BMC Genomics. 2025 Apr 10;26(1):359. doi: 10.1186/s12864-025-11545-6.

ABSTRACT

BACKGROUND: This study assessed the long-term metabolic effects of prenatal nutrition in Nelore bulls through an integrated analysis of metabolome and microbiome data to elucidate the interconnected host-microbe metabolic pathways. To this end, a total of 126 cows were assigned to three supplementation strategies during pregnancy: NP (control)- only mineral supplementation; PP- protein-energy supplementation during the last trimester; and FP- protein-energy supplementation throughout pregnancy. At the end of the finishing phase, blood, fecal, and ruminal fluid samples were collected from 63 male offspring. The plasma underwent targeted metabolomics analysis, and fecal and ruminal fluid samples were used to perform 16 S rRNA gene sequencing. Metabolite and ASV (amplicon sequence variant) co-abundance networks were constructed for each treatment using the weighted gene correlation network analysis (WGCNA) framework. Significant modules (p ≤ 0.1) were selected for over-representation analyses to assess the metabolic pathways underlying the metabolome (MetaboAnalyst 6.0) and the microbiome (MicrobiomeProfiler). To explore the metabolome-metagenome interplay, correlation analyses between host metabolome and microbiome were performed. Additionally, a holistic integration of metabolic pathways was performed (MicrobiomeAnalyst 2.0).

RESULTS: A total of one and two metabolite modules associated with the NP and FP were identified, respectively. Regarding fecal microbiome, three, one, and two modules for the NP, PP, and FP were identified, respectively. The rumen microbiome demonstrated two modules correlated with each of the groups under study. Metabolite and microbiome enrichment analyses revealed the main metabolic pathways associated with lipid and protein metabolism, and regulatory mechanisms. The correlation analyses performed between the host metabolome and fecal ASVs revealed 13 and 12 significant correlations for NP and FP, respectively. Regarding the rumen, 16 and 17 significant correlations were found for NP and FP, respectively. The NP holistic analysis was mainly associated with amino acid and methane metabolism. Glycerophospholipid and polyunsaturated fatty acid metabolism were over-represented in the FP group.

CONCLUSIONS: Prenatal nutrition significantly affected the plasma metabolome, fecal microbiome, and ruminal fluid microbiome of Nelore bulls, providing insights into key pathways in protein, lipid, and methane metabolism. These findings offer novel discoveries about the molecular mechanisms underlying the effects of prenatal nutrition.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:40211121 | DOI:10.1186/s12864-025-11545-6

Mol Med. 2025 Apr 11;31(1):134. doi: 10.1186/s10020-025-01178-6.

ABSTRACT

BACKGROUND: Endometriosis, a common condition affecting 5-10% of women of reproductive age, is the growth of endometrial-like tissue outside the uterus, leading to pain and infertility. Current treatments, such as surgery and hormonal therapy, offer limited long-term benefits. This study investigated the potential of D-chiro inositol (DCI), a natural compound that influences ovarian steroidogenesis, to treat endometriosis and compared its efficacy with a progestin drug such as Dienogest (DG).

METHODS: We established a non-surgical mouse model of endometriosis in CD1 mice. Uterine horns were removed from donor mice, cut into fragments and inoculated in recipient mice by intraperitoneal injection. Endometriosis progression was assessed at 15, 21 and 28 days after transplantation, with the 28-day window being the most effective. The mice were then randomly assigned to four experimental groups, which received for 28 days: water (EMS); DCI 0.4 mg/die (DCI); DCI 0.2 mg/die and Dienogest 0.33 ng/die (DCI + DG); DG 0.67 ng/die (DG). At the end of the treatments, endometriotic lesions, ovaries and circulating estradiol levels were analyzed.

