PD-1/PD-L1 inhibitors for early and middle stage microsatellite high-instability and stable colorectal cancer: a review.

BACKGROUND: Programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are important immune checkpoint molecules that contribute to tumor immune evasion. However, the main treatment modalities for patients with early and intermediate stage colorectal cancer (CRC) are surgery, and the role of PD-1/PD-L1 inhibitors in these patients is not yet clear. Therefore, this study aims to review the treatment progress of PD-1/PD-L1 inhibitors for early- and intermediate-stage microsatellite high-instability (MSI-H) and stable (MSS) colorectal cancer, in order to provide more options for patients with early- and intermediate-stage colorectal cancer. MATERIALS AND METHODS: A scoping review of clinical trial registries ( Clinicaltrials.gov and EU clinical trial registers) and PubMed/Medline database of trials on PD-1/PD-L1 Inhibitors for early and middle-stage MSI-H and MSS CRC was done up to March 2024. RESULTS: A total of 19 trials related to early to mid-stage MSH-I or MSS CRC were included. Among them, 6 trials are in recruiting status, 3 trials are in active, not recruiting status, 3 trials are completed, 1 trial is terminated, and 1 trial is unknown. Of these, 9 trials involve MSI-H type CRC, and 10 trials involve MSS type CRC. Preclinical phase I/II trials are predominant, with only 3 clinical phase III trials. In trials related to MSI-H type CRC, 4 studies involve PD-1/PD-L1 inhibitors combined with neoadjuvant therapy, and 5 studies involve combination therapy. In trials related to MSS type CRC, 3 studies involve PD-1/PD-L1 inhibitors combined with targeted therapy, 2 studies involve PD-1/PD-L1 inhibitors combined with chemotherapy, 1 study involves PD-1/PD-L1 inhibitor combined immunotherapy, 1 study involves PD-1/PD-L1 inhibitors combined with bacterial therapy, and 3 studies involve PD-1/PD-L1 inhibitors combined with comprehensive therapy. As for primary outcome measures, 4 trials select pathological complete response rates, 3 trials select progression-free survival rate, 3 trials select objective response rate, 3 trials select overall survival rate, 4 trials select disease-free survival rate, 1 trial selects clinical complete response rate, and 1 trial selects percentage of participants with a dose-limiting toxicity. CONCLUSION: For early- and middle-stage MSI-H and MSS CRC, PD-1/PD-L1 inhibitors have shown some therapeutic efficacy, as evidenced by phase I/II studies. However, contemporary trial designs exhibit heterogeneity, with relatively few inclusion criteria, the use of various drug combinations and regimens, and significant variations in reported endpoints. Nevertheless, more double-arm, multicenter, randomized controlled trials are still needed to confirm the efficacy of immunotherapy.

Synthesis of cerium-based flame retardant containing phosphorus and its impact on the flammability of polylactic acid.

The synthesis and characterization of [Ce2(PPPA)4(OH)2]·4H2O, wherein PPPA denotes 3-(hydroxy(phenyl)phosphoryl)propanoate, were conducted. Its potential as a flame-retardant additive for poly(L-lactic acid) (PLA) in conjunction with ammonium polyphosphate (APP) was investigated. Remarkably, with just incorporation of the 1 % Ce-complex and 4 % APP, the resulting PLA composite (PLA-8) meets the V-0 standard, exhibiting an impressive limiting oxygen index (LOI) of 29.4 %. Moreover, the introduction of the Ce-complex leads to a significant extension of ignition time (TTI), a significant 24.1 % decrease in total heat release (THR) compared to pure PLA, and a notable increase in residual carbon rate from 0.3 % to 3.51 %. Although PLA-8 exhibits a minor decline of 8.7 % in tensile strength and 3.4 % in elongation at break, respectively, compared to pure PLA, there is a substantial improvement of 32.2 % in Young's modulus and 29.9 % in impact resistance. These results emphasise the potential of cerium-based phosphorus-containing flame retardants, with cerium playing a key role in enhancing the flammability characteristics of PLA. This study contributes to the development of sustainable and fire-resistant materials in polymer chemistry.

Application of bolus tracking: The effect of ROI positions on the images quality of cervicocerebral CT angiography.

