laboratory findings into field experiments via marker-assisted pyramiding or genetic engineering approaches, and ultimately developing salt-tolerant soybean varieties that produce high and stable yields. Progress has been made in the past decades, and new technologies will help mine novel salt tolerance genes and translate the mechanism of salt tolerance into new varieties via effective routes.