Search Results (98)

This study conducted a genome-wide identification and functional analysis of the glutathione S-transferase (GST) gene family in the xerophytic desert shrub Reaumuria soongorica. A total of 67 GST genes were identified, classified into seven subfamilies, including Phi and Tau, with family expansion primarily attributed to small-scale duplication events. The findings revealed that ResoGST52, a member of the Tau subfamily, serves as a core gene in drought response, exhibiting significant upregulation of 2.40-fold in leaves and 9.01-fold in roots under drought stress. Mechanistic investigations indicated that the expression of ResoGST52 is likely directly regulated by the transcription factor ResoDof17, with specific hydrogen bonding interactions identified between the two. Co-expression network analysis further demonstrated that ResoGST52 cooperates with key pathways such as plant hormone signaling, MAPK cascades, and glutathione metabolism to collectively respond to drought stress. Notably, evolutionary analysis revealed that ResoGST52 has undergone positive selection, with three positively selected sites identified. Among these, the p.Ala115Ser mutation increases the volume of the protein’s active site pocket, while the remaining mutations enhance surface hydrophobicity, thereby improving protein stability and catalytic efficiency under extreme drought conditions. In summary, this study not only systematically identifies the GST gene family in R. soongorica but also elucidates the central role of ResoGST52 in drought adaptation through multiple layers—from transcriptional regulation and co-expression networks to protein structural adaptive evolution—providing valuable candidate genes and theoretical insights for genetic improvement of drought tolerance in crops. Full article

This paper presents the results of a study of the dynamic performance of an aerostatic thrust bearing with a microgroove and simple diaphragms. The objective of this study was to determine the influence of the lubrication gap thickness and the volume of the microgroove and pockets on the structural dynamics. Unlike most studies that typically use the second-order harmonic oscillator equation as the characteristic equation, the root criteria are determined with high accuracy when the characteristic equation is of an order no lower than the fourth order. The presented formulas allow one to find the optimal calculated dimensional gap, microgroove and pocket volume in terms of the best dynamic performance. For a well-damped thrust bearing, the required response speed and sufficient stability margin can only be achieved within a narrow range of 1–2 times the bearing gap volume. Calculations have shown that to ensure satisfactory thrust bearing dynamics, the calculated gap should not exceed 10–15 µm. Full article

PDMS SlipChips are vital for precision medicine, but their performance often degrades when solutions leak or air pockets become trapped between layers. These failures stem from the inherent stickiness of PDMS and uneven surface contact, as the sliding nature of the device prevents permanent sealing. This work addresses these technical hurdles by integrating magnetic clamping with oil-infused lubrication and refined microwell geometries. A 3D-printed magnetic fixture maintains steady contact pressure during operation, while custom-made microstages provide the precise control needed to align microwells across the x–y plane. By allowing the porous PDMS to absorb silicone oil, we created a stable lubricating interface that prevents leakage and reduces friction without sacrificing mobility. We found that a microwell-to-channel width ratio of five substantially suppresses bubble formation compared with narrower designs. These enhancements ensure the generation of consistent, discrete concentration gradients and establish a reliable platform for high-throughput assays using minute sample volumes. Full article

Complex hydraulic transients induced during load adjustment of turbine units in long tailrace tunnels pose significant threats to the safety and stability of tailwater systems. In view of this, based on VOF multiphase flow and compressible water–air models, a three-dimensional full-flow-channel numerical model of long tailrace system incorporating surge shaft and downstream river channel was developed using computational fluid dynamics (CFD) software to explore the transient impact of load changes on flow rate, water level, and pressure pulsations under different flow regimes in the tailrace tunnel, including open channel flow, pressurized flow, and free-surface-pressurized flow. The results indicate that the discharge at the outlet of the tailrace tunnel exhibits attenuated oscillations in response to load variations, with the most severe fluctuations occurring due to the intense air–water interface mixing during free-surface-pressurized flow. Flow regime transitions are accompanied by air pocket phenomena, resulting in significant fluctuations in air volume fraction. Pressure pulsations show periodic variations, with energy gradually dissipating as they propagate downstream. Open channel flows predominantly feature high-frequency waves, while pressurized flows exhibit intense low-frequency pulsations. Additionally, load changes in one unit have an ultra-low-frequency impact on another unit sharing the same tailrace tunnel, with high-frequency waves being filtered out by the surge shaft. Full article

