Exploring ALK fusion in colorectal cancer: a case series and comprehensive analysis.

Anaplastic lymphoma kinase (ALK) fusion-positive colorectal cancer (CRC) is a rare and chemotherapy-refractory subtype that lacks established and effective treatment strategies. Additionally, the efficacy and safety of ALK inhibitors (ALKi) in CRC remain undetermined. Herein, we examined a series of ALK-positive CRC patients who underwent various lines of ALKi treatment. Notably, we detected an ALK 1196M resistance mutation in a CRC patient who received multiple lines of chemotherapy and ALKi treatment. Importantly, we found that Brigatinib and Lorlatinib demonstrated some efficacy in managing this patient, although the observed effectiveness was not as pronounced as in non-small cell lung cancer cases. Furthermore, based on our preliminary analyses, we surmise that ALK-positive CRC patients are likely to exhibit inner resistance to Cetuximab. Taken together, our findings have important implications for the treatment of ALK-positive CRC patients.

The Property of a Key Amino Acid Determines the Function of Farnesyl Pyrophosphate Synthase in Sporobolomyces pararoseus NGR.

Farnesyl pyrophosphate synthase (FPPS) catalyzes the synthesis of C15 farnesyl diphosphate (FPP) from C5 dimethylallyl diphosphate (DMAPP) and two or three C5 isopentenyl diphosphates (IPPs). FPP is an important precursor for the synthesis of isoprenoids and is involved in multiple metabolic pathways. Here, farnesyl pyrophosphate synthase from Sporobolomyces pararoseus NGR (SpFPPS) was isolated and expressed by the prokaryotic expression system. The SpFPPS full-length genomic DNA and cDNA are 1566 bp and 1053 bp, respectively. This gene encodes a 350-amino acid protein with a predicted molecular mass of 40.33 kDa and a molecular weight of 58.03 kDa (40.33 kDa + 17.7 kDa), as detected by SDS-PAGE. The function of SpFPPS was identified by induction, purification, protein concentration and in vitro enzymatic activity experiments. Structural analysis showed that Y90 was essential for chain termination and changing the substrate scope. Site-directed mutation of Y90 to the smaller side-chain amino acids alanine (A) and lysine (K) showed in vitro that wt-SpFPPS catalyzed the condensation of the substrate DMAPP or geranyl diphosphate (GPP) with IPP at apparent saturation to synthesize FPP as the sole product and that the mutant protein SpFPPS-Y90A synthesized FPP and C20 geranylgeranyl diphosphate (GGPP), while SpFPPS-Y90K hydrolyzed the substrate GGPP. Our results showed that FPPS in S. pararoseus encodes the SpFPPS protein and that the amino acid substitution at Y90 changed the distribution of SpFPPS-catalyzed products. This provides a baseline for potentially regulating SpFPPS downstream products and improving the carotenoid biosynthesis pathway.

Efficient electrochemical reduction of CO2 to CO in a flow cell device by a pristine Cu5tz6-cluster-based metal-organic framework.

The electrochemical reduction of CO2 to CO is a powerful approach to achieving carbon neutrality. Herein, we report a five-nuclear copper cluster-based metal-azolate framework CuTz-1 as an electrocatalyst for the electrochemical CO2 reduction reaction. It achieved a faradaic efficiency (FE) of 62.7% for yielding CO with a partial current density of -35.1 mA cm-2 in flow cell device, which can be preserved for more than ten hours with negligible changes of the current density and FE(CO). Studies of electrocatalytic mechanism studies revealed that the distance of Cu-N was increased, and the coordination number of the Cu ion was reduced, while the oxidation state of Cu was decreased after the electrocatalysis. These findings offer valuable insights into structural changes that influence the performance of the catalyst during the process of the electrochemical reduction of CO2 process.

Cu(II)-Mediated direct 18F-dehydrofluorination of phosphine oxides in high molar activity.

