Categories
Nevin Manimala Statistics

Enhancing lipase activity in Aspergillus niger through CRISPR/Cas9-mediated protease gene knockout and fermentation optimization

Biotechnol Lett. 2025 Sep 25;47(5):114. doi: 10.1007/s10529-025-03657-6.

ABSTRACT

The engineered Aspergillus niger strain AnCALB005 was selected as the research strain, which is a high-yield strain of Candida antarctica B lipase constructed in our laboratory. CRISPR/Cas9-mediated gene knockout was employed to construct the multiple protease-deficient strains targeting five genes (pepA, pepB, pepC, pepE and pepF) in the A. niger AnCALB005. Among the engineered variants, a triple-knockout strain lacking pepA, pepB, and pepF demonstrated 56% enhanced hydrolytic lipase activity relative to the parental strain. Fermentation culture conditions were initially screened through single-factor experiments. Building on these results, critical parameters were statistically determined via Plackett-Burman (PB) design. This was followed by a steepest ascent method combined with Box-Behnken (BB) response surface methodology. Key factors influencing lipase production (identified as maltose concentration, corn steep concentration, and shaking speed) were optimized. The final optimized fermentation conditions comprised: maltose (52 g/L), corn steep (52 g/L), K2HPO4 (5 g/L), soybean cake flour (30 g/L), initial pH 6.5, inoculation amount 10% (v/v), and shaking speed 220 rpm. Under the optimized fermentation conditions, Shake-flask validation of the engineered A. niger yielded a lipase activity of 46.66 U/mL, representing an increase of 92.01%. Scale-up fermentation in a 5 L bioreactor applying these optimized conditions over 120 h of cultivation achieved a lipase activity of 79.31 U/mL.

PMID:40996539 | DOI:10.1007/s10529-025-03657-6

Categories
Nevin Manimala Statistics

Multi-Compartmental Staged Progression Endemic Models with Fast Transitions

J Math Biol. 2025 Sep 25;91(5):49. doi: 10.1007/s00285-025-02291-0.

ABSTRACT

We present a model of infectious disease dynamics where individuals can transition between different compartments, which may have distinct epidemiological characteristics. Within each compartment, epidemic dynamics are represented by a staged progression epidemic model. Individual transitions between compartments occur on a faster time scale, allowing the initial model to be reduced for analysis. In the reduced model, disease eradication and endemicity are characterized by the basic reproduction number. The relationship between this basic reproduction number and those associated with each compartment is analyzed by considering each compartment in isolation. This allows the study of the role of transitions in epidemic dynamics. Endemicity is represented by uniform persistence relative to the total number of infected individuals. It is verified that, for a sufficiently large ratio between time scales, the initial model shares the uniform persistence of the reduced model. The influence of transitions on disease eradication/endemicity is illustrated by different results. In particular, the conditions for transition rates are determined so that endemicity (eradication) in each isolated compartment results in global eradication (endemicity). These results can provide some tools for managing epidemics in the context of individuals transiting between compartments with different epidemiological properties.

PMID:40996532 | DOI:10.1007/s00285-025-02291-0

Categories
Nevin Manimala Statistics

Dementia(associated) deaths in Bavaria-analysis of comorbidities based on multiple cause of death statistics from 2020 to 2022

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2025 Sep 25. doi: 10.1007/s00103-025-04130-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Dementia is already one of the leading causes of death in Germany. Due to the demographic change, the number of dementia-related deaths will continue to rise in the future. The diversity of “dementia” and the increasing importance of multimorbidity require all diseases listed on the death certificate to be included in the analyses. The aim of this article is to analyse all persons deceased “from” and “with” dementia in Bavaria (= dementia-associated deaths) with regard to their socio-demographic characteristics and to group them based on their comorbidities.

METHOD: Since 2020, multiple causes of death statistics have been available in Bavaria. This allows for the inclusion of all other diseases contributing to death to be used in the analyses. The Bavarian dementia-related deaths from 2020 to 2022 were grouped into clusters based on their comorbidities using latent class analysis.

RESULTS: Approximately 19% of all deaths were dementia related. Among these, seven clusters were found: one multimorbidity cluster, one cardiovascular cluster, two infection clusters, two clusters with neurodegenerative diseases and one vascular cluster. The deceased of the clusters differed significantly in terms of age, gender, underlying cause and comorbidities.

DISCUSSION: The results of the multiple cause of death analysis indicated a possible underestimation of more specific types of dementia such as vascular dementia. In addition, identifying different combinations of diseases in dementia-related deaths can provide information on suitable treatment methods, preventive measures and possibilities to adapt care structures.