Background: Cervicocerebral CT angiography (CTA) using the bolus tracking technique has been widely used for the assessment of cerebrovascular diseases. Regions of interest (ROI) can be placed in the descending aorta, ascending aorta, and the aortic arch. However, no study has compared the arteries and veins display when when the region of interest (ROI) is placed at different sites. In this study, we showed the impact of ROI positions on the image quality of cervicocerebral CTA. Methods: Two hundred and seventy patients who underwent cervicocerebral CTA with bolus tracking technique were randomly divided into three groups based on the position of the ROI placement: ascending aorta (Group 1, n = 90), aortic arch (Group 2, n = 90), and descending aorta (Group 3, n = 90). The scanning parameters and contrast agent injection protocols were consistent across all groups. Three observers independently assessed the objective image quality, while two observers jointly assessed the subjective image quality using a grade scale: poor (grade 1), average (grade 2), good (grade 3), and excellent (grade 4). The differences in intravascular CT values, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), AVCR (arterial venous contrast ratio), and subjective image quality scores were compared among the three groups. Results: The CT values of the intracranial veins (superior sagittal sinus, ethmoid sinus and great cerebral vein) in group 1 were significantly lower than those in group 3 (p < 0.001). However, no significant differences were observed in CT values, SNR and CNR in the internal carotid artery and middle cerebral artery among the three groups. The proportion of images with grade 4 was significantly higher in group 1 than group 2 and 3 (41.1% vs 15.6% and 13.3%, p < 0.001). The proportion of images with grade 1 was significantly lower in group 1 than group 2 and 3 (1.1% vs 6.6% and 17.8%, p < 0.001). Conclusion: The ROI positions for cervicocerebral CTA did not affect the arterial image quality, but venous structures imaging was affected when the ROI was placed in the ascending aorta.

Improving automatic segmentation of liver tumor images using a deep learning model.

Liver tumors are one of the most aggressive malignancies in the human body. Computer-aided technology and liver interventional surgery are effective in the prediction, identification and management of liver neoplasms. One of the important processes is to accurately grasp the morphological structure of the liver and liver blood vessels. However, accurate identification and segmentation of hepatic blood vessels in CT images poses a formidable challenge. Manually locating and segmenting liver vessels in CT images is time-consuming and impractical. There is an imperative clinical requirement for a precise and effective algorithm to segment liver vessels. In response to this demand, the current paper advocates a liver vessel segmentation approach that employs an enhanced 3D fully convolutional neural network V-Net. The network model improves the basic network structure according to the characteristics of liver vessels. First, a pyramidal convolution block is introduced between the encoder and decoder of the network to improve the network localization ability. Then, multi-resolution deep supervision is introduced in the network, resulting in more robust segmentation. Finally, by fusing feature maps of different resolutions, the overall segmentation result is predicted. Evaluation experiments on public datasets demonstrate that our improved scheme can increase the segmentation ability of existing network models for liver vessels. Compared with the existing work, the experimental outcomes demonstrate that the technique presented in this manuscript has attained superior performance on the Dice Coefficient index, which can promote the treatment of liver tumors.

Threading the needle: Achieving simplicity and performance in cellulose alkanoate ω-carboxyalkanoates for amorphous solid dispersion.

Most active pharmaceutical ingredients (APIs) suffer from poor water solubility, often keeping them from reaching patients. To overcome the issues of poor drug solubility and subsequent low bioavailability, amorphous solid dispersions (ASDs) have garnered much attention. Cellulose ester derivatives are of interest for ASD applications as they are benign, sustainable-based, and successful in commercial drug delivery systems, e.g. in osmotic pump systems and as commercial ASD polymers. Synthesis of carboxy-pendant cellulose esters is a challenge, due in part to competing reactions between carboxyls and hydroxyls, forming ester crosslinks. Herein we demonstrate proof-of-concept for a scalable synthetic route to simple, yet highly promising ASD polymers by esterifying cellulose polymers through ring-opening of cyclic succinic or glutaric anhydride. We describe the complexity of such ring-opening reactions, not previously well-described, and report ways to avoid gelation. We report synthesis, characterization, and preliminary in vitro ASD evaluations of fifteen such derivatives. Synthetic routes were designed to accommodate these criteria: no protecting groups, no metal catalysts, mild conditions with standard reagents, simple purification, and one-pot synthesis. Finally, these designed ASD polymers included members that maintained fast-crystallizing felodipine in solution and release it from an ASD at rather high 20 % drug loading (DL).

First Report of Monosporascus cannonballus causing Root Rot and Vine Decline in Watermelon (Citrullus lanatus) in China.