Human immunodeficiency virus (HIV-1) and SARS-CoV-2 continue to co-burden global health, motivating discovery of broad-spectrum small molecules. Conessine, a steroidal alkaloid, has reported membrane-active and antimicrobial properties but remains underexplored as a dual antiviral chemotype. To interrogate conessine’s multi-target antiviral potential against key enzymatic and entry determinants of HIV-1 and SARS-CoV-2 and to benchmark performance versus approved comparators. Eight targets were modeled: HIV-1 reverse transcriptase (RT, 3V81), protease (PR, 1HVR), integrase (IN, 3LPT), gp120–gp41 trimer (4NCO); and SARS-CoV-2 main protease (M^pro, 6LU7), papain-like protease (PL^pro, 6W9C), RNA-dependent RNA polymerase (RdRp, 7BV2), spike RBD (6M0J). Ligands (conessine; positive controls: dolutegravir for HIV-1, nirmatrelvir for SARS-CoV-2) were prepared with standard protonation, minimized, and docked using AutoDock Vina v 1.2.0exhaustiveness 4; 20 poses). Binding modes were profiled in 2D/3D. Protocol robustness was verified by re-docking co-crystallized ligands (RMSD ≤ 2.0 Å). Atomistic MD (explicit TIP3P, OPLS4, 300 K/1 atm, NPT; 50–100 ns) assessed pose stability (RMSD/RMSF), pocket compaction (Rg, volume), and interaction persistence; MM/GBSA provided qualitative energy decomposition. ADMET was predicted in silico. Conessine showed coherent, hydrophobically anchored binding across both viral panels. Best docking scores (kcal·mol⁻¹) were: HIV-1—PR −6.910, RT −6.672, IN −5.733; SARS-CoV-2—spike RBD −7.025, M^pro −5.745, RdRp −5.737, PL^pro −5.024. Interaction maps were dominated by alkyl/π-alkyl packing to catalytic corridors (e.g., PR Ile50/Val82, RT Tyr181/Val106; M^pro His41/Met49; RBD L455/F486/Y489) with occasional carbon-/water-mediated H-bonds guiding orientation. MD sustained low ligand RMSD (typically ≤1.6–2.2 Å) and damped RMSF at catalytic loops, indicating pocket rigidification; MM/GBSA trends (≈ −30 to −40 kcal·mol⁻¹, dispersion-driven) supported persistent nonpolar stabilization. Benchmarks behaved as expected: dolutegravir bound strongly to IN (−6.070) and PR (−7.319) with stable MD; nirmatrelvir was specific for M^pro and displayed weaker, discontinuous engagement at PL^pro/RdRp/RBD under identical settings. ADMET suggested conessine has excellent permeability/BBB access (high logP), but liabilities include poor aqueous solubility, predicted hERG risk, and CYP2D6 substrate dependence.Conessine operates as a hydrophobic, multi-target wedge with the most favorable computed engagement at HIV-1 PR/RT and the SARS-CoV-2 spike RBD, while maintaining stable poses at M^pro and RdRp. The scaffold merits medicinal-chemistry optimization to improve solubility and de-risk cardiotoxicity/CYP interactions, followed by biochemical and cell-based validation against prioritized targets. Full article

Chitin deacetylases (CDAs), which catalyze the deacetylation of chitin to produce chitosan, have garnered significant interest due to their environmental compatibility and ability to control product quality. However, the low conversion efficiency resulting from chitin’s high molecular weight and crystallinity, as well as structural limitations of CDAs, has impeded their industrial application. In this study, we present the integrated approach combining bioinformatics and computational tools (adaptive Poisson–Boltzmann solver, Fpocket, and ProteinPlus) to systematically analyze sequence features and variations in active pocket properties among CDAs from diverse origins. Experimental evaluation of the deacetylation activity of AnCDA, AsCDA, BaCDA, and ScCDA, each with distinct pocket characteristics, on chitin substrates with varying molecular parameters revealed that CDAs with high hydrophobicity scores and low surface-to-volume ratios exhibited superior efficiency in converting high-molecular-weight chitin. These findings guide the rational selection and engineering of CDAs for industrial biocatalysis. Full article