BACKGROUND: The 18F/19F-isotope exchange method employing P(V)-centered prosthetic groups demonstrates advantages in addressing mild one-step aqueous 18F-labeling of peptides and proteins. However, the molar activity (Am) achieved through isotope exchange remains relatively low, unless employing a high initial activity of [18F]F-. To overcome this drawback, our work introduces a novel approach through a Cu-mediated direct 18F-dehydrofluorination of phosphine oxides. This method leverages the straightforward separation of the 18F-labeled product from the phosphine oxide precursors, aiming to primarily increase Am. RESULTS: Through a 19F-dehydrofluorination efficiency test, Cu(OAc)2 was identified as the optimal oxidative metal salt, exhibiting a remarkable 100% conversion within one hour. Leveraging the straightforward separation of phosphine oxide precursors and phosphinic fluoride products, the Am of an activated ester, [18F]4, sees an impressive nearly 15-fold increase compared to the 18F/19F-isotope exchange, with the same initial activity of [18F]F-. Furthermore, this Cu(II)-mediated 18F-dehydrofluorination approach demonstrates tolerance up to 20% solvent water content, which enables the practical radiosynthesis of 18F-labeled water-soluble molecules under non-drying conditions. CONCLUSIONS: The direct 18F-dehydrofluorination of phosphine oxide prosthetic groups has been successfully accomplished, achieving a high Am via Cu(II)-mediated oxidative addition and reductive elimination.

Research Progress for Probiotics Regulating Intestinal Flora to Improve Functional Dyspepsia: A Review.

Functional dyspepsia (FD) is a common functional gastrointestinal disorder. The pathophysiology remains poorly understood; however, alterations in the small intestinal microbiome have been observed. Current treatments for FD with drugs are limited, and there are certain safety problems. A class of active probiotic bacteria can control gastrointestinal homeostasis, nutritional digestion and absorption, and the energy balance when taken in certain dosages. Probiotics play many roles in maintaining intestinal microecological balance, improving the intestinal barrier function, and regulating the immune response. The presence and composition of intestinal microorganisms play a vital role in the onset and progression of FD and serve as a critical factor for both regulation and potential intervention regarding the management of this condition. Thus, there are potential advantages to alleviating FD by regulating the intestinal flora using probiotics, targeting intestinal microorganisms. This review summarizes the research progress of probiotics regarding improving FD by regulating intestinal flora and provides a reference basis for probiotics to improve FD.

Coagulation Status in Women with a History of Missed Abortion.

The purpose of this study assess the status of coagulation function in a large series of reproductive-age women with a history of missed abortion in China. Likewise, we want to explore the association between coagulation and missed abortions, in order to evaluate whether they could be used as early predictive factors for missed abortions. A total of 11,182 women who suffered from missed abortion from Peking University Third Hospital and 5298 healthy age-matched reproductive-age women were enrolled in our study. Coagulation function tests (prothrombin time, activated partial thromboplastin time), fibrinolysis status detection (fibrinogen, D-Dimer), anticoagulation function tests (protein C, protein S and antithrombin III), and lupus anticoagulants (LAC) were examined. In addition, platelet counts were detected by automated hematology analyzer. Platelet aggregation (PAgT) was tested by light transmission aggregometry (LTA). Compared with healthy reproductive-age women, the level of D-Dimer, dRVVT-R, PC, PAgT, and platelet count was higher, and the antithrombin III (AT-III) activity was lower in women with a history of missed abortion. (P < 0.05). A total of 13.1% patients with a history of missed abortion were positive for LAC, and platelet aggregation rates were increased in 47.4% patients. Moreover, multivariate logistic regression analysis showed that D-Dimer, dRVVT-R, AT-III, PC, and PAgT had significant predictive value for missed abortion. In addition, a model based on coagulation function tests for predicting missed abortion was developed. These findings provide evidence of hypercoagulability in patients with a history of missed abortion. Lupus anticoagulant, PAgT, and D-Dimer were the strongest predictors of missed abortion.was to.

A randomized non-inferiority trial of 577nm subthreshold micropulse laser versus half-dose photodynamic therapy for acute central serous chorioretinopathy.

