A biosynthetic gene cluster for chevalone E (1) and its oxidized derivatives have been identified within the genome of the endophytic fungus Aspergillus versicolor 0312, by a mining strategy ...targeting a polyketide-diterpenoid hybrid molecule. The biosynthetic pathway has been successfully reconstituted in the heterologous fungus Aspergillus oryzae. Interestingly, two P450 monooxygenases, Cle2 and Cle4, were found to transform 1 into seven new analogues including 7 and 8 that possess a unique five-membered lactone ring. Furthermore, the replacement of the terpene cyclase gene with that from another fungus led to the production of sartorypyrone D (11), which has a monocyclic terpenoid moiety. Finally, some of the compounds obtained in this study synergistically enhanced the cytotoxicity of doxorubicin (DOX) in breast cancer cells.
The primary purpose of this study was to determine whether elasticity quantification of the levator ani muscle (LAM) using shear wave elastography (SWE) is different between women with and without ...pelvic organ prolapse (POP) and to determine whether LAM elasticity is associated with the prolapse stage or the dimensions of the levator hiatus. The secondary aim was to evaluate the intraobserver and interobserver reliability of LAM elasticity measurements using SWE.
The study participants included 20 women with normal pelvic support and 38 women with prolapse (stages I-III). The levator hiatus was imaged by transperineal 3-dimensional ultrasound, and LAM elasticity and the elastic modulus were measured by SWE at rest and while performing the Valsalva maneuver.
The elastic modulus increased significantly from rest to during to maximal Valsalva maneuver (29.2 versus 54.1 kPa; P < .05) in all women. Levator ani muscle elasticity was significantly higher under prolapse conditions than under normal conditions at rest (27.9 versus 31 kPa; P < .001) but was lower during the maximal Valsalva maneuver than under normal conditions (57.3 versus 53.1 kPa; P < .05). Levator ani muscle elasticity at rest was associated with the hiatus area during the Valsalva maneuver (Spearman r = 0.608; P < .001) and distensibility of the levator hiatus (r = 0.594; P < .001), and the hiatus area decreased as the LAM elastic modulus increased during the maximal Valsalva maneuver (r = -0.414; P < .05). Moreover, LAM elasticity was associated with the severity of prolapse (P < .001).
As a noninvasive quantitative method, SWE, may be used to assess the biomechanical properties of the pelvic floor muscle, providing some research basis for a thorough understanding of POP and its treatment and prevention.
•Baseline default mode network connectivity predict treatment response in depression.•rTMS treatment performs better than other treatment strategies.•Perigenual anterior cingulate cortex plays ...crucial role in treatment response.
Previous neuroimaging studies revealed abnormal resting-state functional connectivity between distributed brain areas in patients with major depressive disorder. Those abnormalities were normalized after treatment. Moreover, the functional connectivity could predict clinical response to those treatments. However, there has currently been no meta-analysis to verify these findings.
The current study aimed to investigate how the resting-state connectivity patterns predict antidepressant response to various treatments across depressive studies by using coordinate-based meta-analysis named activation likelihood estimation. The relevant articles were obtained by searching on PubMed and Web of Science.
Following exclusion criteria of inappropriate studies, seventeen papers with 392 individual depressive patients were included. Those articles contained repetitive transcranial magnetic stimulation (rTMS) treatment, pharmacotherapy, cognitive behavioral therapy (CBT), electroconvulsive therapy (ECT) and transcutaneous vagus nerve stimulation in patients with depression. Meta-analysis revealed that clinical response to all treatments could be predicted by baseline default mode network connectivity in patients with depression. The rTMS treatment had larger effect size compared to other treatment strategies. Furthermore, subgroup meta-analysis showed that the baseline connectivity of perigenual anterior cingulate cortex (pgACC) and ventral medial prefrontal cortex could predict symptoms improvement of rTMS treatment.
More resting-state connectivity studies of CBT and ECT treatment are needed.
