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Chemistry & Biology[JOURNAL]

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Integrative transcriptomics and peptidomics approach reveals unexpectedly diverse endogenous secretory peptides in Odorrana grahami frog skin.

Liu J, Zhu W, Chang L … +5 more , Zhao T, Zhang M, Wang B, Xie F, Jiang J

BMC Biol · 2025 Nov · PMID 41316154 · Full text

BACKGROUND: Endogenous secretory peptides (ESPs) play crucial roles in amphibian skin, yet their identification remains challenging in species lacking genomic data. This study developed an innovative pipeline integrating... BACKGROUND: Endogenous secretory peptides (ESPs) play crucial roles in amphibian skin, yet their identification remains challenging in species lacking genomic data. This study developed an innovative pipeline integrating transcriptomics and peptidomics to identify ESPs in the skin of Odorrana grahami. This approach enhances endogenous secretory protein prediction accuracy by rescuing candidates erroneously discarded during SignalP-based screening. Such false negatives typically result from inaccurate annotation of N-terminal start sites within 5'-UTRs by protein prediction tools like TransDecoder. RESULTS: Our approach enhanced potential endogenous secretory protein identification rates by 61.6%, discovering 107 putative ESPs (16 validated at the protein level). Among these, 74 ESPs are newly reported in O. grahami (including 62 novel peptides). These ESPs span 14 known families (11 newly reported in O. grahami, 8 of which are first reported within the genus Odorrana). The frog skin active peptide (FSAP) family (n = 83)-comprising the largest subset of ESPs identified in this study-showed unexpected diversity between our studied individual and previously reported individuals within the population. Collectively, O. grahami (n = 226) and Odorrana andersonii (n = 205) currently hold the highest documented counts of FSAP family peptides in amphibians. Phylogenetic analysis delineated five FSAP clades (A-E) containing 18 clustered groups, with the hypervariable clade D harboring diverse non-AMPs and tachykinin-convergent peptides. GO and KEGG pathway analyses indicated that ESPs in O. grahami skin are predominantly immunity-related. CONCLUSIONS: This study highlights underestimated FSAP family peptide diversity in Odorrana and provides an adaptable framework for ESP discovery across taxa.

Less Severe Inflammation in Cyclic GMP-AMP Synthase (cGAS)-Deficient Mice with Rabies, Impact of Mitochondrial Injury, and Gut-Brain Axis.

Areekul P, Bhunyakarnjanarat T, Suebnuson S … +6 more , Somsri K, Trakultritrung S, Taveethavornsawat K, Tencomnao T, Boonyasuppayakorn S, Leelahavanichkul A

Biology (Basel) · 2025 Nov · PMID 41300373 · Full text

Activation of cGAS, a receptor recognizing cytosolic DNA, in macrophages might be associated with rabies (an RNA virus) through mitochondrial damage. A similar mortality rate was observed between cGAS-deficient (cGAS-/-)... Activation of cGAS, a receptor recognizing cytosolic DNA, in macrophages might be associated with rabies (an RNA virus) through mitochondrial damage. A similar mortality rate was observed between cGAS-deficient (cGAS-/-) and wild-type (WT) mice post-CVS-11 strain injection. However, 2 out of 12 cGAS-/- mice (but not WT) survived for 15 days post-injection. At 7 days post-infection, less severe brain inflammation in cGAS-/- mice was demonstrated by the viral abundance in the hippocampus, the expression of proinflammatory genes ( and ), and the Evans blue dye assay (blood-brain barrier defect) with the presence of higher anti-inflammatory genes ( and ). Fecal Proteobacteria was more prominent in the infected WT mice, while serum cytokines (TNF-α and IL-1β) were similar in both mouse strains. There were less prominent responses against the rabies virus in cGAS-/- macrophages than in WT cells, as indicated by supernatant IL-6 and the gene expression of , , , and . On the other hand, mitochondrial injury and cGAS activation were more prominent in WT macrophages over cGAS-/- cells, as indicated by cGAS expression, supernatant cGAMP (a secondary messenger of cGAS), and mitochondrial oxidative stress (MitoSox) together with a decrease in mitochondrial DNA and maximal respiration (extracellular flux analysis). In conclusion, (i) rabies-damaged mitochondria led to cGAS activation that was less severe in cGAS-/- than in WT, (ii) rabies-induced dysbiosis was demonstrated, and (iii) cGAS manipulation and gut-brain axis-associated inflammation warrants further investigation.

