He Y, Lu S, Fu P
… +3 more, Chen S, Zhang P, Song X
Biology (Basel)
· 2026 Feb · PMID 41744627
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To clarify the age-related differences in growth performance, meat quality, and the underlying molecular mechanisms of Shanbei white cashmere (SWC) goats, the slaughter performance and meat quality of 6-month-old (S grou...To clarify the age-related differences in growth performance, meat quality, and the underlying molecular mechanisms of Shanbei white cashmere (SWC) goats, the slaughter performance and meat quality of 6-month-old (S group) and 12-month-old (T group) male goats were analyzed. This was combined with muscle transcriptome and untargeted metabolome analyses. The results showed that the T group had better growth performance, while the S group had superior meat quality. A total of 138 differentially expressed genes (DEGs) and 158 differentially expressed metabolites (DEMs) were identified, which are enriched in multiple pathways, and a meat quality-related gene-metabolite regulatory network was constructed. This study reveals the molecular mechanisms of age-dependent differences, providing theoretical support for goat breeding and slaughter strategy optimization.
Sriburin S, Shinsuphan N, Klamrak A
… +9 more, Saengkun Y, Janpan P, Jangpromma N, Patramanon R, Kulchat S, Chaveerach A, Areemit J, Daduang J, Daduang S
Biology (Basel)
· 2026 Feb · PMID 41744625
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The venom of the Asian hornet () comprises a complex mixture of biologically active substances, including various enzymes such as phospholipase A and hyaluronidase; amines such as histamine, serotonin, and catecholamines...The venom of the Asian hornet () comprises a complex mixture of biologically active substances, including various enzymes such as phospholipase A and hyaluronidase; amines such as histamine, serotonin, and catecholamines; peptides such as mastoparan and vespakinin; and other components including acetylcholine and antigen 5. This complexity reflects the highly evolved nature of as a venomous insect. The composition of animal venoms often exhibits a certain degree of variability, making the study of biogenic amines particularly intriguing. The objective of this research was to confirm and identify the presence of tetradecylamine in the venom of using the scientific computational analysis software MetFrag. In addition, the study aimed to construct the biosynthetic pathway of this compound and to predict its potential biological roles. The predicted biosynthetic route of tetradecylamine suggested its possible involvement in antibacterial activity. Antibacterial assays were performed against four bacterial strains , , , and . The results revealed that tetradecylamine exhibited notable inhibitory effects, with minimum inhibitory concentration (MIC) values of 2, 4, 8, and 4 µg/mL, and minimum bactericidal concentration (MBC) values of 2, 4, 8, and 4 µg/mL, respectively. Furthermore, molecular docking studies were conducted using penicillin-binding protein 2x (PBP2x, PDB ID: 5OIZ) as the target protein. Among eight tested ligands, streptomycin exhibited the highest binding affinity with a docking score of 64.76. In contrast, biogenic amines such as 2-phenylethylamine and tetradecylamine showed docking scores of 33.74 and 48.2, respectively. In the MurA protein (PDB ID: 3VCY), the biogenic amine ligand tetradecylamine exhibited a binding affinity comparable to that of certain reference drugs. Specifically, tetradecylamine achieved a GOLD score of 52.58, whereas ampicillin showed a higher score of 61.53. Notably, tetradecylamine demonstrated a higher binding affinity to the target protein compared with certain conventional antibiotics such as doxycycline and gentamycin.
