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Understanding the molecular mechanisms underlying genetic diseases is challenging due to environmental and genetic factors. Genome-wide association studies (GWAS) have identified numerous genetic loci, but their functional implications are largely unknown. Single-cell multiomics sequencing has emerged as a powerful tool to study disease-specific cell types and their relationship with genetic variants. However, comprehensive databases for exploring these mechanisms across different tissues are lacking. We present the Disease-Related Cell Type database (DRCTdb), integrating GWAS and single-cell multiomics data to identify disease-related cell types and elucidate their regulatory mechanisms. DRCTdb contains well-processed data from 16 studies, covering 4 million cells within 28 tissues. Users can browse relationships and regulatory mechanisms between SNPs of 42 genetic diseases and cell types based on GWAS and single-cell data. DRCTdb also offers data downloads and is available at https://singlecellatlas.top/DRCTDB ., (© 2024. The Author(s).)

ortho -Quinone methides ( o -QMs) are a class of highly reactive intermediates that serve as important nonisolable building blocks (NBBs) in organic synthesis and small-molecule library construction. Because of their instability and nonisolability, most reported o -QMs are generated through in situ chemical synthesis, and only a few natural o -QMs have been reported due to the lack of directed discovery strategies. Herein, a new natural o -QM precursor (trichophenol A, 2 ) was identified from the fungal strain of Trichoderma sp. AT0167 through genome mining, which was generated by trilA (nonreducing polyketide synthase) and trilB (2-oxoglutarate dependent dioxygenase). Combinatorial biosynthesis via two other known NRPKS genes with trilA and trilB was performed, leading to the generation of five new trichophenol o -QM oligomers (trichophenols D-H, 5 - 9 ). The strategy combining genome mining with combinatorial biosynthesis not only targetedly uncovered a new natural o -QM precursor but also produced various new molecules through oligomerization of the new o -QM and its designated o -QM acceptors without chemical synthesis and isolation of intermediates, which was named NBB genome mining-combinatorial biosynthesis strategy for o -QM molecule library construction. This study provides a new strategy for the targeted discovery of natural o -QMs and small-molecule library construction with natural o -QMs.

Bombyx mori ELAV-like-1 (BmEL-1) and B. mori ELAV-like-2 (BmEL-2) are 2 members of the ELAV-like family of RNA-binding proteins. Mutations in Bmel-1 and Bmel-2 resulted in 5.8% and 28.5% decreases in larval weight on the 3rd day of the 5th instar larva (L5D3), respectively. Triglycerides (TG) are the most important energy resource and are the main component of neutral fat (NF) in animals. To investigate the role of Bmelav-like genes in the synthesis and decomposition of TG, transcriptomic, and metabolic analyses were performed on the whole bodies on the 1st day of the 2nd instar larvae (L2D1) and on fat bodies on L5D3 of Bmel-1 - and Bmel-2 - mutants, respectively. As compared with the control silkworm, differentially expressed genes generated in both mutants were mainly enriched in lysine degradation, fatty acid (FA) metabolism, and unsaturated FAs biosynthesis. The diglyceride and phosphatide contents were significantly lower in Bmel-1 - and Bmel-2 - fat bodies than those of the control group. Consistently, the NF content of both mutants' fat bodies were reduced by 50% and 60%, respectively. BmEL-2 positively regulates BmAGPATγ (B. mori 1-acyl-sn-glycerol-3-phosphate acyltransferase gamma, LOC101741736) and BmFaF2 (B. mori fatty acid synthetase-associated factor 2, LOC101739090) expression by binding to the specific regions of their 3' untranslated regions in BmN cells. This study suggests that BmEL-2 may be an important regulator of BmAGPATγ and BmFAF2 expression and thereby participates in TG metabolism in the silkworm fat body., (© 2024 Institute of Zoology, Chinese Academy of Sciences.)

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., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

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 β 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 β wave powers in the frontal and parietal lobes, with a rising trend in the β/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 Aβ, GSK-3β, P-Tau, IL-1β, 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.

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.

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., (© 2024 Royal Entomological Society.)

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.

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., (© 2024. The Author(s).)

Current biodiversity loss is generally considered to have been caused by anthropogenic disturbance, but it is unclear when anthropogenic activities began to affect biodiversity loss. One hypothesis suggests it began with the Industrial Revolution, whereas others propose that anthropogenic disturbance has been associated with biodiversity decline since the early Holocene. To test these hypotheses, we examined the unique vegetation of evergreen broadleaved forests (EBLFs) in East Asia, where humans have affected landscapes since the early Holocene. We adopted a genomic approach to infer the demographic history of a dominant tree (Litsea elongata) of EBLFs. We used Holocene temperature and anthropogenic disturbance factors to calculate the correlation between these variables and the historical effective population size of L. elongata with Spearman statistics and integrated the maximum-entropy niche model to determine the impact of climate change and anthropogenic disturbance on fluctuation in its effective population size. We identified 9 well-defined geographic clades for the populations of L. elongata. Based on the estimated historical population sizes of these clades, all the populations contracted, indicating persistent population decline over the last 11,000 years. Demographic history of L. elongata and human population change, change in cropland use, and change in irrigated rice area were significantly negatively correlated, whereas climate change in the Holocene was not correlated with demographic history. Our results support the early human impact hypothesis and provide comprehensive evidence that early anthropogenic disturbance may contribute to the current biodiversity crisis in East Asia., (© 2023 Society for Conservation Biology.)

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.

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., (© 2023. The Author(s).)

As communications are increasingly taking place virtually, the ability to present well online is becoming an indispensable skill. Online speakers are facing unique challenges in engaging with remote audiences. However, there has been a lack of evidence-based analytical systems for people to comprehensively evaluate online speeches and further discover possibilities for improvement. This paper introduces SpeechMirror, a visual analytics system facilitating reflection on a speech based on insights from a collection of online speeches. The system estimates the impact of different speech techniques on effectiveness and applies them to a speech to give users awareness of the performance of speech techniques. A similarity recommendation approach based on speech factors or script content supports guided exploration to expand knowledge of presentation evidence and accelerate the discovery of speech delivery possibilities. SpeechMirror provides intuitive visualizations and interactions for users to understand speech factors. Among them, SpeechTwin, a novel multimodal visual summary of speech, supports rapid understanding of critical speech factors and comparison of different speech samples, and SpeechPlayer augments the speech video by integrating visualization of the speaker's body language with interaction, for focused analysis. The system utilizes visualizations suited to the distinct nature of different speech factors for user comprehension. The proposed system and visualization techniques were evaluated with domain experts and amateurs, demonstrating usability for users with low visualization literacy and its efficacy in assisting users to develop insights for potential improvement.

