Plant "intelligence" and "sensation" are controversial notions in contemporary botany. While some scientists argue that sensory awareness, learning, memory, communication, and possibly a kind of consciousness should be ascribed to plants, a substantial part of the scientific community dismisses such claims because of insufficient evidence and the lack of neural systems in plants. In this paper, I will examine this issue from a historical and epistemological perspective. First, I will go back to a crucial precedent that is often evoked in these debates, i.e., Darwin's remarks on plant "sensation" and "behavior" and his analogy between roots and brains in the 1880 book The Power of Movement in Plants. I will point out that the issue was already well known and controversial in the nineteenth century. I will then examine contemporary debates starting from new experiments and evidence on plant cognitive powers. I will argue that current debates are partly based on elements that have been available since Darwin, such as postulates of biological continuity among living beings and the use of analogy, leading to an epistemological contrast between the need to avoid ungrounded anthropomorphic projections and the argument that kinds of cognitive states could be realized in plants. I also finally point out that investigations on animal ethics and the revaluation of non-Western views on animism and ecology have recently been introduced into this debate to break the epistemological balance between opposing views.
Jumping spiders, a diverse and charismatic group of invertebrates, are renowned for their highly specialized visual systems, complex courtship behaviours, and broad ecological adaptability. However, the persistent lack of high-quality genomic resources has hindered investigations into the genetic basis and phenotypic evolution of these key traits. To address this gap, we performed a de novo assembly of a chromosome-level genome for Spartaeus platnicki, a species representing the basal lineages of jumping spiders. This assembly, achieved by integrating PacBio HiFi long reads, Illumina short reads, RNA-seq, and Hi-C data, comprises 15 pseudo-chromosomes including the X1 and X2 sex chromosomes, spanning a total length of 3.71 Gb with a scaffold N50 of 262 Mb and a BUSCO completeness of 98.60%. Repetitive elements account for approximately 65.57% of the genome. We annotated 15,660 protein-coding genes, achieving a BUSCO completeness of 97.60%. This high-quality genome establishes a foundational resource for investigating the genetic architecture underlying key traits and their phenotypic evolution in jumping spiders.
Until recently, Na2-salt of 4-acetamido-4'-isothiocyano-stilbene-2,2'-disulfonic acid (SITS or stilbene reagent) was applied to study transport of anions into bacterial cells by conventional methods; SITS has not yet been used for biosensor investigations of transport. In this study, SITS was first employed in a biosensor method to examine the stilbene reagent effect on process of substrate transport into intact and immobilized cells of cultures-receptors of microbial sensor devices. The biosensor-based technique (biosensor method for assessment of features of metabolism, BMAFM) for studying transport of substrate into microbial cells is currently under further development. To explore substrate transport, laboratory models of reactor and membrane microbial electrochemical sensor devices with the Clark-type oxygen electrode as a transducer and Pseudomonas sp. or Rhodococcus opacus 1CP as a culture-receptor were used in this study. For R. opacus cells stored for 7 months in non-growth conditions, an activating effect on benzoate 1,2-dioxygenase was observed for cells washed after treating with SITS. Using the electrochemical biosensor method, it has been shown that SITS inhibited transport of maltose/benzoate into both intact and immobilized cells of P. sp. and R. opacus leading to a decrease in the cells' response to substrate. Thus, SITS can be used as an inhibitor of anion transport while studying substrate transport into microbial cells by means of the biosensor method. Furthermore, the stilbene reagent-assisted biosensor technique may significantly facilitate and provide rapid measurements during research process.