RESULTS: The results showed that treatment with DCI, both alone and in combination with DG, significantly reduced the number, size and vascularization of endometriotic lesions compared to the EMS control group. Histological analysis confirmed a decrease in endometriotic foci across all treatment groups, with the most pronounced effects in the DCI group. To investigate the underlying molecular mechanisms, we found that DCI led to a significant reduction in the expression of Sirt1 and an increase in E-Cadherin, indicating a reduction in EMT transition relevant for lesion development. In addition, DCI decreased cell proliferation and,blood vessel formation, as evaluated by PCNA and CD34, respectively. Futhermore, in the ovary, DCI treatment downregulated the expression of aromatase (Cyp19a1), the enzyme critical for estrogen biosynthesis, and increased the number of primordial to antral follicles, suggesting a beneficial effect on ovarian folliculogenesis.

CONCLUSIONS: By modulating proliferation, EMT transition and aromatase activity, DCI emerges as a promising compound for endometriosis treatment.

PMID:40211112 | DOI:10.1186/s10020-025-01178-6

Mol Psychiatry. 2025 Apr 10. doi: 10.1038/s41380-025-03013-0. Online ahead of print.

ABSTRACT

Dopamine modulates corticostriatal plasticity in both the direct and indirect pathways of the cortico-striato-thalamo-cortical (CSTC) loops. These gradual changes in corticostriatal synaptic strengths produce long-lasting changes in behavioral responses. Under normal conditions, these mechanisms enable the selection of the most appropriate responses while inhibiting others. However, under dysregulated dopamine conditions, including a lack of dopamine release or dopamine signaling, these mechanisms could lead to the selection of maladaptive responses and/or the inhibition of appropriate responses in an experience-dependent and task-specific manner. In this review, we propose that preventing or reversing such maladaptive synaptic strengths and erasing such aberrant "memories" could be a disease-modifying therapeutic strategy for many neurological and psychiatric disorders. We review evidence from Parkinson's disease, drug-induced parkinsonism, L-DOPA-induced dyskinesia, obsessive-compulsive disorder, substance use disorders, and depression as well as research findings on animal disease models. Altogether, these studies allude to an emerging theme in translational neuroscience and promising new directions for therapy development. Specifically, we propose that combining pharmacotherapy with behavioral therapy or with deep brain stimulation (DBS) could potentially cause desired changes in specific neural circuits. If successful, one important advantage of correcting aberrant synaptic plasticity is long-lasting therapeutic effects even after treatment has ended. We will also discuss the potential molecular targets for these therapeutic approaches, including the cAMP pathway, proteins involved in synaptic plasticity as well as pathways involved in new protein synthesis. We place special emphasis on RNA binding proteins and epitranscriptomic mechanisms, as they represent a new frontier with the distinct advantage of rapidly and simultaneously altering the synthesis of many proteins locally.

PMID:40210977 | DOI:10.1038/s41380-025-03013-0

Sci Rep. 2025 Apr 10;15(1):12246. doi: 10.1038/s41598-025-95893-z.

ABSTRACT

The rapid evolution of SARS-CoV-2 during the pandemic was characterized by the fixation of a plethora of mutations, many of which enable the virus to evade host resistance, likely altering the virus' genome compositional structure (i.e., the arrangement of compositional domains of varying lengths and nucleotide frequencies within the genome). To explore this hypothesis, we summarize the evolutionary effects of these mutations by computing the Sequence Compositional Complexity (SCC) in random stratified datasets of fully sequenced genomes. Phylogenetic ridge regression of SCC against time reveals a striking downward evolutionary trend, suggesting the ongoing adaptation of the virus's genome structure to the human host. Other genomic features, such as strand asymmetry, the effective number of K-mers, and the depletion of CpG dinucleotides, each linked to the virus's adaptation to its human host, also exhibit decreasing phylogenetic trends throughout the pandemic, along with strong phylogenetic correlations to SCC. We hypothesize that viral CpG depletion (throughout C➔U changes), promoted by directional mutational pressures exerted on the genome by the host antiviral defense systems, may play a key role in the decrease of SARS-CoV-2 genome compositional heterogeneity, with specific adaptation to the human host occurring as a form of genetic mimicry. Overall, our findings suggest a decelerating evolution of reduced compositional complexity in SCC, whereas the number of K-mers and the depletion of CpG dinucleotides are still increasing. These results indicate a genome-wide evolutionary trend toward a more symmetric and homogeneous genome compositional structure in SARS-CoV-2, which is partly still ongoing.