Microbial exopolysaccharides (EPSs) can promote plants growth and protect them against various abiotic stresses, but the role of actinobacteria-produced EPSs in plant growth promoting is still less known. Here, we aim to explore the effect of EPSs from an endophyte Glutamicibacter halophytocota KLBMP 5180 on tomato seeds germination and seedlings growth under salt stress. Our study revealed that 2.0 g/L EPSs resulted in increased seed germination rate by 23.5 % and 11.0 %, respectively, under 0 and 200 mM NaCl stress conditions. Further pot experiment demonstrated that EPSs significantly promoted seedlings growth under salt stress, with increased height, root length and fibrous roots number. Plant physiological traits revealed that EPSs increased chlorophyll content, enhanced the activity of antioxidant enzymes, soluble sugar, and K + concentration in seedlings; malondialdehyde and Na + contents were reduced. Additionally, auxin, abscisic acid, jasmonic acid, and salicylic acid were accumulated significantly in seedlings after EPSs treatment. Furthermore, we identified 1233 differentially expressed genes, and they were significantly enriched in phytohormone signal transmission, phenylpropanoid biosynthesis, and protein processing in endogenous reticulum pathways, etc. Our results suggest that KLBMP 5180-produced EPSs effectively ameliorated NaCl stress in tomato plants by triggering complex regulation mechanism, and showed application potentiality in agriculture., Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

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.

Competing Interests: The authors declare that they have no conflict of interest.

Background: Human respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection and hospitalization, especially in children. Highly mutagenic nature and antigenic diversity enable the RSV to successfully survive in human population. We conducted a molecular epidemiological study during 2017-2021 to investigate the prevalence and genetic characteristics of RSV., Methods: A total of 6499 nasopharyngeal (NP) swabs were collected from hospitalized children at Department of Pediatrics, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong, China. All NP swab specimens were preliminary screened for common respiratory viruses and then tested for RSV using specific PCR assays. Partial G genes of RSV were amplified for phylogenetic analysis and genetic characterization., Results: The overall detection rate for common respiratory viruses was 16.12% (1048/6499). Among those, 405 specimens (6.20%, 405/6499) were found positive for RSV. The monthly distribution of RSV and other respiratory viruses was variable, and the highest incidence was recorded in Autumn and Winter. Based on the sequencing of hypervariable region of G gene, 93 RSV sequences were sub-grouped into RSV-A (56, 60.2%) and RSV-B (37, 39.8%). There was no coinfection of RSV-A and RSV-B in the tested samples. Phylogenetic analysis revealed that RSV-A and RSV-B strains belonged to ON1 and BA9 genotypes respectively, indicating predominance of these genotypes in Guangzhou. Several substitutions were observed which may likely change the antigenicity and pathogenicity of RSV. Multiple glycosylation sites were noticed, demonstrating high selection pressure on these genotypes., Conclusion: This study illustrated useful information about epidemiology, genetic characteristics, and circulating genotypes of RSV in Guangzhou China. Regular monitoring of the circulating strains of RSV in different parts of China could assist in the development of more effective vaccines and preventive measures., (© 2023. The Author(s).)

Cancer stem cells (CSCs) are crucial in the pathogenesis of human cancers. Existing studies reported that microRNA (miRNA) modulates the stemness of CSCs. We discovered that renal cell CSCs have suppressed miR-381. Suppression of miR-381 promotes renal cell tumorigenesis and CSC-like properties. Furthermore, the forced expression of miR-381 prevents the renal cell tumorigenesis and CSC-like properties. Mechanistically, renal cell CSCs have been found to interact with SOX4 through miR-381 directly. miR-381 inhibits renal cell CSC-like properties and tumorigenesis via downregulating SOX4. Examination of the patient-derived xenografts (PDX) and patient cohorts reveals that miR-381 may be able to forecast the advantages of Sunitinib in RCC patients. Moreover, the introduction of SOX4 could reverse the sensitivity of miR-381 overexpression RCC cells to Sunitinib-induced cell apoptosis. These results indicated that miR-381 is critical in renal cell CSC-like properties and tumorigenesis, making it the ideal therapeutic target for RCC., Competing Interests: The authors have no conflict of interest., (© 2023 The Authors. Published by Elsevier B.V.)

From the fungus Trichoderma sp., we isolated seven novel 18-residue peptaibols, neoatroviridins E-K (1-7), and six new 14-residue peptaibols, harzianins NPDG J-O (8-13). Additionally, four previously characterized 18-residue peptaibols neoatroviridins A-D (14-17) were also identified. The structural configurations of the newly identified peptaibols (1-13) were determined by comprehensive nuclear magnetic resonance (NMR) and high-resolution electrospray ionization tandem mass spectrometry (HR-ESI-MS/MS) data. Their absolute configurations were further determined using Marfey's method. Notably, compounds 12 and 13 represent the first 14-residue peptaibols containing an acidic amino acid residue. In antimicrobial assessments, all 18-residue peptaibols (1-7, 14-17) exhibited moderate inhibitory activities against Staphylococcus aureus 209P, with minimum inhibitory concentration (MIC) values ranging from 8-32 μg·mL -1 . Moreover, compound 9 exhibited moderate inhibitory effect on Candida albicans FIM709, with a MIC value of 16 μg·mL -1 ., (Copyright © 2023 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

19-Hydroxybrevianamide M (1) and 6 R-methoxybrevianamide V (2), two new alkaloids, were isolated from an extract of the endophytic fungus Aspergillus sp. JNU18HC0517J, together with six known analogues ( 3- 8 ). Their structures were elucidated by extensive spectroscopic analyses, NMR calculations, and ECD calculations. 6  R -methoxybrevianamide V (2) was the first L-proline indole DKP alkaloid with substitution at C-6 on the proline ring. Furthermore, the cytotoxities and antimicrobial activities of these isolated compounds were also evaluated. Compound 8 exhibited moderate antibacterial activity against Staphylococcus aureus 209 P with a minimal inhibitory concentration (MIC) value of 16 µg/ml.[Figure: see text].