In June 2023, a sudden outbreak root rot and vine decline symptoms was observed during a watermelon (Citrullus lanatus T.) variety demonstration trial located in Taizhou City, Zhejiang Province, China, with an incidence rate ranging from 75% to 100% and an affected area of nearly 2,000 square meters. The disease initially appeared with a rapid and alarming invasion of root rot and vine decline symptoms within watermelon plants. Affected plants exhibited rapid deterioration, showing symptoms of wilting, yellowing and eventual demise, predominantly during the pre-harvest stage. Notably, numerous black, spherical, erumpent perithecia were clearly visible on the watermelon's root epidermis, a characteristic trait of the disease. Symptomatic plant samples were rigorously disinfected with 75% ethanol, and plated on potato dextrose agar medium for incubation at 25°C, successfully isolate two potential strains. These isolates were inoculated in oatmeal agar and incubated in a 25℃ light incubator. After 30 days, mature perithecia, the same as those found on the watermelon's root epidermis, reached a diameter of 500 µm. Each perithecium contained several pear-shaped asci, 56 to 108.5 µm in length and 30.5 to 46.4 µm in width, typically holding 1, rarely 2 ascospores. These characteristics align precisely with the typical strains of Monosporascus cannonballus Pollack and Uecker (1974). Additionally, sequencing the internal transcribed spacer region of ribosomal DNA (ITS) gene (White et al., 1990), large subunit ribosomal RNA (LSU) gene (Rehner and Samuels 1995), and beta-tubulin (TUB) gene (Glass and Donaldson, 1995) were performed. BLAST analysis indicated the highest nucleotide sequence identity with M. cannonballus CBS 586.93 reference sequence (ITS: 100%, JQ771930; TUB: 98.99%, JQ907292). Representative sequences of isolate ZJUP0990-2 from these regions were deposited in GenBank (Accession No.: OR357656 for ITS; OR474500 for LSU; OR365762 for TUB). A multigene phylogenomic analysis (ITS-LSU-TUB) was undertaken to ascertain the exact phylogenetic position of M. cannonballus within the genus Monosporascus. The amalgamation of both morphological and molecular insights consistently reaffirmed the accurate classification of the causative agent as M. cannonballus. To validate the pathogenicity of M. cannonballus, a controlled greenhouse experiment was conducted using watermelon (cv. Nabite) as the subject. Mycelium fragments, harvested from the edge of the colony ZJUP0990-2, were inoculated into oat liquid medium and cultivated under dark conditions at a consistent temperature of 30°C for 7 days. After 20 days, the inoculated plants exhibited root rot and wilting, mirroring the symptoms observed during the field outbreak. In contrast, the control plants did not exhibit any signs of disease. M. cannonballus was successfully re-isolated from the symptomatic roots of the inoculated plants, satisfying Koch's postulates. This experiment was repeated three times. This pathogenic fungus has previously been documented as a menace to melons in various regions including Mexico (Chew-Madinaveitia et al., 2012) and Brazil (Sales et al., 2004), as well as watermelons in Brazil (Sales et al., 2010), northern Mexico (Gaytan-Mascorro et al., 2012), and Saudi Arabia (Karlatti et al., 1997). To our knowledge, this is the first reported presence of M. cannonballus on watermelons in China. This new disease poses a serious threat to watermelon production, potentially leading to severe economic losses and impacting food security.

Antifungal Effect of Bacillus velezensis ZN-S10 against Plant Pathogen Colletotrichum changpingense and Its Inhibition Mechanism.

In order to optimize crop production and mitigate the adverse impacts associated with the utilization of chemical agents, it is necessary to explore new biocontrol agents. Bacillus velezensis has been widely studied as a biocontrol agent because of its efficient and ecofriendly plant disease control mechanisms. This study shows that the strain ZN-S10 effectively reduces the area of leaf spots caused by the pathogen Colletotrichum changpingense ZAFU0163-1, which affects conidia production and germination, inhibits mycelium growth, and induces mycelium deformation. In antifungal experiments with crude extracts, we observed a delay in the cell cycle of conidia, which may be responsible for the inhibition of conidial germination. Among the bioactive metabolites detected through integrated LC-MS- and GC-MS-based untargeted metabolomics, 7-O-Succinyl macrolactin A, telocinobufagin, and surfactin A may be the main antifungal metabolites of strain ZN-S10. The presence of 7-O-Succinyl macrolactin A could explain the cell damage in germ tubes. This is the first report of telocinobufagin detected in B. velezensis. These results are significant for understanding the inhibitory mechanisms employed by B. velezensis and should serve as a reference in the production of biocontrol agents.

Short-term and long-term efficacy in robot-assisted treatment for mid and low rectal cancer: a systematic review and meta-analysis.