Histone Post-Translational Modifications and DNA Double-Strand Break Repair in Neurodegenerative Diseases: An Epigenetic Perspective.

Yeasmin A, Torrente MP

Biology (Basel) · 2025 Nov · PMID 41300346 · Full text

DNA damage is a hallmark of the fatal process of neurodegeneration in the central nervous system (CNS). As neurons are terminally differentiated, they accumulate metabolic and oxidative burdens over their whole life span... DNA damage is a hallmark of the fatal process of neurodegeneration in the central nervous system (CNS). As neurons are terminally differentiated, they accumulate metabolic and oxidative burdens over their whole life span. Unrepaired DNA develops into DNA double-strand breaks (DSBs), which are repaired through homologous recombination (HR) or non-homologous end joining (NHEJ). Being post-mitotic and unable to normally undergo HR, damage and defective repair is especially burdensome to CNS neurons. Current research has not produced treatment to prevent and halt progression of neurodegeneration. Hence, novel targeting strategies are desperately needed. Recent investigations in histone post-translational modifications (PTMs) reveal new mechanistic insight and highlight unexplored targets to ameliorate neurodegeneration. As various histone PTMs dictate and facilitate DSB repair, they represent an underexploited area in investigating DNA damage and incorrect repair aiding neurodegeneration. Here, we review the histone PTM alterations in several neurodegenerative diseases: Amyotrophic Lateral Sclerosis/Frontotemporal Dementia, Parkinson's Disease, Alzheimer's Diseases, Multiple Sclerosis, and Huntington's Disease. These findings emphasize that histone PTM alterations can enable an aberrant DNA damage response (DDR) leading to neurodegeneration. Further research into the connections between histone PTMs and DNA damage in decaying neurons will illuminate novel targets to dampen the aberrant DDR and promote neuronal survival.

Sustainable Cultivation and Functional Bioactive Compounds of Mushrooms: Advances, Challenges, and Future Prospects.

Liu M, Jiang W, Huang K … +8 more , Li L, Meng Q, You X, Pu K, Cheng M, Gao Z, Qi J, Li M

Biology (Basel) · 2025 Nov · PMID 41300345 · Full text

The genus , and specifically the species , is a globally significant edible fungus with a long history of cultivation and notable nutritional and medicinal properties. This review systematically examines the taxonomic cl... The genus , and specifically the species , is a globally significant edible fungus with a long history of cultivation and notable nutritional and medicinal properties. This review systematically examines the taxonomic classification, morphological and physiological characteristics, and bioactive components (such as polysaccharides, melanin, proteins and polyphenols) of , as well as their pharmacological effects and industrial applications. Recent molecular biological advances have clarified taxonomic uncertainties, including the reclassification of 'heimuer' as , and emphasized the species' genetic diversity. thrives in temperate and subtropical regions, with cultivation techniques evolving from traditional wood log inoculation to modern substrate-based methods. However, sustainability challenges persist, including reliance on virgin wood substrates and the need for improved spent substrate management. The fungus exhibits remarkable nutritional properties, with polysaccharides (up to 66.1% of dry weight) demonstrating hypoglycemic, antitumor, immunomodulatory, and antioxidant activities. Melanin and proteins further contribute to hepatoprotection, antimicrobial effects, and metabolic regulation. Industrial applications of species extend beyond food into pharmaceuticals and functional materials. Polysaccharides are explored as drug carriers, while melanin shows promise in antioxidant and antibacterial formulations. Despite these advances, gaps remain in understanding the mechanistic basis of bioactive compound functions and optimizing cultivation for sustainable production. Future research should integrate multi-omics approaches to elucidate genetic regulation, enhance substrate formulations, and develop value-added products. This review underscores the potential of species as a functional food and biotechnological resource, advocating for interdisciplinary efforts to address current challenges and unlock its full industrial potential.

Deciphering the Contribution of TATA Box and 5'UTR to Defense Signaling in Rice Under Blast Infection.