Biology (Basel)
· 2026 Feb · PMID 41744605
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Autoimmune diseases result from a breakdown of immune tolerance influenced by genetic and environmental factors. Regulatory T cells (Tregs) maintain immune homeostasis, while interferon-γ (IFNγ) has context-dependent pro...Autoimmune diseases result from a breakdown of immune tolerance influenced by genetic and environmental factors. Regulatory T cells (Tregs) maintain immune homeostasis, while interferon-γ (IFNγ) has context-dependent proinflammatory and regulatory roles. In B10.S mice, mercury-induced autoimmunity (HgIA) emerges within approximately 4 weeks of Hg exposure and is marked by antinucleolar antibody (ANoA) production, polyclonal B-cell activation, and deposition of immune complexes in the kidney. We investigated whether Tregs attenuate HgIA and evaluated IFNγ's role in this regulation. Female WT and IFNγ B10.S mice received HgCl or water for 4 weeks until all mice developed ANoA. CD4CD25Foxp3 Tregs or CD4CD25Foxp3 cells were transferred into HgCl-exposed WT recipients and monitored for 13 weeks. Compared with Hg-primed non-Tregs, Hg-primed WT Tregs were statistically associated with significantly reduced autoantibody levels, lower IgG1/IgG2a, and significantly decreased glomerular IgG/C3c deposition, suggesting that Hg exposure may modulate Treg function. Conversely, both water- and Hg-primed Tregs and non-Tregs from IFNγ donors elicited profoundly diminished autoantibody production and renal pathology in recipients. IFNγ mice lacked fibrillarin-specific responses, highlighting its requirement for HgIA initiation. While non-Treg transfer failed to suppress HgIA, Treg transfer reduced HgIA and highlighted relevance for immune-regulatory therapies, especially where environmental toxicants may drive autoimmune disease.
BACKGROUND: Ultraviolet (UV)-induced reactive oxygen species (ROS) production, DNA damage, and chronic inflammation lead to skin aging and cancers. Ginkgetin (GK), a biflavonoid derived from Ginkgo biloba, has known anti...BACKGROUND: Ultraviolet (UV)-induced reactive oxygen species (ROS) production, DNA damage, and chronic inflammation lead to skin aging and cancers. Ginkgetin (GK), a biflavonoid derived from Ginkgo biloba, has known anti-inflammatory and antioxidant activities, but its anti-photoaging effect remains unclear. OBJECTIVE: This study aimed to determine whether GK could alleviate UV-induced photoaging by reducing oxidative stress and promoting DNA repair. METHODS: The efficacy of microneedle-assisted topical GK was evaluated in a UV-induced SKH-1 mouse model of photoaging using dermoscopy and histopathological analysis. We conducted transcriptomic profiling and network pharmacology to identify the underlying mechanism. In UV-irradiated human dermal fibroblasts (HDFs), cellular senescence markers were assessed by SA-β-gal staining and Western blotting. Intracellular ROS levels and mitochondrial membrane potential were measured using DCFH-DA and JC-1 staining, respectively. Apoptosis, cell cycle progression, and senescence-associated secretory phenotype (SASP)-related cytokine expression were analyzed by flow cytometry, Western blotting, RT-qPCR, and ELISA. DNA damage and repair in UV-irradiated HaCaT cells were evaluated by comet assay and γ-H2AX immunofluorescence. Homologous recombination repair (HRR)-related proteins and RAD51 foci formation were analyzed by Western blotting and confocal microscopy, respectively. Functional validation was performed using the AKT inhibitor MK2206 and the HRR inhibitor B02. RESULTS: GK significantly reduced wrinkle formation, epidermal hyperplasia, and collagen loss in UV-induced mice. It decreased ROS levels, restored mitochondrial potential, reduced senescence markers, suppressed SASP cytokines and MMP1/2 expression, promoted cell cycle progression, and inhibited apoptosis by regulating the BCL2/BAX ratio. Importantly, GK enhanced DNA repair by promoting HRR, as directly demonstrated by the upregulation of key HRR proteins (BRCA2, RAD51) and the acceleration of RAD51 foci formation. Critically, these DNA repair-enhancing effects were abolished by inhibition of either AKT or HRR, demonstrating that the AKT-HRR axis is indispensable for GK's repair-promoting function. CONCLUSION: GK may serve as a potential therapeutic candidate for UV-induced photoaging by virtue of its dual capacity to scavenge ROS and enhance AKT-mediated DNA repair.
