RESUMEN

Apple ring rot, caused by the pathogenic fungus Botryosphaeria dothidea, has inflicted substantial economic losses and caused significant food safety concerns. In this study, a pimarane-type diterpenoid, diaporthein B (DTB), isolated from a marine-derived fungus, exhibited significant antifungal activity against B. dothidea, with an EC50 value of 8.8 µg/mL. Transcriptome, metabolome, and physiological assays revealed that DTB may target mitochondria and disrupt the tricarboxylic acid (TCA) cycle and oxidative phosphorylation processes. This interference led to increased accumulation of reactive oxygen species and subsequent lipid peroxidation, ultimately inhibiting fungal growth. Furthermore, DTB exhibited an inhibitory potency against apple ring rot at a concentration of 31.2 µg/mL, achieving rates ranging from 67.7 to 81.6% across four distinct apple cultivars. These results indicated that DTB could serve as a novel fungicide for controlling apple ring rot in apple cultivation, transportation, and storage.

RESUMEN

Adzuki bean, an important legume crop, exhibits poor tolerance to low temperatures. To investigate the effect of exogenous abscisic acid (ABA) on the physiological metabolism and yield resistance of adzuki bean under low-temperature stress, we conducted a potted experiment using Longxiaodou 4 (LXD 4) and Tianjinhong (TJH) as test materials and pre-sprayed with exogenous ABA at flowering stage continuously for 5 days with an average of 12°C and an average of 15°C, respectively. We found that, compared with spraying water, foliar spraying exogenous ABA increased the activities of antioxidants and the content of non-enzymatic antioxidants, effectively inhibited the increase of malondialdehyde (MDA), hydrogen peroxide (H2O2) content, O2-· production rate. Exogenous ABA induced the activation of endogenous protective mechanisms by increasing antioxidant enzymes activities such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), as well as elevated levels of non-enzymatic antioxidants including ascorbic acid (ASA) and glutathione (GSH). Moreover, the yield loss of 5.81%-39.84% caused by chilling stress was alleviated by spraying ABA. In conclusion, foliar spraying exogenous ABA can reduce the negative effects of low-temperature stress on the yield of Adzuki beans, which is essential to ensure stable production of Adzuki beans under low-temperature conditions.

Asunto(s)

RESUMEN

We report an investigation on the structures and chemical bonding in a series of di-lanthanum boron clusters, La2Bn- (n = 4-6), using photoelectron spectroscopy and theoretical calculations. Well-resolved photoelectron spectra are obtained and used to verify the global minima of the lanthanide boron clusters. The structures of La2B4- and La2B5- are found to consist of open B4 and B5 rings, respectively, around the La2 dimer equatorially. Theoretical evidence of La-La σ bonding is obtained in La2B4-, whereas the bonding in La2B5- is similar to that of an incomplete inverse sandwich without real La-La bonding. The global minimum of La2B6- is completely different, where one of the La atoms can be viewed as substituting a B atom of the B7 cluster due to the high electronic stability of the B73- borozene. The resulting lanthaborozene [LaB6]3- forms a half-sandwich structure with the second La atom, with evidence of La-La σ bonding. Lanthanide-lanthanide bonds are relatively rare in chemistry. The current work suggests that binary lanthanide boron clusters provide interesting systems to study lanthanide-lanthanide bonding.

RESUMEN

A rhodium-catalyzed one-pot access to valuable polycyclic frameworks of fluorenone-4-carboxylic acids and diphenic anhydrides via the oxidative dimeric cyclization of aromatic acids has been developed. This transformation proceeded via carboxyl-assisted 2-fold C-H activation followed by intramolecular Friedel-Crafts or dehydration reactions. The silver salt additive plays a vital role in the chemoselectivity of the products. Diphenic anhydride 3l exhibits a maximum fluorescence quantum yield of up to 59%.