PURPOSE: To compare the effectiveness of 577nm subthreshold micropulse laser (SML) with half-dose photodynamic therapy (Hd-PDT) for acute central serous chorioretinopathy (CSC). METHOD: A non-inferiority clinical trial was performed with a non-inferiority margin of eight letters. Sixty-eight eyes of 68 patients with acute CSC were randomized to the Hd-PDT group or 577 nm SML group. Best-corrected visual acuity (BCVA ), the subretinal fluid (SRF), and the central foveal thickness (CFT) were evaluated at 6 months. RESULTS: The visual acuity significantly improved from 70.38 ± 10.37 at baseline to 83.24 ± 3.03 at 6 months after treatment in the SML group (P < 0.001), from 71.09 ± 10.50 to 84.35 ± 2.09 in the PDT group (P < 0.001). SML was non-inferior to the PDT (mean difference: -0.41, 95% CI: -5.51 - 4.68, P = 0.0021). At the endpoint, CFT was significantly reduced in the two groups, but no statistical difference (P = 0.7694). The complete resolution of SRF reached 82.35% (28/34) in the SML group and 91.18% (31/34) in the PDT group, respectively,but no statistical difference (P = 0.3724). CONCLUSIONS: SML was non-inferiority to half-dose PDT in improving the visual acuity for CSC, and it is a viable alternative, especially when the verteporfin in PDT is unavailable.

A Regulable Polyporous Graphite/Melamine Foam for Heat Conduction, Sound Absorption and Electromagnetic Wave Absorption.

To reduce electromagnetic interference and noise pollution within communication base stations and servers, it is necessary for electromagnetic wave absorption (EWA) materials to transition from coating to multifunctional devices. Up to now, the stable and effective integration of multiple functions into one material by a simple method has remained a large challenge. Herein, a foam-type microwave absorption device assembled with multicomponent organic matter and graphite powder is synthesized by a universal combination process. Melamine and phenolic aldehyde amine work as the skeleton and cementing compound, respectively, in which graphite is embedded in the cementing compound interconnected into the mesoscopic 3D electric conductive and heat conductive network. Interestingly, the prepared flexible graphite/melamine foam (CMF) delivers a great EWA performance, with a great effective absorption bandwidth of 9.8 GHz, ultrathin thickness of 2.60 mm, and a strong absorption reflection loss of -41.7 dB. Moreover, the CMF possesses porosity and flexibility, endowing it with sound absorption ability. The CMF is unique in its integration of EWA, heat conduction, sound absorption, and mechanical robustness, as well as its cost-effective and scalable manufacturing. These attributes make CMF promising as a multifunctional device widely used in communication base stations, servers, and chips protection.

ERp29 Attenuates Nicotine-Induced Endoplasmic Reticulum Stress and Inhibits Choroidal Neovascularization.

Nicotine-induced endoplasmic reticulum (ER) stress in retinal pigment epithelium (RPE) cells is thought to be one pathological mechanism underlying age-related macular degeneration (AMD). ERp29 attenuates tobacco extract-induced ER stress and mitigates tight junction damage in RPE cells. Herein, we aimed to further investigate the role of ERp29 in nicotine-induced ER stress and choroidal neovascularization (CNV). We found that the expression of ERp29 and GRP78 in ARPE-19 cells was increased in response to nicotine exposure. Overexpression of ERp29 decreased the levels of GRP78 and the C/EBP homologous protein (CHOP). Knockdown of ERp29 increased the levels of GRP78 and CHOP while reducing the viability of ARPE-19 cells under nicotine exposure conditions. In the ARPE-19 cell/macrophage coculture system, overexpression of ERp29 decreased the levels of M2 markers and increased the levels of M1 markers. The viability, migration and tube formation of human umbilical vein endothelial cells (HUVECs) were inhibited by conditioned medium from the ERp29-overexpressing group. Moreover, overexpression of ERp29 inhibits the activity and growth of CNV in mice exposed to nicotine in vivo. Taken together, our results revealed that ERp29 attenuated nicotine-induced ER stress, regulated macrophage polarization and inhibited CNV.

Changes in the choroid detected by ultrawide-field optical coherence tomography angiography in type 2 diabetes mellitus patients without diabetic retinopathy.