PMID:40210974 | DOI:10.1038/s41598-025-95893-z

Nat Commun. 2025 Apr 11;16(1):3429. doi: 10.1038/s41467-025-58520-z.

ABSTRACT

The biotransformation of nanoparticles plays a crucial role in determining their biological fate and responses. Although a few engineering strategies (e.g., surface functionalization and shape control) have been employed to regulate the fate of nanoparticles, the genetic control of nanoparticle biotransformation remains an unexplored avenue. Herein, we utilized a CRISPR-based genome-scale knockout approach to identify genes involved in the biotransformation of rare earth oxide (REO) nanoparticles. We found that the biotransformation of REOs in lysosomes could be genetically controlled via SMPD1. Specifically, suppression of SMPD1 inhibited the transformation of La2O3 into sea urchin-shaped structures, thereby protecting against lysosomal damage, proinflammatory cytokine release, pyroptosis and RE-induced pneumoconiosis. Overall, our study provides insight into how to control the biological fate of nanomaterials.

PMID:40210885 | DOI:10.1038/s41467-025-58520-z

Sci China Life Sci. 2025 Apr 8. doi: 10.1007/s11427-024-2860-5. Online ahead of print.

ABSTRACT

Access to structurally-defined human proteoforms is essential to the biochemical studies on human health and medicine. Chemical protein synthesis provides a bottom-up and atomic-resolution approach for the preparation of homogeneous proteoforms bearing any number of post-translational modifications of any structure, at any position, and in any combination. In this review, we summarize the development of chemical protein synthesis, focusing on the recent advances in synthetic methods, product characterizations, and biomedical applications. By analyzing the chemical protein synthesis studies on human proteoforms reported to date, this review demonstrates the significant methodological improvements that have taken place in the field of human proteoform synthesis, especially in the last decade. Our analysis shows that although further method development is needed, all the human proteoforms could be within reach in a cost-effective manner through a divide-and-conquer chemical protein synthesis strategy. The synthetic proteoforms have been increasingly used to support biomedical research, including spatial-temporal studies and interaction network analysis, activity quantification and mechanism elucidation, and the development and evaluation of diagnostics and therapeutics.

PMID:40210795 | DOI:10.1007/s11427-024-2860-5

Appl Microbiol Biotechnol. 2025 Apr 10;109(1):89. doi: 10.1007/s00253-025-13477-3.

ABSTRACT

The low frequency of homologous recombination together with poor efficiency in introducing DNA into the cell are the main factors hampering genetic manipulation of some bacterial strains. We faced this problem when trying to construct mutants of Streptomyces iranensis DSM 41954, a strain in which conjugation is particularly inefficient, and suicidal vectors had failed to yield any exconjugants. In this work, we report the construction and application of a conjugative replicative vector, pDS0007, which allows selection of exconjugants even with poor conjugation efficiency. The persistence of the construct inside the cell for as long as required facilitates the homologous recombination events leading to single and double crossovers. While it was confirmed that the vector is frequently lost without selection, the recognition sequence for the I-SceI endonuclease was included in the backbone of pDS0007. The presence of a I-SceI recognition sequence would allow to force the loss of the vector and the appearance of double crossover recombinants by introducing a second construct (e.g. pIJ12742) that expresses a Streptomyces codon-optimised gene encoding the I-SceI endonuclease. To facilitate screening for vector-free clones, the construct also carries a Streptomyces codon-optimised gusA gene encoding the β-glucuronidase expressed from a constitutive promoter. We prove the usefulness of this vector and strategy with the strain S. iranensis DSM 41954, in which we could readily delete an essential gene of a newly discovered biosynthetic pathway for a phosphonate-containing natural product, which led to loss of phosphonate production according to 31P NMR spectroscopy. KEY POINTS: • pDS0007 is a new vector for gene-targeting in difficult-to-manipulate streptomycetes. • pDS0007 is self-replicative but easy to cure, targetable and allows visual screening. • pDS0007 was used to prove the discovery of a novel phosphonate biosynthetic pathway.