OBJECTIVE: This study aims to conduct a meta-analysis to evaluate the short-term and long-term therapeutic effects of robot-assisted laparoscopic treatment in patients with mid and low rectal cancer. METHODS: A comprehensive search strategy was employed to retrieve relevant literature from PubMed, NCBI, Medline, and Springer databases, spanning the database inception until August 2023. The focus of this systematic review was on controlled studies that compared the treatment outcomes of robot-assisted (Rob) and conventional laparoscopy (Lap) in the context of mid and low rectal cancer. Data extraction and literature review were meticulously conducted by two independent researchers (HMW and RKG). The synthesized data underwent rigorous analysis utilizing RevMan 5.4 software, adhering to established methodological standards in systematic reviews. The primary outcomes encompass perioperative outcomes and oncological outcomes. Secondary outcomes include long-term outcomes. RESULT: A total of 11 studies involving 2239 patients with mid and low rectal cancer were included (3 RCTs and 8 NRCTs); the Rob group consisted of 1111 cases, while the Lap group included 1128 cases. The Rob group exhibited less intraoperative bleeding (MD = -40.01, 95% CI: -57.61 to -22.42, P < 0.00001), a lower conversion rate to open surgery (OR = 0.27, 95% CI: 0.09 to 0.82, P = 0.02), a higher number of harvested lymph nodes (MD = 1.97, 95% CI: 0.77 to 3.18, P = 0.001), and a lower CRM positive rate (OR = 0.46, 95% CI: 0.23 to 0.95, P = 0.04). Additionally, the Rob group had lower postoperative morbidity rate (OR = 0.66, 95% CI: 0.53 to 0.82, P < 0.0001) and a lower occurrence rate of complications with Clavien-Dindo grade ≥ 3 (OR = 0.60, 95% CI: 0.39 to 0.90, P = 0.02). Further subgroup analysis revealed a lower anastomotic leakage rate (OR = 0.66, 95% CI: 0.45 to 0.97, P = 0.04). No significant differences were observed between the two groups in the analysis of operation time (P = 0.42), occurrence rates of protective stoma (P = 0.81), PRM (P = 0.92), and DRM (P = 0.23), time to flatus (P = 0.18), time to liquid diet (P = 0.65), total hospital stay (P = 0.35), 3-year overall survival rate (P = 0.67), and 3-year disease-free survival rate (P = 0.42). CONCLUSION: Robot-assisted laparoscopic treatment for mid and low rectal cancer yields favorable outcomes, demonstrating both efficacy and safety. In comparison to conventional laparoscopy, patients experience reduced intraoperative bleeding and a lower incidence of complications. Notably, the method achieves comparable short-term and long-term treatment results to those of conventional laparoscopic surgery, thus justifying its consideration for widespread clinical application.

Bacillus velezensis ZN-S10 Reforms the Rhizosphere Microbial Community and Enhances Tomato Resistance to TPN.

Tomato pith necrosis (TPN) is a highly destructive disease caused by species of the Pseudomonas genus and other bacteria, resulting in a significant reduction in tomato yield. Members of the genus Bacillus are beneficial microorganisms extensively studied in the rhizosphere. However, in most cases, the potential of Bacillus members in controlling TPN and their impact on the rhizosphere microbial composition remain rarely studied. In this study, Bacillus velezensis ZN-S10 significantly inhibited the growth of Pseudomonas viridiflava ZJUP0398-2, and ZN-S10 controlled TPN with control efficacies of 60.31%. P. viridiflava ZJUP0398-2 significantly altered the richness and diversity of the tomato rhizobacterial community, but pre-inoculation with ZN-S10 mitigated these changes. The correlation analysis revealed that ZN-S10 maybe inhibits the growth of nitrogen-fixing bacteria and recruits beneficial bacterial communities associated with disease resistance, thereby suppressing the occurrence of diseases. In summary, the comparative analysis of the rhizosphere microbiome was conducted to explore the impact of ZN-S10 on the composition of rhizosphere microorganisms in the presence of pathogenic bacteria, aiming to provide insights for further research and the development of scientific and eco-friendly control strategies for this disease.

Leucine to tryptophane substitution in the pore helix IIP1 confer sodium channel resistance to pyrethroids and DDT.