Fan X, Naz M, Zhang Y … +1 more , Afzal MR

Biology (Basel) · 2025 Oct · PMID 41300312 · Full text

The TATA box and 5'untranslated region (5'UTR) are critical regulatory elements that influence gene expression in plant defense responses. In rice (), these elements modulate transcriptional and translational regulation... The TATA box and 5'untranslated region (5'UTR) are critical regulatory elements that influence gene expression in plant defense responses. In rice (), these elements modulate transcriptional and translational regulation during infection by the blast pathogen . This study investigates the functional significance of the TATA box and 5'UTR in rice defense signaling by analyzing promoter and 5'UTR variations in key defense-related genes. Through comparative genomics, expression profiling, and mutagenesis assays, we show that 60% of defense genes with specific TATA box motifs exhibit enhanced transcription, while 5'UTR variants increase translational efficiency by up to 2-fold, contributing to blast resistance. These regulatory mechanisms provide a framework for targeted breeding and biotechnological interventions to enhance disease resistance in rice. Our findings highlight the importance of these elements in fine-tuning rice immune responses and suggest potential targets for improving disease resistance in rice cultivars.

The Human Omental Adipose Depot Mitigates Inflammation, Immune Response, and Oxidative Stress Pathways in Response to Injury via Its Secretome.

Krause-Hauch M, Patel RS, Wang B … +3 more , Jones B, Albear P, Patel NA

Biology (Basel) · 2025 Oct · PMID 41300301 · Full text

Human intraperitoneal omental adipose tissue, part of the visceral adipose depots, surrounds the abdominal organs and has functions distinct from the subcutaneous adipose depots. In the clinical setting, it is observed t... Human intraperitoneal omental adipose tissue, part of the visceral adipose depots, surrounds the abdominal organs and has functions distinct from the subcutaneous adipose depots. In the clinical setting, it is observed that the omentum is beneficial to combat internal sources of inflammation, oxidative stress, and injury-related stress. However, the molecular mechanisms involved in these functions are not fully understood. We previously demonstrated that adipose stem cells derived from human omental adipose tissue (om-hASCs) secrete exosomes (exos). We and others have extensively evaluated the subcutaneous adipose depot-derived exosomes; however, the role of adipose stem cells derived from the human omental depot (om-hASCs) remains less known. In this study, we postulated that exosomes from om-hASCs (om-hASCexos) drive the repair ability of the omentum to heal organs after internal injury and insults. First, we characterized the om-hASCexos using a proteomic analysis which identified the distinct cargo. Using in vitro injury models, we show that om-hASCexos significantly improve cell migration and proliferation, while decreasing oxidative stress and inflammation. To study acute in vivo healing, a rat wound model was evaluated. Om-hASCexos significantly improved the healing rate of injuries. RNAseq revealed that om-hASCexo treatment acts upon pathways associated with lipid and fatty acid metabolism, apoptosis, immune response, and cell differentiation. The pathway analysis indicated that om-hASCexos significantly regulate the expression of and in the immune response pathway. Overall, we demonstrate the singular properties of om-hASCexos that are distinct from other sources of hASC. Thus, this study provides an understanding of the unique ability of the omental adipose depot to combat internal injuries.

Novel Model for Stomatal Conductance: Enhanced Accuracy Under Variable Irradiance and CO in C Plant Species.

Ye Z, An T, Yang X … +2 more , Kang H, Wang F

Biology (Basel) · 2025 Oct · PMID 41300293 · Full text

This study analyzes stomatal conductance () in L., L., and L. under varying environmental conditions. Light-response curves for photosynthesis (-) at 420 μmol mol CO were used to determine saturating irradiance () usi... This study analyzes stomatal conductance () in L., L., and L. under varying environmental conditions. Light-response curves for photosynthesis (-) at 420 μmol mol CO were used to determine saturating irradiance () using a light-response model for photosynthesis, and CO-response curves for photosynthesis (-) were measured at and half for these C plant species. The Ball-Woodrow-Berry (BWB) model, Medlyn model, and a new model were compared for their ability to describe the net photosynthetic rate () relative to under changing irradiance or CO. The BWB model overestimated response, simplifying stomatal behavior, while the Medlyn model deviated at high values, indicating limitations in dynamic responses. The new model showed a better empirical fit under the tested conditions, achieving high values and low AIC values across all three species, and demonstrated a strong alignment with empirical data. Our findings highlight the complexity of regulation and the need for improved models to better represent stomatal dynamics under different environmental conditions. This research is vital for optimizing water use efficiency, enhancing crop productivity, and understanding plant resilience to climate change.