RESUMEN

Traditional σ, π, and δ types of covalent chemical bonding have been extensively studied for nearly a century. In contrast, ϕ-type bonding involving nf (n = 4, 5) orbitals has received less attention due to their high contraction and minimal orbital overlap. Herein, we theoretically predict a singly occupied ϕ···Ï• bonding between two 5f orbitals, facilitated by B6 group orbitals in the hexa-boron diuranium inverse sandwich structure of U2B6. From ab initio quantum chemical calculations, the global minimum structure has a septuplet state with D6h symmetry. Chemical bonding analyses reveal that the 5f and 6d atomic orbitals of the two uranium atoms interact with the ligand orbitals of the central B6 ring, exhibiting favorable energy matching and symmetry compatibility to form delocalized σ-, π-, δ-, and ϕ-type bonding orbitals. Notably, even though the ϕ···Ï• bonding orbital is singly occupied, it still has a significant role in stability and cannot be overlooked. Furthermore, the U2B6 cluster model can be viewed as a building block of UB2 solid materials from both geometric and electronic perspectives. This work predicts the first example of ϕ···Ï• bonding, highlighting the complexity and diversity of chemical bonds formed in actinide boride clusters.

RESUMEN

[This corrects the article DOI: 10.1016/j.apsb.2019.12.012.].

RESUMEN

BACKGROUND: The imaging manifestations of oral and maxillofacial myofibroma/myofibromatosis can vary among patients. Although many clinical cases have been reported, a consensus on the clinicopathological features of and treatment principles for this disease is lacking. PURPOSE: This study aimed to summarize the clinicopathological features of solitary myofibroma of the oral and maxillofacial regions in pediatric patients. METHODS: The clinical data, histological features, and immunohistochemical characteristics of ten pediatric patients who underwent surgical removal and subsequent pathological diagnosis of myofibroma were collected and retrospectively and cross-sectionally analyzed. RESULTS: Seven patients were male, and 3 were female, with ages ranging from 3 months to 6 years (mean: 2.6 years). The patients presented with solitary lesions involving the mandibular gingiva and adjacent mandible (4 patients), mandible (2 patients), oral floor and submandibular area and adjacent mandible (1 patient), gingiva (1 patient), maxilla (1 patient), and oropharynx (1 patient). Light microscopy revealed spindle-shaped tumor cells organized in bundles or vortex patterns, forming a hemangiopericytoma-like perivascular pattern, whereas immunohistochemical staining revealed diffuse smooth muscle actin (SMA) positivity. All patients underwent surgical resection, and none experienced recurrence over the 12- to 82-month follow-up. CONCLUSIONS: Solitary myofibroma in the oral and maxillofacial regions is predominantly observed in infants and young children, with a higher incidence among males. The prognosis is favorable following localized lesion resection or curettage of jawbone lesions. Accurate recognition of the clinical, radiological, and pathological features of the disease will reduce the misdiagnosis rate.

RESUMEN

Interferon Gamma Inducible Protein 30 (IFI30), also known as Gamma-Interferon-Inducible Lysosomal Thiol Reductase (GILT), is predominantly found in lysosomes and the cytoplasm. As the sole enzyme identified to catalyze disulfide bond reduction in the endocytic pathway, IFI30 contributes to both major histocompatibility complex (MHC) class I-restricted antigen cross-presentation and MHC class II-restricted antigen processing by decreasing the disulfide bonds of endocytosed proteins. Remarkably, emerging research has revealed that IFI30 is involved in tumorigenesis, tumor development, and the tumor immune response. Targeting IFI30 may provide new strategies for cancer therapy and improve the prognosis of patients. This review provided a comprehensive overview of the research progress on IFI30 in tumor progression, cellular redox status, autophagy, tumor immune response, and drug sensitivity, with a view to providing the theoretical basis for pharmacological intervention of IFI30 in tumor therapy, particularly in immunotherapy.

RESUMEN

The mislocalization of proteins leads to breast cancer, one of the world's most prevalent cancers, which can be identified from immunohistochemical images. Here, based on the deep learning framework, location prediction models were constructed using the features of breast immunohistochemical images. Ultimately, six differentially localized proteins that with stable differentially predictive localization, maximum localization differences, and whose predicted results are not affected by removing a single image are obtained (CCNT1, NSUN5, PRPF4, RECQL4, UTP6, ZNF500). Further verification reveals that these proteins are not differentially expressed, but are closely associated with breast cancer and have great classification performance. Potential mechanism analysis shows that their co-expressed or co-located proteins and RNAs may affect their localization, leading to changes in interactions and functions that further causes breast cancer. They have the potential to help shed light on the molecular mechanisms of breast cancer and provide assistance for its early diagnosis and treatment.