PMID:40210783 | DOI:10.1007/s00253-025-13477-3

Trends Plant Sci. 2025 Apr 9:S1360-1385(25)00094-9. doi: 10.1016/j.tplants.2025.03.017. Online ahead of print.

ABSTRACT

Excessive use of agrochemicals poses an ongoing threat to ecosystems. Using an interdisciplinary approach, Sun et al. recently revealed that selenium nanoparticles (SeNPs) biosynthesized by selenobacteria recruit beneficial microbes via chemotaxis and biofilm formation, enriching rhizosphere diversity. This ability to manipulate plant-microbe interactions using SeNPs offers a novel approach for sustainable agriculture.

PMID:40210496 | DOI:10.1016/j.tplants.2025.03.017

Genome Res. 2025 Apr 10. doi: 10.1101/gr.279365.124. Online ahead of print.

ABSTRACT

In mammals, cohesin and CTCF organize the 3D genome into topologically associating domains (TADs) to regulate communication between cis-regulatory elements. Many organisms, including S. cerevisiae, C. elegans, and A. thaliana contain cohesin but lack CTCF. Here, we used C. elegans to investigate the function of cohesin in 3D genome organization in the absence of CTCF. Using Hi-C data, we observe cohesin-dependent features called "fountains," which have also been reported in zebrafish and mice. These are population average reflections of DNA loops originating from distinct genomic regions and are ∼20-40 kb in C. elegans Hi-C analysis upon cohesin and WAPL-1 depletion supports the idea that cohesin is preferentially loaded at sites bound by the C. elegans ortholog of NIPBL and loop extrudes in an effectively two-sided manner. ChIP-seq analyses show that cohesin translocation along the fountain trajectory depends on a fully intact complex and is extended upon WAPL-1 depletion. Hi-C contact patterns at individual fountains suggest that cohesin processivity is unequal on each side, possibly owing to collision with cohesin loaded from surrounding sites. The putative cohesin loading sites are closest to active enhancers, and fountain strength is associated with transcription. Compared with mammals, the average processivity of C. elegans cohesin is about 10-fold shorter, and the binding of NIPBL ortholog does not depend on cohesin. We propose that preferential loading and loop extrusion by cohesin is an evolutionarily conserved mechanism that regulates the 3D interactions of enhancers in animal genomes.

PMID:40210441 | DOI:10.1101/gr.279365.124

Exp Eye Res. 2025 Apr 8:110381. doi: 10.1016/j.exer.2025.110381. Online ahead of print.

ABSTRACT

PURPOSE: The signaling of flash visual evoked potential (fVEP) derives from the retina, but how retinal activity influences fVEP remains unclear. This work aimed to decipher the specific retinal kinetic contributions to fVEP response.

METHODS: Monocular and simultaneous recordings of flash VEP and electroretinogram were performed. Healthy and adult mice C57BL/6J were used. The right eye was injected intravitreally with 1 μL of PBS containing 25 mM APB, 10 mM Bicuculline, 30 mM DNQX, 100 mM Glutamate, 100 mM GABA, 5 mM TPMPA, or 25 mM HEPES. The left eye was injected with 1 μL of PBS and then wore an opaque patch. The amplitude and latency of fVEP were analyzed in detail.