Heavy Metal Contamination in Adaptogenic Herbal Dietary Supplements: Experimental, Assessment and Regulatory Safety Perspectives.

Jasińska-Balwierz A, Krypel P, Świsłowski P … +3 more , Rajfur M, Balwierz R, Ochędzan-Siodłak W

Biology (Basel) · 2025 Oct · PMID 41300272 · Full text

While adaptogens are popular in dietary supplements for their health-promoting properties, their safety is compromised by the risk of heavy metal contamination, a threat amplified by inconsistent regulatory standards. Th... While adaptogens are popular in dietary supplements for their health-promoting properties, their safety is compromised by the risk of heavy metal contamination, a threat amplified by inconsistent regulatory standards. This study aimed to assess the extent of heavy metal contamination in adaptogenic supplements on the Polish market and evaluate their compliance with international safety limits. Eleven commercially available supplements (tablets, powders, dried materials) containing , , , and were analyzed for lead (Pb), cadmium (Cd), mercury (Hg), nickel (Ni), and other elements using flame atomic absorption spectroscopy (FAAS) and mercury analysis (AMA 254). Results demonstrated widespread contamination, primarily with Pb and Ni. In processed forms (tablets and dried fruits), Pb concentrations exceeded permissible limits by up to 235%, while Ni levels were exceeded by up to 321%. preparations showed the highest contamination levels. Furthermore, raw materials from India contained significantly higher Ni concentrations than those from China ( < 0.01). These findings reveal that a majority of the tested supplements fail to meet toxicological safety criteria, posing a significant health risk to consumers. This underscores a critical regulatory gap and highlights the urgent need for harmonized standards and stringent quality control for dietary supplements.

Ecotone-Driven Vegetation Transitions Reshape Soil Nitrogen Cycling Functional Genes in Black Soils of Northeast China.

Ding J, Wang Y, Yu S

Biology (Basel) · 2025 Oct · PMID 41300267 · Full text

Forest-wetland ecotones are transitional ecosystems characterized by pronounced hydrological and biogeochemical heterogeneity, yet the microbial mechanisms regulating nutrient cycling in these zones remain insufficiently... Forest-wetland ecotones are transitional ecosystems characterized by pronounced hydrological and biogeochemical heterogeneity, yet the microbial mechanisms regulating nutrient cycling in these zones remain insufficiently understood. This study investigated how vegetation transitions across a forest-wetland ecotone in the black-soil region of Northeast China shape soil microbial communities and nitrogen-cycling functions. Soils were collected from four vegetation types: mixed forest (MF), coniferous forest (CF), wetland edge (WE), and natural wetland (NW). Quantitative PCR was used to quantify key nitrogen-cycling functional genes (, , , , ), and PICRUSt2 was applied to predict microbial functional potentials. Forest soils (MF and CF) exhibited higher microbial diversity, stronger network connectivity, and greater abundances of and , indicating enhanced nitrogen fixation and nitrification under oxic conditions. In contrast, wetland soils harbored denitrification-enriched communities with higher and abundances but lower diversity. The WE vegetation type acted as a functional hotspot where alternating oxic-anoxic conditions facilitated the coexistence of nitrifiers and denitrifiers, thereby enhancing carbon-nitrogen coupling and functional resilience. Redundancy and Mantel analyses identified soil organic carbon, total nitrogen, water content, and enzyme activities as major environmental drivers of microbial structural and functional variation. This study reveals that vegetation transitions reorganize microbial community assembly and nitrogen-cycling functions through hydrological and biogeochemical heterogeneity, providing mechanistic insights into nutrient turnover and ecological regulation in black-soil ecotones.

Climate Change Enhances the Cultivation Potential of Bur. in China: Insights from Ensemble Modeling and Niche Analysis.