Carboxylesterases play critical roles in drug metabolism and detoxification, and there is an urgent need for tools capable monitoring of CES activity in pathological states. Herein, we developed N-OAC, a novel fluorescen...Carboxylesterases play critical roles in drug metabolism and detoxification, and there is an urgent need for tools capable monitoring of CES activity in pathological states. Herein, we developed N-OAC, a novel fluorescent probe based on ICT mechanism, for the highly selective and sensitive detection of CES. Upon CES activation, N-OAC exhibited a significant fluorescence enhancement at 585 nm with a large 145 nm Stokes shift, achieving ultrasensitive detection limit of 3.42 × 10 U/mL and excellent linearity (R = 0.9986). HRMS and DFT studies collectively confirmed the proposed mechanism wherein CES hydrolyzes the acetoxy group, thereby re-establishing the ICT pathway and leading to fluorescence recovery. N-OAC demonstrated exceptional selectivity over biological interferents and was successfully applied to monitor CES fluctuations in HepG2 cells under DILI and organophosphorus pesticide exposure. Notably, N-OAC visualized CES upregulation by NAC in APAP-injured liver tissues, offering a promising tool for assessing DILI severity and therapeutic efficacy.
In this work, a one-pot method for microRNA (miRNA) sensing was developed based on palindrome-mediated isothermal cascade DNA amplification and continuous fluorescent nanosignal transduction. With rational palindrome des...In this work, a one-pot method for microRNA (miRNA) sensing was developed based on palindrome-mediated isothermal cascade DNA amplification and continuous fluorescent nanosignal transduction. With rational palindrome design, only a functionally integrated palindromic hairpin (IPH) and a pair of enzymes were needed to realize streamlined two-step miRNA detection. Initially, target miRNA specifically unfolded the IPH, and then initiated multiple isothermal cycles driven by palindrome hybridization and enzymatic nicking/polymerization to complete target recognition and DNA amplification. Subsequently, the large number of DNA templates accumulated from the isothermal reaction facilely guided in-situ formation of fluorescent copper nanoparticles, achieving immediate nanosignal readout. Efficient isothermal amplification combined with effortless signal transduction enabled sensitive miRNA-155 detection in a straightforward protocol. Besides, owing to its high specificity and robustness, this method could clearly identify cancer cells from normal cells through analysis of cellular miRNA-155. Furthermore, the method can also be adapted to sense various miRNAs just by redesigning the target recognition sequence within IPH, which demonstrates the adaptable versatility and substantial potential of the method in molecular diagnostics.
The increasing demand for compact LED-based illuminators in contemporary photodynamic therapy necessitates innovative design approaches. This study presents the development of a scanless tunable LED illuminator operated...The increasing demand for compact LED-based illuminators in contemporary photodynamic therapy necessitates innovative design approaches. This study presents the development of a scanless tunable LED illuminator operated at 660 nm engineered to provide uniform irradiation across an area of a standard 96-well plate, with power outputs ranging from 1 to 20 mW/cm. We assessed the temporal stability of the output power, emission spectrum, and temperature of the proposed design to ensure consistent and reproducible light dosages. The practical efficacy of the compact LED illuminator was evaluated through experiments involving CT26, U-87, 4T1, N2A, 22RV1 and B16F10 cell cultures, utilizing photodynamic dyes Photoditazine (PD) and aluminum tetrasulfophthalocyanine chloride, an analogue of Photosens (PS).