Background: Caesarean section (CS) is a critical intervention, yet stark inequities in access persist across low- and middle-income countries (LMICs). Over the last decade, governments have introduced policies to eliminate or subsidize user fees; however, the collective impact of these initiatives on utilization, equity, and financial protection has not been fully synthesized. Methods: We conducted a systematic review in line with PRISMA 2020 guidelines. Searches were conducted in PubMed, Dimensions, Google Scholar, Scopus, Web of Science, and government portals for studies published between 1 January 2009 and 30 May 2025. Eligible studies evaluated government-initiated financing reforms, including full user-fee exemptions, partial subsidies, vouchers, insurance schemes, and provider-payment restructuring. Two reviewers independently applied the PICOS criteria, extracted data using a 15-item template, and assessed the study quality. Given heterogeneity, results were synthesized narratively. Results: Thirty-seven studies from 28 LMICs were included. Most (70%) evaluated fee exemptions. Mixed-methods and cross-sectional designs predominated, while only six studies employed interrupted time series designs. Twenty-two evaluations (59%) reported increased CS uptake, ranging from a 1.4-fold rise in Senegal to a threefold increase in Kano State, Nigeria. Similar surges were also observed in non-African contexts such as Iran and Georgia, where reforms included incentives for vaginal delivery or punitive tariffs to curb overuse. Fourteen of 26 fee-exemption studies documented pro-rich or pro-urban drift, while catastrophic expenditure persisted for 12–43% of households, despite the implementation of “free” policies. Median out-of-pocket costs ranged from USD 14 in Burkina Faso to nearly USD 300 in Dakar’s slums. Only one study linked reforms to a reduction in neonatal mortality (a 30% decrease in Mali/Benin), while none demonstrated an impact on maternal mortality. Qualitative evidence highlighted hidden costs, delayed reimbursements, and weak accountability. At the same time, China and Bangladesh demonstrated how demographic reforms or voucher schemes could inadvertently lead to CS overuse or expose gaps in service readiness. Conclusions: Government-led financing reforms consistently increased CS volumes but fell short of ensuring equity, financial protection, or sustained quality. Effective initiatives combined fee removal with investments in surgical capacity, timely reimbursement, and transparent accountability. Future CS policies must integrate real-time monitoring of equity and quality and adopt robust quasi-experimental designs to enable mid-course correction. Full article

Monitoring environmental risks in operational landfills that contain closed cells requires non-invasive techniques capable of accurately characterizing subsurface contaminant dynamics. Electrical Resistivity Tomography (ERT) was selected because it enables continuous imaging across capped cells without intrusive drilling, with high sensitivity to the strong conductivity/resistivity contrasts that differentiate leachate (very low resistivity) from landfill gas or dry waste (high resistivity). This study employed ERT to spatially characterize contaminant distribution in closed cells within a landfill system in the Caribbean region of Colombia. Fifteen geophysical survey lines were acquired using Wenner, Dipole–Dipole, and Gradient arrays and processed through 2D, 2.5D, and 3D inversion models. The results revealed extensive low-resistivity zones (<2.1 Ω·m) in the southeastern sector, interpreted as leachate accumulations, some reaching the surface. Conversely, high-resistivity anomalies (>154 Ω·m) were identified in the southwestern area, associated with potential biogas pockets. Although these high-resistivity volumes represent <1.1% of the total modeled volume, their location and depth may pose geoenvironmental risks due to internal pressure build-up and preferential migration pathways. Existing leachate and gas collection systems showed adequate performance, though targeted corrective actions are recommended. ERT proved to be a precise, scalable, and cost-effective method for mapping subsurface contamination, offering critical insights for post-closure landfill management in tropical settings. Full article