The production of precision workpieces from long products by shearing remains a challenging problem due to bending deformation, end-face cracking, and insufficient dimensional accuracy. Dies with differentiated clamping represent a promising solution; however, the influence of their design parameters on force transmission, energy efficiency, and deformation localization remains insufficiently understood. The aim of this study is to investigate the technological and design features of dies with differentiated clamping of long products and to establish quantitative relationships between wedge mechanism parameters, friction conditions, and process performance. A systematic classification of die designs was developed based on clamping method, force-transmission mechanism, blade kinematics, and structural configuration. Analytical models were derived to describe force transmission in wedge mechanisms and to determine the relationship between clamping force, shearing force, friction conditions, and mechanism efficiency. Finite-element simulations of the shearing process were performed using DEFORM 3D to analyze stress-strain state evolution, deformation localization, and damage development. Experimental investigations were carried out on a 2.5 MN crank press using strain-gauge measurements to validate the theoretical predictions and evaluate workpiece quality. The results demonstrate that force transmission efficiency and the clamping-to-shearing force ratio are strongly governed by wedge geometry and friction conditions. Rational ranges of force-transmission angles were identified, providing an optimal balance between force amplification and energy efficiency. Numerical simulations revealed that differentiated clamping localizes plastic deformation and damage accumulation within a narrow region adjacent to the blade clearance, suppresses workpiece bending, and promotes stable crack propagation along the intended separation plane. Experimental validation confirmed the adequacy of the developed analytical model, with the discrepancy between calculated and measured peak shearing forces not exceeding 8%. Magnetic particle and dye penetrant inspections verified the absence of end-face cracks in workpieces produced from Steel 0 and Steel 40H. The developed die design improved geometric accuracy while reducing overall dimensions and weight compared with conventional solutions. The scientific novelty of the work lies in establishing quantitative relationships between wedge geometry, friction conditions, force transmission efficiency, and deformation localization during shearing with differentiated clamping. The obtained results provide a scientific basis for controlling the stress-strain state and fracture behavior during precision separation of long products and may be used for the design and optimization of energy-efficient shearing technologies.
Breast cancer remains a global challenge, with rising incidence rates. While treatment advancements have improved outcomes, systemic administration of cytostatic agents continues to cause severe adverse effects, including myelosuppression, heart failure, and infertility, due to non-specific biodistribution. Nanoparticle-based drug delivery systems have been explored as an alternative approach to improve therapeutics delivery and reduce non-specific effects. Zinc-based nanoparticles demonstrate ability to induce cytotoxic responses in cancer cells in vitro, making them suitable systems for probing cell-type-specific effects. In this study, we evaluated the in vitro cytotoxic effects of spherical zinc peroxide (ZnO₂) nanoparticles (20-80 nm and 50-300 nm), commercial ZnO nanoparticles, and tetrapodal ZnO (T-ZnO) microparticles in MCF-7 breast cancer cells and RMF-EG fibroblasts. ZnO₂ nanoparticles demonstrated dose-dependent cytotoxicity (1 µg/mL-10 mg/mL), inducing a significantly higher death rate of cancer cells than normal fibroblasts, which retained >75% viability at comparable doses. Flow cytometry investigations revealed that ZnO₂ nanoparticles exhibited preferential cellular uptake in MCF-7 cells as compared to fibroblasts. Overall, these findings indicate different cytotoxic responses of ZnO-based micro and nanoparticles between MCF-7 cells and RMF-EG fibroblasts under in vitro conditions. Further studies are required to validate these observations in more complex biological systems and to clarify the underlying mechanisms.
Building upon the ODE model describing the dynamics of healthy and leukemic cells introduced in Kumar et al. (2024); Stiehl and Marciniak-Czochra (2012), we propose an extended framework that incorporates a control variable representing the effects of chemotherapy. This extension aims to provide a more refined mathematical basis for investigating anti-cancer strategies. First, we perform a stability analysis of the equilibria associated with healthy and leukemic states, partly estimated from clinical data. This analysis reveals a complex structure, including the emergence of a continuum of coexistence states and bifurcation thresholds that play a key role in the subsequent optimization stage. Based on these findings, we investigate an optimal control problem to minimize leukemia stem cells while limiting drug toxicity. Pontryagin's Maximum Principle provides necessary conditions for optimality, and direct numerical optimization confirms the predicted structures, motivating the study of the static problem. This static formulation reveals an unconventional feature: the cost functional becomes set-valued due to the continuum of equilibria, placing the problem outside the scope of standard methods. Simulations reveal a turnpike phenomenon, where over long time horizons the dynamic trajectories closely approximate the ideal static structure. Finally, a sensitivity analysis of the performance criterion with respect to key parameters complements the study, providing preliminary insights into which biological mechanisms may influence the optimal therapeutic outcomes. We conclude with a discussion of these findings.