AIM: The study objective was to investigate the choroidal changes in type 2 diabetes mellitus (T2DM) patients without diabetic retinopathy (DR). METHODS: This was a cross-sectional study. Controls without diabetes and T2DM patients without DR (NDR) were included. Ultrawide-field (24 × 20 mm2) optical coherence tomography angiography (OCTA) was performed to analyse choroidal thickness and vessel density. All OCTA images were divided into 3 × 3 grids. The grid centre was considered the central area, while the rest was defined as the peripheral area. RESULTS: No differences between groups were observed in the flow density of the choriocapillaris (CC), choroidal thickness (ChT) and choroidal vascular index (CVI) of the large and medium choroidal vessel (LMCV) in the central area. In the eight peripheral areas, the mean flow density of the CC did not differ between the groups, while the mean CVI and ChT were decreased in the NDR group (P< 0.05). In each peripheral area, the mean CVI and ChT were decreased in the NDR group (P< 0.05, except in the infratemporal area and nasal area for ChT and in the infratemporal area for CVI). In the correlation analysis, both mean peripheral CVI and ChT correlated with age and the duration of diabetes. CONCLUSION: Early choroidal lesions tended to be peripheral in the LMCV in patients with diabetes without DR and correlated with age and the duration of diabetes.

Serum exosomal microRNA-1258 may as a novel biomarker for the diagnosis of acute exacerbations of chronic obstructive pulmonary disease.

Acute exacerbation chronic obstructive pulmonary disease (AECOPD) has a high mortality rate. However, there is no efficiency biomarker for diagnosing AECOPD. The purpose of this study was to find biomarkers that can quickly and accurately diagnose AECOPD.45 normal controls (NC), 42 patients with stable COPD (SCOPD), and 66 patients with AECOPD were enrolled in our study. Serum exosomes were isolated by ultracentrifuge and verified by morphology and specific biomarkers. Fluorescent quantitation polymerase chain reaction (qRT-PCR) was used to detect the expression of micro RNAs (miRNAs), including miR-660-5p, miR-1258, miR-182-3p, miR-148a-3p, miR-27a-5p and miR-497-5p in serum exosomes and serum. Logistic regression and machine learning methods were used to constructed the diagnostic models of AECOPD. The levels of miR-1258 in the patients with AECOPD were higher than other groups (p < 0.001). The ability of exosomal miR-1258 (AUC = 0.851) to identify AECOPD from SCOPD was superior to other biomarkers, and the combination of exosomal miR-1258 and NLR can increase the AUC to 0.944, with a sensitivity of 81.82%, and specificity of 97.62%. The cross-validation of the models displayed that the logistic regression model based on exosomal miR-1258, NLR and neutrophil count had the best accuracy (0.880) in diagnosing AECOPD from SCOPD. The three most correlated biomarkers with serum exosome miR-1258 were neutrophil count (r = 0.57, p < 0.001), WBC (r = 0.50, p < 0.001) and serum miR-1258 (r = 0.33, p < 0.001). In conclusion, serum exosomal miR-1258 is associated with inflammation, and can be used as a valuable and reliable biomarker for the diagnosis of AECOPD, and the establishment of diagnostic model based on miR-1258, NLR and neutrophils count can help to improving the accuracy of AECOPD diagnosis.

A lateral flow immunoassay method for the rapid detection of acetochlor and alachlor in vegetable oil by sensitivity enhancement by using dimethyl-ß-cyclodextrin.

Acetochlor is an endocrine disruptor. The acetochlor residue is strongly lipophilic and can be enriched into products during the manufacturing process. In this study, we found that dimethyl-ß-cyclodextrin (DM-ß-CD) solution could decrease the apparent oil/water partition coefficient (Koil-w) of acetochlor and increase the sensitivity of fluorescence lateral flow immunoassay (LFIA) for acetochlor simultaneously. Based on this, a simple LFIA method for the determination of acetochlor and alachlor residues in vegetable oil was established. The detection process only involves vortex mixing of an oil sample and dimethyl-ß-cyclodextrin solution in a 1 : 3 (V/V) ratio, loading the water phase onto the immunoassay strips and reading the results. Under optimized conditions, the LOD for acetochlor in oil was 3.53 ng g-1, and the working range was 12.03-2000.00 ng g-1. The recoveries of spiked samples ranged from 91.69% ± 1.12% to 112.23% ± 2.20%. Meanwhile, the cross reactivity for alachlor was 108.22%, while for other investigated acetochlor analogues it was less than 1%, and the recoveries of alachlor were from 92.90% ± 8.03% to 113.53% ± 3.40%, which indicate that this method can detect acetochlor and alachlor simultaneously. Compared with the traditional detection method, the pre-treatment process of the proposed method is "green" and simple, and can be applied to the on-site rapid detection of acetochlor and alachlor in vegetable oil and can provide inspiration for the detection of other lipophilic pollutants.