Liu M, Qin Y, Yang J … +6 more , Li X, Zhu F, Ma Z, Zhao C, Su R, Chen Y

Biology (Basel) · 2025 Oct · PMID 41300265 · Full text

Climate change is reshaping plant distribution and ecological adaptation worldwide. Bur., a perennial resource plant native to Southwest and South China, has not been systematically assessed for its future cultivation p... Climate change is reshaping plant distribution and ecological adaptation worldwide. Bur., a perennial resource plant native to Southwest and South China, has not been systematically assessed for its future cultivation potential. In this study, we used the Biomod2 ensemble modeling framework, integrating 12 algorithms with 469 occurrence records and 16 environmental variables, to predict the potential distribution and niche dynamics of under current and future climate scenarios (SSP126, SSP370, and SSP585). The ensemble model achieved high predictive accuracy based on multiple algorithms and cross-validation. The minimum temperature of the coldest month (bio6, 43.5%), maximum temperature of the warmest month (bio5, 25.0%), and annual precipitation (bio12, 10.3%) were identified as the dominant factors shaping its distribution. Model projections suggest that suitable habitats will generally expand northwestward, while contracting in the southeast. Core areas, such as the Yunnan-Guizhou Plateau and the Sichuan Basin, are predicted to remain highly stable. In contrast, southeastern marginal regions are likely to experience a decline in suitability due to intensified heat stress. Niche analyses further revealed strong niche conservatism (overlap D = 0.83-0.94), suggesting that the species maintains stable climatic tolerance and adapts primarily through range shifts rather than evolutionary change. This finding suggests limited adaptive flexibility in response to rapid warming. Overall, climate warming may enhance cultivation opportunities for at higher latitudes and elevations, while emphasizing the importance of protecting stable core habitats, planning climate adaptation corridors, and integrating this species into climate-resilient agroforestry strategies. These findings provide practical guidance for biodiversity conservation and land-use planning, offering a scientific basis for regional policy formulation under future climate change.

Biomimetic polydopamine-intercalated MgAl-layered double hydroxide for effective skin photoprotection and photodamage recovery.

Zhu P, Sun X, Cai Y … +3 more , Zhao M, Zhang R, Sun J

J Photochem Photobiol B · 2026 Jan · PMID 41297116 · Publisher ↗

Excessive ultraviolet (UV) radiation is harmful to human health, leading to a range of skin issues including photoaging, sunburn, and skin cancer. Using sunscreen can help alleviate or provide temporary protection agains... Excessive ultraviolet (UV) radiation is harmful to human health, leading to a range of skin issues including photoaging, sunburn, and skin cancer. Using sunscreen can help alleviate or provide temporary protection against the harmful effects of UV radiation. Commercial sunscreens frequently have low effectiveness and raise safety concerns. Therefore, a novel biocompatible polydopamine-intercalated MgAl-layered double hydroxides nanocomposite (PDA-LDH) was synthesized via in situ oxidation of dopamine within the interlayer of LDH at room temperature and without any additives. LDH can serve as an effective base to facilitate the formation of PDA without the need for an additional base, due to the ordered arrangement of basic hydroxyl groups on the surface of the LDH. The intercalation of PDA in the LDH interlayer ensures good biosafety, effective UV shielding, and excellent antioxidative and anti-inflammatory properties of PDA-LDH, making it suitable for skin photoprotection and the repair of photodamaged skin. PDA-LDH is poised to be a promising next-generation biomimetic sunscreen, designed to assist in the photoprotection and repair of photodamaged skin.

The details and entropy demons in a transmembrane allosteric machine.

Luisi BF

PLoS Biol · 2025 Nov · PMID 41296789 · Full text

In the model gram-negative bacterium Escherichia coli, three of the four Type VII ATP-binding cassette (ABC) transporter systems have been well characterized structurally and functionally. A new study reports the cryo-EM... In the model gram-negative bacterium Escherichia coli, three of the four Type VII ATP-binding cassette (ABC) transporter systems have been well characterized structurally and functionally. A new study reports the cryo-EM structures of the fourth Type VII ABC system, YbbAP-TesA, and provides evidence for its role in extracting hydrophobic compounds from the bacterial inner membrane and their subsequent hydrolytic transformation.

A sulfonate-modified cyanine-based photoacoustic probe for selective detection of hydroxyl radicals in diabetic liver injury.