Spondyloarthropathies (SpA) are characterized by low back pain and limited mobility. Therefore, physical activity (PA) is an essential part of the treatment, yielding positive effects on clinical symptoms. Digital health applications (DHAs) present new opportunities to promote clinical outcomes, however, their long-term effectiveness is often limited by low adherence and high dropout rates.This study investigates whether integrating personalized or AI-driven coaching enhances the therapeutic benefits of DHA in patients with SpA. SpAs patients were randomized into one of 3 groups. They were instructed to exercise at least 2-3 times per week for 6 months with the DHA according to their group (intervention groups: ViViRA (with personal coaching) or Kaia Health (with AI-based coaching); control group: ViViRA (without coaching)). Personal coaching consisted of a one-time, 30-min online coaching session prior to using DHA, while the AI coaching consisted of video-based AI integrated into DHA to provide movement guidance during each session. At baseline, after 3 and 6 months sociodemographic, questionnaires and mobility were assessed. Data from 78 participants were analyzed (mean age 51 years; 68% female). All three digital interventions showed a significant improvement in mobility (Bath Ankylosing Spondylitis Metrology Index (BASM), range: 0-10, lower scores = better mobility; BL-3 month: mean BASMI change - 0.6 to - 0.7; all p < 0.001). Pain intensity decreased substantially in all arms (PainDETECT, neuropathic pain, range: 0-38, higher scores = more severe pain; BL-6 month: mean reduction - 4.6 to - 6.6 points; all p ≤ 0.006). PAHCO (Physical Activity-related Health Competence) control competence increased over time and reached statistical significance only in the ViViRA + coaching group (PAHCO: higher scores = better physical activity-related health competence; BL-6 month: + 1.02, p = 0.013) but did not exceed the other interventions in a direct comparison. Overall, none of the coaching strategies showed significant superiority over the stand-alone digital therapy. Adherence was the same in all groups after 3 months (2-3 weekly use of DHA). Digital movement therapy with the use of DHA improves mobility and pain independently of coaching in SpAs patients. In contrast, personal coaching has been shown to improve health-related skills which could indicate potential benefits for self-management and long-term treatment adherence.Trial registration The study is registered in the German clinical trial registry (DRKS) under the following ID: DRKS00035191, https://www.drks.de/search/de/trial/DRKS00035191/details, Registration date: 01.10.2024.
Prematurity and term low birth weight (LBW) are important contributors to neonatal morbidity and mortality in Afghanistan. Evidence from hospital-based studies in Herat remains limited, particularly studies that distinguish prematurity from term LBW. This study aimed to identify maternal, socioeconomic, obstetric, and pregnancy-related factors associated with prematurity and term LBW among newborns delivered in Herat, western Afghanistan. An unmatched hospital-based case-control study was conducted at Herat Midwifery Hospital from June 15 to September 15, 2023. The study included 176 premature infants, 84 term LBW infants, and 290 full-term normal-birth-weight controls. Prematurity was defined as birth before 37 completed weeks of gestation, and term LBW was defined as birth at ≥ 37 completed weeks with birth weight < 2500 g. Data were collected from hospital records and maternal interviews. Separate adjusted binary logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for prematurity and term LBW compared with full-term normal-birth-weight controls. Statistical significance was set at p < 0.05. Prematurity was associated with medium perceived economic status (OR = 2.21, 95% CI: 1.04-4.73), bad perceived economic status (OR = 5.16, 95% CI: 2.06-12.91), preeclampsia (OR = 5.98, 95% CI: 1.72-20.76), pregnancy-related health problems (OR = 13.76, 95% CI: 5.32-35.61), substance use during pregnancy (OR = 2.88, 95% CI: 1.11-7.45), and cesarean section (OR = 3.37, 95% CI: 1.99-5.73). Term LBW was associated with medium perceived economic status (OR = 3.98, 95% CI: 1.29-12.30), bad perceived economic status (OR = 19.62, 95% CI: 5.09-75.63), pregnancy-related health problems (OR = 8.88, 95% CI: 2.46-32.02), and cesarean section (OR = 9.76, 95% CI: 4.85-19.65). Poor perceived economic status and pregnancy-related health problems were associated with both prematurity and term LBW. Preeclampsia and substance use were associated mainly with prematurity. Cesarean section should be interpreted as a marker of high-risk obstetric conditions rather than as a direct causal factor. These findings support strengthening antenatal risk detection, management of pregnancy complications, and targeted maternal health interventions in Herat.
