An unusual aromatase/cyclase programs the formation of the phenyldimethylanthrone framework in anthrabenzoxocinones and fasamycin.

Aromatic polyketides are renowned for their wide-ranging pharmaceutical activities. Their structural diversity is mainly produced via modification of limited types of basic frameworks. In this study, we characterized the biosynthesis of a unique basic aromatic framework, phenyldimethylanthrone (PDA) found in (+)/(-)-anthrabenzoxocinones (ABXs) and fasamycin (FAS). Its biosynthesis employs a methyltransferase (Abx(+)M/Abx(-)M/FasT) and an unusual TcmI-like aromatase/cyclase (ARO/CYC, Abx(+)D/Abx(-)D/FasL) as well as a nonessential helper ARO/CYC (Abx(+)C/Abx(-)C/FasD) to catalyze the aromatization/cyclization of polyketide chain, leading to the formation of all four aromatic rings of the PDA framework, including the C9 to C14 ring and a rare angular benzene ring. Biochemical and structural analysis of Abx(+)D reveals a unique loop region, giving rise to its distinct acyl carrier protein-dependent specificity compared to other conventional TcmI-type ARO/CYCs, all of which impose on free molecules. Mutagenic analysis discloses critical residues of Abx(+)D for its catalytic activity and indicates that the size and shape of its interior pocket determine the orientation of aromatization/cyclization. This study unveils the tetracyclic and non-TcmN type C9 to C14 ARO/CYC, significantly expanding our cognition of ARO/CYCs and the biosynthesis of aromatic polyketide framework.

A nonstructural protein encoded by a rice reovirus induces an incomplete autophagy to promote viral spread in insect vectors.

Viruses can hijack autophagosomes as the nonlytic release vehicles in cultured host cells. However, how autophagosome-mediated viral spread occurs in infected host tissues or organs in vivo remains poorly understood. Here, we report that an important rice reovirus, rice gall dwarf virus (RGDV) hijacks autophagosomes to traverse multiple insect membrane barriers in the midgut and salivary gland of leafhopper vector to enhance viral spread. Such virus-containing double-membraned autophagosomes are prevented from degradation, resulting in increased viral propagation. Mechanistically, viral nonstructural protein Pns11 induces autophagy and embeds itself in the autophagosome membranes. The autophagy-related protein 5 (ATG5)-ATG12 conjugation is essential for initial autophagosome membrane biogenesis. RGDV Pns11 specifically interacts with ATG5, both in vitro and in vivo. Silencing of ATG5 or Pns11 expression suppresses ATG8 lipidation, autophagosome formation, and efficient viral propagation. Thus, Pns11 could directly recruit ATG5-ATG12 conjugation to induce the formation of autophagosomes, facilitating viral spread within the insect bodies. Furthermore, Pns11 potentially blocks autophagosome degradation by directly targeting and mediating the reduced expression of N-glycosylated Lamp1 on lysosomal membranes. Taken together, these results highlight how RGDV remodels autophagosomes to benefit viral propagation in its insect vector.

A plant reovirus hijacks endoplasmic reticulum-associated degradation machinery to promote efficient viral transmission by its planthopper vector under high temperature conditions.