Bisabosqual-type meroterpenoids are fungi-derived polyketide-terpenoid hybrids bearing a 2,3,3a,3a 1 ,9,9a-hexahydro-1 H -benzofuro[4,3,2- cde ]chromene skeleton (6/6/6/5 ring system) or its seco -C-ring structure, and exhibit diverse bioactivities. Their unique structural architecture and impressive biological activities have led to considerable interest in discovering new analogues. However, to date, only nine analogues have been identified. Herein, we reported the isolation and identification of six new bisabosqual-type meroterpenoids stachybisbins C-H (1-6), together with one known compound bisabosqual C (7), from Stachybotrys bisbyi PYH05-7. Intriguingly, we found that 7, which contains the intact tetracyclic skeleton, can be non-enzymatically converted into its seco derivative stachybisbin I (8), unveiling the biosynthetic relationship between bisabosquals and seco -bisabosquals. Moreover, based on CRISPR/Cas9-mediated gene disruption, we revealed that the three-gene cluster responsible for the formation of LL-Z1272β is associated with the biosynthesis of bisabosqual-type meroterpenoids, and then proposed a plausible route to 1-8.

Introduction: Fruit diseases have a serious impact on fruit production, causing a significant drop in economic returns from agricultural products. Due to its excellent performance, deep learning is widely used for disease identification and severity diagnosis of crops. This paper focuses on leveraging the high-latitude feature extraction capability of deep convolutional neural networks to improve classification performance. Methods: The proposed neural network is formed by combining the Inception module with the current state-of-the-art EfficientNetV2 for better multi-scale feature extraction and disease identification of citrus fruits. The VGG is used to replace the U-Net backbone to enhance the segmentation performance of the network. Results: Compared to existing networks, the proposed method achieved recognition accuracy of over 95%. In addition, the accuracies of the segmentation models were compared. VGG-U-Net, a network generated by replacing the backbone of U-Net with VGG, is found to have the best segmentation performance with an accuracy of 87.66%. This method is most suitable for diagnosing the severity level of citrus fruit diseases. In the meantime, transfer learning is applied to improve the training cycle of the network model, both in the detection and severity diagnosis phases of the disease. Discussion: The results of the comparison experiments reveal that the proposed method is effective in identifying and diagnosing the severity of citrus fruit diseases identification., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Jiang, Huang, Qin and Yang.)

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., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Kunming Institute of Botany, Chinese Academy of Sciences. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

The evergreen versus deciduous leaf habit is an important functional trait for adaptation of forest trees and has been hypothesized to be related to the evolutionary processes of the component species under paleoclimatic change, and potentially reflected in the dynamic history of evergreen broadleaved forests (EBLFs) in East Asia. However, knowledge about the shift of evergreen versus deciduous leaf with the impact of paleoclimatic change using genomic data remains rare. Here, we focus on the Litsea complex (Lauraceae), a key lineage with dominant species of EBLFs, to gain insights into how evergreen versus deciduous trait shifted, providing insights into the origin and historical dynamics of EBLFs in East Asia under Cenozoic climate change. We reconstructed a robust phylogeny of the Litsea complex using genome-wide single-nucleotide variants (SNVs) with eight clades resolved. Fossil-calibrated analyses, diversification rate shifts, ancestral habit, ecological niche modelling and climate niche reconstruction were employed to estimate its origin and diversification pattern. Taking into account studies on other plant lineages dominating EBLFs of East Asia, it was revealed that the prototype of EBLFs in East Asia probably emerged in the Early Eocene (55-50 million years ago [Ma]), facilitated by the greenhouse warming. As a response to the cooling and drying climate in the Middle to Late Eocene (48-38 Ma), deciduous habits were evolved in the dominant lineages of the EBLFs in East Asia. Up to the Early Miocene (23 Ma), the prevailing of East Asian monsoon increased the extreme seasonal precipitation and accelerated the emergence of evergreen habits of the dominant lineages, and ultimately shaped the vegetation resembling that of today., (© 2023 John Wiley & Sons Ltd.)

Bombyx mori nucleopolyhedrovirus (BmNPV) is a serious threat to sericulture. Nevertheless, no effective control strategy is currently available. The innate immunity of silkworm is critical in the antiviral process. Exploring its molecular mechanism provides theoretical support for the prevention and treatment of BmNPV. Insect hormone receptors play an essential role in regulating host immunity. We found a correlation between Bombyx mori ecdysone receptor B1 ( BmEcR-B1 ) and BmNPV infection, whereas the underlying mechanism remains unclear. In this study, the expression patterns and sequence characteristics of BmEcR-B1 and its isoform, BmEcR-A , were initially analyzed. BmEcR-B1 was found to be more critical than BmEcR-A in silkworm development and responses to BmNPV. Moreover, RNAi and an overexpression in BmN cells showed BmEcR-B1 had antiviral effects in the presence of 20-hydroxyecdysone (20E); Otherwise, it had no antiviral activity. Furthermore, BmEcR-B1 was required for 20E-induced apoptosis, which significantly suppressed virus infection. Finally, feeding 20E had no significant negative impacts on larval growth and the cocoon shell, suggesting the regulation of this pathway has practical value in controlling BmNPV in sericulture. The findings of this study provide important theoretical support for understanding the mechanism of the silkworm innate immune system in response to BmNPV infection.