Asunto(s)

RESUMEN

BACKGROUND: Diabetes mellitus (DM) presents impediment to wound healing. While ultraviolet B (UVB) exposure showed therapeutic potential in various skin conditions, its capacity to mediate diabetic wound healing remains unclear. To investigate the efficacy of UVB on wound healing and its underlying basis. MATERIALS AND METHODS: Male C57BL/6 mice were subjected to the high-fat diet followed by streptozotocin administration to establish the diabetic model. Upon confirmation of diabetes, full-thickness wounds were inflicted and the treatment group received UVB radiation at 50 mJ/cm2 for 5 min every alternate day for 2 weeks. Wound healing rate was then assessed, accompanied by evaluations of blood glucose, lipid profiles, CD31 expression, and concentrations of ghrelin and leptin. Concurrently, in vitro studies were executed to evaluate the protective role of ghrelin on human umbilical vein endothelial cells (HUVEC) under high glucose (HG) conditions. RESULTS: Post UVB exposure, there was a marked acceleration in wound healing in DM mice without alterations in hyperglycemia and lipid profiles. Compared to non-UVB-exposed mice, the UVB group showed enhanced angiogenesis manifested by a surge in CD31 expression. This trend appeared to be in harmony with the elevated ghrelin levels. In vitro experiments indicated that ghrelin significantly enhanced the migratory pace and angiogenic properties of HUVEC under HG-induced stress, potentially mediated by an upregulation in vascular endothelial growth factor expression. CONCLUSION: UVB exposure bolstered wound healing in diabetic mice, plausibly mediated through augmented angiogenesis induced by ghrelin secretion. Such findings underscore the vast potential of UVB-induced ghrelin in therapeutic strategies targeting diabetic wound healing.

Asunto(s)

RESUMEN

PURPOSE: To investigate the influence of transarterial embolization (TAE) on programmed cell death-ligand 1(PD-L1) expression and CD8+T tumour infiltrative lymphocyte cytotoxicity in the Sprague-Dawley (SD) rat model of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: An orthotopic HCC model was established in twenty SD rats treated with TAE (lipiodol, n = 10) or sham (normal saline, n = 10) using homologous N1S1 hepatoma cells. Rats were euthanized 1 week after embolization. Flow cytometry was used to assess the proportion of CD4+T, CD8+T and programmed cell death-1+(PD-1+) CD8+T lymphocytes in the spleens and tumours. Distribution of CD8+T, granzyme-B+CD8+T lymphocytes and PD-L1+ cells was assessed by immunohistochemistry (IHC) or multiplex IHC. p value < 0.05 was considered statistically significant. RESULTS: The CD4/CD8 ratio and PD-1+CD8+ T lymphocytes exhibited higher values in TAE-treated tumours compared to sham-treated tumours (p = 0.021 and p = 0.071, respectively). Conversely, the number of CD8+T lymphocytes was decreased in TAE-treated tumours (p = 0.043), especially in the central region (p = 0.045). However, more CD8+T lymphocytes were found infiltrating the marginal region than central region in TAE-treated tumours (p = 0.046). The proportion of granzyme-B+CD8+T lymphocytes and the PD-L1 positive areas was elevated in tumours that treated with TAE (p all < 0.05). There was a negative correlation between PD-L1 expression and the number of infiltration of CD8+ T lymphocytes (p = 0.036). CONCLUSIONS: Immune cells are distributed unevenly in the tumours after TAE. The intrinsic induction state of the tumour after embolization may be insufficient to elicit a maximal response to PD-1/PD-L1 inhibitors.

RESUMEN

BACKGROUND AIMS: The immunomodulatory capacity of mesenchymal stem/stromal cells (MSCs) is a key feature that makes them particularly valuable for regenerative medicine. However, this potential is affected by the chronological aging of the donors and the cell expansion procedures in culture. We have demonstrated that GATA binding protein 6 (GATA6) plays a pivotal role in the aging of MSCs and inhibiting GATA6 rejuvenates the characteristics of MSCs. METHODS: In this study, we compared the immunomodulatory capabilities of young and old MSC models, using induced pluripotent stem cells-derived rejuvenated MSCs (rMSCs) and their parental MSCs (pMSCs), respectively, to identify a key mechanism involved in the differential regulation of these capabilities. Additionally, we explored the role of GATA6 in mediating the mechanism. RESULTS: Our results demonstrated that rMSCs exhibited downregulated aging-associated regulators, including p53, p21 and GATA6, and showed enhanced suppression of T cell proliferation compared to pMSCs. Through analyzing our previous RNA-seq data and employing target gene knockdown, we determined both suppressors of cytokine signaling 3 (SOCS3) and interleukin 6 were involved in GATA6-induced regulation, collectively affecting the expression of programmed death ligand 1 (PDL1) in both pMSCs and rMSCs. CONCLUSIONS: Our findings underline the significance of the GATA6/SOCS3/PDL1 pathway in regulating aging-associated changes in MSC immunomodulatory activity, providing valuable insights into the potential use of rMSCs in the treatment of immune diseases and regenerative medicine.