Aedes aegypti is responsible for transmitting a variety of arboviral infectious diseases such as dengue and chikungunya. Insecticides, particularly pyrethroids, are used widely for mosquito control. However, intensive used of pyrethroids has led to the selection of kdr mutations on sodium channels. L982W, locating in the PyR1 (Pyrethroid receptor site 1), was first reported in Ae. aegypti populations collected from Vietnam. Recently, the high frequency of L982W was detected in pyrethroid-resistant populations of Vietnam and Cambodia, and also concomitant mutations L982W + F1534C was detected in both countries. However, the role of L982W in pyrethroid resistance remains unclear. In this study, we examined the effects of L982W on gating properties and pyrethroid sensitivity in Xenopus oocytes. We found that mutations L982W and L982W + F1534C shifted the voltage dependence of activation in the depolarizing direction, however, neither mutations altered the voltage dependence of inactivation. L982W significantly reduced channel sensitivity to Type I pyrethroids, permethrin and bifenthrin, and Type II pyrethroids, deltamethrin and cypermethrin. No enhancement was observed when synergized with F1534C. In addition, L982W and L982W + F1534C mutations reduced the channel sensitivity to DDT. Our results illustrate the molecular basis of resistance mediates by L982W mutation, which will be helpful to understand the interacions of pyrethroids or DDT with sodium channels and develop molecular markers for monitoring pest resistance to pyrethroids and DDT.

First report of Trunk Canker Caused by Botryosphaeria dothidea on Cinnamomum camphora in China.

Cinnamomum camphora, an essential woody plant in China, experienced a severe outbreak of trunk canker affecting an area of 540,000 square meters in the Xiaoshan District of Zhejiang province during the early summer of 2022. The observed symptoms included stem canker, dieback, twig blight, and extensive vascular discoloration, with an incidence rate ranging from 45% to 70%. To investigate the etiology of the disease, symptomatic plant samples were subjected to rigorous surface sterilization involving washing with running tap water, followed by surface sterilization using 75% ethanol. The samples were then rinsed twice with sterile distilled water, plated on potato dextrose agar (PDA) medium, and incubated at a temperature of 28°C. The isolated fungi exhibited characteristics consistent with the species Botryosphaeria dothidea. Fungal isolates displayed abundant white aerial mycelium, which darkened to grey after five to seven days, eventually giving rise to black pycnidia. Single hyphal tip cultures of putative two isolates were stored at the Agricultural Experiment Station of Zhejiang University. Conidia formed on pycnidia were one-celled, hyaline, aseptate, and fusiform, with dimensions of 18.34-27.12 µm x 3.77-6.84 µm (average 22.90 µm x 5.20 µm) (one hundred conidia were measured). To determine the fungal species, genomic DNA was extracted from individual isolates ZJUP0868, and subjected to DNA sequence analysis of four gene regions: the internal transcribed spacer (ITS) using the primer-pair ITS4 and ITS1 (White et al., 1990), the large subunit (LSU) gene with LR0R and LR5 (Rehner and Samuels, 1995), the small subunit (SSU) gene with SR1R and SR7 (Zoller et al., 1999), and the translation elongation factor 1-alpha (tef1) with EF1-983F and EF1-2218R (Rehner and Buckley, 2005). Furthermore, DNA sequence analysis of above four genes was performed. BLAST analysis indicated the highest nucleotide sequence identity with Botryosphaeria dothidea CBS 115476 reference sequence (ITS: 99.59%, KF766151; LSU: 99.88%, DQ377852; SSU: 100%, NG_062738; tef1: 98.93%, AY236898). Representative sequences of isolate ZJUP0868 from these regions were deposited in GenBank (ITS: Accession No. OR192838; LSU: Accession No:OR248147; SSU: Accession No:OR248174; tef1: Accession No. OR262053). A phylogenomic analysis was conducted to determine the phylogenetic position of Botryosphaeria dothidea in the family Botryosphaeriaceae. The combined morphological and molecular findings confirmed the identification of the pathogen as Botryosphaeria dothidea. Pathogenicity tests were conducted by stem inoculation of two-year-old Cinnamomum camphora baranches. Mycelial plugs (2-3 mm in diameter) from actively growing colonies of B. dothidea (PDA) were applied to bark of similar size on the middle point of the stems. Inoculated barks were wrapped with Parafilm, while control branches received sterile PDA plugs. Inoculated and control branches (7 each) were maintained in a greenhouse at 28°C. After two weeks, all inoculated plants exhibited dark vascular stem tissue, whereas the control plants remained healthy. B. dothidea was re-isolated from symptomatic tissues, thus fulfilling Koch's postulates. No symptoms were observed in the control branched, and B. dothidea was not re-isolated from their tissues. B. dothidea , the type species of Botryosphaeria (Botryosphaeriaceae, Botryosphaeriales), is commonly associated with cankers and dieback in woody plants. Previous reports have identified Botryosphaeria dothidea as a pathogen causing stem dieback and trunk canker on Glycine max (Chen et al., 2020), Camellia oleifera (Hao et al., 2022), and Gleditsia sinensis (Huang et al., 2020). Additionally, B. dothidea has been reported to cause leave wilt on various plant species in China, including Daimyo oak (Liu et al., 2023) and Cornus officinalis (Zhang et al., 2022). To the best of our knowledge, this is the first report of B. dothidea on C. camphora in China. This findings contribute to a better understanding of the pathogens affecting Cinnamomum camphora in the China.