In fungi, there is a rare group of natural products harboring the 2,3,3a,9a-tetrahydro-4 H -furo[2,3- b ]chromene skeleton, represented by xyloketal B, which display a wide range of biological activities and have drawn significant attention. In this work, four new analogues simpliketals A-D (1-4), as well as two other new compounds simplilactones A and B (5 and 6), were isolated from Simplicillium sp. AHK071-01. Their structures were elucidated by extensive NMR spectroscopic methods, 13 C NMR calculation, single-crystal X-ray diffraction, and ECD calculation. In addition, five known compounds (7-11) including alboatrin (7) were also obtained. Based on the structural similarity of the above compounds, we inferred that compounds 5, 6, and 8-11 might be biosynthetically related with 1-4 and 7, which allowed us to propose an alternative biosynthetic route to generate the furan-fused chromene skeleton of this class of compounds, instead of a previously presumed polyketide-terpenoid hybrid pathway. Finally, cytotoxicity assays showed that 1-4 exhibited weak inhibitory activity on PANC-1 cells and that 2 and 3 possessed moderate activity against SH-SY5Y cells.

Background: Gastric cancer is the second most common cause of cancer death worldwide with poor overall prognosis. It is important to study the molecular mechanism of stomach adenocarcinoma (STAD). MAGED4B, a member of the melanoma antigen gene (MAGE) family, is highly expressed in many tumor cells and is associated with tumor progression. Its prognostic value in and the function of the encoded protein are still unclear., Methods: The data of 415 STAD tissues was retrieved from TCGA database, and the expression level of MAGED4B mRNA was evaluated. The correlation between the expression of MAGED4B mRNA and the progression free survival (PFS) time of STAD patients was evaluated by Kaplan Meier analysis. The STAD cell lines with overexpressed and silent MAGED4B were constructed, and the effects of MAGED4B on the viability, migration and proliferation were evaluated by the CCK-8, scratch test and EDU test. The flow cytometry was used to detect apoptosis with overexpressed and silent MAGED4B under the cisplatin treatment, and WB was used to detect the expressions of related proteins, such as TNF-α., Results: The expression level of MAGED4B mRNA in the STAD tissues was higher than that in the normal tissues, and its high expression was related to poor PFS. The overexpression of MAGED4B in the STAD cell lines can promote the vitality, motility and proliferation of the STAD cells, while the silencing of MAGED4B can inhibit the above three cell functions of the STAD cells. The overexpression of MAGED4B can reduce the cisplatin induced apoptosis and increase the cisplatin IC 50 ; the silencing of MAGED4B can promote the cisplatin induced apoptosis and reduce the cisplatin IC 50 . The overexpression of MAGED4B reduced the protein levels of TRIM27 and TNF- α., Conclusion: MAGED4B could be a valuable prognostic biomarker and a therapeutic target for gastric adenocarcinoma of great interest., Competing Interests: The authors have no relevant financial or non-financial interests to disclose., (© 2023 Luo et al.)

Termites are social insects that live in the soil or in decaying wood, where exposure to pathogens should be common. However, these pathogens rarely cause mortality in established colonies. In addition to social immunity, the gut symbionts of termites are expected to assist in protecting their hosts, though the specific contributions are unclear. In this study, we examined this hypothesis in Odontotermes formosanus , a fungus-growing termite in the family Termitidae , by 1) disrupting its gut microbiota with the antibiotic kanamycin, 2) challenging O. formosanus with the entomopathogenic fungus Metarhizium robertsii , and finally 3) sequencing the resultant gut transcriptomes. As a result, 142531 transcripts and 73608 unigenes were obtained, and unigenes were annotated following NR, NT, KO, Swiss-Prot, PFAM, GO, and KOG databases. Among them, a total of 3,814 differentially expressed genes (DEGs) were identified between M. robertsii infected termites with or without antibiotics treatment. Given the lack of annotated genes in O. formosanus transcriptomes, we examined the expression profiles of the top 20 most significantly differentially expressed genes using qRT-PCR. Several of these genes, including APOA2, Calpain-5, and Hsp70, were downregulated in termites exposed to both antibiotics and pathogen but upregulated in those exposed only to the pathogen, suggesting that gut microbiota might buffer/facilitate their hosts against infection by finetuning physiological and biochemical processes, including innate immunity, protein folding, and ATP synthesis. Overall, our combined results imply that stabilization of gut microbiota can assist termites in maintaining physiological and biochemical homeostasis when foreign pathogenic fungi invade., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tang, Kong, Qin, Merchant, Shi, Zhou, Li and Wang.)

Ultrabithorax ( Ubx ) is a member of the Hox gene group involved in cell fate decisions, cell proliferation and organ identity. Its function has been extensively researched in Drosophila melanogaster but little is known about it in Lepidoptera. To uncover the function of Ubx in the development of lepidopterans, we constructed the Ubx overexpression (Ubx OE ) strain based on the Nistari strain of Bombyx mori . The Ubx OE strain showed a small body size, transparent intersegmental membrane and abnormal posterior silk gland (PSG). In the current study, we focused on the effect of Ubx overexpression on the posterior silk gland. As the major protein product of PSG, the mRNA expression of fibroin heavy chain ( Fib-H ) and fibroin light chain ( Fib-L ) was upregulated three times in Ubx OE , but the protein expression of Fib-H and Fib-L was not significantly different. We speculated that the overexpression of Ubx downregulated the expression of Myc and further caused abnormal synthesis of the spliceosome and ribosome. Abnormalities of the spliceosome and ribosome affected the synthesis of protein in the PSG and changed its morphology.