Global navigation satellite systems (GNSS) can provide high-quality location information in outdoor environments. In indoor environments, GNSS cannot achieve accurate and stable location information due to the obstruction and attenuation of buildings together with the influence of multipath effects. Due to the rapid development of micro-electro-mechanical system (MEMS) sensors, today’s smartphones are equipped with various low-cost and small-volume MEMS sensors. Therefore, it is of great significance to study indoor pedestrian positioning technology based on smartphones. In order to provide pedestrians with high-precision and reliable location information in indoor environments, we propose a pedestrian dead reckoning (PDR) method based on Transformer+TCN (temporal convolutional network). Firstly, we use IMU (inertial measurement unit)/PDR pre-integration to suppress the inertial navigation divergence. Secondly, we propose a step length estimation algorithm based on Transformer+TCN. The Transformer and TCN networks are superimposed to improve the ability to capture complex dependencies and improve the generalization and reliability of step length estimation. Finally, we propose factor graph optimization (FGO) models based on sliding windows (SW-FGO) to provide accurate posture, which use accelerometer (ACC)/gyroscope/magnetometer (MAG) data to establish factors. We designed a fusion positioning estimation test and a comparison test on step length estimation algorithm. The results show that the fusion method based on SW-FGO proposed by us improves the positioning accuracy by 29.68% compared with the traditional FGO algorithm, and the absolute position error of the step length estimation algorithm based on Transformer+TCN in pocket mode is mitigated by 42.15% compared with the LSTM algorithm. The step length estimation model error of Transformer+TCN is 1.61%, and the step length estimation accuracy is improved by 24.41%. Full article

Previous studies have demonstrated that Helianthus tuberosus L. polysaccharide (HTLP) exhibits potent immunomodulating activity. The aim of this study was to investigate the molecular mechanisms underlying this activity and explore its potential applications in various anti-inflammatory models. We examined the anti-inflammatory potential of HTLP using in vitro and in vivo models. In vitro, we assessed the impact of HTLP on the expression of key inflammatory genes (TNFA, IL1B, IL6, IL12B, IL23, CD40, CD80, CD274, CSF1, and NAMPT) in lipopolysaccharide (LPS)-stimulated THP-1 cells. In vivo, we employed rat pocket granuloma and formalin- and carrageenan-induced oedema models. HTLP significantly reduced oedema volume in the in vivo models. In the carrageenan-induced oedema model, HTLP exhibited efficacy significantly higher than that of ibuprofen, reducing oedema by 76% at 8 h (p < 0.01). In the air pouch granuloma model, HTLP showed comparable anti-inflammatory activity to ibuprofen. In the formalin-induced oedema model, HTLP reduced oedema, demonstrating less efficacy than ibuprofen, with a reduction of 58% versus ibuprofen’s 65% (p < 0.001). The anti-inflammatory mechanism of HTLP involves not only the suppression of pro-inflammatory cytokine expression (TNFA, IL1B, IL6, IL12B, IL23, CD40, CD80, CD274, and CSF1) but also the activation of cell survival and cellular defence mechanisms (NAMPT) and the upregulation of the anti-inflammatory cytokine (IL10). The observed biological activity of HTLP suggests its potential as a valuable therapeutic agent for inflammatory conditions. The combination of functional and molecular evidence demonstrates HTLP’s potent anti-inflammatory properties across multiple models, with efficacy approaching or exceeding that of ibuprofen in certain models. However, further studies are necessary to fully elucidate its mechanism of action and to evaluate its long-term efficacy and safety. Full article