Silencing of dre4 Contributes to Mortality of Phyllotreta striolata.

The striped flea beetle, Phyllotreta striolata, is one of the most destructive pests of Cruciferae crops worldwide. RNA interference (RNAi) is a promising alternative strategy for pest biological control, which overcomes the weakness of synthetic insecticides, such as pest resistance, food safety problems and toxicity to non-target insects. The homolog of Spt16/FACT, dre4 plays a critical role in the process of gene transcription, DNA repair, and DNA replication; however, the effects of dre4 silencing in P. striolata remain elusive. In this study, we cloned and characterized the full-length dre4 from P. striolata and silenced Psdre4 through microinjection and oral delivery; it was found that the silencing of dre4 contributed to the high mortality of P. striolata in both bioassays. Moreover, 1166 differentially regulated genes were identified after Psdre4 interference by RNA-seq analysis, which might have been responsible for the lethality. The GO analysis indicated that the differentially regulated genes were classified into three GO functional categories, including biological process, cellular component, and molecular function. The KEGG analysis revealed that these differentially regulated genes are related to apoptosis, autophagy, steroid hormone biosynthesis, cytochrome P450 and other signaling pathways. Our results suggest that Psdre4 is a fatal RNAi target and has significant potential for the development of RNA pesticides for P. striolata management.

Effects of Preparation Methods on the Microstructure and Mechanical Properties of Graphene-Reinforced Alumina Matrix Composites.

Recent years have witnessed a growing research interest in graphene-reinforced alumina matrix composites (Al2O3-G). In this paper, to better achieve the dispersion of graphene in composites, a ball milling method for adding raw materials step by step, called stepwise feeding ball milling, was proposed. The Al2O3-1.0 wt % graphene composites were prepared by this stepwise feeding ball milling and hot pressing. Then, the effects of sintering temperature and sintering pressure on the microstructure and mechanical properties of composites were studied. Results showed that the bending strength, fracture toughness and Vickers hardness of composites increased firstly and then decreased with increasing sintering temperature. The mechanical properties of composites were all at their maximum with the sintering temperature of 1550 °C. For example, the bending strength of composites reached 754.20 MPa, which was much bigger than 478.03 MPa at 1500 °C and 364.01 MPa at 1600 °C. Analysis suggested that the strength of composites was mainly related to the grain size, microflaw size and porosity.

The Predictive Value of the Perivascular Adipose Tissue CT Fat Attenuation Index for Coronary In-stent Restenosis.

Objectives: To investigate the association between the perivascular adipose tissue (PVAT) fat attenuation index (FAI) derived from coronary computed tomography angiography (CCTA) and the prevalence of in-stent restenosis (ISR) in patients with coronary stent implantation. Methods: A total of 117 patients with previous coronary stenting referred for invasive coronary angiography (ICA) were enrolled in this retrospective observational analysis. All patients underwent CCTA between July 2016 and November 2021. The deep learning-based (DL-based) method was used to analyze and measure the peri-stent FAI value. Additionally, the relationship between hematological and biochemical parameters collected from all the patients was also explored. The least absolute shrinkage and selection operator (LASSO) method was applied to the most useful feature selection, and binary logistic regression was used to test the association between the selected features and ISR. The predictive performance for ISR of the identified subgroups was evaluated by calculating the area under the curve (AUC) of receiver operator curves plotted for each model. The Pearson correlation coefficient was used to assess the correlation of peri-stent FAI values with degrees of ISR. Results: The peri-stent FAI values in the ISR group were significantly higher than those in the non-ISR group (-78.1 ± 6.2 HU vs. -87.2 ± 7.3 HU, p < 0.001). The predictive ISR features based on the LASSO analysis were peri-stent FAI, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), and high-sensitivity c-reactive protein (hs-CRP), with an AUC of 0.849, 0.632, 0.620, and 0.569, respectively. Binary logistic regression analysis determined that peri-stent FAI was uniquely and independently associated with ISR after adjusting for other risk factors (odds ratio [OR] 1.403; 95% CI: 1.211 to 1.625; p < 0.001). In the subgroup analysis, the AUCs of the left anterior descending coronary artery (LAD), left circumflex coronary artery (LCx), and right coronary artery (RCA) stents groups were 0.80, 0.87, and 0.96, respectively. The Pearson's correlation coefficient indicated a term moderately correlation between ISR severity and peri-stent FAI values (r = 0.579, P < 0.001). Conclusions: The peri-stent FAI can be used as an independently non-invasive biomarker to predict ISR risk and severity after stent implantation.