In the field, many insect-borne crop viral diseases are more suitable for maintenance and spread in hot-temperature areas, but the mechanism remains poorly understood. The epidemic of a planthopper (Sogatella furcifera)-transmitted rice reovirus (southern rice black-streaked dwarf virus, SRBSDV) is geographically restricted to southern China and northern Vietnam with year-round hot temperatures. Here, we reported that two factors of endoplasmic reticulum-associated degradation (ERAD) machinery, the heat shock protein DnaJB11 and ER membrane protein BAP31, were activated by viral infection to mediate the adaptation of S. furcifera to high temperatures. Infection and transmission efficiencies of SRBSDV by S. furcifera increased with the elevated temperatures. We observed that high temperature (35°C) was beneficial for the assembly of virus-containing tubular structures formed by nonstructural protein P7-1 of SRBSDV, which facilitates efficient viral transmission by S. furcifera. Both DnaJB11 and BAP31 competed to directly bind to the tubule protein P7-1 of SRBSDV; however, DnaJB11 promoted whereas BAP31 inhibited P7-1 tubule assembly at the ER membrane. Furthermore, the binding affinity of DnaJB11 with P7-1 was stronger than that of BAP31 with P7-1. We also revealed that BAP31 negatively regulated DnaJB11 expression through their direct interaction. High temperatures could significantly upregulate DnaJB11 expression but inhibit BAP31 expression, thereby strongly facilitating the assembly of abundant P7-1 tubules. Taken together, we showed that a new temperature-dependent protein quality control pathway in the ERAD machinery has evolved for strong activation of DnaJB11 for benefiting P7-1 tubules assembly to support efficient transmission of SRBSDV in high temperatures. We thus deduced that ERAD machinery has been hitchhiked by insect-borne crop viruses to enhance their transmission in tropical climates.

Application of Semiconductor Metal Oxide in Chemiresistive Methane Gas Sensor: Recent Developments and Future Perspectives.

The application of semiconductor metal oxides in chemiresistive methane gas sensors has seen significant progress in recent years, driven by their promising sensitivity, miniaturization potential, and cost-effectiveness. This paper presents a comprehensive review of recent developments and future perspectives in this field. The main findings highlight the advancements in material science, sensor fabrication techniques, and integration methods that have led to enhanced methane-sensing capabilities. Notably, the incorporation of noble metal dopants, nanostructuring, and hybrid materials has significantly improved sensitivity and selectivity. Furthermore, innovative sensor fabrication techniques, such as thin-film deposition and screen printing, have enabled cost-effective and scalable production. The challenges and limitations facing metal oxide-based methane sensors were identified, including issues with sensitivity, selectivity, operating temperature, long-term stability, and response times. To address these challenges, advanced material science techniques were explored, leading to novel metal oxide materials with unique properties. Design improvements, such as integrated heating elements for precise temperature control, were investigated to enhance sensor stability. Additionally, data processing algorithms and machine learning methods were employed to improve selectivity and mitigate baseline drift. The recent developments in semiconductor metal oxide-based chemiresistive methane gas sensors show promising potential for practical applications. The improvements in sensitivity, selectivity, and stability achieved through material innovations and design modifications pave the way for real-world deployment. The integration of machine learning and data processing techniques further enhances the reliability and accuracy of methane detection. However, challenges remain, and future research should focus on overcoming the limitations to fully unlock the capabilities of these sensors. Green manufacturing practices should also be explored to align with increasing environmental consciousness. Overall, the advances in this field open up new opportunities for efficient methane monitoring, leak prevention, and environmental protection.

Reactivity and Recyclability of Ligand-Protected Metal Cluster Catalysts for CO2 Transformation.

It remains a significant challenge to construct an integrated catalyst that combines advantages of homogeneous and heterogeneous catalysis with clarified mechanism and high performance. Here we show atomically precise CuAg cluster catalysts for CO2 capture and utilization, where two functional units are combined into the clusters: metal and ligand. Due to atomic resolution on total and local structures of such catalysts to be achieved, which disentangles heterogeneous imprecise systems and permits tracing the reaction processes via experiments coupled with theory, site-specific catalysis induced by metal-ligand synergy can be accurately elucidated. The CuAg cluster catalysts exhibit excellent reactivity and recyclability to forge the C-N bonding from CO2 formylation with secondary amines that can make the cluster catalysts more unique compared with typically homogeneous complexes.

Engineering the Substrate Specificity of a P450 Dimerase Enables the Collective Biosynthesis of Heterodimeric Tryptophan-Containing Diketopiperazines.