The movement protein (MP) and coat protein (CP) of tobamoviruses play critical roles in viral cell-to-cell and long-distance movement, respectively. Cucumber green mottle mosaic virus (CGMMV) is a member of the genus Tobamovirus. The functions of CGMMV MP and CP during viral infection remain largely unclear. Here, we show that CGMMV MP can interact with CP in vivo, and the amino acids at positions 79-128 in MP are vital for the MP-CP interaction. To confirm this finding, we mutated five conserved residues within the residue 79-128 region and six other conserved residues flanking this region, followed by in vivo interaction assays. The results showed that the conserved threonine residue at the position 107 in MP (MP T107 ) is important for the MP-CP interaction. Substitution of T107 with alanine (MP T107A ) delayed CGMMV systemic infection in Nicotiana benthamiana plants, but increased CGMMV local accumulation. Substitutions of another 10 conserved residues, not responsible for the MP-CP interaction, with alanine inhibited or abolished CGMMV systemic infection, suggesting that these 10 conserved residues are possibly required for the MP movement function through a CP-independent manner. Moreover, two movement function-associated point mutants (MP F17A and MP D97A ) failed to cause systemic infection in plants without impacting on the MP-CP interaction. Furthermore, we have found that co-expression of CGMMV MP and CP increased CP accumulation independent of the interaction. MP and CP interaction inhibits the salicylic acid-associated defence response at an early infection stage. Taken together, we propose that the suppression of host antiviral defence through the MP-CP interaction facilitates virus systemic infection., (© 2022 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) is an established site for green herbicide discovery. In this work, based on structural analysis, we develop an active fragment exchange and link (AFEL) approach to designing a new class of N -1,4-diketophenyltriazinones I - III as potent Nicotiana tabacum PPO (PPO) inhibitors. After systematic structure-activity relationship optimizations, a series of new compounds with K i values in the single-digit nanomolar range toward NtPPO and promising herbicidal activity were discovered. Among them, Ii ( K i = 0.11 nM) displays 284- and 90-fold improvement in NtPPO inhibitory activity over trifludimoxazin ( K i = 31 nM) and saflufenacil ( K i = 10 nM), respectively. In addition, Ip ( K i = 2.14 nM) not only exhibited good herbicidal activity at 9.375-37.5 g ai/ha but also showed high crop safety to rice at 75 g ai/ha by the postemergence application, indicating that Ip could be developed as a potential herbicide for weed control in rice fields. Additionally, our molecular dynamic simulation clarified the molecular basis for the interactions of these molecules with NtPPO. The metabolism studies in planta showed that IIIc could be converted to Ic , which displayed higher herbicidal activity than IIIc . The density functional theory analysis showed that due to the effect of two sulfur atoms at the triazinone moiety, IIIc is more reactive than Ic , making it more easily degraded in planta . Our work indicates that the AFEL strategy could be used to design new molecules with improved bioactivity.

Aims: The aim of this study was to evaluate the clinicopathological features, immunophenotype, differential diagnosis, molecular genetic features and prognosis of spindle cell rhabdomyosarcoma with TFCP2 rearrangement., Methods: Two cases of spindle cell rhabdomyosarcoma with FET::TFCP2 gene fusion were included in this study. Samples were collected and evaluated through histological observation, immunohistochemistry, fluorescence in-situ hybridisation and high-throughput gene sequencing and previous findings., Results: The tumour tissues mainly comprised spindle cells and epithelioid cells, which expressed striated muscle markers, and exhibited high expression levels of CK and ALK protein markers. Molecular detection showed that the FET::TFCP2 gene was fused. A rare case with TIMP3::ALK and FUS::TFCP2 double-fusion was observed in this study., Conclusions: A case with double fusion of ALK and TFCP2 was reported in rhabdomyosarcoma for the first time in this study, which provides information on the molecular characteristic of the tumour. Spindle cell rhabdomyosarcoma with FET::TFCP2 fusion is characterised by histological, immunohistochemical and genetic changes. The tumour is aggressive, with poor prognosis and poor response to radiotherapy and chemotherapy. The efficacy of targeted therapy for ALK should be explored through more clinical studies., (© 2022 John Wiley & Sons Ltd.)

Fernane-type triterpenoids are a small group of natural products mainly found in plants and fungi with a wide range of biological activities. Polytolypin is a representative fernane-type triterpenoid from fungi and possesses potent antifungal activity. So far, biosynthesis of fungal-derived fernane-type triterpenoids has not been characterized, which hinders the expansion of their structural diversity using biosynthetic approaches. Herein, we identified the biosynthetic gene cluster of polytolypin and elucidated its biosynthetic pathway through heterologous expression in Aspergillus oryzae NSAR1, which involves a new triterpene cyclase for the biosynthesis of the hydrocarbon skeleton motiol, followed by multiple oxidations via three P450 enzymes. Moreover, two new triterpene cyclases for the biosynthesis of two other fernane-type skeletons isomotiol and fernenol were identified from fungi, and were individually co-expressed with the three P450 enzymes involved in polytolypin biosynthesis. These studies led to the generation of 13 fernane-type triterpenoids including eight new compounds, and two of them showed stronger antifungal activity towards Candida albicans FIM709 than polytolypin.