Molecular and functional characterization of a conserved odorant receptor from Aedes albopictus.

BACKGROUND: The Asian tiger mosquito Aedes albopictus is a competent vector of several viral arboviruses including yellow fever, dengue fever, and chikungunya. Several vital mosquito behaviors (e.g., feeding, host-seeking, mating, and oviposition) are primarily dependent on the olfactory system for semiochemicals detection and discrimination. However, the limited number of studies hampers our understanding of the relationships between the Ae. albopictus olfactory system and the complex chemical world. METHODS: We performed RT-qPCR assay on antennae of Ae. albopictus mosquitoes of different sexes, ages and physiological states, and found odorant receptor 11 (AalbOr11) enriched in non-blood-fed female mosquitoes. Then, we examined the odorant preference with a panel of physiologically and behaviorally relevant odorants in Xenopus oocytes. RESULTS: The results indicated that AalbOr11 could be activated by ten aromatics, seven terpenes, six heterocyclics, and three alcohols. Furthermore, using post-RNA interference (RNAi) hand-in-cage assay, we found that reducing the transcript level of AalbOr11 affected the repellency activity mediated by (+)-fenchone at a lower concentration (0.01% v/v). CONCLUSIONS: Using in vitro functional characterization, we found that AalbOr11 was a broadly tuned receptor. Moreover, we found that AalbOr11 shared a conserved odorant reception profile with homologous Anopheles gambiae Or11. In addition, RNAi and bioassay suggested that AablOr11 might be one of the receptors mediating (+)-fenchone repellency activity. Our study attempted to link odor-induced behaviors to odorant reception and may lay the foundation for identifying active semiochemicals for monitoring or controlling mosquito populations.

Effects of different technical substitutions on reducing replant disease of Radix pseudostella-riae and the underlying mechanism.

Radix pseudostellariae is a traditional Chinese medicinical herb, with tuberous roots being used as a medicine. Serious continuous monoculture problems were suffered from process of artificial and intensive cultivation. To explore the effective technical methods to overcome the monoculture problems, the effects of different technical substitution patterns on soil environment remediation, photosynthetic physiology and yield performance of R. pseudostellariae were assessed under continuous cropping system with four technical substitution treatments in the phase between two crops after the newly harvested R. pseudostellariae (first crop): fallow (RP-F-RP), fallow treated with microbial fertilizer (RP-F-BF), water flooding (RP-WF), and water flooding treated with specific microbial fertilizer (RP-WF-BF). Results showed that RP-WF-BF pattern was the single one that could effectively restore R. pseudostellariae yield under two-year monoculture and three-year monoculture to more than 90% and 70% of the newly planted respectively. All the other patterns did not significantly improve R. pseudostellariae yield under two-year monoculture. The contents of polysaccharide and total saponin in R. pseudostellariae under RP-WF-BF treatment were significantly increased by 15.3% and 16.5% compared with those of the newly planted, respectively. The abundance of beneficial microorganisms in the rhizosphere soil of R. pseudostellariae significantly increased. A reverse pattern occurred for pathogens under RP-WF-BF pattern. Moreover, soil nitrogen cycling was improved. The expression of AOB, nosZ and nirK was increased by 931%, 124% and 100% compared with those in the RP-F-RP pattern, respectively. Soil acidification under RP-WF-BF pattern was alleviated. The alleviation of soil biological and abiotic stress enhanced the stability of the antioxidant enzyme system, thereby improving the growth and development of R. pseudostellariae at the seedling and the early expand stages. The chlorophyll content, leaf area index and photosynthesis rate of leaves were increased, with the dry matter translocation improved and accumulation of underground dry matter accelerated, which ultimately increased yield and quality under RP-WF-BF pattern. In this study, the separate water flooding treatment (RP-WF) and microbial fertilizer treatment (RP-F-BF) failed to significantly reduce the continuous cropping obstacles of R. pseudostellariae, while the combination of them could produce a multiplication effect of sustainable strengthening on rhizosphere environment. The findings suggested that effective technical substitution could reduce replant disease of R. pseudostellariae.

Micro-CT image denoising with an asymmetric perceptual convolutional network.

Micro-CT has important applications in biomedical research due to its ability to perform high-precision 3D imaging of micro-architecture in a non-invasive way. Because of the limited power of the radiation source, it is difficult to obtain a high signal-to-noise image under the requirement of temporal resolution. Therefore, low-dose CT image denoising has attracted considerable attention to improve the image quality of micro-CT while maintaining time resolution. In this paper, an end-to-end asymmetric perceptual convolutional network (APCNet) is proposed to enhance the network's ability to capture and retain image details by improving the convolutional layer and introducing an edge detection layer. Compared with the previously proposed denoising models such as DnCNN, CNN-VGG, and RED-CNN, experiments proved that our proposed method has achieved better results in both numerical indicators and visual perception.