This study highlighted crucial role of DMN, especially the pgACC, in understanding the underlying treatment mechanism of depression.
An L1‐type difference scheme on graded meshes for time fractional mixed diffusion‐wave equation with two Caputo derivatives of fractional order
and
is established and analyzed. In particular, the ...solution of governing equation typically exhibits a weak regular behavior at an initial time. A fully discrete numerical scheme based on finite difference method is proposed and detailed theoretical analysis for the scheme is also investigated. The novelty of this paper is to show that the L1‐type difference scheme for the model problem under consideration is temporal second‐order accurate over graded meshes. Numerical tests are presented to support our theoretical results.
Marine picocyanobacteria belonging to Synechococcus are major contributors to the global carbon cycle, however the genomic information of its cold-adapted members has been lacking to date. To fill ...this void the genome of a cold-adapted planktonic cyanobacterium
sp. CS-601 (SynAce01) has been sequenced. The genome of the strain contains a single chromosome of approximately 2.75 MBp and GC content of 63.92%. Gene prediction yielded 2984 protein coding sequences and 44 tRNA genes. The genome contained evidence of horizontal gene transfer events during its evolution. CS-601 appears as a transport generalist with some specific adaptation to an oligotrophic marine environment. It has a broad repertoire of transporters of both inorganic and organic nutrients to survive in inhospitable environments. The cold adaptation of the strain exhibited characteristics of a psychrotroph rather than psychrophile. Its salt adaptation strategy is likely to rely on the uptake and synthesis of osmolytes, like glycerol or glycine betaine. Overall, the genome reveals two distinct patterns of adaptation to the inhospitable environment of Antarctica. Adaptation to an oligotrophic marine environment is likely due to an abundance of genes, probably acquired horizontally, that are associated with increased transport of nutrients, osmolytes, and light harvesting. On the other hand, adaptations to low temperatures are likely due to prolonged evolutionary changes.
This study aimed to analyze the impact of the lockdown period due to COVID-19 pandemic on the mental health status of healthcare workers and identify the related risk factors of psychosomatic ...distress. We conducted an online questionnaire survey to investigate the general demographic characteristics, perceived stress level, adult attachment style (AAS), family cohesion and adaptability, social support, sleep state, emotional state, and physical health of healthcare workers during the lockdown period due to the pandemic in 2022. We compared the mental health status between doctors and nurses, and further analyzed the factors influencing sleep, emotions, physical symptoms, and severe psychosomatic distress separately. For factors that showed statistical significance in the univariate analysis, forward stepwise regression was used for logistic regression analysis to identify risk factors for the corresponding issues. A total of 622 healthcare workers participated in the survey. Among the participants, 121 (19.5%) reported sleep problems, 209 (33.6%) had negative emotional states, and 147 (23.6%) reported physical health problems. There were 48 (7.7%) healthcare workers with severe psychosomatic distress. Compared to the group of nurses, the group of doctors exhibit a higher prevalence of emotional issues, physical health problems and psychosomatic distress. Perceived stress was identified as a risk factor for sleep disturbance, while living with others during quarantine and family adaptability were identified as protective factors. Higher educational background and perceived stress were identified as risk factors for negative emotion, while subjective support was identified as a protective factor. Perceived stress and coming from a rural area were also identified as risk factors for physical health. Overall, for the comparison between the no psychosomatic distress and severe psychosomatic distress groups, perceived stress was identified as a risk factor for severe psychosomatic distress, while subjective support was identified as a protective factor. Healthcare workers' potential mental and physical health problems are related to their educational background, family cohesion and adaptability, perceived stress and social support. This makes it clearer on how to deal with and prevent adverse consequences when facing stressful situations.