Melanoma occurs in both humans and dogs, reinforcing the importance of comparative oncology, and photodynamic therapy (PDT) stands out as a promising, minimally invasive and selective treatment strategy. In this study, w...Melanoma occurs in both humans and dogs, reinforcing the importance of comparative oncology, and photodynamic therapy (PDT) stands out as a promising, minimally invasive and selective treatment strategy. In this study, we evaluate the photodynamic effects of palladium(II)-complexed meso-tetra-cationic porphyrins, 3-Pd(PPh), 3-Pd(dppf), 3-Pd(PEPSI), 4-Pd(PPh), 4-Pd(dppf), and 4-Pd(PEPSI), on human (A375 and SK-MEL 28) and oral canine (CMGD-2, CMGD-5 and TLM1) melanoma cell lines. Photophysical analysis, aggregation study, photostability and singlet oxygen (O) generation assays are conducted for all examples. Cytotoxicity was evaluated using the MTT assay, live/dead assays and mechanisms of cell death were further investigated via qRT-PCR analysis, comparing responses between human and canine melanoma cells. The results indicate that porphyrins 3-Pd(PPh), 3-Pd(dppf) and 3-Pd(PEPSI) exhibit potent photosensitizing activity, reducing cell viability by up to 80% at higher concentrations upon light activation. Among them, 3-Pd(dppf) and 3-Pd(PPh) showed lower IC₅₀ values across all cell lines than 3-Pd(PEPSI), which lacks coordinated ligands, in both species. Consequently, further analyses focused on these two most effective compounds. Both porphyrins showed selective cytotoxicity, low dark toxicity, increased oxidative stress, and triggered apoptotic and non-apoptotic cell death in both species. These findings highlight the potential of palladium-complexed porphyrins as PDT agents for melanoma treatment, reinforcing the translational relevance of canine models in comparative oncology.
BACKGROUND: Plastics count as one of the most potent threats to the habitats and survival of global flora and fauna. Reports keep accumulating globally about the ever-exploding load of plastic wastes, but the need and ec...BACKGROUND: Plastics count as one of the most potent threats to the habitats and survival of global flora and fauna. Reports keep accumulating globally about the ever-exploding load of plastic wastes, but the need and economics of multiple industrial and household processes compel the production of more plastic materials. It has always been imperative to look for natural sources of degradation of plastic. The identification of plastic-degrading microbes, therefore, remains a major focus of the microbial fraternity. While the discoveries of Ideonella sakaiensis or later, Rhizobacter gummiphilus were more out of providence, the structure determination of the enzyme responsible for PET degradation does provide a fillip to efforts towards the identification of more such prokaryotic entities. RESULTS: In this work, a comprehensive profiling of prokaryotic sequences has been undertaken to look for the presence of similar plastic-degradation abilities across the kingdom. The identification of twenty-seven such 'hits' across different bacterial species led us to believe in the natural diversity of plastic-degradation enzymes. Moreover, there seems to be conservation of the structural motif that renders such ability, as has been observed from the constructed models and analysis of their interfaces. Docking of BHET, one of the key products of PET, against these 27 entities showed considerable interactions with the above and pointed towards the possible roles of these bacteria as natural plastic degradation models. Eight of these proteins have very close similarity in binding interactions and surface properties to the PETase from I. sakaiensis and were shortlisted as prospective candidates. CONCLUSIONS: Of these eight, three PETases from Halopseudomonas pertucinogena, Halopseudomonas bauzanensis and Ketobacter sp. revealed significant similarity in structure and conformational stability to the PETase from I. sakaiensis, as was evident from the analysis of their molecular dynamics parameters. Principal Component Analysis and the free energy landscape during binding to BHET also validated the hypothesis, and these three PETases could be immediately explored for possible plastic degradation activity.
RNA structures are essential for understanding their biological functions and developing RNA-targeted therapeutics. However, accurate RNA structure prediction from sequence remains a crucial challenge. We introduce DRfol...RNA structures are essential for understanding their biological functions and developing RNA-targeted therapeutics. However, accurate RNA structure prediction from sequence remains a crucial challenge. We introduce DRfold2, a deep learning framework that integrates a novel pre-trained RNA Composite Language Model (RCLM) with a denoising structure module for end-to-end RNA structure prediction. Based solely on single sequence, DRfold2 achieves superior performance in both global topology and secondary structure predictions over other state-of-the-art approaches across multiple benchmark tests from diverse species. Detailed analyses reveal that the improvements primarily stem from the RCLM's ability to capture co-evolutionary pattern and the effective denoising process, with a more than 100% increase in contact prediction precision compared to existing methods. Furthermore, DRfold2 demonstrates high complementarity with AlphaFold3, achieving statistically significant accuracy gains when integrated into our optimization framework. By uniquely combining composite language modeling, denoising-based end-to-end learning, and deep learning-guided post-optimization, DRfold2 establishes a distinct direction for advancing ab initio RNA structure prediction.