Arctium lappa L. is one of the medicinal and food homologous plants in China, which is rich in nutrients and medicinal ingredients. The use of plant growth-promoting (PGP) endophytic bacteria is an alternative to reducing chemical fertilizers in agricultural production. The aim of this study was to analyze the diversity of endophytic bacteria in different cultivars of A. lappa L. collected from two geographical locations in China and evaluate PGP traits of the isolates and their potential PGP ability in greenhouse condition. Endophytic bacterial community was investigated by culture-dependent and culture-independent methods. Isolates were screened and investigated for multiple PGP traits, and representative strains were inoculated host seedlings to evaluate the growth promoting effect. A total of 348 endophytic bacteria were obtained and they were distributed into 4 phyla and 30 genera. In addition, high throughput sequencing revealed more abundant bacterial community, including 17 bacterial phyla and 207 genera. A high proportion of PGP traits were detected, including production of indole acetic acid, siderophore, ammonia and phosphate solubilization. Four representative strains with multiple PGP traits of the most dominant genera (Bacillus, Pantoea, Microbacterium and Pseudomonas) were further selected for host inoculation and growth promoting evaluation, and they significantly increase seedlings length, root length and fresh weight. This study demonstrated that A. lappa L. harbors abundant endophytic bacteria, and some endophytic bacteria showed good potential for the development of microbial fertilizer in the future., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Nucleopolyhedrovirus (NPV), one of the baculoviruses, is a promising biopesticide for pest control. Lepidopteran account for 70% of pests, therefore investigation on highly conserved genes associated with viral infections in the lepidopteran model, the silkworm, will serve as a valuable reference for improving the effectiveness of pest management. BmE74A is a member of the erythroblast transformation-specific (ETS) family of transcription factors in Bombyx mori, which we previously found to be highly conserved and closely associated with BmNPV. This study aimed to elucidate the role of BmE74A in viral infection., Results: A significantly high expression of BmE74A in eggs indicated its important role in embryonic development, as did relatively high expressions in the hemolymph and midgut. Significant differences in BmE74A expression in different resistant strains after BmNPV infection suggested its involvement as a response to viral infection. Moreover, RNA interference (RNAi) and overexpression experiments confirmed the important role of BmE74A in promoting viral infection. BmNPV infection was significantly suppressed and enhanced by BmE74A knockdown and overexpression, respectively. Besides, BmE74A was found to regulate the expression of BmMdm2 and Bmp53. Furthermore, the binding of ETS, the functional domain of BmE74A, to occlusion-derived virus proteins was confirmed by far-western blotting, and four viral proteins that may interact with ETS proteins were identified by mass spectrometry. Similarly, a homolog of BmE74A in Spodoptera litura was also found to be involved in larval susceptibility to BmNPV., Conclusion: BmE74A promotes BmNPV proliferation by directly interacting with the virus, which may be related to the suppression of the p53 pathway. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Objective: To compare the effect of managing neonatal lung disease with lung ultrasound (LUS) or chest X-ray (CXR) monitoring on health outcomes and cost-effectiveness., Methods: The data obtained from the NICU of the Beijing Chaoyang District Maternal and Child Healthcare Hospital were used as the study group, as LUS has completely replaced CXR in managing newborn lung disease in the hospital for the past 5 years. The primary outcomes of this study were the misdiagnosis rate of respiratory distress syndrome (RDS), the using status of mechanical ventilation, the incidence rate of bronchopulmonary dysplasia (BPD) and the survival rate in hospitalized infants. The secondary outcomes included the use pulmonary surfactant (PS), and the mortality rate of severe diseases (such as pneumothorax, pulmonary hemorrhage and RDS, etc.)., Results: Managing neonatal lung disease with LUS monitoring may enable the following effects: The frequency of ventilator use reducing by 40.2%; the duration of mechanical ventilation reducing by 67.5%; and the frequency of ventilator weaning failure being totally avoided. A misdiagnosis rate of 30% for RDS was also avoided. The dosage of PS was significantly reduced by 50% to 75%. No BPD occurred in the LUS-based care group for 5 years. The fatality rates of RDS, pneumothorax and pulmonary hemorrhage decreased by 100%. The poor prognosis rate of VLBW infants decreased by 85%, and the total mortality rate of hospitalized infants decreased by 90%. Therefore, the cost of LUS-based care was inevitably saved., Conclusions: Diagnosing and managing neonatal lung diseases with LUS monitoring have significant benefits, and this technology should be widely promoted and applied around the world.

Papillary thyroid carcinoma (PTC) is prone to regional lymph node metastasis, which is more common in central lymph nodes and lateral cervical lymph nodes, and retropharyngeal lymph node metastasis (RLNM) is extremely rare. A male with PTC presented with extensive cervical lymph node metastasis and the initial RLNM. After full evaluation by preoperative imaging examination, the patient underwent total thyroidectomy + left central lymph node dissection + left neck lymph node dissection (II III IV V) + left retropharyngeal tumor resection, and the postoperative recovery was good without recurrence long-term complications, and no local recurrence and metastasis were found during one-year follow-up., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Twenty new malabaricane triterpenoids, astramalabaricosides A-T ( 1 - 20 ), were isolated from the roots of Astragalus membranaceus var. mongholicus (Astragali Radix). Their structures were determined by spectroscopic analysis, and the use of the circular dichroism exciton chirality method, quantum chemical calculations, and chemical methods. Malabaricane triterpenoids, an unusual group with the 6-6-5-tricyclic core, are distributed in plants (e.g., Simaroubaceae, Polypodiaceae, and Fabaceae), a marine sponge, and fungi, and their number obtained to date is limited. Compounds 1 - 20 were characterized as glycosides with a highly oxygenated side chain, and 13 - 20 were the first cyclic carbonate derivatives among the malabaricane triterpenoids. The stereocluster formed from the continuous hydroxylated chiral carbons in each highly oxygenated side chain and the 6-6-5-tricyclic core system were entirely segregated, and the independent identification of their stereoconfigurations required considerable effort. The migratory inhibitory and antiproliferative activities of 1 - 20 were evaluated by wound-healing and cell-viability assays, respectively. Most compounds showed significant migratory inhibitory activity, and a preliminary structure-activity relationship was developed. Malabaricane triterpenoids are being reported in the genus Astragalus for the first time.

Bombyx mori , domesticated from wild silkworms, is an economic insect that feeds on mulberry leaves and produces silk. In the current study, we demonstrated the contribution of BmAbl1 in silk protein synthesis. The inhibition and knockout of BmAbl1 can reduce the larva weight and CSW. The effect on CSW of BmAbl1 is not on the transcriptional level, but on the translational level. RNA-sequencing data suggested that amino acid synthesis and the metabolism process had a great difference between the BmAbl1 - and Control strain, particularly glutathione metabolism. An abnormality in glutathione metabolism led to the reduction of free glycine and serine content, which are the main components of fibroin protein. Finally, fibroin protein synthesis has been reduced, including fibroin-heavy chain, fibroin-light chain, and p25 protein. This finding brought to light the role of BmAbl1 in the silk protein synthesis process.

Fusicoccane-type terpenoids are a subgroup of diterpenoids featured with a unique 5-8-5 ring system. They are widely distributed in nature and possess a variety of biological activities. Up to date, only five fusicoccane-type diterpene synthases have been identified. Here, we identify a two-gene biosynthetic gene cluster containing a new fusicoccane-type diterpene synthase gene tadA and an associated cytochrome P450 gene tadB from Talaromyces wortmannii ATCC 26942. Heterologous expression reveals that TadA catalyzes the formation of a new fusicoccane-type diterpene talaro-7,13-diene. D 2 O isotope labeling combined with site-directed mutagenesis indicates that TadA might employ a different C2,6 cyclization strategy from the known fusicoccane-type diterpene synthases, in which a neutral intermediate is firstly formed and then protonated by an environmental proton. In addition, we demonstrate that the associated cytochrome P450 enzyme TadB is able to catalyze multiple oxidation of talaro-7,13-diene to yield talaro-6,13-dien-5,8-dione., (Copyright © 2022, Huang et al.)