ABSTRACT
Roots are fundamental for plants to adapt to variable environmental conditions. The development of a robust root system is orchestrated by numerous genetic determinants and, among them, the ...MADS‐box gene ANR1 has garnered substantial attention. Prior research has demonstrated that, in chrysanthemum, CmANR1 positively regulates root system development. Nevertheless, the upstream regulators involved in the CmANR1‐mediated regulation of root development remain unidentified. In this study, we successfully identified bric‐a‐brac, tramtrack and broad (BTB) and transcription adapter putative zinc finger (TAZ) domain protein CmBT1 as the interacting partner of CmANR1 through a yeast‐two‐hybrid (Y2H) screening library. Furthermore, we validated this physical interaction through bimolecular fluorescence complementation and pull‐down assays. Functional assays revealed that CmBT1 exerted a negative influence on root development in chrysanthemum. In both in vitro and in vivo assays, it was evident that CmBT1 mediated the ubiquitination of CmANR1 through the ubiquitin/26S proteasome pathway. This ubiquitination subsequently led to the degradation of the CmANR1 protein and a reduction in the transcription of CmANR1‐targeted gene CmPIN2, which was crucial for root development in chrysanthemum. Genetic analysis suggested that CmBT1 modulated root development, at least in part, by regulating the level of CmANR1 protein. Collectively, these findings shed new light on the regulatory role of CmBT1 in degrading CmANR1 through ubiquitination, thereby repressing the expression of its targeted gene and inhibiting root development in chrysanthemum.
The BTB/TAZ domain protein CmBT1 functions as a scaffold protein and negatively regulates root development by binding and degrading the MADS‐box protein CmANR1 through the ubiquitin/26S proteasome pathway in chrysanthemum root development.
Gregatin A (1) is a fungal polyketide featuring an alkylated furanone core, but the biosynthetic mechanism to furnish the intriguing molecular skeleton has yet to be elucidated. Herein, we have ...identified the biosynthetic gene cluster of gregatin A (1) in Penicillium sp. sh18 and investigated the mechanism that produces the intriguing structure of 1 by in vivo and in vitro reconstitution of its biosynthesis. Our study established the biosynthetic route leading to 1 and illuminated that 1 is generated by the fusion of two different polyketide chains, which are, amazingly, synthesized by a single polyketide synthase GrgA with the aid of a trans-acting enoylreductase GrgB. Chain fusion, as well as chain hydrolysis, is catalyzed by an α/β hydrolase, GrgF, hybridizing the C11 and C4 carbon chains by Claisen condensation. Finally, structural analysis and mutational experiments using GrgF provided insight into how the enzyme facilitates the unusual chain-fusing reaction. In unraveling a new biosynthetic strategy involving a bifunctional PKS and a polyketide fusing enzyme, our study expands our knowledge concerning fungal polyketide biosynthesis.
To describe contrast-enhanced ultrasound (CEUS) features and evaluate differential diagnosis value of CEUS and conventional ultrasound for patients with benign and malignant gallbladder lesions.
This ...study included 105 gallbladder lesions. Before surgical resection and pathological examination, conventional ultrasound and CEUS were performed to examine for lesions. Then, all the lesions were diagnosed as (1) benign, (2) probably benign, (3) probably malignant or (4) malignant using both conventional ultrasound and CEUS. The CEUS features of these gallbladder lesions were analyzed and diagnostic efficiency between conventional ultrasound and CEUS was compared.
There were total 17 cases of gallbladder cancer and 88 cases of benign lesion. Some gallbladder lesions had typical characteristics on CEUS (
., gallbladder adenomyomatosis had typical characteristics of small nonenhanced areas on CEUS). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of CEUS were 94.1%, 95.5%, 80.0%, 98.8% and 95.2%, respectively. These were significantly higher than conventional ultrasound (82.4%, 89.8%, 60.9%, 96.3% and 88.6%, respectively). CEUS had an accuracy of 100% for gallbladder sludge and CEUS helped in differential diagnosis among gallbladder polyps, gallbladder adenoma and gallbladder cancer.
CEUS may provide more useful information and improve the diagnosis efficiency for the diagnosis of gallbladder lesions than conventional ultrasound.
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