Devarakonda SS, Basha S, Ameera K
… +3 more, Mishra A, Chandra S, Mahato KK
J Photochem Photobiol B
· 2026 Mar · PMID 41687209
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Photobiomodulation (PBM) is widely reported to influence cellular function through light-induced biochemical signaling; however, the contribution of direct protein-photon interactions to PBM-associated optical responses...Photobiomodulation (PBM) is widely reported to influence cellular function through light-induced biochemical signaling; however, the contribution of direct protein-photon interactions to PBM-associated optical responses remains insufficiently understood. The current study investigated whether PBM-relevant wavelengths can modulate intrinsic protein autofluorescence independent of cellular photoreceptors. Purified human serum albumin (HSA) and fibrinogen were irradiated with 632.8 nm and 830 nm lasers using fluences selected to preserve protein photostability. Autofluorescence spectroscopy was performed under ultraviolet excitation to assess wavelength- and dose-dependent changes in intrinsic fluorophore emission. In parallel, SH-SY5Y cells were irradiated under comparable conditions, followed by protein extraction, SDS-PAGE, and fluorescence fingerprinting. Both purified proteins exhibited significant modulation of autofluorescence intensity without detectable spectral shifts, indicating preservation of the local fluorophore environment and absence of gross conformational denaturation. HSA displayed a dose-dependent biphasic response characterized by fluorescence enhancement at lower fluences and attenuation at higher doses, whereas fibrinogen showed predominantly fluorescence quenching, with a partial biphasic trend observed only under near-infrared irradiation. In contrast, cellular protein extracts demonstrated a largely monotonic decrease in autofluorescence intensity with increasing irradiation dose, despite preserved electrophoretic profiles. These findings demonstrate that PBM wavelengths can directly influence intrinsic protein photophysics in a protein-specific manner, independent of cellular signaling pathways. While such direct light-protein interactions may contribute to baseline optical changes observed during PBM, the distinct responses observed in cellular systems highlight the critical role of cellular organization in shaping functional PBM outcomes. This work provides experimental evidence supporting a protein-level component in PBM-associated optical responses.
Little is known about how sex and diet interact at the level of chromatin organization. A comprehensive analysis of diet-induced chromatin dynamics can reveal how the liver mounts a rapid adaptive response to environment...Little is known about how sex and diet interact at the level of chromatin organization. A comprehensive analysis of diet-induced chromatin dynamics can reveal how the liver mounts a rapid adaptive response to environmental cues and uncover mechanisms underlying sex differences. Here, we employed an integrative strategy to construct a nucleosome accessibility atlas of the mouse liver under different dietary conditions. Stringent analysis revealed a largely preserved hepatic chromatin landscape across feeding states, with sex being the critical factor driving changes in chromatin accessibility. Notably, lipid-rich diet preferentially enriched CCAAT-binding motifs in females, while nutrient-sensing nuclear receptor motifs were more strongly enriched in males. Furthermore, using the Four Core Genotypes model (XX ovaries / XY testes / XX testes / XY ovaries), we disentangled the effects of gonadal and chromosomal sex on diet-induced gene regulation. By leveraging this framework with multiple mouse models and molecular approaches, we identified a suppressive role of testosterone in regulating the sex-dimorphic GWAS gene PNPLA3. Overall, we establish an unbiased transcriptomic resource that revealed chromatin dynamics and identified gene clusters associated with distinct sex-related factors.