PMID:40996526 | DOI:10.1007/s00103-025-04130-5

Categories
Nevin Manimala Statistics

Effect of the Chelating Agent Alendronic Acid versus EDTA on the Physicochemical Properties of Dentine

Eur Endod J. 2025 Sep;10(5):397-405. doi: 10.14744/eej.2025.28482.

ABSTRACT

OBJECTIVE: The present study aimed to evaluate the changes in the physicochemical properties of dentine after irrigation with a solution of 0.22% alendronic acid (AA) as a chelating agent compared to 17% ethylene-diaminetetraacetic acid (EDTA).

METHODS: A total of 48 extracted premolars and molars that were intact, free of caries or cracks, without root canal treatment and restorations were collected. The roots were randomised into three groups (n=16): Group A: Distilled Water (dH2O); Group B: 17% EDTA, and Group C: 0.22% AA. Longitudinal sections of the dentine with a root of 1x1x10 mm were made with a diamond disc and a low-speed handpiece for bending tests (n=9). For morphological analysis, images were taken with a scanning electron microscope, crystallographic analysis with X-ray diffraction, and chemical analysis with Fourier Transform Infrared Spectroscopy (FTIR) and Vickers Hardness. For this purpose, cross-sections were made through the root using the Isomet to obtain 3 mm thick dentine discs (n=14). The samples were stored in dH2O for up to 24 h before use and dried at room temperature before exposure to chelating solutions for 1 h in a Stuart STR6D mixer at 50 rpm. For data comparison, the Kruskal-Wallis statistical test was used (α=0.05).

RESULTS: The chelating solutions of EDTA and AA cause alterations in the physicochemical structure of dentine, attacking mainly the inorganic part (Hydroxyapatite), which was observed in the decrease in intensity of the peaks in the X-ray diffraction pattern of hydroxyapatite. This generated a greater exposure of the collagen fibres that were observed in SEM and the increase in the bands characteristic to Collagen Type I in the infrared spectrum at 1645, 1550, and 1240 cm-1 belonging to amide I (C=O), amide II (N-H) and amide III (C-N), significantly affecting its dentine hardness (p=0.001).

CONCLUSION: AA can be used as a chelating agent in the area of dentistry. It does not generate a significant demineralising effect that modifies the physicochemical properties of dentine, as observed with EDTA.

PMID:40995721 | DOI:10.14744/eej.2025.28482

Categories
Nevin Manimala Statistics

Healing Outcome of Different Aqueous-based Calcium Hydroxide Intracanal Medicament in Patients with Pulpal Necrosis and Symptomatic Apical Periodontitis: A Randomised Controlled Trial

Eur Endod J. 2025 Sep;10(5):365-373. doi: 10.14744/eej.2025.04909.

ABSTRACT

OBJECTIVE: This study aimed to assess and compare the healing outcome associated with different aqueous-based calcium hydroxide intracanal medicaments in patients with pulpal necrosis and symptomatic apical periodontitis.

METHODS: Seventy five patients with pulpal necrosis and symptomatic apical periodontitis in permanent mandibular molar teeth were selected as the part of this study. The participants were randomly allocated to three groups, each comprising 25 patients, based on the type of intracanal medicament used during the treatment procedure. Group 1 consisted of calcium hydroxide (CH) mixed with 0.9% saline (NS), Group 2 contained CH combined with 2% lidocaine, and Group 3 included CH with 2% chlorhexidine (CHX). The Periapical Index Score was utilized to assess the healing of periapical lesions in preoperative and post-operative periapical radiographs at 3 month intervals for 12 months. The Kruskal-Wallis test was used to determine the significance, with Post Hoc Dunn tests for multiple comparisons.

RESULTS: At the 12-month follow-up, the CH+CHX group demonstrated significantly improved periapical healing, with a mean PAI score of 1.57 +- 0.66, compared to CH+LA (2.27+-0.63) and CH+NS (2.48+-0.79), with Kruskal-Wallis p<0.05. The mean time to achieve a healthy periapical status (PAI ≤2) was shortest in the CH+CHX group (8.10+-3.28 months), followed by CH+NS (8.23+-3.28 months) and CH+LA (8.25+-3.31 months), with the multivariate Log-Rank test indicating a statistically significant difference among the groups (p<0.05).

CONCLUSION: The findings of this study indicate that CH when combined with 2% CHX as an aqueous vehicle demonstrated superior healing of periapical lesions in patients with pulpal necrosis and symptomatic apical periodontitis compared to saline or lidocaine.

PMID:40995720 | DOI:10.14744/eej.2025.04909

Categories
Nevin Manimala Statistics

Impact of Different Nickel-titanium Instruments on Apical Micro-cracks Formation and Residual Amount of Root Canal Filling Materials Following Retreatment Procedure

Eur Endod J. 2025 Sep;10(5):420-431. doi: 10.14744/eej.2025.09226.