Heterodimeric tryptophan-containing diketopiperazines (HTDKPs) are an important class of bioactive secondary metabolites. Biosynthesis offers a practical opportunity to access their bioactive structural diversity, however, it is restricted by the limited substrate scopes of the HTDKPs-forming P450 dimerases. Herein, by genome mining and investigation of the sequence-product relationships, we unveiled three important residues (F387, F388 and E73) in these P450s that are pivotal for selecting different diketopiperazine (DKP) substrates in the upper binding pocket. Engineering these residues in NasF5053 significantly expanded its substrate specificity and enabled the collective biosynthesis, including 12 self-dimerized and at least 81 cross-dimerized HTDKPs. Structural and molecular dynamics analysis of F387G and E73S revealed that they control the substrate specificity via reducing steric hindrance and regulating substrate tunnels, respectively.

[Automatic Delineation of Clinical Target Volume and Organ at Risk by Deep Learning for Prostate Cancer Adaptive Radiotherapy].

Adaptive radiotherapy can modify the treatment plan online based on the clinical target volume (CTV) and organ at risk (OAR) contours on the cone-beam CT (CBCT) before treatment, improving the accuracy of radiotherapy. However, manual delineation of CTV and OAR on CBCT is time-consuming. In this study, a deep neural network-based method based on U-Net was purposed. CBCT images and corresponding mask were used for model training and validation, showing superior performance in terms of the segmentation accuracy. The proposed method could be used in the clinic to support rapid CTV and OAR contouring for prostate adaptive radiotherapy.

Poor recovery of cardiac function in myocardial infarction patients with metabolic syndrome and microalbuminuria.

BACKGROUND: This study aimed to investigate the impact of metabolic syndrome (MetS) with microalbuminuria on the improvement of cardiac function after acute myocardial infarction (AMI). METHODS: Nondiabetic patients with acute ST segment elevation MI (STEMI) who underwent coronary revascularization from 2013 to 2017 were included. They were grouped according to history of MetS and microalbuminuria test results as follows: microalbuminuria/MetS group, normoalbuminuria/MetS group, microalbuminuria/no MetS group, and normoalbuminuria/no MetS group. Left ventricular ejection fraction (LVEF) and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at the 6­month follow-up were measured and the predictive value of MetS with microalbuminuria on recovery of cardiac function was assessed by multivariable logistic regression modeling. RESULTS: A total of 530 STEMI patients were included (average age = 66.6 years). Analysis of covariance showed that LVEF recovery in the normoalbuminuria/no MetS group was better than that of the normoalbuminuria/MetS, microalbuminuria/no MetS, and microalbuminuria/MetS groups (49.22% vs. 48.92% vs. 47.48% vs. 46.99%, respectively, p < 0.001) when acute phase LVEF was the covariable. The NT-proBNP level of the normoalbuminuria/no MetS group at the 6­month follow-up was lower than that of the microalbuminuria/MetS group (p < 0.001). Further regression analysis revealed that there was a lower probability of complete cardiac function recovery after 6 months in patients with microalbuminuria (odds ratio: 0.455) than in patients without microalbuminuria (95% CI: 0.316-0.655, p < 0.001). CONCLUSION: Although post-AMI cardiac function in MetS patients with microalbuminuria can be improved after revascularization, the improvement is not as good as that of patients without microalbuminuria, suggesting that clinical attention should be paid to this subgroup.

Precisely Constructed Silver Active Sites in Gold Nanoclusters for Chemical Fixation of CO2.

Precise control of the composition and structure of active sites in an atom-by-atom fashion remains insuperable for heterogeneous catalysts. Here, we introduce tailor-made catalytic sites for the cycloaddition of CO2 to epoxides achieved by implementing Ag atoms at different levels of liberation in atomically precise Au nanoclusters. Our results reveal that a single open Ag site on the Au19 Ag4 cluster improves the ring-opening of epoxides and sequent CO2 insertion, while the partially exposed Ag site on the Au20 Ag1 cluster exhibits a weak affinity for epoxides and poor efficiency for CO2 capture. Structural tunability imparted by the atom-by-atom tailoring and unusual atomic charges distributed on Au and Ag atoms of the three clusters seem to be crucial for promoting challenging bond cleavages and formations in the chemical utilization of CO2 .