RESULTS: In the control group, at light intensity ≤ 0.1 cd·s/m2, four robust components of the fVEP recordings, N1, P1, N2, and P2, were identified in dark adaptation conditions. After administration reagents, N1 and P1 components were abolished by APB, Bicuculline, DNQX or TPMPA, but were preserved by GABA/Glutamate or HEPES. Notably, N2 and P2 components were always kept. The latency and amplitude of fVEP were shown to be stimulus-dependent. Nevertheless, the amplitude showed greater inter-individual variability than latency.

CONCLUSION: N1 and P1 components are strongly related to rod photoreceptor activity and/or the level of horizontal cell excitation. Latency, rather than fVEP amplitude, could be a good biomarker for clinical and diagnostic purposes, particularly the P2 latency in the rod-driven scotopic response.

PMID:40210193 | DOI:10.1016/j.exer.2025.110381

Cell Rep. 2025 Apr 6:115354. doi: 10.1016/j.celrep.2025.115354. Online ahead of print.

ABSTRACT

Flamenco (Flam) is a prominent Piwi-interacting RNA (piRNA) locus expressed in Drosophila ovarian follicle cells that silences gypsy/mdg4 transposons to ensure female fertility. Promoter-bashing reporter assays in ovarian somatic sheet (OSS) cells uncover compact enhancer sequences within Flam. We confirm the enhancer sequence relevance in vivo with Drosophila Flam deletion mutants that compromise Flam piRNA levels and female fertility. Proteomic analysis of proteins associated with Flam enhancer sequences discover the transcription factor Traffic Jam (TJ). Tj knockdown in OSS cells causes a decrease in Flam transcripts, Flam piRNAs, and multiple Piwi pathway genes. TJ chromatin immunoprecipitation sequencing (ChIP-seq) analysis confirms TJ binding at enhancer sequences deleted in our distinct Flam mutants. TJ also binds multiple Piwi pathway gene enhancers and long terminal repeats of transposons that decrease in expression after Tj knockdown. TJ plays an integral role in the ongoing arms race between selfish transposons and their suppression by the host Piwi pathway and Flam piRNA locus.

PMID:40209716 | DOI:10.1016/j.celrep.2025.115354

Redox Biol. 2025 Mar 29;82:103624. doi: 10.1016/j.redox.2025.103624. Online ahead of print.

ABSTRACT

Humans exposed to chlorine (Cl2) due to industrial accidents or acts of terrorism may develop lung injury culminating to Acute Respiratory Distress syndrome and death from respiratory failure. Early molecular targets of inhaled oxidant gases suitable for pharmacologic modulation have not been established. Because the mitochondrial genome is highly sensitive to oxidant stress, we tested the hypothesis that mice exposure to Cl2 gas causes oxidative damage to the mitochondrial DNA (mtDNA) that triggers the development of acute and chronic lung injury. Cl2 gas-exposed C57BL/6 mice and returned to room air, developed progressive loss of lung DNA glycosylase OGG1, followed by oxidative mtDNA damage. This resulted in activation of inflammatory pathways by circulating DNA, progressive increased airway resistance, alveolar injury and acute pulmonary edema due to loss of epithelial amiloride-sensitive sodium channels. Mice not succumbing acutely displayed a delayed syndrome of progressive increase in airway resistance and emphysematous-like changes in lung morphology. Global proteomics of lungs harvested 24 h post Cl2 exposure revealed alterations in over 1500 lung proteins, including 14 key mitochondrial proteins. Intranasal instillation of a recombinant protein targeting OGG1 to mitochondria (mitoOGG1) at 1 h post exposure decreased oxidized lung mtDNA, alterations to the lung and mitochondrial proteomes, severity of the acute and delayed lung injury and increased survival. These data show that injury to the mt-genome is a key contributor to the development of acute and chronic lung injury after Cl2 gas exposure and point to mtDNA oxidation as a target for pharmacologic intervention.

PMID:40209617 | DOI:10.1016/j.redox.2025.103624

Science. 2025 Apr 11;388(6743):eadq1709. doi: 10.1126/science.adq1709. Epub 2025 Apr 11.