Fan DX, Zhang RW, Liu JL … +4 more , Fan L, Xiang HX, Cheng ZY, Wang K

J Photochem Photobiol B · 2026 Jan · PMID 41289757 · Publisher ↗

Hydroxyl radicals (•OH) play a critical role in oxidative stress-related diseases, yet their real-time detection in vivo remains challenging. We developed a hydroxyl radical-responsive photoacoustic probe (OHP) by modify... Hydroxyl radicals (•OH) play a critical role in oxidative stress-related diseases, yet their real-time detection in vivo remains challenging. We developed a hydroxyl radical-responsive photoacoustic probe (OHP) by modifying IR780-SOH with enhanced hydrophilicity (logP = -1.051) for improved biodistribution. Structural characterization confirmed the selective reduction of the conjugated system, while in vitro studies demonstrated OHP's selective and linear response to •OH with minimal interference from other ROS/RNS. In diabetic mice, OHP enabled dynamic monitoring of hepatic •OH levels, revealing elevated oxidative stress that was attenuated by metformin treatment. Ex vivo fluorescence imaging and histopathology validated the imaging results, showing strong correlation with disease severity. Biosafety assessments confirmed negligible cytotoxicity in cells and mice. OHP represents a sensitive, selective, and biocompatible tool for non-invasive •OH detection, offering potential for studying oxidative stress and therapeutic interventions.

A novel targeting domain directs essential components of the cytosolic iron-sulfur cluster assembly pathway to the mitochondrion of Toxoplasma parasites.

Hodgson ER, Hayward JA, Leonard RA … +2 more , Makota FV, van Dooren GG

PLoS Biol · 2025 Nov · PMID 41289326 · Full text

The assembly of iron-sulfur (FeS) clusters for cytosolic and nuclear proteins is essential for eukaryotic cell biology. This assembly is mediated by the Cytosolic Iron-sulfur Assembly (CIA) pathway, which localizes to th... The assembly of iron-sulfur (FeS) clusters for cytosolic and nuclear proteins is essential for eukaryotic cell biology. This assembly is mediated by the Cytosolic Iron-sulfur Assembly (CIA) pathway, which localizes to the cytosol of most eukaryotes. We showed previously that the scaffold protein on which cytosolic FeS clusters assemble localizes to the mitochondrion of the apicomplexan parasite Toxoplasma gondii. The localization and importance of the remainder of the pathway in these parasites, however, remained unclear. Here, we undertake a comprehensive analysis of the CIA pathway in T. gondii parasites. We present evidence that the CIA pathway localizes predominantly to the mitochondrion of the parasite and is essential for parasite survival. We show that the three proteins that make up the CIA Targeting Complex (CTC), which facilitates the transfer of FeS clusters to cytosolic and nuclear client proteins, exhibit dual localization to the mitochondrion and cytosol. We reveal that mitochondrial targeting of the CTC is mediated by a novel loop on the CIA1 protein of the complex, and that this loop is critical for parasite survival. We show that an aromatic amino acid motif in the loop facilitates mitochondrial targeting, and that this loop is functionally conserved in apicomplexans and their closest free-living relatives. Our study provides a comprehensive analysis of the CIA pathway in an important group of intracellular parasites, and elucidates pivotal differences in an otherwise ancient and highly conserved biosynthetic pathway that may reflect an evolutionary fitness advantage conferred on Toxoplasma and related organisms.

The novel GlcNAc 6-phosphate dehydratase NagS governs a metabolic checkpoint that controls nutrient signaling in Streptomyces.

Li C, Urem M, Kotsogianni I … +12 more , Lau J, Du C, Elsayed SS, Martin NI, McNae IW, Voskamp P, Mayer C, Rigali S, Pannu N, Abrahams JP, Schada von Borzyskowski L, van Wezel GP

PLoS Biol · 2025 Nov · PMID 41289323 · Full text

Streptomyces bacteria are renowned for their multicellular lifestyle and as Nature's medicine makers, producing the majority of the clinical antibiotics. A landmark event during early development is the lytic dismantling... Streptomyces bacteria are renowned for their multicellular lifestyle and as Nature's medicine makers, producing the majority of the clinical antibiotics. A landmark event during early development is the lytic dismantling of the substrate mycelium. Degradation of the hyphal cell-wall leads to the accumulation of N-acetylglucosamine (GlcNAc) in the colonies, which is a metabolic checkpoint during the onset of development and antibiotic production. Here, we show that GlcNAc sensing requires a toxicity pathway dependent on the enzyme GlcNAc-6P dehydratase (NagS). Dehydration of GlcNAc-6P by NagS to 6P-chromogen I is an unprecedented reaction in central metabolism that is highly conserved in - and limited to - the Streptomycetaceae. 6P-chromogen I is metabolized into a structural analogue of ribose by a promiscuous activity of GlcNAc-6P deacetylase NagA. Toxicity is relieved by supplementing the growth media with ribose. Structure-function analysis of NagS not only highlighted key residues in the active site of the enzyme in interaction with its substrate GlcNAc-6P, but also revealed 6-phosphogluconate as its catalytic inhibitor. Our work uncovers a conserved metabolic toxicity pathway in Streptomyces that revolves around a novel enzyme that plays a key role in nutrient signaling.