[Application of New Posture Fixation Device Compatible with Magnetic Resonance Simulation Positioning in Head and Neck Radiotherapy].

OBJECTIVE: Whether the developed new type of radiotherapy auxiliary fixation device compatible with the head and neck joint coil can improve the quality of magnetic resonance images in radiotherapy and verify whether it can be applied to clinical treatment. METHODS: The clinical trial selected patients with brain metastases and nasopharyngeal cancer patients, using thermoplastic film and head and shoulder molds for posture fixation, and treatment on the ELekta Versa accelerator. SPSS 20.0 statistical software was used to analyze the data. The measurement data were expressed by X±S, and the t test was used. P<0.05 was considered as statistically significant. RESULTS: Considering the influence of the outer contour of the device, the target dose meets the clinical requirements. The setting error is less than 2 mm in the three translation directions, and the rotation error is less than 2o in the three rotation directions. CONCLUSIONS: There is no statistical difference between the treatment results of patients using the new type of fixation device and the conventional method. The target area threatens the organ dose, and the positioning error meets the treatment requirements.

[Improved Design and Acceptance Test of Localization Couch for New Type of CT Simulator].

Accurate CT simulation is the key link of precision radiotherapy, and the performance of the localization couch of CT simulator directly affects the accuracy of radiotherapy. With the rapid development of precision radiotherapy, conventional large aperture radiotherapy special CT simulator is difficult to meet the needs of precision radiotherapy localization, so most radiotherapy centers choose high-end diagnostic CT machines equipped with a flat tabletop for radiotherapy localization. In clinical work, the performance testing of the CT simulator localization couch is easy to be ignored. In addition, there are some problems such as insufficient precision in transforming the cradle-shaped couch top of diagnostic CT into a special flat couch top for radiotherapy. This paper provided an in-depth description of the improved design and performance test of the localization couch of the first special GE Revolution CT simulator for radiotherapy introduced by West China Hospital of Sichuan University. After the improvement, all the acceptance tests of the localization couch are in line with the standard, and the performance meets the high-precision radiotherapy localization needs of patients with different body weight in the center.

[Application of Statistical Process Control in Evaluation of Performance for Beam-matched Medical Electron Linacs].

Clinically, beam matching can greatly improve the flexibility and efficiency of treating patients between different medical electron linacs. However, in addition to the regular quality assurance (QA) test of the machine performance of linacs, there is still a lack of comprehensive evaluation of the clinical radiotherapy performance of beam-matched linacs. In this paper, the performance of volumetric modulated arc therapy (VMAT) between three closely matched linacs was evaluated by statistical process control (SPC) technology. It was found that the average and median γ passing rates of the VMAT QA processes of the three linacs had little difference, but the process capability levels were at three different levels. The results show that SPC technology can effectively evaluate the performance of beam matching for medical electron linacs, improve the patient-specific VMAT QA processes, and guide clinical decision-making.

Combined construction of injectable tissue-engineered bone with CPC and BMMSCs and its study of repair effect on rabbit bone defect model.

OBJECTIVE: to investigate the combined construction of injectable tissue-engineered bone with calcium phosphate bone cement composite (CPC) and bone marrow mesenchymal stem cells (BMMSCs). METHODS: The proliferation activity of BMMSCs encapsulated was detected by CCK8 method on the 7th day after its self-coagulation by CPC. qRT-PCR was used to detect the expressions of mRNA. The microcapsules of BMMSCs combined with CPC were completely filled in the defect site in the experimental group, and the control group not filled. The two groups were sutured and routinely reared, double upper limb X-ray examination performed after operation. RESULTS: Those of two groups were on the rise over time, which were higher at the 1st, 3rd, 5th and 7th days than those at the previous time points (all P<0.05). The relative expressions of ALP and CALCR at the 7th day were higher than those at the day in BMMSCs combined with the CPC group and BMMSCs group (all P<0.05). The relative expression of CALCR was significantly higher in BMMSCs combined with the CPC group than that in the BMMSCs group on the 7th day (P<0.05). CONCLUSION: With good cell activity and biological activity, the combined construction of the tissue-engineered bone with BMMSCs and CPC can be used as an ideal treatment material for bone tissue repair and connection.