ABSTRACT

OBJECTIVE: This study aimed to evaluate and compare the dentinal defects caused by three different retreat-ment systems [Endostar RE Endo, XP-endo Retreatment, and MANI Gutta-Percha Removal (GPR)] and to assess the percentage of residual root canal filling material following the retreatment procedure.

METHODS: Sixty extracted mandibular second premolars with straight oval canals were used. The roots were standardized to a length of 14 mm. All samples were instrumented with NiTi instruments up to size 30.04, then filled using single cone technique with AH plus sealer and gutta-percha. Four groups were created from the samples. Group 1 served as the negative control (n=15), while the remaining three groups (n=15 each) were categorized based on the retreatment system used. Stereomicroscope at magnification 45 x was used to evaluate the incidence of crack formation and propagation at apex of the roots and the residual volume percentage of root filling materials in groups of Endostar RE, MANI GPR, Xp retreatment systems assessed using CBCT. Fisher’s exact test was used to analyze the incidence and propagation of cracks, while one-way ANOVA and Tukey’s post hoc test were applied to assess differences in residual filling material volume among the groups P values at 0.05.

RESULTS: There is significance difference (p=0.028) between the Endostar and Xp retreatment system. The highest of dentinal defect (1015) with Endostar retreatment system followed by (415) with GPR system and (215) with XP endo retreatment system.Highest residual filling material mean at Endostar RE retreatment system (51.97) and lowest mean (39.07) at Xp retreatment system A statistically significant difference was observed between the groups (p<0.001), particularly between the Endostar and XP retreatment systems.

CONCLUSION: No system was capable of completely eliminating obturated materials. The XP-endo Retreat-ment system showed the lowest incidence of crack formation and propagation and proved to be the most effective in removing gutta-percha and sealer.

PMID:40995718 | DOI:10.14744/eej.2025.09226

Categories
Nevin Manimala Statistics

Comparative Buckling Strength and Metallurgical Analysis of Five Classic NiTi Endodontic Rotary Files

Eur Endod J. 2025 Sep;10(5):411-419. doi: 10.14744/eej.2025.43760.

ABSTRACT

OBJECTIVE: Nickel-titanium (NiTi) rotary instruments have revolutionized endodontic practice through continuous advancements in metallurgy and design. Despite these improvements, mechanical failure remains a clinical concern. This study aimed to evaluate and compare the design features, metallurgical properties, and buckling resistance of five widely used NiTi rotary endodontic systems.

METHODS: A total of 250 new NiTi rotary instruments from five systems (ProTaper Next, Mtwo, ProFile, EndoSequence, and GT Series X) were analyzed. Design features were assessed using dental microscopy and scanning electron microscopy. Metallurgical properties were evaluated through energy-dispersive X-ray spectroscopy and differential scanning calorimetry. Buckling resistance was measured using a universal testing machine equipped with a 1 kN load cell, applying a compressive load at 1 mm/min until 1 mm of lateral displacement was achieved. Statistical analysis was performed using the Shapiro-Wilk test to assess normality, followed by the non-parametric Kruskal-Wallis test to compare groups. A significance level of p<0.05 was adopted.

RESULTS: ProFile instruments exhibited the highest number of spirals (19) and spiral density (1.19 spirals/mm), while GT Series X featured the shortest cutting blade length (≤12 mm). All systems demonstrated near-equiatomic nickel-titanium ratios. ProTaper Next and GT Series X showed higher R-phase and austenitic transformation temperatures. Buckling resistance was significantly greater in the ProFile (0.04 and 0.06 taper) and EndoSequence 35/.06 and 40/.06 instruments (p<0.05). In contrast, EndoSequence 0.04 files, Mtwo, and ProTaper Next exhibited lower resistance.

CONCLUSION: Design features, taper, and metallurgical composition significantly influence the buckling resistance of NiTi rotary endodontic instruments.

PMID:40995717 | DOI:10.14744/eej.2025.43760

Categories
Nevin Manimala Statistics

Mechanical Evaluation of Boron Nanoparticle-Modified Silicone Elastomers for Maxillofacial Prostheses

J Biomed Mater Res B Appl Biomater. 2025 Oct;113(10):e35659. doi: 10.1002/jbm.b.35659.