Background/Objectives: Pregnancies complicated by idiopathic polyhydramnios are linked to a heightened risk of numerous maternal and perinatal complications. We aim to study the implications of polyhydramnios in term pregnancies complicated with gestational diabetes mellitus (GDM). Methods: A prospective cohort study including 340 GDM cases was conducted. An ultrasound scan was conducted at term between 37 and 40 weeks and amniotic fluid volume (AFV) was assessed by measuring the amniotic fluid index (AFI) and the single deepest pocket (SDP). Maternal demographics and obstetric and perinatal outcomes were evaluated after delivery. We performed comparisons between groups with normal AFV and polyhydramnios (AFI ≥ 24 cm or SDP ≥ 8 cm), and between groups with normal and increased AFV (AFI or SDP ≥ 75th centile). A multivariate logistic regression analysis was performed to study association between AVF measurements and adverse maternal and perinatal outcomes. Results: We found that women with GDM and polyhydramnios at term had a higher risk of maternal (54.3 vs. 27.5%, p < 0.001) and perinatal adverse outcomes (65.7% vs. 46.5%, p < 0.03). The increased AFV group showed a higher risk of fetal overgrowth (LGA: 21.4% vs. 8.2%, p < 0.001 and macrosomia: 19.8% vs. 5.4%, p < 0.001, respectively) and a lesser risk of delivering an SGA fetus (6.3% vs. 13.6%, respectively). Both AFI and SDP showed a significant correlation with newborn weight (r = 0.27; p < 0.001 and r = 0.28; p < 0.001, respectively) and newborn centile (r = 0.26; p < 0.001 and r = 0.26 for both). Subsequent to conducting a multivariate logistic regression analysis adjusted for pregestational BMI, nulliparity, and insulin treatment, both AFI and SDP were significantly associated with perinatal complications, but AFI showed a stronger association with fetal overgrowth (aOR 1.11; p = 0.004 for a LGA fetus and aOR 1.12; p = 0.002 for macrosomia) and with lower risk of delivering an SGA fetus (aOR 0.89; p = 0.009) or IUGR fetus (aOR 0.86; p = 0.03). ROC analysis showed a poor diagnostic performance of both AFI and SDP for identifying macrosomia (AUC 0.68 for AFI, and 0.65 for SDP). Conclusions: Detection of polyhydramnios at term, whether using AFI or SDP, identifies a subgroup of women with gestational diabetes with higher risks of obstetric and perinatal complications. Cases with increased AFV (AFI ≥ 18 cm or SDP ≥ 6.5 cm) are also associated with an increased risk of fetal overgrowth and may require more intensive monitoring for management and optimal delivery timing, with the aim of improve perinatal outcomes. Full article

Previous studies showed a potent anti-inflammatory activity of Solanum tuberosum L. polysaccharide (STP), which inhibited pro-inflammatory cytokines and stimulated anti-inflammatory ones in peptic ulcer models. Thus, the main goal of this study was to find out the molecular background of such activity and possible applications in different anti-inflammatory models. This study investigated the anti-inflammatory potential of the polysaccharide STP using model of LPS-induced inflammation in THP-1 macrophage-like cells (on the expression of IL1B, IL6, IL10, TNF, NFKB1, BCL2, NRF2, and BAX—genes involved in the regulation of inflammatory processes and oxidative stress), rat pocket granuloma, and carrageenan-induced oedema models. STP significantly reduced oedema volume, exhibiting a comparable anti-exudative effect to ibuprofen and surpassing the control group. The anti-inflammatory mechanism of STP extends beyond suppression of proinflammatory cytokine (IL1B, IL6, TNF) expression, as it also activates cellular defence mechanisms (NRF2, BCL2, BAX) and expression of anti-inflammatory cytokine (IL10). This complex, multifactorial action suggests that STP may possess significant therapeutic value for inflammatory conditions. The combined functional and molecular findings underscore STP’s potent anti-inflammatory properties, comparable to ibuprofen. Full article

Background: The increasing global incidence of breast cancer calls for the identification of new therapeutic targets and the assessment of possible neem-derived inhibitors by means of computational modeling and integrated genomic research. Methods: Originally looking at 59,424 genes throughout 42 samples, we investigated gene expression data from The Cancer Genome Atlas—Breast Cancer (TCGA-BRCA) dataset. We chose 286 genes for thorough investigation following strict screening for consistent expression. R’s limma package was used in differential expression analysis. The leading candidate’s protein modeling was done with Swiss-ADME and Discovery Studio. Molecular docking studies, including 132 neem compounds, were conducted utilizing AutoDock Vina. Results: Among the 286 examined, mitochondrially encoded cytochrome C oxidase III (MT—CO3) turned out to be the most greatly overexpressed gene, showing consistent elevation across all breast cancer samples. Protein modeling revealed a substantial hydrophobic pocket (volume: 627.3 ų) inside the structure of MT—CO3. Docking investigations showed five interesting neem-derived inhibitors: 7-benzoylnimbocinol, nimolicinol, melianodiol, isonimocinolide, and stigmasterol. Strong binding affinities ranging from −9.2 to −11.5 kcal/mol and diverse interactions with MT—CO3, mostly involving the residues Phe214, Arg221, and Trp58, these molecules displayed. With hydrophobic interactions dominant across all chemicals, fragment contribution analysis revealed that scaffold percentage greatly influences binding effectiveness. Stigmasterol revealed greater drug-likeness (QED = 0.79) despite minimal interaction variety, while 7-benzoylnimbocinol presented the best-balanced physicochemical profile. Conclusion: Connecting traditional medicine with current genomics and computational biology, this work proposes a methodology for structure-guided drug design and development using neem-derived chemicals and finds MT—CO3 as a potential therapeutic target for breast cancer. Full article

