Biosynthesis of Enfumafungin-type Antibiotic Reveals an Unusual Enzymatic Fusion Pattern and Unprecedented C-C Bond Cleavage.

Enfumafungin-type antibiotics, represented by enfumafungin and fuscoatroside, belong to a distinct group of triterpenoids derived from fungi. These compounds exhibit significant antifungal properties with ibrexafungerp, a semisynthetic derivative of enfumafungin, recently gaining FDA's approval as the first oral antifungal drug for treating invasive vulvar candidiasis. Enfumafungin-type antibiotics possess a cleaved E-ring with an oxidized carboxyl group and a reduced methyl group at the break site, suggesting unprecedented C-C bond cleavage chemistry involved in their biosynthesis. Here, we show that a 4-gene (fsoA, fsoD, fsoE, fsoF) biosynthetic gene cluster is sufficient to yield fuscoatroside by heterologous expression in Aspergillus oryzae. Notably, FsoA is an unheard-of terpene cyclase-glycosyltransferase fusion enzyme, affording a triterpene glycoside product that relies on enzymatic fusion. FsoE is a P450 enzyme that catalyzes successive oxidation reactions at C19 to facilitate a C-C bond cleavage, producing an oxidized carboxyl group and a reduced methyl group that have never been observed in known P450 enzymes. Our study thus sets the important foundation for the manufacture of enfumafungin-type antibiotics using biosynthetic approaches.

Liquid biopsy in T-cell lymphoma: biomarker detection techniques and clinical application.

T-cell lymphoma is a highly invasive tumor with significant heterogeneity. Invasive tissue biopsy is the gold standard for acquiring molecular data and categorizing lymphoma patients into genetic subtypes. However, surgical intervention is unfeasible for patients who are critically ill, have unresectable tumors, or demonstrate low compliance, making tissue biopsies inaccessible to these patients. A critical need for a minimally invasive approach in T-cell lymphoma is evident, particularly in the areas of early diagnosis, prognostic monitoring, treatment response, and drug resistance. Therefore, the clinical application of liquid biopsy techniques has gained significant attention in T-cell lymphoma. Moreover, liquid biopsy requires fewer samples, exhibits good reproducibility, and enables real-time monitoring at molecular levels, thereby facilitating personalized health care. In this review, we provide a comprehensive overview of the current liquid biopsy biomarkers used for T-cell lymphoma, focusing on circulating cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), Epstein-Barr virus (EBV) DNA, antibodies, and cytokines. Additionally, we discuss their clinical application, detection methodologies, ongoing clinical trials, and the challenges faced in the field of liquid biopsy.

Development and Validation of a Recurrence-Free Survival Prediction Model for Locally Advanced Esophageal Squamous Cell Carcinoma with Neoadjuvant Chemoradiotherapy.

BACKGROUND: A recurrence-free survival (RFS) prediction model was developed and validated for patients with locally advanced esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy (NCRT) in combination with surgery. PATIENTS AND METHODS: We included 282 patients with esophageal squamous cell carcinoma who received neoadjuvant chemoradiotherapy (NCRT) combined with surgery, constructed three models incorporating pathological factors, investigated the discrimination and calibration of each model, and compared the clinical utility of each model using the net reclassification index (NRI) and the integrated discrimination index (IDI). RESULTS: Multivariable analysis showed that pathologic complete response (pCR) and lymph node tumor regression grading (LN-TRG) (p < 0.05) were independent prognostic factors for RFS. LASSO regression screened six correlates of LN-TRG, vascular invasion, nerve invasion, degree of differentiation, platelet grade, and a total diameter of residual cancer in lymph nodes to build model three, which was consistent in terms of efficacy in the training set and validation set. Kaplan-Meier (K-M) curves showed that all three models were able to distinguish well between high- and low-risk groups (p < 0.01). The NRI and IDI showed that the clinical utility of model 2 was slightly better than that of model 1 (p > 0.05), and model 3 was significantly better than that of model 2 (p < 0.05). CONCLUSIONS: Clinical prediction models incorporating LN-TRG factors have high predictive efficacy, can help identify patients at high risk of recurrence after neoadjuvant therapy, and can be used as a supplement to the  AJCC/TNM staging system while offering a scientific rationale for early postoperative intervention.

Uridine diphosphate glucosyltransferase is vital for fenpropathrin resistance in Bombyx mori (Lepidoptera).

The silkworm (Bombyx mori) is an important model lepidopteran insect and can be used to identify pesticide resistance-related genes of great significance for biological control of pests. Uridine diphosphate glucosyltransferases (UGTs), found in all organisms, are the main secondary enzymes involved in the metabolism of heterologous substances. However, it remains uncertain if silkworm resistance to fenpropathrin involves UGT. This study observes significant variations in BmUGT expression among B. mori strains with variable fenpropathrin resistance post-feeding, indicating BmUGT's role in fenpropathrin detoxification. Knockdown of BmUGT with RNA interference and overexpression of BmUGT significantly decreased and increased BmN cell activity, respectively, indicating that BmUGT plays an important role in the resistance of silkworms to fenpropathrin. In addition, fenpropathrin residues were significantly reduced after incubation for 12 h with different concentrations of a recombinant BmUGT fusion protein. Finally, we verified the conservation of UGT to detoxify fenpropathrin in Spodoptera exigua: Its resistance to fenpropathrin decreased significantly after knocking down SeUGT. In a word, UGT plays an important role in silkworm resistance to fenpropathrin by directly degrading the compound, a function seen across other insects. The results of this study are of great significance for breeding silkworm varieties with high resistance and for biological control of pests.