Colorectal cancer is one of the most malignant cancers worldwide, and efforts have been made to elucidate the mechanism of colorectal carcinogenesis. Cellular senescence is a physiological process in cell life, but it is also found in cancer initiation and progression. Lines of evidence show that senescence may influence the development and progression of colorectal carcinogenesis. Here, the authors review the characteristics of senescence and the recent findings of a relationship between senescence and colorectal cancer.

Background and Objective: Lung ultrasound (LUS) has been widely used in the diagnosis and differential diagnosis of neonatal lung diseases (NLDs), but whether it can replace the routine use of chest X-ray (CXR) in neonatal intensive care units (NICUs) remains controversial. This paper summarizes the clinical practice of our neonatal intensive care unit (NICU) during the past three years to explore the feasibility and necessity of using LUS instead of CXR to diagnose NLDs in the NICU setting., Methods: The clinical data and LUS examination results from 1,381 newborn infants with respiratory difficulty who were hospitalized in our NICU from March 2017 to February 2020 were retrospectively collected to analyze the types of lung diseases diagnosed and the reliability of LUS for diagnosing NLDs., Results: (1) During this period, 1381 newborn infants with dyspnea were admitted to our NICU, accounting for 41.2% of all hospitalized children. (2) Among the 1381 infants, 17 patients with respiratory distress were confirmed as having severe heart disease by echocardiography, while the remaining 1364 patients had different kinds of lung diseases: pneumonia (697 patients, 51.1%), respiratory distress syndrome (251 patients, 17.4%), transient tachypnea of the newborn (197 patients, 13.3%), atelectasis (89 patients, 5.6%), pneumothorax (46 patients, 3.2%), pulmonary hemorrhage (69 patients, 4.5%), severe pleural effusion (18 patients, 1.32%), congenital pulmonary sequestration (3 patients, 0.22%), bullae of the lung (2 patients, 0.15%), and congenital cystic adenomatoid malformation (2 patients). (5) Among the 1381 infants, 217 received CXR examination before admission, which resulted in misdiagnosis in 45 patients (20.7%) and missed diagnosis in 12 patients (5.5%); the missed diagnosis and misdiagnosis rate was 26.3%., Conclusion: Our 3-year clinical practice experience indicated that LUS could completely replace chest X-ray for the diagnosis and differential diagnosis of NLDs in the NICU. Compared with X-ray, LUS had higher accuracy and reliability in diagnosing NLDs.

For 3d 1 (V 4+ ) impurity in 30PbO-5Bi 2 O 3 -(65-x)SiO 2 glass systems with different concentrations x of V2O5, the defect structures and gyromagnetic factors are theoretically investigated by using the perturbation formulas of g factors for a tetragonally compressed octahedral 3d 1 group. The concentration dependences of d-d transition band and g factors are suitably explained from the Fourier type concentration functions of the cubic crystal field parameter Dq, covalency factor N and relative tetragonal compression ratio ρ. The above concentration dependences of these quantities are suitably illustrated by the modifications of the local crystal field strength and electron cloud distribution with increasing x. The concentration variations of the electrical conductivity and dielectric relaxation are further analyzed from the stability of the systems in view of two competitive factors (increasing network polymerization and bulk stability at low concentrations and decreasing former SiO 2 and stability at high concentrations)., (© 2022 John Wiley & Sons, Ltd.)

Pesticides are frequently used to control pests in agriculture due to their ease of use and effectiveness, but their use causes serious economic losses to sericulture when their production overlaps with agriculture. However, no suitable internal reference genes (RGs) have been reported in the study of silkworms in response to pesticides. In this study, a standard curve was established to detect the expression levels of seven RGs in different tissues of different silkworm strains after feeding with pesticides using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), including BmGAPDH, BmActin3, BmTBP, BmRPL3, Bm28sRNA, Bmα-tubulin, and BmUBC, and the stability of them was evaluated by using NormFinder, geNorm, Delta CT, BestKeeper, and RefFinder. The results showed that BmGAPDH and Bmα-tubulin were relatively stable in the midgut after feeding with fenvalerate, BmGAPDH and Bmactin3 were relatively stable in the fat body, and Bmα-tubulin and Bmactin3 were relatively stable in the hemolymph, indicating that Bmactin3 was the most suitable RG when evaluating fenvalerate, followed by BmGAPDH and Bmα-tubulin. Besides, BmGAPDH and Bmactin3 were relatively stable in the midgut after treatment with DDVP, BmGAPDH and Bmα-tubulin were relatively stable in the fat body, and BmGAPDH and Bmα-tubulin were relatively stable in the hemolymph, indicating that Bmα-tubulin was the most stable RG when evaluating DDVP, followed by BmGAPDH and Bmactin3. Of note, BmGAPDH was shared by the two pesticides. The results will be valuable for RG selection in studying the pesticide response mechanism of silkworms and other lepidopteran insects., (© 2022 Wiley Periodicals LLC.)

Titanium nanotube (Ti-NT) is an attractive substrate for local drug delivery, however, it is difficult to control the burst drug release and achieve sustained release from these nanotubes. In the present study, we investigated the feasibility of controlling drug release from Ti-NT within polydopamine and hyaluronic acid films, to achieve antibacterial activity and osteogenic promotion. Vancomycin was loaded into the Ti-NT by lyophilisation. Dopamine and hyaluronic acid were immobilized on the vancomycin-loaded Ti-NT surface through alternate deposition technique. The anti-infective and osteogenic abilities of the polydopamine and hyaluronic acid-modified Ti-NT were then investigated. Our results demonstrated that polydopamine and hyaluronic acid-modified Ti-NT exhibited improved drug loading and release control for 7 days. Compared with the vancomycin-loaded Ti-NT, the polydopamine and hyaluronic acid-modified Ti-NT exhibited better antibacterial ability, and the hyaluronic acid-modified Ti-NT promoted the osteogenic differentiation of rat bone marrow stem cells. Our results demonstrated that Ti-NT biofunctionalized with polydopamine and hyaluronic acid can help overcome the limitations of Ti-NT, by improving drug loading, antibacterial activity and osteogenic ability., (Copyright © 2022. Published by Elsevier B.V.)