Regulation of cell differentiation to promote pullulan synthesis in Aureobasidium pullulans NG.

Pullulan is a polymer produced by Aureobasidium spp. The yield of pullulan production can be impacted by the cellular differentiation of Aureobasidium spp., which changes with alterations in the growth environment. To improve pullulan yield, identifying key factors that regulate cellular differentiation is crucial. In this study, the main form of pullulan synthesis in Aureobasidium pullulans NG was through swollen cells (SC). The results showed that citric acid (CA) can regulate the cellular differentiation of Aureobasidium pullulans NG by accumulating higher levels of CA in the cells to maintain growth in SC form and increase pullulan production. The addition of 1.0% CA to Aureobasidium pullulans NG for 96 h resulted in a significant increase in pullulan production, producing 18.32 g/l compared to the control group which produced 10.23 g/l. Our findings suggest that controlling cellular differentiation using CA is a promising approach for enhancing pullulan production in Aureobasidium pullulans. KEY POINTS: • The regulation of cell differentiation in Aureobasidium pullulans NG is demonstrated to be influenced by citric acid. • Intracellular citric acid levels in Aureobasidium pullulans NG have been shown to support the growth of swollen cells. • Citric acid has been found to increase pullulan production in Aureobasidium pullulans NG.

Long-Term Real-World Outcomes of Corneal Changes in Proliferative Diabetic Retinopathy: Panretinal Photocoagulation vs. Intravitreal Conbercept.

PURPOSE: To compare long-term real-world outcomes of corneal thickness (CT) alterations in proliferative diabetic retinopathy (PDR) patients treated with panretinal photocoagulation (PRP) and intravitreal conbercept (IVC). METHODS: This retrospective study included 69 eyes of 69 patients with PDR (42 PRP and 27 IVC). Full corneal thickness (FCT), corneal epithelial thickness (CET) and corneal stromal thickness (CST) measured by anterior segment optical coherence tomography at baseline were compared between groups. These CT changes at last follow-up from baseline were also compared between groups and within each group. RESULTS: During a mean follow-up of more than two years, the IVC group demonstrated a significantly increased corneal thickness from baseline compared to the PRP group in some areas (PRP vs. IVC: FCT 0-2 mm: -0.59 ± 9.31 vs. 5.59 ± 9.23 µm, p = 0.009; CST 0-2 mm: -2.05 ± 8.79 vs. 3.48 ± 7.52 µm, p = 0.015; CST 2-5 mm: -1.78 ± 13.27 vs. 5.68 ± 14.53 µm, p = 0.046). In within-group comparisons, a significantly increased FCT from baseline was found in the 0-2 mm area in the IVC group (p = 0.004), but no significant change was observed in the PRP group (p = 0.691). For CET changes, a significantly increased CT was observed in the 0-2 mm, 2-5 mm and 5-7 mm areas in both groups respectively (all p < 0.05). Regarding CST, an increased CT was found in the 0-2 mm area in the IVC group (p = 0.037), while a decreased trend was observed in 0-2 mm and 2-5 mm areas in the PRP group (all p > 0.05). CONCLUSION: When using PRP or IVC in the long-term management of PDR, CT changes should be considered. This may provide evidence for corneal protection during PDR treatment.

Calpeptin may reverse glucocorticoid-resistance of allergic rhinitis associated with cigarette smoke exposure by down-regulating interferon regulatory factor 1.