Reanalysis of genomic data in rare disease is highly effective in increasing diagnostic yields but remains limited by manual approaches. Automation and optimization for high specificity will be necessary to ensure scalability, adoption and sustainability of iterative reanalysis. We developed Talos, an open-source tool that automates variant prioritization by integrating dynamically updated gene-disease and variant-level evidence with inheritance-aware filtering and validated its performance using data from 1,089 individuals with rare disease. Trio-based analysis identified 90% of known diagnoses, returning 1.3 variants per case on average. Variant burden reduced to one variant per 200 cases on iterative monthly reanalysis. Application to an unselected cohort of 4,735 undiagnosed individuals identified 241 diagnoses (5.1% yield): 78 (32%) due to new gene-disease relationships, 54 (22%) due to new variant-level evidence and 109 (45%) due to improved analysis strategies. Our automated, iterative reanalysis model demonstrates the feasibility of delivering frequent, systematic reanalysis at scale.
Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) represents a significant worldwide public health challenge. Toll-like receptors (TLRs) serve as essential components of the innate immune system; however, their involvement as genetic predisposition factors for HBV-ACLF remains incompletely understood. The present investigation aimed to explore the relationship between genetic variants in TLR2, TLR4, and TLR9 and the association with HBV-ACLF (compared to CHB patients). 160 individuals with HBV-ACLF, 280 subjects diagnosed with chronic hepatitis B (CHB), and 280 healthy controls were recruited for this study. Two primary laboratory techniques were utilized in this study. First, serum concentrations of TLR2, TLR4, and TLR9 were assessed using an enzyme-linked immunosorbent assay (ELISA). Second, a PCR-restriction fragment length polymorphism (PCR-RFLP) assay was adopted for the detection of specific genetic variants. HBV-ACLF patients exhibited substantially higher serum concentrations of TLR2, TLR4, and TLR9 than both CHB patients and healthy controls (all p < 0.05). Compared to the CHB control group, two specific polymorphisms emerged as significant risk factors for HBV-ACLF: TLR2 - 196 to - 174 del (D/D genotype: OR = 1.87, 95% CI 1.14-3.05, p = 0.012; D allele: OR = 1.53, 95% CI 1.16-2.03, p = 0.003) and TLR9 rs187084 (C/C genotype: OR = 2.66, 95% CI 1.22-5.78, p = 0.021; C allele: OR = 1.69, 95% CI 1.14-2.50, p = 0.011). The remaining loci showed no meaningful associations (p > 0.05) Elevated serum concentrations of TLRs are observed in individuals diagnosed with HBV-ACLF. Additionally, the TLR2 - 196 to - 174 deletion variant and the TLR9 rs187084 polymorphism demonstrate a robust association with HBV-ACLF when compared to CHB controls. These factors warrant further investigation in prospective cohorts to determine their potential value in predicting disease progression.
Numerous mood and behavior disorders have developmental origins resulting from genetic and environmental interactions. Maternal tryptophan hydroxylase 1 (TPH-1)-dependent serotonin (5-HT) depletion alters embryonic brain development, but its long-term impact on adult progeny has never been investigated. Here we demonstrate that adult WT male offspring born to hyposerotonergic Tph1+/- dams ( ~ 60% deficit) display hyperlocomotion, impaired self-care and an increased anxiety relative to those from WT dams. Concomitantly, norepinephrine (NE) levels and dopamine (DA) turnover are significantly reduced in the mesencephalon and brainstem, whereas monoaminergic cell density is not affected. In the frontal cortex of the offspring, maternal hyposerotonergic status results in significant reduction in DA, NE and 5-HT levels, accompanied by transcriptomic changes, notably in monoaminergic system signaling, synaptic function and plasticity, methylation processes and myelination. Myelination is also impaired as revealed by a reduced thickness of the corpus callosum. Maternal hyposerotonemia thus appears sufficient to affect the phenotype of the adult WT progeny. TPH-1-dependent 5-HT deficit during pregnancy could be considered as a risk factor for neurodevelopmental disorders in the offspring.