Background: Advanced platelet-rich fibrin + (A-PRF+) represents a third generation of autologous platelet derivatives. Appropriate centrifugation conditions cause the formation of a clot containing platelets, which slowly release growth factors that influence healing. The objective of this article was to undertake a review of the available literature on the effectiveness of A-PRF+ use in hard tissue procedures. Materials and methods: In order to ensure the most accurate and relevant results, only randomized clinical trials regarding bone regeneration techniques/bone healing that compared the effect of the A-PRF+ addition in dentistry were included in this study. Articles taken into consideration for the review were published between the beginning of 2014 and 31 December 2024. The search of manuscripts for the review was conducted using the PubMed, Scopus, Google Scholar, and Cochrane databases. For this study, 10 articles focusing on A-PRF+ were qualified. Results: A-PRF+ was found to increase the post-surgical vertical and horizontal alveolar ridge dimensions. The bone formed in the surgical site presented a higher volume of vital and non-vital bone and a more optimal bone composition, at the same time providing a lower percentage of connective tissue inclusions. When combined with other grafting biomaterials, A-PRF+ enhanced their performance and integration. A-PRF+ did not have any significant effect on the mineral bone density compared with other grafting materials. Compared with PRF and other blood derived plasmas rich in growth factors, the performance of A-PRF+ was generally better, but often with no statistical significance. The treatment of periodontal defects measured by the reduction in pocket depth and clinical attachment level also fared better with the A-PRF+ addition, although there was no differences noted between A-PRF+ and biphasic calcium phosphate and xenograft. Finally, the A-PRF+ addition improved the primary implant stability in the evaluated studies. Conclusions: The A-PRF+ addition to the surgical protocols significantly enhanced the healing of the bone and when combined with biomaterials improved their integration and increased the implant insertion torque, improving the primary and secondary stability. It may be a viable alternative for patients that express their concern towards human- and animal-derived biomaterials. Full article

Background: The aim of this study was to analyse the results of the mastoid obliteration technique with sticky bone (SB) and compare them with those obtained using bioactive glass S53P4 (BAG). Methods: This prospective preliminary study comprised 28 adults who underwent canal wall down (CWD) surgery using two mastoid obliterative techniques: SB (n = 21) or BAG (n = 7). The SB group was treated with the patients’ own bone dust and injectable platelet rich fibrin (IPRF) (n = 13%) or bone dust, IPRF, and additionally allogenic lyophilised demineralised bone (n = 9%). Results: Nine months after the surgery, in the SB group, retroauricular depression was observed in three (14%) patients, temporary retroauricular fistula in one (5%), and a conical and smooth external auditory canal (EAC) was achieved in 15 (71%). Mean EAC capacity was 0.6 mL higher than in the contralateral ear. In the SB group, the tympanic membrane (TM) of nineteen (91%) patients was fully healed, one (5%) had TM perforation, and one (5%) developed a retraction pocket. In the BAG group, retroauricular depression was observed in four (57%) patients, temporary retroauricular fistula was present in one (14%), and a conical and smooth EAC was achieved in five (71%). Mean EAC capacity was 0.3 mL higher than on the opposite side. In the BAG group, we stated six (86%) patients with fully healed TM and one (14%) with a retraction pocket. One cholesteatoma was found in the BAG group and two in SB, (14% vs. 10%). After 9 months, all patients in both groups achieved a dry and self-cleaning cavity. Conclusions: Mastoid obliteration in CWD surgery using SB or BAG allows for reconstruction of the conical shape of the EAC with a volume similar to that of a healthy ear. Both techniques seem to have a minimal risk of complications and result in a dry, self-cleaning cavity. Further studies concerning a larger series of cases are necessary to confirm the findings of this preliminary analysis. Full article