[Preliminary study on monitoring patient-specific volumetric modulated arc therapy quality assurance process with statistical process control methodology on the basis of TG-218 report].

Patient-specific volumetric modulated arc therapy (VMAT) quality assurance (QA) process is an important component of the implementation process of clinical radiotherapy. The tolerance limit and action limit of discrepancies between the calculated dose and the delivered radiation dose are the key parts of the VMAT QA processes as recognized by the AAPM TG-218 report, however, there is no unified standard for these two values among radiotherapy centers. In this study, based on the operational recommendations given in the AAPM TG-218 report, treatment site-specific tolerance limits and action limits of gamma pass rate in VMAT QA processes when using ArcCHECK for dose verification were established by statistical process control (SPC) methodology. The tolerance limit and action limit were calculated based on the first 25 in-control VMAT QA for each site. The individual control charts were drawn to continuously monitor the VMAT QA process with 287 VMAT plans and analyze the causes of VMAT QA out of control. The tolerance limits for brain, head and neck, abdomen and pelvic VMAT QA processes were 94.56%, 94.68%, 94.34%, and 92.97%, respectively, and the action limits were 93.82%, 92.54%, 93.23%, and 90.29%, respectively. Except for pelvic, the tolerance limits for the brain, head and neck, and abdomen were close to the universal tolerance limit of TG-218 (95%), and the action limits for all sites were higher than the universal action limit of TG-218 (90%). The out-of-control VMAT QAs were detected by the individual control chart, including one case of head and neck, two of the abdomen and two of the pelvic site. Four of them were affected by the setup error, and one was affected by the calibration of ArcCHECK. The results show that the SPC methodology can effectively monitor the IMRT/VMAT QA processes. Setting treatment site-specific tolerance limits is helpful to investigate the cause of out-of-control VMAT QA.

Reactivity and Lability Modulated by a Valence Electron Moving in and out of 25-Atom Gold Nanoclusters.

The emergence of atomically precise metal nanoclusters with unique electronic structures provides access to currently inaccessible catalytic challenges at the single-electron level. We investigate the catalytic behavior of gold Au25 (SR)18 nanoclusters by monitoring an incoming and outgoing free valence electron of Au 6s1 . Distinct performances are revealed: Au25 (SR)18 - is generated upon donation of an electron to neutral Au25 (SR)18 0 and this is associated with a loss in reactivity, whereas Au25 (SR)18 + is generated from dislodgment of an electron from neutral Au25 (SR)18 0 with a loss in stability. The reactivity diversity of the three Au25 (SR)18 clusters stems from different affinities with reactants and the extent of intramolecular charge migration during the reactions, which are closely associated with the valence occupancies of the clusters varied by one electron. The stability difference in the three clusters is attributed to their different equilibria, which are established between the AuSR dissociation and polymerization influenced by one electron.

LncRNA LINC00460 promotes the papillary thyroid cancer progression by regulating the LINC00460/miR-485-5p/Raf1 axis.