Studies of brain morphology in mental illness often focus on a few neuroimaging phenotypes. Here we present a comprehensive morphological characterization in obsessive-compulsive disorder (OCD) in a large sample (2255 OCD, 2264 controls) using nine cortical and four subcortical phenotypes, including several not previously examined in OCD, among them a subcortical structural similarity network phenotype developed here. Spatially distinct regional alterations emerged across structural phenotypes: cortical curvature alterations in default mode and frontoparietal networks, increased structural similarity network node degree in sensorimotor regions, widespread volume reductions associated with medication use, and localized subcortical shape alterations. In brain-behavior predictive models, curvature phenotypes showed the strongest associations with clinical features. Cortical alterations, especially in structural similarity networks, were associated with specific gene expression patterns, implicating dysregulation of excitatory neurons. RNA-sequencing data from tissue collected during functional neurosurgery revealed that genes downregulated in the dorsolateral prefrontal cortex in OCD contributed to the gene expression patterns linked to cortical alterations. Previously reported differentially expressed genes from postmortem brain studies of OCD also contributed. These findings support the importance of a comprehensive approach to characterizing brain morphology and suggest that cortical curvature and structural similarity alterations reflect key pathophysiological processes in OCD.
Weld quality is an important parameter in ensuring the overall safety and integrity of pipelines made from high-strength steel used for the transmission of oil and natural gas. In multi-layer pipeline welding, poor heat input control can result in excessive reinforcement, lack of fusion, unsatisfactory microstructural changes, and poor mechanical properties. Hence, in the current research, the effects of Low Heat Input (LHI) and High Heat Input (HHI) on the shape, thermal behaviour, and mechanical properties of API 5 L L415Q pipeline steel were analyzed via welding using the GTAW-SMAW process. The GTAW process is used for the root pass, while the SMAW process is used for the hot, fill, and cap passes. A combination of Taguchi experimental design and desirability-based multi-response optimization was used to determine the optimal values of welding current, welding voltage, welding travel speed, heat input, and reinforcement properties for individual passes. Welding parameters were verified through tensile tests, impact energy tests, hardness tests, bend tests, macroexamination, non-destructive testing, and field-scale application of the developed welding technique. Both LHI and HHI welding conditions produced welded joints that met the API pipeline welding specifications. LHI welding conditions offered better penetration consistency and a more uniform hardness distribution, since the thermal cycle was lower and the cooling rate was higher. In contrast, HHI welding conditions yielded higher impact energy in the weld metal at the fusion line and in the heat-affected zones, due to variations in the thermal cycle. The heat-input optimization strategy also resulted in reduced grain coarsening and a balanced metallurgical balance between strength and toughness. Moreover, industrial-scale validation of 250 pipeline girth welds has indicated consistent welding quality, acceptable geometry, and the absence of critical weld defects on radiographic testing.
Erysiphe corylacearum is the main causal agent of hazelnut powdery mildew, causing substantial damage in the Black Sea region of Türkiye. Despite its economic importance, molecular resources for this obligate biotrophic pathogen remain severely limited. This study presents the first comprehensive transcriptomic dataset for E. corylacearum obtained through Illumina sequencing of mRNA from naturally infected hazelnut leaves. Using targeted epidermal peeling to enrich fungal material while minimizing host contamination, over 66 million high-quality paired-end reads were generated. De novo Trinity-based assembly yielded an initial set of 135,404 unigenes for annotation, and the final NCBI-cleaned TSA submission contains 100,824 transcript sequences. Functional annotation assigned database matches to 71% of the initial unigene set, including sequences related to pathogenicity, sexual compatibility, and reproduction. The dataset also includes over 29,000 high-confidence intra-sample sequence variants from this single metatranscriptomic sample providing a candidate resource for future marker development, diagnostic assays, and comparative analyses pending validation across additional isolates. This transcriptomic resource will facilitate investigations into pathogen biology, host-pathogen interactions, and improved disease management strategies.