ABSTRACT

We used Hi-C, imaging, proteomics, and polymer modeling to define rules of engagement for SMC (structural maintenance of chromosomes) complexes as cells refold interphase chromatin into rod-shaped mitotic chromosomes. First, condensin disassembles interphase chromatin loop organization by evicting or displacing extrusive cohesin. Second, condensin bypasses cohesive cohesins, thereby maintaining sister chromatid cohesion as sisters separate. Studies of mitotic chromosomes formed by cohesin, condensin II, and condensin I alone or in combination lead to refined models of mitotic chromosome conformation. In these models, loops are consecutive and not overlapping, implying that condensins stall upon encountering each other. The dynamics of Hi-C interactions and chromosome morphology reveal that during prophase, loops are extruded in vivo at ∼1 to 3 kilobases per second by condensins as they form a disordered discontinuous helical scaffold within individual chromatids.

PMID:40208986 | DOI:10.1126/science.adq1709

Science. 2025 Apr 11;388(6743):176-180. doi: 10.1126/science.ads3888. Epub 2025 Apr 10.

ABSTRACT

Denisovans are an extinct hominin group defined by ancient genomes of Middle to Late Pleistocene fossils from southern Siberia. Although genomic evidence suggests their widespread distribution throughout eastern Asia and possibly Oceania, so far only a few fossils from the Altai and Tibet are confidently identified molecularly as Denisovan. We identified a hominin mandible (Penghu 1) from Taiwan (10,000 to 70,000 years ago or 130,000 to 190,000 years ago) as belonging to a male Denisovan by applying ancient protein analysis. We retrieved 4241 amino acid residues and identified two Denisovan-specific variants. The increased fossil sample of Denisovans demonstrates their wider distribution, including warm and humid regions, as well as their shared distinct robust dentognathic traits that markedly contrast with their sister group, Neanderthals.

PMID:40208980 | DOI:10.1126/science.ads3888

Elife. 2025 Apr 10;13:RP97313. doi: 10.7554/eLife.97313.

ABSTRACT

The spike protein is essential to the SARS-CoV-2 virus life cycle, facilitating virus entry and mediating viral-host membrane fusion. The spike contains a fatty acid (FA) binding site between every two neighbouring receptor-binding domains. This site is coupled to key regions in the protein, but the impact of glycans on these allosteric effects has not been investigated. Using dynamical nonequilibrium molecular dynamics (D-NEMD) simulations, we explore the allosteric effects of the FA site in the fully glycosylated spike of the SARS-CoV-2 ancestral variant. Our results identify the allosteric networks connecting the FA site to functionally important regions in the protein, including the receptor-binding motif, an antigenic supersite in the N-terminal domain, the fusion peptide region, and another allosteric site known to bind heme and biliverdin. The networks identified here highlight the complexity of the allosteric modulation in this protein and reveal a striking and unexpected link between different allosteric sites. Comparison of the FA site connections from D-NEMD in the glycosylated and non-glycosylated spike revealed that glycans do not qualitatively change the internal allosteric pathways but can facilitate the transmission of the structural changes within and between subunits.

PMID:40208235 | DOI:10.7554/eLife.97313

Infect Immun. 2025 Apr 10:e0061824. doi: 10.1128/iai.00618-24. Online ahead of print.