Characterization and Genomic Analysis of ɸSHP3, a New Transposable Bacteriophage Infecting Stenotrophomonas maltophilia.

This study describes a novel transposable bacteriophage, ɸSHP3, continuously released by Stenotrophomonas maltophilia strain c31. Morphological observation and genomic analysis revealed that ɸSHP3 is a siphovirus with a 37,611-bp genome that encodes 51 putative proteins. Genomic comparisons indicated that ɸSHP3 is a B3-like transposable phage. Its genome configuration is similar to that of Pseudomonas phage B3, except for the DNA modification module. Similar to B3-like phages, the putative transposase B of ɸSHP3 is a homolog of the type two secretion component ExeA, which is proposed to serve as a potential virulence factor. Moreover, most proteins of ɸSHP3 have homologs in transposable phages, but only ɸSHP3 carries an RdgC-like protein encoded by gene 3, which exhibits exonuclease activity in vitro Two genes and their promoters coding for ɸSHP3 regulatory proteins were identified and appear to control the lytic-lysogenic switch. One of the proteins represses one promoter activity and confers immunity to ɸSHP3 superinfection in vivo The short regulatory region, in addition to the canonical bacterial promoter sequences, displays one LexA and two CpxR recognition sequences. This suggests that LexA and the CpxR/CpxA two-component system might be involved in the control of the ɸSHP3 genetic switch.IMPORTANCES. maltophilia is an emerging global pathogenic bacterium that displays genetic diversity in both environmental and clinical strains. Transposable phages have long been known to improve the genetic diversity of bacterial strains by transposition. More than a dozen phages of S. maltophilia have been characterized. However, no transposable phage infecting S. maltophilia has been reported to date. Characterization of the first transposable phage, ɸSHP3, from S. maltophilia will contribute to our understanding of host-phage interactions and genetic diversity, especially the interchange of genetic materials among S. maltophilia.

Imaging and clinical features of giant multilocular prostatic cystadenoma: A case report.

RATIONALE: Giant multilocular prostatic cystadenoma (GMPC) is a rare type of prostatic epithelial neoplasm. Thus, the imaging features of this condition are not well known. We report the imaging and clinical manifestations of a case of GMPC. PATIENT CONCERNS: The case reported here relates to a 71-year-old man who complained of urination frequency and excessive urination at night. He underwent computed tomography (CT) and magnetic resonance imaging (MRI) examination before surgery, both tests revealed a mass body in the prostate. DIAGNOSIS: Ultrasound-guided fine needle aspiration was performed and a diagnosis of GMPC was made by histological examination. INTERVENTIONS: The patient received radical pelvic tumor resection successfully. OUTCOMES: Two months after surgery, the follow-up CT and magnetic MRI re-examination found no signs of recurrence. LESSONS: GMPC is a rare prostatic neoplasm with atypical clinical symptoms. MRI provides valuable information about GMPC. In case of a giant multilocular prostatic mass with well-defined boundary and abundant vascularity, benign feature on diffusion-weighted imaging, GMPC should be considered.

Comparative Transcriptome Analysis Reveals the Mechanism Related to Fluazinam Stress of Panonychus citri (Acarina: Tetranychidae).

The use of a large number of chemical acaricides to control these pest mites has led to an increasing problem of pesticide resistance, which has always been the difficulty in integrated pest management (IPM). Fluazinam has a good control effect on Panonychus citri, the serious pest on citrus; however, we only know the mechanism of action of fluazinam as a fungicide and its mechanism of action on mites remains unclear. Through analysis using Illumina high-throughput transcriptomic sequencing and differential expression genes in P. citri treated with fluazinam, 59 cytochrome P450 genes, 23 glutathione s-transferase genes, five carboxylate esterase genes, 11 superoxide dismutase genes and 15 catalase genes were identified. The Gene Ontology enrichment and the enrichment of KEGG results showed that the treatment were enrichment for redox enzyme pathways. Evaluating the efficacy of fluazinam, and analyzing the transcriptome data of P. citri under fluazinam stress, potentially provide a new agent for prevention and control of P. citri, and also preliminary research results for exploring the mechanism of action of fluazinam on P. citri. Given the up-regulated expression levels of genes for Mn-superoxide dismutase and catalase, we speculate that they play an important role in fluazinam-stress action on P. citri.