Land-use changes in tropical dry forests (TDF) have rapidly reduced native vegetation, disrupting gene flow dynamics of tree species. Bursera cuneata is a co-dominant TDF tree in central Mexico, which is threatened by habitat loss and overexploitation. We investigated landscape drivers of functional connectivity of B. cuneata across scales to inform species conservation efforts. We genotyped 227 B. cuneata individuals from 33 populations across five hydrological basins: covering western, central, and southern Mexico, at 10,499 single-nucleotide polymorphism (SNP) loci. We examined spatial patterns of genetic structure among hydrological basins and the landscape correlates of gene flow. We applied gravity models that incorporated within-site (i.e., local conditions within populations; slope and east aspect) and between-site (terrain roughness, habitat suitability, and habitat cover) factors associated with B. cuneata gene flow. Clustering analyses showed genetic structure among basins, with higher differentiation in more isolated regions. Gravity models revealed that functional connectivity is a scale-dependent process. Specifically, terrain roughness was the primary factor of connectivity at finer scales (1000-3000 m), while TDF cover became the main driver at regional scales (>4000 m). We recommend protecting and prioritizing crucial TDF remnants to maintain large-scale gene flow by integrating urban natural parks as important links to prevent genetic isolation between urban and rural populations.
Undisturbed marine soft clay from Daya Bay in Shenzhen poses severe geotechnical challenges owing to its high sensitivity and low shear strength. In this study, the microstructural evolution and underlying mechanical mechanisms of this soft clay under one-dimensional consolidation were systematically investigated. A multi-scale analytical approach was adopted, integrating Mercury Intrusion Porosimetry (MIP), dual-energy synchrotron X-ray Micro-Computed Tomography (Micro-CT) with phase recovery technology, and Discrete Element Method (DEM) simulations implemented in PFC3D 6.0. The results show that one-dimensional consolidation induces a distinct structural transition of the clay's pore size distribution from bimodal to unimodal, with the connectivity of macropores being completely destroyed under high consolidation pressure. Two structural yield stresses were identified at 62 kPa and 676 kPa, corresponding to the structural failure of inter-cluster aggregates and intra-cluster particles, respectively, which characterizes the mechanical transformation of the clay from aggregate rearrangement to intra-aggregate compression. Numerical simulation results further demonstrate that the increase in consolidation pressure leads to a gradual rise in the particle coordination number and a significant decrease in the contact-sliding ratio, thereby enhancing the structural stability of the clay skeleton. These findings establish a quantitative correlation between the microscopic pore structure reorganization and macroscopic mechanical response of soft clay, and provide a robust mechanistic basis for accurate settlement prediction and ground improvement design in coastal geotechnical engineering.
The genetic landscape of human infertility is complex with diverse etiologies. Identifying the underlying etiology is crucial for guiding reproductive decisions and improving management for infertile couples. Here, we aim to report on the molecular spectrum of monogenic genetic causes of reproductive failure. Over a 3-year period, we recruited all infertile couples considering assisted reproductive technologies (ART) for whom the underlying genetic cause had been identified, in either partner, using exome sequencing (ES). Clinical data of all participants along with their hormonal profiles, sonographic findings and spermograms were recorded. The study included 50 couples with primary infertility. Clinically, male factor infertility was documented in 26 patients, female factor infertility in 10, while reproductive failure was unexplained in the remaining 14 couples. All participating couples had potentially disease-causing variants in infertility genes. ES identified variants related to male infertility in 26 men, while variants in female infertility-related genes were detected in the remaining couples (n = 24). According to ACMG classification criteria, 78% (39/50) of couples harbored pathogenic/likely pathogenic (P/LP) variants, whereas 22% (11/50) carried variants of uncertain significance (VUS). In view of the identified genetic etiologies, the cohort was stratified into two groups based on the predicted reproductive outcome: (1) couples with significantly impaired reproductive potential, and (2) couples who can have biological children using appropriate medical interventions. However, classifications involving VUS were interpreted cautiously and considered exploratory. This study provides further evidence for the molecular heterogeneity of human infertility and highlights the usefulness of genetic testing for infertile couples pursuing ARTs.