RESUMEN

Despite the critical importance of essential genes, systems-level investigations of their contribution to antibiotic sensitivity have been limited. Using CRISPR Adaptation-mediated Library Manufacturing (CALM), we generated ultra-dense CRISPR interference (CRISPRi) libraries in methicillin-sensitive and -resistant strains of Staphylococcus aureus, which allowed us to quantify gene fitness on a global scale across ten clinically relevant antibiotics. This led to the identification of a comprehensive set of known and novel biological processes modulating bacterial fitness in the antibiotics. Notably, we found that essential genes from diverse processes dominated antibiotic-gene interactions, including a large number of synergistic interactions between bactericidal antibiotics and processes such as cell wall synthesis/cell division (CC), DNA replication/DNA recombination (DD), protein export, and coenzyme A biosynthesis. Simultaneous genetic perturbations of diverse CC and DD processes aggravated bacterial fitness, revealing a widespread synergy between the two highly coordinated processes. In contrast, perturbation of transcriptional, translational, and select energy processes antagonized the effects of bactericidal antibiotics. Finally, we show that small molecule inhibitors recapitulated synergistic antibiotic-gene interactions, providing a rational foundation for developing novel combinatorial antimicrobial therapies.

RESUMEN

Metal-organic cages form well-defined microenvironments that can enhance the catalytic proficiency of encapsulated transition metal complexes (TMCs). We introduce a screening protocol to efficiently identify TMCs that are promising candidates for encapsulation in the Ga4L612- nanocage. We obtain TMCs from the Cambridge Structural Database with geometric and electronic characteristics amenable to encapsulation and mine the text of associated manuscripts to curate TMCs with documented catalytic functionality. By docking candidate TMCs inside the nanocage cavity and carrying out electronic structure calculations, we identify a subset of successfully optimized candidates (TMC-34) and observe that encapsulated guests occupy an average of 60% of the cavity volume, in line with previous observations. Notably, some guests occupy as much as 72% of the cavity as a result of linker rotation. Encapsulation has a universal effect on the electrostatic potential (ESP), systematically decreasing the ESP at the metal center of each TMC in the TMC-34 data set, while minimally altering TMC metal partial charges. Collectively these observations support geometry-based screening of potential guests and suggest that encapsulation in Ga4L612- cages could electrostatically stabilize diverse cationic or electropositive intermediates. We highlight candidate guests with associated known reactivity and solubility most amenable for encapsulation in experimental follow-up studies.

RESUMEN

A photocatalytic method for the ring-closing 1,7-enyne metathesis using the α-amino radical as an alkene deconstruction auxiliary is present. Preliminary mechanistic studies suggest that intramolecular 1,5-hydrogen atom transfer is the key to the generation and ß-scission of the α-amino radical, while the dearomatization of arenes and ring opening of cyclopropanes are the key to construct spirocyclic quinolin-2-ones. This approach highlights the potential of ring-closing 1,7-enyne metathesis, providing a green, efficient, and step-economical way for the synthesis of spirocyclic quinolin-2-ones.