ABSTRACT

This study evaluated the effects of boron nanoparticles (BNPs) on the mechanical properties of two silicone elastomers, A-2000 and A-2006. Tensile, tear, hardness, and elongation tests were conducted in accordance with ASTM and ISO standards. A total of 180 specimens were prepared, comprising control groups without BNPs and experimental groups containing 1 and 3 wt% BNPs. Tensile and tear strength tests were performed using a device with a 1 kN capacity at a crosshead speed of 100 mm/min; hardness was measured using Shore A tests, and Atomic Force Microscopy (AFM) was employed to assess surface roughness. Tensile testing revealed that the A-2000 control group exhibited the highest tensile strength, with significant reductions observed in both BNP-incorporated subgroups. In A-2006, tensile strength decreased significantly with 1 wt% BNPs but partially recovered at 3 wt%. Tear strength in A-2000 significantly decreased at 1 wt% but returned to control levels at 3 wt%, whereas no statistically significant differences were observed among the A-2006 subgroups. Hardness significantly increased with 3 wt% BNPs in A-2000 and with both 1 and 3 wt% BNPs in A-2006. Regarding elongation, A-2000 showed no significant change compared with the control, although the 1 and 3 wt% groups differed significantly from each other. In A-2006, both 1 and 3 wt% BNP groups showed significant reductions in elongation compared with the control. Overall, A-2000 exhibited superior tensile and tear strength, while A-2006 demonstrated greater elongation capacity. These findings indicate that BNP incorporation depends on both the elastomer type and concentration, with potential trade-offs between improved hardness and decreased flexibility. Both A-2000 and A-2006 remain viable options for maxillofacial prostheses, although optimization of BNP concentration is essential to balance strength, durability, and flexibility.

PMID:40995686 | DOI:10.1002/jbm.b.35659

Categories
Nevin Manimala Statistics

Rethinking the AI Paradigm for Solubility Prediction of Drug‑Like Compounds with Dual-Perspective Modeling and Experimental Validation

Adv Sci (Weinh). 2025 Sep 25:e11667. doi: 10.1002/advs.202511667. Online ahead of print.

ABSTRACT

Aqueous solubility is a crucial property for drug development, as it not only influences the drug delivery process but also determines the bioavailability of drugs. However, solubility prediction remains a formidable challenge, even after decades of research. Most previously-reported machine learning (ML) models generalize poorly on external sets due to the vast chemical space of drug compounds. In this report, the largest aqueous solubility dataset of drug and drug-like molecules so far is compiled, based on which reliable models for drug solubility prediction are developed by comparative modelling with assorted regression and classification algorithms. Under current circumstances, even advanced deep learning models are found less accurate than the stacking of multiple statistical ML algorithms due to data limitation. Analysis of applicability domain further verifies the generalization capability of the models for the drug domain, based on which the entries without experimental solubility in the DrugBank database are populated and categorized. Finally, the solubility of ten potential drug molecules is experimentally determined for the first time, again revealing the high reliability of our models. Hence, this work is believed to provides a comprehensive benchmark for future solubility prediction models and a powerful tool to guide new drug discovery.

PMID:40995668 | DOI:10.1002/advs.202511667

Categories
Nevin Manimala Statistics

Simultaneous arthroscopic treatment of adhesive capsulitis and rotator cuff tear: a retrospective analysis of clinical outcomes

Acta Orthop Traumatol Turc. 2025 Sep 12;59(5):265-267. doi: 10.5152/j.aott.2025.25441.

ABSTRACT

Objective: This study aimed to evaluate the clinical and functional outcomes of patients who underwent simultaneous arthroscopic capsular release for adhesive capsulitis and rotator cu! repair. Methods: A retrospective analysis was performed on patients treated between 2014 and 2023 who underwent arthroscopic global capsular release combined with rotator cu! repair. Preoperative and postoperative outcomes, including range of motion (ROM), Visual Analogue Scale (VAS) scores, and Constant scores, were assessed with a minimum follow-up of six months. Results: Among 69 patients undergoing capsular release, 29 patients (20 females, 9 males; mean age: 56 years) received concurrent rotator cu! repair. The mean follow-up period was 14 months. Most tears involved the supraspinatus (25 full-thickness, 4 partial bursal-side). Complications were minimal, with only two diabetic patients displaying persistent ROM limitations and there were no re-tear in followup period. Statistically significant di!erences seen in ROM, VAS and Constant scores, VAS decreased from 7.1 to 1.2, Constant score improved from 37.5 to 72.3 (P < .05). Conclusion: Simultaneous arthroscopic management of adhesive capsulitis and rotator cu! tears provides favorable clinical and functional outcomes with lower complication rates compared to current literature, supporting its value as an e!ective treatment option. However, the limited sample size and relatively short follow-up should be considered when interpreting these results. Level of Evidence: Level IV, Therapeutic study.

PMID:40995665 | DOI:10.5152/j.aott.2025.25441