BACKGROUND: Papillary thyroid cancer (PTC) is the most common malignancy of all thyroid cancers. LncRNA LINC00460 has been proved to play roles in the oncogenesis and progression of various tumors, including papillary thyroid cancer. However, the potential molecular mechanism of LINC00460 in PTC is poorly investigated. RESULTS: LINC00460 was upregulated in PTC tissues and cells. Raf1 was upregulated in PTC tissues, but miR-485-5p was down-regulated. High LINC00460 expression was associated with poor prognosis. LINC00460 knockdown suppressed proliferation, migration, invation and EMT of PTC cells. Bioinformatics prediction revealed that LINC00460 had binding sites with miR-485-5p, which was validated by luciferase reporter assay. In addition, miR-485-5p was confirmed to directly target Raf1 3'-UTR. Moreover, LINC00460 promoted PTC progression by sponging miR-485-5p to elevate the expression of Raf1. Knockdown of LINC00460 restrained tumor growth in vivo. CONCLUSION: LINC00460 induced proliferation, migration, invation and EMT of PTC cells by regulating the LINC00460/miR-485-5p/Raf1 axis, which indicated that LINC00460 may be a potential biomarker and therapeutic target for PTC.

Compressive sensing-based topology identification of multilayer networks.

Recovering network topologies is of great significance in the study of complex networks. In this paper, a method for identifying structures of multilayer networks is proposed via compressive sensing and Taylor expansion. By using this method, the topologies of multilayer networks with unknown node dynamical functions can be identified from a relatively small number of observations. Numerical experiments are provided to show the effectiveness and efficiency of the method on different types of multilayer networks, where the intralayer topology and the interlayer topology of a multilayer network can be identified simultaneously. In particular, the topology of one layer can be identified even when nodes of the other layer are unobservable.

[Feasibility Research of the New Fixation Device Compatible with Head and Neck Coil of MRI for Radiotherapy].

MRI simulation images quality of head and neck coil scanning is better than that of radiotherapy surface coil, but currently the head and neck coil is not compatible with radiotherapy positioning devices. In this paper, a new fixation device is developed based on computer reverse engineering technology, which can be used in combination with head and neck coil. This article focuses on discussing the feasibility of the new device in radiotherapy. The obtained ACR phantom and Cat phantom 504 images were used to analyze MR and CT images quality assurance indicators. The dose attenuation of 6 MV photons was measured using the ionization chamber. The results showed each index met the clinical application requirements of intracranial tumor radiotherapy, thereby it can be used in intracranial tumor radiotherapy.

Low Serum Levels of miR-101 Are Associated with Poor Prognosis of Colorectal Cancer Patients After Curative Resection.

BACKGROUND Recent studies showed low expression of microRNA (miR)-101 in various malignancies. However, the association of serum miR-101 and colorectal cancer (CRC) remains unknown. We investigated diagnostic and prognostic significance of serum miR-101 in CRC. MATERIAL AND METHODS A total of 263 consecutive CRC patients and 126 healthy controls were enrolled in this study. Serum miR-101 levels were measured using real-time quantitative reverse transcription polymerase chain reactions. The association between serum miR-101 level and survival outcome was analyzed. RESULTS Serum miR-101 in CRC patients was significantly lower than in healthy volunteers (P<0.001). Low serum miR-101 level was significantly associated with advanced cancer stage. Moreover, survival analysis demonstrated that patients with a low serum miR-101 had poorer 5-year overall survival than patients with a high serum miR-101 level (p=0.041). Serum miR-101 level also were confirmed as an independent risk factor for CRC in multivariate analysis (hazard ratio, 1.468; 95%CI, 0.981-1.976; p<0.001). CONCLUSIONS Serum miR-101 level was significantly downregulated in CRC patients and was closely correlated with poor clinical outcome, suggesting that serum miR-101 might be a useful diagnostic and prognostic marker for CRC.

[A review of progress of real-time tumor tracking radiotherapy technology based on dynamic multi-leaf collimator].

While radiation treatment to patients with tumors in thorax and abdomen is being performed, further improvement of radiation accuracy is restricted by the tumor intra-fractional motion due to respiration. Real-time tumor tracking radiation is an optimal solution to tumor intra-fractional motion. A review of the progress of real-time dynamic multi-leaf collimator(DMLC) tracking is provided in the present review, including DMLC tracking method, time lag of DMLC tracking system, and dosimetric verification.