Structural characterization of the YbbAP-TesA ABC transporter identifies it as a lipid hydrolase complex that extracts hydrophobic compounds from the bacterial inner membrane.

McAndrew MBL, Cook J, Gill A … +4 more , Sahoo K, Thomas C, Stansfeld PJ, Crow A

PLoS Biol · 2025 Nov · PMID 41289308 · Full text

Type VII ABC transporters are ATP-powered membrane protein complexes that drive key biological processes in the bacterial cell envelope. In Escherichia coli, three of the four Type VII ABC systems have been extensively c... Type VII ABC transporters are ATP-powered membrane protein complexes that drive key biological processes in the bacterial cell envelope. In Escherichia coli, three of the four Type VII ABC systems have been extensively characterized, including: the FtsEX-EnvC cell division complex, the LolCDE-LolA lipoprotein trafficking machinery, and the MacAB-TolC efflux pump. Here we describe a fourth E. coli Type VII ABC system, YbbAP-TesA, which combines a Type VII ABC transporter with a multifunctional hydrolytic enzyme. Structures of the complete YbbAP-TesA complex, and of YbbAP with and without bound ATP analogues, capture implied long-range transmembrane conformational changes that are the hallmark of this ABC superfamily's mechanotransmission mechanism. We further show that YbbAP-TesA can hydrolyze a variety of ester and thioester substrates and experimentally confirm a constellation of active site residues in TesA. Our data suggests YbbAP has a role in extracting hydrophobic molecules from the inner membrane and presenting these to TesA for hydrolysis. The work extends collective knowledge of the remarkable diversity of the ABC superfamily and establishes a new function for Type VII ABC transporters in bacterial cells.

Cyclic electron transport pathways around photosystems I and II: Working together.

Lysenko V, Guo Y, Ignatova M … +8 more , Tarik E, Aslanyan V, Varduny T, Toptunova A, Plyaka P, Kirichenko E, Dmitriev P, Krasnov V

J Photochem Photobiol B · 2026 Jan · PMID 41285089 · Publisher ↗

The processes of cyclic electron transport around photosystems I and II (CET-PSI and CET-PSII) do not lead to O evolution and CO assimilation and are referred to as anoxygenic photosynthesis a broad sense, in contrast to... The processes of cyclic electron transport around photosystems I and II (CET-PSI and CET-PSII) do not lead to O evolution and CO assimilation and are referred to as anoxygenic photosynthesis a broad sense, in contrast to specific processes in bacteria, which are commonly referred to as anoxygenic photosynthesis in a narrow sense. CET-PSI has been studied much more extensively than CET-PSII. Attempts to quantify CET-PSI have yielded contradictory results. It is not detected in non-stressed C3-plants using photoacoustic methods but is commonly considered as being observed when using Antimycin А which was had previously been proposed as a CET-PSI inhibitor. However, most researchers ignore recent data showing that Antimycin А primarily inhibits rather CET-PSII then CET-PSI. These facts, along with others, suggest that the contribution of CET-PSI to photosynthesis of non-stressed C3-plants has been overestimated. Our analysis of the data in this field also shows the possibility of underestimating CET-PSII, as well as anoxygenic photosynthesis in total, which is not excluded from being dominated over oxygenic photosynthesis. We point out that CET-PSI and CET-PSII cannot be studied separately. The difficulties in the quantitative evaluation of CET-PSII can be solved using photoacoustic techniques, which are highly promising in studies of anoxygenic photosynthesis.

STUPPIT is a proximity labeling tool for labeling intermediary proteins that bridge two non-interacting proteins.