Changes in liver and kidney function, red blood cell count and hemoglobin levels 1 day after ultrasound-guided percutaneous microwave ablation for uterine fibroids.

OBJECTIVE: To investigate the changes in liver and kidney function, red blood cell (RBC) count and hemoglobin (HGB) levels in patients undergoing ultrasound-guided percutaneous microwave ablation (UPMWA) for uterine fibroids on postoperative day 1. METHODS: The changes in liver and kidney function, RBC count and HGB levels in 181 patients who underwent selective UPMWA in the Second Affiliated Hospital of Shantou University Medical College, China, between August 2017 and January 2023 were retrospectively analyzed. RESULTS: All patients underwent UPMWA for uterine fibroids; 179 patients had multiple uterine fibroids and 2 patients had single uterine fibroids. The maximum fibroid diameter ranged from 18 to 140 mm, with an average of 68.3 mm. Ultrasound imaging was used to confirm that the blood flow signal within the mass had disappeared in all patients, indicating that the ablation was effective. Within 24 h, compared with before UPMWA, levels of total bilirubin, direct bilirubin, indirect bilirubin and aspartate aminotransferase had significantly increased (p < 0.01), whereas levels of total protein, albumin, globulin, alanine aminotransferase, creatinine and urea had significantly decreased (p < 0.01). Acute kidney injury (AKI) occurred in 1 of the 181 patients. The RBC count and HGB levels decreased significantly after UPMWA (p < 0.01). CONCLUSION: Ultrasound-guided percutaneous microwave ablation for uterine fibroids can impose a higher detoxification load on the liver and cause thermal damage to and the destruction of RBCs within local circulation, potentially leading to AKI. Protein levels significantly decreased after UPMWA. Therefore, perioperative organ function protection measures and treatment should be actively integrated into clinical practice to improve prognosis and enhance recovery.

Study on the Effect of Dalbergia pinnata (Lour.) Prain Essential Oil on Electroencephalography upon Stimulation with Different Auditory Effects.

Dalbergia pinnata (Lour.) Prain (D. pinnata) is a valuable medicinal plant, and its volatile parts have a pleasant aroma. In recent years, there have been a large number of studies investigating the effect of aroma on human performance. However, the effect of the aroma of D. pinnata on human psychophysiological activity has not been reported. Few reports have been made about the effects of aroma and sound on human electroencephalographic (EEG) activity. This study aimed to investigate the effects of D. pinnata essential oil in EEG activity response to various auditory stimuli. In the EEG study, 30 healthy volunteers (15 men and 15 women) participated. The electroencephalogram changes of participants during the essential oil (EO) of D. pinnata inhalation under white noise, pink noise and traffic noise stimulations were recorded. EEG data from 30 electrodes placed on the scalp were analyzed according to the international 10-20 system. The EO of D. pinnata had various effects on the brain when subjected to different auditory stimuli. In EEG studies, delta waves increased by 20% in noiseless and white noise environments, a change that may aid sleep and relaxation. In the presence of pink noise and traffic noise, alpha and delta wave activity (frontal pole and frontal lobe) increased markedly when inhaling the EO of D. pinnata, a change that may help reduce anxiety. When inhaling the EO of D. pinnata with different auditory stimuli, women are more likely to relax and get sleepy compared to men.

BmRRS1 Protein Inhibits the Proliferation of Baculovirus Autographa californica Nucleopolyhedrovirus in Silkworm, Bombyx mori.

The study of functional genes involved in baculovirus infection is vital for its wide application in pest biocontrol. This study utilized the Autographa californica nucleopolyhedrovirus (AcMNPV) and silkworm as models to elucidate the role of BmRRS1, which has been found to exhibit notable differential expression between resistant and susceptible silkworm strains. The results showed that it was evolutionarily conserved in selected species. Among different tissues, it was expressed at the highest level in the gonads, followed by the hemolymph and silk glands; among the different developmental stages, it was the highest in the second instar, followed by the pupae and adults. Moreover, its vital role in suppressing AcMNPV infection was verified by the decreased expression of lef3 and vp39 protein after overexpression of BmRRS1 as well as by the increased expression of the viral gene lef3 and the viral protein vp39 after siRNA treatment against BmRRS1 expression in BmN cells. Additionally, the direct interaction between BmRRS1 and AcMNPV was detected by the GST pull-down assay. Finally, the homologue of BmRRS1 in Spodoptera frugiperda was found to be involved in larval resistance to AcMNPV. In a word, BmRRS1 plays a vital role in AcMNPV resistance in silkworms, and this might be related to the direct interaction with AcMNPV. The results of this study provide a potential target for protecting silkworm larvae from virus infection and controlling agricultural and forestry pests.