Cigarette smoke exposure is an important factor in chronic inflammation in patients with allergic rhinitis (AR); however, the relationship between cigarette smoke and AR-related glucocorticoid resistance requires further study. In mice, calpeptin significantly reduces inflammation of the lower respiratory tract caused by cigarette smoke, but whether it can treat glucocorticoid-resistant AR caused by cigarette smoke requires further research. In this study, we confirmed that cigarette smoke exposure can aggravate the Th2 inflammatory response in AR leading to glucocorticoid resistance. The underlying mechanism may be related to decreased expression of DNA methyltransferase 3a (Dnmt3a), and increased expression of interferon regulatory factor 1 (IRF1). In addition, we found that calpeptin can inhibit the expression of IRF1 and thus treat AR-associated glucocorticoid resistance in rats exposed to cigarette smoke. These data suggest that calpeptin may downregulate IRF1 and therefore treat glucocorticoid resistance in AR-associated with cigarette smoke exposure.

Long-term real-world outcomes of retinal microvasculature changes in proliferative diabetic retinopathy treated with panretinal photocoagulation vs. intravitreal conbercept.

PURPOSE: To compare long-term real-world outcomes of retinal microvasculature changes in proliferative diabetic retinopathy (PDR) treated with panretinal photocoagulation (PRP) vs. intravitreal conbercept (IVC) and to explore the potential factors affecting these changes. METHODS: This study retrospectively included 96 treatment-naïve PDR eyes of 96 type 2 diabetes mellitus patients [59 PRP and 37 IVC]. Baseline characteristics and treatment details were collected. Optical coherence tomography angiography (OCTA) data of macular vessel density (VD) and optic disc capillary density (CD) at baseline and at the last follow-up were compared between groups. The differences between the baseline and the last follow-up OCTA data in each group were also tested for significance. The correlation between the change in each OCTA parameter from baseline and each baseline characteristic/treatment parameter was investigated in each group. RESULTS: During a mean follow-up of two years, greater superficial (SCP) (p = 0.004) and deep capillary plexus (DCP) VD (p < 0.001) were observed in the foveal area in the PRP than in the IVC. Compared to the baseline, SCP VD in the foveal area increased in the PRP (p = 0.012), while an increased SCP VD in some sectors in the parafoveal and perifoveal areas (p < 0.05), rather than the foveal area (p = 0.908), was seen in the IVC. For both groups, eyes with a higher VD/CD at baseline tended to develop capillary dropout more intensively (all p < 0.05). In the IVC group, foveal avascular zone (FAZ) area change showed a negative correlation with baseline FAZ area (p = 0.020), and complementary PRP exerted a negative influence on FAZ area change (p = 0.002). In the PRP group, SCP VD change was positively correlated with follow-up frequency, and was negatively correlated with diastolic blood pressure (all p < 0.05); DCP VD change showed a positive correlation with PRP shot number (p = 0.019). CONCLUSION: The aforementioned microvasculature changes should be considered when PRP or IVC is adopted in PDR long-term management.

Responses of rhizosphere microbial community structure and metabolic function to heavy metal coinhibition.

Metal mineral mining results in releases of large amounts of heavy metals into the environment, and it is necessary to better understand the response of rhizosphere microbial communities to simultaneous stress from multiple heavy metals (HMs), which directly impacts plant growth and human health. In this study, by adding different concentrations of cadmium (Cd) to a soil with high background concentrations of vanadium (V) and chromium (Cr), the growth of maize during the jointing stage was explored under limiting conditions. High-throughput sequencing was used to explore the response and survival strategies of rhizosphere soil microbial communities to complex HM stress. The results showed that complex HMs inhibited the growth of maize at the jointing stage, and the diversity and abundance of maize rhizosphere soil microorganisms were significantly different at different metal enrichment levels. In addition, according to the different stress levels, the maize rhizosphere attracted many tolerant colonizing bacteria, and cooccurrence network analysis showed that these bacteria interacted very closely. The effects of residual heavy metals on beneficial microorganisms (such as Xanthomonas, Sphingomonas, and lysozyme) were significantly stronger than those of bioavailable metals and soil physical and chemical properties. PICRUSt analysis revealed that the different forms of V and Cd had significantly greater effects on microbial metabolic pathways than all forms of Cr. Cr mainly affected the two major metabolic pathways: microbial cell growth and division and environmental information transmission. In addition, significant differences in rhizosphere microbial metabolism under different concentrations were found, and this can serve as a reference for subsequent metagenomic analysis. This study is helpful for exploring the threshold for the growth of crops in toxic HM soils in mining areas and achieving further biological remediation.