RESUMEN

BACKGROUND AND AIMS: Biopterins, including tetrahydrobiopterin (BH4), dihydrobiopterin (BH2), and biopterin (B), were crucial enzyme cofactors in vivo. Despite their recognized clinical significance, there remain notable research gaps and controversies surrounding experimental outcomes. This study aims to clarify the biopterins-related issues, including analytical art, physiological intervals, and pathophysiological implications. MATERIALS AND METHODS: A novel LC-MS/MS method was developed to comprehensively profile biopterins in plasma, utilizing chemical derivatization and cold-induced phase separation. Subsequently, apparently healthy individuals were enrolled to investigate the physiological ranges. And the relationships between biopterins and biochemical indicators were analyzed to explore the pathophysiological implications. RESULTS: The developed method was validated as reliable for detecting biopterins across the entire physiological range. Timely anti-oxidation was found to be essential for accurate assessment of biopterins. The observed overall mean ± SDs levels were 3.51 ± 0.94, 1.54 ± 0.48, 2.45 ± 0.84 and 5.05 ± 1.14 ng/mL for BH4, BH2, BH4/BH2 and total biopterins. The status of biopterins showed interesting correlations with age, gender, hyperuricemia and overweight. CONCLUSION: In conjunction with proper anti-oxidation, the newly developed method enables accurate determination of biopterins status in plasma. The observed physiological intervals and pathophysiological implications provide fundamental yet inspiring support for further clinical researches.

Asunto(s)

RESUMEN

Trichoderma reesei is an economically important enzyme producer with several unique meiotic features. spo11, the initiator of meiotic double-strand breaks (DSBs) in most sexual eukaryotes, is dispensable for T. reesei meiosis. T. reesei lacks the meiosis-specific recombinase Dmc1. Rad51 and Sae2, the activator of the Mre11 endonuclease complex, promote DSB repair and chromosome synapsis in wild-type and spo11Δ meiosis. DNA methyltransferases (DNMTs) perform multiple tasks in meiosis. Three DNMT genes (rid1, dim2 and dimX) differentially regulate genome-wide cytosine methylation and C:G-to-T:A hypermutations in different chromosomal regions. We have identified two types of DSBs: type I DSBs require spo11 or rid1 for initiation, whereas type II DSBs do not rely on spo11 and rid1 for initiation. rid1 (but not dim2) is essential for Rad51-mediated DSB repair and normal meiosis. rid1 and rad51 exhibit a locus heterogeneity (LH) relationship, in which LH-associated proteins often regulate interconnectivity in protein interaction networks. This LH relationship can be suppressed by deleting dim2 in a haploid rid1Δ (but not rad51Δ) parental strain, indicating that dim2 and rid1 share a redundant function that acts earlier than rad51 during early meiosis. In conclusion, our studies provide the first evidence of the involvement of DNMTs during meiotic initiation and recombination.

Asunto(s)

RESUMEN

Fall armyworm, Spodoptera frugiperda (J. E. Smith), is a widely recognized global agricultural pest that has significantly reduced crop yields all over the world. S. frugiperda has developed resistance to various insecticides. Insect cytochrome P450 monooxygenases (CYPs or P450s) play an important role in detoxifying insecticides, leading to increased resistance in insect populations. However, the function of the specific P450 gene for lambda-cyhalothrin resistance in S. frugiperda was unclear. Herein, the expression patterns of 40 P450 genes in the susceptible and lambda-cyhalothrin-resistant populations were analyzed. Among them, CYP321A7 was found to be overexpressed in the resistant population, specifically LRS (resistance ratio = 25.38-fold) derived from a lambda-cyhalothrin-susceptible (SS) population and FLRS (a population caught from a field, resistance ratio = 63.80-fold). Elevated enzyme activity of cytochrome P450 monooxygenases (P450s) was observed for LRS (2.76-fold) and the FLRS (4.88-fold) as compared to SS, while no significant differences were observed in the activities of glutathione S-transferases and esterases. Furthermore, the knockdown of CYP321A7 gene by RNA interference significantly increased the susceptibility to lambda-cyhalothrin. Remarkably, the knockdown of CYP321A7 reduced the enzymatic activity of P450 by 43.7%, 31.9%, and 22.5% in SS, LRS, and FLRS populations, respectively. Interestingly, fourth-instar larvae treated with lambda-cyhalothrin at the LC30 dosage had a greater mortality rate due to RNA interference-induced suppression of CYP321A7 (with increases of 61.1%, 50.0%, and 45.6% for SS, LRS, and FLRS populations, respectively). These findings suggest a link between lambda-cyhalothrin resistance and continual overexpression of CYP321A7 in S. frugiperda larvae, emphasizing the possible importance of CYP321A7 in lambda-cyhalothrin detoxification in S. frugiperda.

Asunto(s)