Kenny K, Niesman IR, Moon KS
… +4 more, Sussman M, Wright MK, Dawood D, Phillips JA
Biology (Basel)
· 2026 Feb · PMID 41677741
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Age-related chronic, low-grade inflammation, known as inflammaging, contributes to tissue damage and disease. In the lungs, inflammaging leads to abnormal tissue remodeling, reduced function, and decreased immunity. A ke...Age-related chronic, low-grade inflammation, known as inflammaging, contributes to tissue damage and disease. In the lungs, inflammaging leads to abnormal tissue remodeling, reduced function, and decreased immunity. A key factor in inflammaging is declining acetylcholine signaling, which normally suppresses inflammation and promotes tissue repair. We tested whether increasing acetylcholine responsiveness could reverse age-related lung damage. Aged mice were treated with donepezil to increase acetylcholine availability. After six months, blood oxygen saturation and voluntary activity were significantly improved. Histologically, treated mice showed a reversal of alveolar enlargement (a hallmark of emphysema) and complete restoration of elastic fibers. Donepezil treatment also dramatically increased bronchus-associated lymphoid tissue (iBALT) formation. iBALT is the repository of tissue-resident memory lymphocytes, including memory cholinergic lymphocytes that produce acetylcholine to suppress inflammation during secondary infections. The age-related loss of iBALT contributes to the increased risks associated with respiratory infection in the elderly. This indicates that age-related lung function and respiratory immune deficits can be modulated by improving acetylcholine signaling. Repurposing an approved medication provides a direct pathway to clinical application for improving respiratory health and infection resistance during aging.
Zhang Y, Sun X, Xu M
… +7 more, Liu H, Wang S, Cai Z, Guo X, Xu S, Ji S, Sima Y
Biology (Basel)
· 2026 Jan · PMID 41677716
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The high bioavailability and low toxicity of organic selenium underscore its potential for nutritional fortification. This study investigated the biological effects of a novel 3-selenoureidoindole derivative (3-SeU-Ind)...The high bioavailability and low toxicity of organic selenium underscore its potential for nutritional fortification. This study investigated the biological effects of a novel 3-selenoureidoindole derivative (3-SeU-Ind) as a dietary selenium source in the invertebrate model organism silkworm (). When reared on natural mulberry leaves, supplementation with 3-SeU-Ind (4-400 mg/L) had no significant effect on larval weight, pupal weight, or cocoon production performance. However, under compound diet conditions, the highest concentration (400 mg/L) significantly reduced both larval and pupal weights. Selenium was effectively accumulated in larval tissues and the pupal body. Under high-temperature stress, supplementation with 3-SeU-Ind (100 and 400 mg/L) significantly enhanced silkworm survival, which was associated with the upregulation of key antioxidant genes, including , , , and . Furthermore, the supplementation altered methionine and lysine levels in the hemolymph in a sex-specific manner. Thus, 3-SeU-Ind demonstrated potential as a safe and effective selenium supplement.
Biology (Basel)
· 2026 Jan · PMID 41677708
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The influence of ocean chemistry on Early Triassic biotic recovery is poorly understood in the Chaohu Area. Here, we evaluate the influence of ocean chemistry following the Permian-Triassic crisis using pyrite content, δ...The influence of ocean chemistry on Early Triassic biotic recovery is poorly understood in the Chaohu Area. Here, we evaluate the influence of ocean chemistry following the Permian-Triassic crisis using pyrite content, δC, and S isotopic composition of pyrite. The pyrite content, V/(V + Ni) ratio, and S isotopic composition of pyrite in the Early Triassic from the northern Pingdingshan section of the Chaohu area in eastern China reveal recurrent and long-term ocean anoxia and two episodes of oxic conditions that occurred in the earliest Spathian and the late early Spathian. A positive δC shift of ~4‱ around the Smithian/Spathian boundary (SSB) in the lowermost Spathian was associated with significant biotic recovery, coincident with a positive δS excursion of ~25‱ and a low V/(V + Ni) ratio. The results suggest that the oxic conditions contributed to this recovery. Enhanced global ocean circulation during the SSB climate cooling may also have promoted this recovery. Frequent environmental perturbations may have aborted the biotic recovery, although the second episode of oxic conditions occurred in the late early Spathian. Sustained recovery did not appear in the Early Triassic because of the recurrent and long-term ocean anoxia.