The analysis of the function, diversity, and evolution of the Bacillus phage genome.

BACKGROUND: Phages play a pivotal role in the evolution of microbial populations. The interactions between phages and their hosts are complex and may vary in response to host physiology and environmental conditions. Here, we have selected the genomes of some representative Bacillus prophages and lysosomes from the NCBI database for evolutionary analysis. We explored their evolutionary relationships and analyzed the protein information encoded by hundreds of Bacillus phages. RESULTS: We obtained the following conclusions: First, Bacillus phages carried some known functional gene fragments and a large number of unknown functional gene fragments, which might have an important impact on Bacillus populations, such as the formation of spores and biofilms and the transmission of virulence factors. Secondly, the Bacillus phage genome showed diversity, with a clear genome boundary between Bacillus prophages and Bacillus lytic phages. Furthermore, genetic mutations, sequence losses, duplications, and host-switching have occurred during the evolution of the Bacillus phage, resulting in low genome similarity between the Bacillus phages. Finally, the lysis module played an important influence on the process of Bacillus phage cross-species infestation. CONCLUSIONS: This study systematically described their protein function, diversity, and genome evolution, and the results of this study provide a basis for evolutionary diversity, horizontal gene transfer and co-evolution with the host in Bacillus phages.

Surfactants Accelerate Isotope Exchange-Based 18F-Fluorination in Water.

Radiochemical yields (RCYs) of isotope exchange-based 18F-fluorination of non-carbon-centered substrates in water are rationally enhanced by adding surfactants, which increases both the rate constant k and local reactant concentrations. Among 12 surfactants, the cationic surfactant cetrimonium bromide (CTAB) and two nonionic surfactants (Tween 20 and Tween 80) were selected for their superior catalytic effects, namely, electrostatic effects or solubilization effects. For a model substrate, bis(4-methoxyphenyl)phosphinic fluoride, the 18F-fluorination rate constant (k) increased up to 7-fold, while its saturation concentration rose up to 15-fold due to micelle formation, encapsulating 70-94% of the substrate. With 30.0 mmol/L CTAB, the required 18F-labeling temperature of a typical organofluorosilicon prosthesis ([18F]SiFA) decreased from 95 °C to room temperature, achieving an RCY of 22%. For an E[c(RGDyK)]2-derived peptide tracer with an organofluorophosphine prosthesis, the RCY in water at 90 °C achieved 25%, correspondingly increasing the molar activity (Am). After high-performance liquid chromatography (HPLC) or solid-phase purification, the residual selected surfactant concentrations in the tracer injections were well below the FDA DII (Inactive Ingredient Database) limits or the LD50 in mice.

68Ga-Labeled TMTP1 Derivatives with Moderate Hydrophilicity for Positron Emission Tomography of Hepatocellular Carcinoma in High Contrast.

The reported specific positron emission tomography (PET) probes for the diagnosis of highly metastatic hepatocellular carcinoma (HCC) suffer from excessively high background uptake and fast blood clearance. Herein, five 68Ga-labeled polyethylene glycol (PEG)-modified derivatives of the TMTP1 peptide were synthesized. The log D values decreased from -1.70 (non-PEGylated) to -1.97 to -2.94 corresponding to the increase of PEG chain length. Subnanomolar and nanomolar affinities comparable to the non-PEGylated TMTP1 derivative were revealed by the IC50 values in SMMC-7721 cells. [68Ga]Ga-NOTA-PEG2-TMTP1 presented a significantly higher tumor/liver ratio (4.19 ± 0.54, at 30 min post intravenous injection) and tumor/muscle ratio (2.14 ± 0.17) compared to the others and the previously radiolabeled TMTP1 derivatives. Small HCC lesions (<2 mm) in situ were detected with high tumor/liver ratio and low tumor/muscle ratio. The improved pharmacokinetics and blood clearance rate of 68Ga-labeled TMTP1 derivatives indicated that moderate hydrophilicity due to PEGylation contributed to high-contrast PET of HCC.