Colletotrichum species are important plant pathogens, causing anthracnose in virtually every crop grown throughout the world. However, little is known about the species that infect watermelon. A total of 526 strains were isolated from diseased watermelon samples of eight major watermelon growing provinces in China. Phylogenetic analyses using seven loci (ITS, gadph , chs-1 , his3 , act , tub2 , and gs ) coupled with morphology of 146 representative isolates showed that they belonged to 12 known species of Colletotrichum , including C. aenigma , C. chlorophyti , C. fructicola , C. jiangxiense , C. karstii , C. magnum , C. nymphaeae , C. nigrum , C. orbiculare , C. plurivorum , C. sojae , and C. truncatum and three new species, here described as C. citrulli , C. kaifengense , and C. qilinense . Colletotrichum orbiculare was the dominant species. Pathogenicity tests revealed that all isolates of the species described above were pathogenic, with C. magnum and C. kaifengense being the most aggressive to leaves and fruits, respectively. This is the first report of C. aenigma , C. chlorophyti , C. fructicola , C. jiangxiense , C. nymphaeae , C. nigrum , C. plurivorum , and C. sojae on watermelon. These findings shed light on the Colletotrichum spp. involved in watermelon anthracnose and provide useful information for implementing effective control of watermelon anthracnose in China.

Bombyx mori is an important economic insect, its economic value mainly reflected in the silk yield. The major functional genes affecting the silk yield of B. mori have not been determined yet. Bombyx mori vacuolar protein sorting-associated protein 13d (BmVps13d) has been identified, but its function is not reported. In this study, BmVps13d protein shared 30.84% and 34.35% identity with that of in Drosophila melanogaster and Homo. sapiens, respectively. The expressions of BmVps13d were significantly higher in the midgut and silk gland of JS (high silk yield) than in that of L10 (low silk yield). An insertion of 9 bp nucleotides and two deficiencies of adenine ribonucleotides in the putative promoter region of BmVps13d gene in L10 resulted in the decline of promoter activity was confirmed using dual luciferase assay. Finally, the functions of BmVps13d in B. mori were studied using the CRISPR/Cas9 system, and the mutation of BmVps13d resulted in a 24.7% decline in weight of larvae, as well as a 27.1% (female) decline and a 11.8% (male) decline in the silk yield. This study provides a foundation for studying the molecular mechanism of silk yield and breeding the silkworm with high silk yield., Competing Interests: The authors declare that they have no competing interests.

Background: Xuan-Fu-Hua decoction is a traditional Chinese medicine formula widely used for the treatment of inflammation-related disease in the lung and liver. This study aimed to investigate the effect of Xuan-Fu-Hua decoction treatment on liver cancer cells and its mechanism of action., Methods: The impact of Xuan-Fu-Hua decoction treatment on the proliferation and apoptosis of SMMC-7721 liver cancer cells with or without 5-fluorouracil (5-FU) cotreatment was determined in both in vitro and in vivo settings. Alterations in gene expression patterns in SMMC-7721 cells induced by Xuan-Fu-Hua decoction treatment were explored by transcriptomic sequencing. Effective components of Xuan-Fu-Hua decoction and their target proteins were investigated using network pharmacology approaches., Results: Xuan-Fu-Hua decoction alone did not significantly influence SMMC-7721 liver cancer cell growth, but it significantly increased the 5-Fu-induced growth inhibition and apoptosis of SMMC-7721 liver cancer cells in vitro and in vivo . Most differentially expressed genes in SMMC-7721 liver cancer cells with or without Xuan-Fu-Hua decoction treatment were enriched in cell apoptosis-related pathways. Xuan-Fu-Hua decoction treatment significantly increased the transcription levels of DDIT3, PMAIP1 , and ZMAT3 genes while decreasing that of WNT4, AXIN2, NFE2L2, TGFBR1, MITF , and IGFBP3 genes. An interaction network between the effective components and their possible target proteins was constructed by predicting compound-target protein and protein-protein interactions. Gene set enrichment analysis revealed the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway as well as Bcl-2 and Mcl-1 proteins as potential regulatory targets of Xuan-Fu-Hua decoction in sensitizing SMMC-7721 cells to the cytotoxicity of 5-FU treatment., Conclusions: Xuan-Fu-Hua decoction increased the sensitivity of liver cancer cells to the cytotoxicity of 5-FU treatment, possibly by potentiating cell apoptosis and inhibiting the prosurvival machinery., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-1814/coif). The authors have no conflicts of interest to declare., (2022 Translational Cancer Research. All rights reserved.)

Respiratory syncytial virus (RSV) infection is the most frequent cause of hospitalization in pediatric patients. Current systemic treatment and vaccines are not curative and re-infection is often associated with a more drastic incidence of the disease. Baicalin is a flavonoid isolated from Scutellaria baicalensis with potent anti-viral characteristics, namely against RSV. However, its precise mechanism of action remains unclear. Here, using in vitro methods and an in vivo murine model of RSV infection, we showed that baicalin inhibits RSV replication induces translational upregulation of type I interferons (IFNs), IFN-α and IFN-β, and reverses epithelial thickening in lung tissues. Moreover, baicalin inhibits transcription of the RSV non-structural proteins NS1 and NS2. Molecular docking and surface plasmon resonance-based affinity analysis showed that baicalin also binds to the α3 helix of the NS1 protein with an affinity constant of 1.119 × 10 -5 M. Polysome profiling showed that baicalin inhibits translation of the RSV matrix protein (M) RNA. Baicalin mediates increased release of the ribosomal protein L13a from the large ribosomal subunit, where the extra ribosomal subunit L13a inhibits M RNA translation. These results comprehensively establish the multiple mechanisms by which baicalin induces a potent innate immune response against RSV infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qin, Huang and Qu.)