In this study, chitosan, polydopamine and polydopamine/chitosan coatings were coated on AZ61L magnesium by dip coating process. Thus, the surface characteristics, wettability and in vitro biological properties including bacteria and cell behavior of chitosan (Mg-C), polydopamine (Mg-D), polydopamine/chitosan (Mg-C-D) layers fabricated on AZ61L alloy were investigated in this work. The surfaces were characterized by X-ray diffractometer, scanning electron microscope, energy dispersive spectrometer, contact angle goniometer and surface profilometer. The Mg-D and Mg-C coatings indicated hydrophilic behavior while the Mg-C-D coatings exhibited hydrophobic character. Cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, while cell death was confirmed by acridine orange/propidium iodide fluorescence staining. The results demonstrated that all coated surfaces significantly improved cellular responses compared to bare Mg, with the Mg-C-D coating exhibiting the highest cell viability and enhanced cytocompatibility. Antibacterial activity was determined using the agar diffusion method against Staphylococcus aureus (ATCC6538). Furthermore, antibacterial tests revealed that Mg-C-D surfaces showed superior inhibition against bacterial growth compared to single-layer coatings, indicating a synergistic effect between chitosan and polydopamine. These findings demonstrate that the combined coating strategy provides an effective approach to enhance both biocompatibility and antibacterial performance of Mg-based alloys for biomedical applications.
Two-drug antiretroviral regimens are being investigated as alternatives to standard three-drug therapy for HIV-1. Doravirine/islatravir is a once-daily oral combination with promising efficacy and safety, but its overall clinical performance has not been systematically quantified. This study evaluated the efficacy and safety of doravirine/islatravir compared with standard triple option therapy in adults living with HIV-1. PubMed, Scopus, Web of Science, and the Cochrane Library were systematically searched for phase III randomized controlled trials comparing doravirine/islatravir with standard triple option therapy. Eligible studies were independently screened, and data were extracted and pooled using R software. Six phase III trials involving 3,518 adults were included. At 48 weeks, doravirine/islatravir was associated with a significantly lower risk of virological failure (HIV-1 RNA ≥ 50 copies/mL) compared with standard triple option therapy (RR: 0.51, 95% CI [0.30-0.88]; P = 0.015). Rates of virological suppression (< 50 and < 200 copies/mL) were comparable between groups. No significant differences were observed in overall, serious, or grade 3-4 adverse events, or treatment discontinuation due to adverse events. Dose-stratified analyses showed that the 100/0.75 mg formulation was associated with significant declines in CD4 cell count and total lymphocyte count at 48 weeks, whereas the optimized 100/0.25 mg dose showed no significant immunological differences compared with standard triple option therapy. Doravirine/islatravir is an effective and generally well-tolerated two-drug regimen for HIV-1. The optimized 100/0.25 mg formulation maintained virological efficacy without significant short-term immunological differences versus standard triple option therapy; however, longer follow-up is needed to confirm its long-term immunological safety.
Arsenic (As) contamination of groundwater poses a serious public health risk in many regions worldwide. Zero-valent iron (ZVI)-based systems are widely used for As removal. Nevertheless, their performance is strongly influenced by coexisting groundwater constituents such as phosphorus (P) and silicon (Si). This study systematically investigates the removal mechanisms of arsenite (As(III)) from groundwater using an iron net-based ZVI (IN-ZVI) system. Batch experiments were conducted to evaluate As(III) removal kinetics, iron dissolution behavior, and adsorption isotherms under varying P and Si concentrations. Spectroscopic analyses using X-ray Absorption Fine Structure (XAFS) and X-ray Photoelectron Spectroscopy (XPS) were employed to elucidate As(III) oxidation pathways and surface transformations of the iron net. Results show that As(III) removal followed first-order kinetics, whereas Fe(II) dissolution exhibited zero-order behavior. Increasing P and Si concentrations significantly suppressed both As(III) removal and iron dissolution, with P exerting a stronger inhibitory effect than Si. Langmuir and Freundlich isotherm analyses revealed a progressive decrease in adsorption capacity with increasing P and Si, attributed to competitive site occupation and surface passivation. XAFS results confirmed complete oxidation of As(III) to As(V) in the IN-ZVI system, while XPS analysis demonstrated extensive formation of Fe(III) oxides and deposition of P- and Si-bearing surface scales. These findings indicate that As(III) removal proceeds via corrosion-induced Fe redox cycling, reactive oxygen species-mediated oxidation, and subsequent adsorption of As(V) onto hydrous ferric oxides. The study highlights the critical role of groundwater chemistry in controlling ZVI reactivity and provides mechanistic insights for optimizing iron-based arsenic removal technologies in P and Si rich groundwater.