BACKGROUND: Globally, cancer is a major health issue that poses a significant threat to human health. Traditional treatments and laboratory-based methods have been extensively employed to treat cancer-affected cells. How...BACKGROUND: Globally, cancer is a major health issue that poses a significant threat to human health. Traditional treatments and laboratory-based methods have been extensively employed to treat cancer-affected cells. However, their high processing costs and side effects still limit their efficacy. In the past decade, significant developments in the field of anticancer peptides (ACPs) have shown a promising alternative for developing reliable cancer drugs with low side effects. RESULTS: In this paper, we presented an effective model, pACP-CapsNet, to accurately identify ACPs. The input sequences are converted into structural and localized substitution-based images using SMR and RECM. Subsequently, HOG, DWT, and CLBP-based transformations are applied to the obtained two-dimensional images to produce novel feature spaces, including RECM_DCT, DWT_SMR, HOG_SMR, and RECM_CLBP. These extracted descriptors are then serially integrated to handle the drawbacks of individual descriptors. Additionally, the shuffled frog leaping algorithm is utilized for selecting the high-ranked features from the integrated hybrid vector. Several deep learning models are trained using SFLA features, among which the Capsule Neural Network (CapsNet) achieved higher prediction rates. The proposed pACP-CapsNet obtained an accuracy of 97.0% and an AUC of 0.98 using training samples. Further validation reveals that pACP-CapsNet outperformed available models, demonstrating improvements of approximately 3% and 4% using the ACP240 and ACP740 test sets, respectively. CONCLUSIONS: The confirmed efficiency and stability of the pACP-CapsNet model underscore its potential as a valuable tool in academic research, drug diagnosis, and drug design.
Castillo O, Rivera LM, Albalawi A
… +1 more, Brancaleon L
J Photochem Photobiol B
· 2026 Mar · PMID 41671773
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This study investigates how metal coordination and protein binding modulate the photosensitizing properties of protoporphyrin IX (PpIX) analogues and their potential for creating engineered photoreceptor proteins (EPrP)....This study investigates how metal coordination and protein binding modulate the photosensitizing properties of protoporphyrin IX (PpIX) analogues and their potential for creating engineered photoreceptor proteins (EPrP). Three porphyrins-metal-free PpIX (mfPpIX, normal), hemin (d-type hyperporphyrin), and tin-PpIX (SnPpIX, p-type hyperporphyrin)-were self-assembled with recombinant human serum albumin (rHSA) and irradiated at their Soret band using a 405 nm laser. Steady-state and time-resolved spectroscopic analyses revealed distinct photophysical behaviors. mfPpIX strongly binds rHSA and exhibits efficient photosensitization of singlet oxygen (O), leading to photobleaching and formation of formyl-type photoproducts, suggesting ROS-mediated mechanisms as potential triggers for EPrP. Hemin showed negligible photosensitization, dominated by intramolecular charge transfer to Fe, limiting its suitability for ROS-driven EPrP. SnPpIX retained significant O photosensitization and photoproduct formation both free and protein-bound, but its weak interaction with rHSA may constrain its applicability. These findings highlight mfPpIX as the most promising candidate for EPrP development and provide novel quantitative data on absorption, fluorescence, and lifetime properties of aqueous porphyrins, including the first reported parameters for SnPpIX and PpIX photoproducts, besides the identification of the contribution of aqueous monomeric PpIX to the emission properties.
Li J, Li X, Wu L
… +4 more, Lv H, Liu T, Yao H, Jiang J
J Photochem Photobiol B
· 2026 Mar · PMID 41666531
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Inflammatory responses associated with pyroptosis have been shown to promote reactive oxygen species (ROS) production. Among these ROS, hypochlorite (ClO) plays a pivotal role in regulating inflammatory progression. Here...Inflammatory responses associated with pyroptosis have been shown to promote reactive oxygen species (ROS) production. Among these ROS, hypochlorite (ClO) plays a pivotal role in regulating inflammatory progression. Herein, red-emissive carbon dots (N-CDs) with a maximum emission at 611 nm and a fluorescence quantum yield of 24.1% were developed. The N-CDs exhibit sensitive and selective fluorescence modulation toward ClO, achieving a low detection limit of 0.056 μM. The N-CDs function as versatile fluorescent nanoprobes for monitoring exogenous ClO dynamics in living cells, evaluating inflammatory status in cellular and zebrafish models, and assessing gouty arthritis in rats. Notably, the N-CDs enable real-time visualization of pyroptosis in living cells through distinct fluorescence signal evolution. Such fluorescence modulation provides a reliable readout for monitoring pyroptosis-associated oxidative stress. This work establishes a sensitive and specific platform for ClO detection in inflammatory environments and highlights the potential applicability of red-emissive carbon dots for dynamic monitoring of inflammation-related cellular processes.