The Therapeutic Potential of Dalbergia pinnata (Lour.) Prain Essential Oil in Alzheimer's Disease: EEG Signal Analysis In Vivo, SH-SY5Y Cell Model In Vitro, and Network Pharmacology.

Alzheimer's disease (AD) is a neurodegenerative disorder that is projected by the WHO to affect over 100 million people by 2050. Clinically, AD patients undergoing long-term antipsychotic treatment often experience severe anxiety or depression in later stages. Furthermore, early-stage AD manifests with weakened α waves in the brain, progressing to diminished α and ß waves in late-stage disease, reflecting changes in emotional states and disease progression. In this study, EEG signal analysis revealed that inhalation of Dalbergia pinnata (Lour.) Prain essential oil (DPEO) enhanced δ, θ, α and ß wave powers in the frontal and parietal lobes, with a rising trend in the ß/α ratio in the temporal lobe. These findings suggest an alleviation of anxiety and an enhancement of cognitive functions. Treatment of the AD SH-SY5Y (human neuroblastoma cells) cell model with DPEO resulted in decreased intracellular levels of Aß, GSK-3ß, P-Tau, IL-1ß, TNF-α, IL-6, COX-2, OFR, and HFR, alongside reduced AchE and BchE activities and increased SOD activity. Network pharmacology analysis indicated a potential pharmacological mechanism involving the JAK-STAT pathway. Our study provides evidence supporting DPEO's role in modulating anxiety and slowing AD pathological progression.

Deep genome skimming reveals the hybrid origin of Pseudosasa gracilis (Poaceae: Bambusoideae).

Pseudosasa gracilis (Poaceae: Bambusoideae) is a temperate woody bamboo species endemic to South-central China with a narrow distribution. Previous phylogenetic studies revealed an unexpected, isolated phylogenetic position of Ps. gracilis. Here we conducted phylogenomic analysis by sampling populations of Ps. gracilis and its sympatric species Ps. nanunica and Sinosasa polytricha reflecting different genomic signals, by deep genome skimming. Integrating molecular evidence from chloroplast genes and genome-wide SNPs, we deciphered the phylogenetic relationships of Ps. gracilis. Both plastid and nuclear data indicate that Ps. gracilis is more closely related to Sinosasa, which is discordant with the taxonomic treatment. To further explore this molecular-morphological conflict, we screened 411 "perfect-copy" syntenic genes to reconstruct phylogenies using both the concatenation and coalescent methods. We observed extensive discordance between gene trees and the putative species tree. A significant hybridization event was detected based on 411 genes from the D subgenome, showing Ps. gracilis was a hybrid descendant between Sinosasa longiligulata and Ps. nanunica, with 63.56% and 36.44% inheritance probabilities of each parent. Moreover, introgression events were detected in the C subgenome between Ps. gracilis and S. polytricha in the same distribution region. Our findings suggest that sympatric hybridization and introgression play a crucial role in the origin of Ps. gracilis. By providing an empirical example of bamboo of hybrid origin using comprehensive analyses based on genomic data from different inheritance systems and morphological characters, our study represents a step forward in understanding of reticulate evolution of bamboos.

Aerial signaling by plant-associated Streptomyces setonii WY228 regulates plant growth and enhances salt stress tolerance.

Plant-associated streptomycetes play important roles in plant growth and development. However, knowledge of volatile-mediated crosstalk between Streptomyces spp. and plants remains limited. In this study, we investigated the impact of volatiles from nine endophytic Streptomyces strains on the growth and development of plants. One versatile strain, Streptomyces setonii WY228, was found to significantly promote the growth of Arabidopsis thaliana and tomato seedlings, confer salt tolerance, and induce early flowering and increased fruit yield following volatile treatment. Analysis of plant growth-promoting traits revealed that S. setonii WY228 could produce indole-3-acetic acid, siderophores, ACC deaminase, fix nitrogen, and solubilize inorganic phosphate. These capabilities were further confirmed through genome sequencing and analysis. Volatilome analysis indicated that the volatile organic compounds emitted from ISP-2 medium predominantly comprised sesquiterpenes and 2-ethyl-5-methylpyrazine. Further investigations showed that 2-ethyl-5-methylpyrazine and sesquiterpenoid volatiles were the primary regulators promoting growth, as confirmed by experiments using the terpene synthesis inhibitor phosphomycin, pure compounds, and comparisons of volatile components. Transcriptome analysis, combined with mutant and inhibitor studies, demonstrated that WY228 volatiles promoted root growth by activating Arabidopsis auxin signaling and polar transport, and enhanced root hair development through ethylene signaling activation. Additionally, it was confirmed that volatiles can stimulate plant abscisic acid signaling and activate the MYB75 transcription factor, thereby promoting anthocyanin synthesis and enhancing plant salt stress tolerance. Our findings suggest that aerial signaling-mediated plant growth promotion and abiotic stress tolerance represent potentially overlooked mechanisms of Streptomyces-plant interactions. This study also provides an exciting strategy for the regulation of plant growth and the improvement of horticultural crop yields within sustainable agricultural practices.