Xie L, Gao L, Fu W … +3 more , Wu G, Li H, Ning W

PLoS Biol · 2025 Nov · PMID 41284752 · Full text

Decoding the complexities of signaling pathways is fundamental for deciphering the mechanisms underlying tissue development, homeostasis, and disease pathogenesis. Proximity labeling tools have been instrumental in ident... Decoding the complexities of signaling pathways is fundamental for deciphering the mechanisms underlying tissue development, homeostasis, and disease pathogenesis. Proximity labeling tools have been instrumental in identifying upstream or downstream effectors of specific proteins within signaling pathways. However, currently, there are no tools available to directly label and capture intermediary proteins that bridge two non-interacting proteins. Here, we developed Split-TurboID and PUP-IT based Protein Identification Tool (STUPPIT), a novel method combining split-TurboID and PUP-IT to biotinylate intermediary proteins of two non-interacting proteins through a two-step enzymatic reaction. STUPPIT was validated using three well-characterized protein triads, including YAP1/AMOT/β-actin, YAP1/LATS1/MOB1A, and β-catenin/α-catenin/β-actin using HEK293T human cell lines. Combining STUPPIT and proteomics, we identified novel intermediary proteins including ERC1 and USP7, which interacted both with β-catenin and SMAD4, key components of the Wnt and BMP signaling pathways. In conclusion, STUPPIT represents a powerful tool for labeling and capturing intermediary proteins between non-interacting partners, offering new insights into protein-protein interactions and advancing signal transduction research.

Multifunctional PDA-graphene family nanocomposites for antibacterial and anticancer photothermal therapy.

Kamalzadeh S, Moradi K, Afshar AK … +1 more , Mahmoudifard M

J Photochem Photobiol B · 2026 Jan · PMID 41274090 · Publisher ↗

The increasing demand for multifunctional, biocompatible nanomaterials has spurred the exploration of hybrid systems with synergistic antimicrobial, anticancer, antioxidant, and regenerative properties. In this study, po... The increasing demand for multifunctional, biocompatible nanomaterials has spurred the exploration of hybrid systems with synergistic antimicrobial, anticancer, antioxidant, and regenerative properties. In this study, polydopamine (PDA)-based nanocomposites incorporating graphene oxide (PDA-GO) and graphene quantum dots (PDA-GQD) were synthesized and systematically characterized for their physicochemical and biological functionalities. The nanocomposites raised temperature > 50 °C within 5 min under 808 nm laser irradiation (1.5 W/cm, 250 μg/mL). Both composites showed antibacterial activity against Escherichia coli (E. coli) (Gram-negative) and Staphylococcus aureus (S. aureus) (Gram-positive), achieving >99 % bacterial eradication under 10 min NIR irradiation at 125 μg/mL, indicating a combined photothermal (PT) and oxidative mechanism. In parallel, in vitro cytotoxicity assays revealed selective toxicity toward MCF-7 cancer cells-reducing viability to 95 % viability of normal L929 fibroblasts. Antioxidant assays confirmed >80 % DPPH radical scavenging at 250 μg/mL, supporting their potential in oxidative stress modulation. Furthermore, scratch wound healing assays demonstrated ∼100 % wound closure within 48 h in NIR-irradiated PDA-GO/PDA-GQD groups. Intracellular H₂O₂ generation reached up to 30.5 μM in MCF-7 cells under laser, enabling dual PT-photodynamic (PD) therapy. Altogether, these findings position PDA-GO and PDA-GQD nanocomposites as versatile platforms for integrated antibacterial, anticancer, and wound-healing therapies, highlighting their promise for future biomedical applications beyond conventional monofunctional approaches.

Nanobody-drug conjugates for targeting specific GPCR pairs.

Huang X, Roth BL

PLoS Biol · 2025 Nov · PMID 41269987 · Full text

Bitopic ligands that engage two distinct binding sites offer exciting opportunities for finely tuned control of G protein-coupled receptor signaling. A recent study in PLOS Biology employed click chemistry to generate no... Bitopic ligands that engage two distinct binding sites offer exciting opportunities for finely tuned control of G protein-coupled receptor signaling. A recent study in PLOS Biology employed click chemistry to generate novel nanobody-small molecule conjugates and demonstrated their logic-gated activity at co-expressed receptor pairs with improved signaling profiles.
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