Hernández-Silva D, Matabuena M, Guío-Carrión A
… +9 more, Aguilera J, Martín A, Megias D, Mínguez D, Demessant-Flavigny AL, Castillejo I, Bernerd F, Prieto L, Blasco MA
J Photochem Photobiol B
· 2026 Mar · PMID 41666530
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BACKGROUND: Ultraviolet (UV) radiation contributes to photoaging and skin cancer by causing DNA damage and generating reactive oxygen species (ROS). It also induces telomere shortening, a key factor in cellular aging. Ho...BACKGROUND: Ultraviolet (UV) radiation contributes to photoaging and skin cancer by causing DNA damage and generating reactive oxygen species (ROS). It also induces telomere shortening, a key factor in cellular aging. However, no studies have investigated whether sunscreen can prevent short-term telomere shortening caused by UV exposure to human skin. OBJECTIVES: We have examined whether the use of a broad-spectrum sunscreen product can protect at the telomere level from the harmful effects of UV light. METHODS: Human keratinocytes and a 3D skin model were exposed to 10 J/cm of solar-simulated UV radiation under three conditions: non-exposed, exposed, and exposed with broad-spectrum sunscreen. DNA damage, assessed by γH2AX levels, was measured at 30 min and 24 h post-irradiation. Telomere length was evaluated by high-throughput quantitative fluorescence in situ hybridization (HT Q-FISH) at 24 h post-irradiation. Histological analysis of 3D skin samples was performed using hematoxylin and eosin (H&E) staining to assess tissue integrity. RESULTS: A decrease in cell number, increased DNA damage, and telomere shortening, accompanied by a higher proportion of critically short telomeres, were observed in UV-exposed keratinocytes and reconstructed human skin following exposure to 10 J/cm of solar-simulated UV radiation. The 3D skin architecture was also compromised, showing loss of keratinocytes spatial organization, evidence of epidermal cell death, and significant dermal thinning. However, cells and 3D skin samples protected with a broad-spectrum sunscreen remained comparable to non-exposed controls, showing no detectable structural or molecular alterations. CONCLUSIONS: These findings provide initial evidence that a broad-spectrum sunscreen product can mitigate UV-induced telomere shortening and DNA double-strand damage (DSBs), thereby preventing photodamage associated with solar exposure.
BACKGROUND: Predicting drug-protein interactions (DPI) is essential for effective and safe drug discovery. Although deep learning methods have been extensively applied to DPI prediction, effectively leveraging the multi-...BACKGROUND: Predicting drug-protein interactions (DPI) is essential for effective and safe drug discovery. Although deep learning methods have been extensively applied to DPI prediction, effectively leveraging the multi-structural and multimodal data on drugs and proteins to enhance prediction accuracy remains a significant challenge. RESULTS: This study proposes CMMSCL-DPI, a cross-modal multi-structural contrastive learning model. CMMSCL-DPI applies contrastive learning to the multi-dimensional structural features of proteins and drugs separately and integrates interaction features from a DPI heterogeneous graph network to facilitate cross-modal contrastive learning. This approach effectively captures the key differences and similarities between proteins and drugs, significantly enhancing the model's generalization capabilities for novel drug-target pairs. Experimental results across four benchmark datasets demonstrate that CMMSCL-DPI outperforms five state-of-the-art baseline models in overall performance. Additionally, the model successfully identified an unreported drug-protein interaction, which was subsequently validated through all-atom molecular dynamics simulations. CONCLUSIONS: This case study not only confirms the predictive accuracy of CMMSCL-DPI but also underscores its potential in discovering novel protein-ligand interactions.