ABSTRACT

Bacteriophages are the dominant members of the human enteric virome and can shape bacterial communities in the gut; however, our understanding of how they directly impact health and disease is limited. Previous studies have shown that specific bacteriophage populations are expanded in patients with Crohn's disease (CD) and ulcerative colitis (UC), suggesting that fluctuations in the enteric virome may contribute to intestinal inflammation. Based on these studies, we hypothesized that a high bacteriophage burden directly induces intestinal epithelial responses. We found that filamentous bacteriophages M13 and Fd induced dose-dependent IL-8 expression in the human intestinal epithelial cell line HT-29 to a greater degree than their lytic counterparts, T4 and ϕX174. We also found that M13, but not Fd, reduced bacterial internalization in HT-29 cells. This led us to investigate the mechanism underlying M13-mediated inhibition of bacterial internalization by examining the antiviral and antimicrobial responses in these cells. M13 upregulated type I and III IFN expressions and augmented short-chain fatty acid (SCFA)-mediated LL-37 expression in HT-29 cells. Taken together, our data establish that filamentous bacteriophages directly affect human intestinal epithelial cells. These results provide new insights into the complex interactions between bacteriophages and the intestinal mucosa, which may underlie disease pathogenesis.

PMID:40208028 | DOI:10.1128/iai.00618-24

Environ Health Perspect. 2025 Apr 10. doi: 10.1289/EHP15648. Online ahead of print.

ABSTRACT

BACKGROUND: Electronic cigarette (e-cigarette) liquids and aerosols contain metals, which can be detrimental to human health. Recently marketed ultrasonic cigarettes (u-cigarettes) claim to be less harmful than e-cigarettes that use heating coils.

OBJECTIVES: We quantified chemical elements/metals in multiple flavors of SURGE u-cigarettes, JUUL e-cigarettes, and "Other Brands" of pod-style e-cigarettes.

METHODS: Elements/metals were identified in atomizers of SURGE using a scanning electron microscope/energy-dispersive X-ray spectrometer. Quantitation of elements/metals in fluids and aerosols from SURGE, JUUL and Other Brands was performed using inductively coupled plasma optical emission spectroscopy.

RESULTS: U-cigarettes contained a sonicator, unlike e-cigarettes which had heated coils. Sixteen elements were identified in at least one fluid or aerosol sample. Generally, u-cigarette fluids and aerosols had more elements/metals at higher concentrations than aerosols from 4th generation e-cigarettes. Element concentrations generally increased in fluids after vaping. All products, including SURGE, had silicon in their fluids and aerosols. Nickel, which was present in low concentrations in all fluids except KWIT Stick (up to 66,050 μg/mL), transferred to the aerosols with low efficiency. SURGE, but not e-cigarettes, also had copper and zinc in their fluids, but little transferred to their aerosols. SURGE fluids and aerosols, unlike e-cigarettes, had relatively high concentrations of arsenic and selenium. Arsenic and selenium, which are on the FDA's Harmful and Potentially Harmful List, likely came from poor quality solvents used to produce the e-liquids in SURGE pods and possibly from the sonicator, which heats during use.

DISCUSSION: SURGE u-cigarettes produce aerosols with metals equivalent to heated coil-style e-cigarettes and had high levels of arsenic and selenium, which are a health concern. Regulations limiting arsenic and selenium in these products are needed, and routine surveillance to identify rogue products, such as Kwit Stick, that have abnormally high levels of nickel or other metals could protect human health. https://doi.org/10.1289/EHP15648.

PMID:40207990 | DOI:10.1289/EHP15648

J Med Virol. 2025 Apr;97(4):e70203. doi: 10.1002/jmv.70203.

ABSTRACT

After the coronavirus disease 2019 (COVID-19) pandemic, the postacute effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have gradually attracted attention. To precisely evaluate the health status of convalescent patients with COVID-19, we analyzed symptom and proteome data of 442 plasma samples from healthy controls, hospitalized patients, and convalescent patients 6 or 12 months after SARS-CoV-2 infection. Symptoms analysis revealed distinct relationships in convalescent patients. Results of plasma protein expression levels showed that C1QA, C1QB, C2, CFH, CFHR1, and F10, which regulate the complement system and coagulation, remained highly expressed even at the 12-month follow-up compared with their levels in healthy individuals. By combining symptom and proteome data, 442 plasma samples were categorized into three subtypes: S1 (metabolism-healthy), S2 (COVID-19 retention), and S3 (long COVID). We speculated that convalescent patients reporting hair loss could have a better health status than those experiencing headaches and dyspnea. Compared to other convalescent patients, those reporting sleep disorders, appetite decrease, and muscle weakness may need more attention because they were classified into the S2 subtype, which had the most samples from hospitalized patients with COVID-19. Subtyping convalescent patients with COVID-19 may enable personalized treatments tailored to individual needs. This study provides valuable plasma proteomic datasets for further studies associated with long COVID.

PMID:40207927 | DOI:10.1002/jmv.70203

Nucleic Acids Res. 2025 Apr 10;53(7):gkaf273. doi: 10.1093/nar/gkaf273.

ABSTRACT

Proteins of the BCL7 family (BCL7A, BCL7B, and BCL7C) are among the most recently identified subunits of the mammalian SWI/SNF chromatin remodeler complex and are absent from the unicellular version of this complex. Their function in the complex is unknown, and very limited structural information is available, despite the fact that they are mutated in several cancer types, most notably blood malignancies and hence medically relevant. Here, using cryo-electron microscopy in combination with biophysical and biochemical approaches, we show that BCL7A forms a stable, high-affinity complex with the nucleosome core particle (NCP) through binding of BCL7A with the acidic patch of the nucleosome via an arginine anchor motif. This interaction is impaired by BCL7A mutations found in cancer. Further, we determined that BCL7A contributes to the remodeling activity of the mSWI/SNF complex and we examined its function at the genomic level. Our findings reveal how BCL7 proteins interact with the NCP and help rationalize the impact of cancer-associated mutations. By providing structural information on the positioning of BCL7 on the NCP, our results broaden the understanding of the mechanism by which SWI/SNF recognizes the chromatin fiber.

PMID:40207634 | DOI:10.1093/nar/gkaf273

ACS Catal. 2025 Mar 13;15(7):5257-5272. doi: 10.1021/acscatal.5c00819. eCollection 2025 Apr 4.

ABSTRACT

Halohydrin dehalogenases (HHDHs) are powerful enzymes for the asymmetric diversification of oxyfunctionalized synthons. They feature two characteristic sequence motifs that distinguish them from homologous short-chain dehydrogenases and reductases. Sequence motif 1, carrying a conserved threonine, glycine, and a central aromatic residue, lines the nucleophile binding pocket of HHDHs. It could therefore impact nucleophile binding and presumably also the activity of the enzymes. However, experimental evidence supporting this theory is largely missing. Herein, we systematically studied the mutability of the three conserved motif 1 residues as well as their resulting impact on enzyme activity, stability, and selectivity in two model HHDHs: HheC from Agrobacterium radiobacter AD1 and HheG from Ilumatobacter coccineus. In both HheC and HheG, the conserved threonine and glycine tolerated mutations to only structurally similar amino acids. In contrast, the central aromatic (i.e., phenylalanine or tyrosine) residue of motif 1 demonstrated much higher variability in HheC. Remarkably, some of these variants featured drastically altered activity, stability, and selectivity characteristics. For instance, variant HheC F12Y displayed up to 5-fold increased specific activity in various epoxide ring opening and dehalogenation reactions as well as enhanced enantioselectivity (e.g., an E-value of 74 in the azidolysis of epichlorohydrin compared to E = 22 for HheC wild type) while also exhibiting a 10 K higher apparent melting temperature. QM and MD simulations support the experimentally observed activity increase of HheC F12Y and reveal alterations in the hydrogen bonding network within the active site. As such, our results demonstrate that multiple enzyme properties of HHDHs can be altered through the targeted mutagenesis of conserved motif 1 residues. In addition, this work illustrates that motif 1 plays vital roles beyond nucleophile binding by impacting the solubility and stability properties. These insights advance our understanding of HHDH active sites and will facilitate their future engineering.

PMID:40207069 | PMC:PMC11976700 | DOI:10.1021/acscatal.5c00819