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Defining clinically relevant MET amplification levels in non-small cell lung cancer (NSCLC) remains challenging. We hypothesize that oncogene overlap and MET amplicon size decline with increase in MET plasma copy number (pCN), thus enriching for MET-dependent states.We interrogated cell-free DNA NGS results of 16,782 patients with newly diagnosed advanced NSCLC to identify those with MET amplification as reported using Guardant360. Co-occurring genomic mutations and copy number alterations within each sample were evaluated. An exploratory method of adjusting for tumor fraction was also performed and amplicon size for MET was analyzed when available.MET amplification was detected in 207 (1.2%) of samples. pCN ranged from 2.1 to 52.9. Of these, 43 (20.8%) had an overlapping oncogenic driver, including 23 (11.1%) METex14 skipping or other MET mutations. The degree of (non-MET) oncogene overlap decreased with increases in pCN. Patients with MET pCN ≥ 2.7 had lower rates of overlapping drivers compared to those with MET pCN2.7 (6.1% vs. 16.3%, P = .033). None of the 7 patients with pCN6.7 had an overlapping driver. After adjusting for tumor fraction, adjusted pCN (ApCN) was also lower for those with overlapping drivers than those without (median ApCN 4.9 vs. 7.3, P =.024). There was an inverse relationship between amplicon size and pCN.We propose that a high MET pCN and/or ApCN, together with the absence of overlapping oncogenic drivers and small MET amplicon size, will enrich for patients most likely to derive benefit from MET targeted therapy.

Since there are several limitations in cancer treatment for traditional chemotherapy, such as side effects, poor prognosis and drug resistance, developing new combined therapy is urgently needed. In this work, a biocompatible, simple and tumor microenvironment-responsive nanotheranostics (PCN-Oxpt/PEG) was built to favor the chemotherapy/ferroptosis/immunomodulation synergism in cancer. This nanotheranostics is constructed by modifying oxaliplatin prodrug and PEG on Fe(III) - porphyrin metal-organic frameworks (PCN(Fe) MOFs). After intravenous injection, the cloak of PEG leads to long circulation, and the Fe(III)-porphyrin MOFs enables dual-model guidance with fluorescence (FL) and magnetic resonance imaging (MRI). Inside the tumor, the intracellular H

Graphitic carbon nitride (g-CN) is an attractive electrochemiluminescence (ECL) luminophore. However, g-CN with wavelength-tunable ECL emission is still limited, which limits its application in multicolor ECL sensing and imaging analysis. In this study, porous g-CN (PCN) with nitrogen defects was synthesized through the condensation of melamine by using

PURPOSE This study aimed to evaluate the technical success rate, complications, and radiation doses of ultrasound- and fluoroscopy-guided percutaneous nephrostomy (PCN) in patients with a nondi- lated renal collecting system. METHODS Over a 10-year period, 50 patients were referred for PCN of 60 kidneys with a nondilated renal collecting system. The patients included 22 males and 28 females with a mean age of 63.2 years (range: 35-87 years). The most common reason for PCN in these patients was postoperative ure- teral leaks and/or fistula (21/50 patients). PCN was performed under ultrasound and fluoroscopic guidance. During PCN, intravenous contrast media or diuretics were not used. Technical success rate, complications, procedure time, and radiation exposure of the procedure were retrospec- tively evaluated. RESULTS Ultrasound- and fluoroscopy-guided PCN for nondilated renal collecting system showed a suc- cess rate of 83.3% (50/60 kidneys) in the initial attempt. Four PCNs were repeated and were suc- cessful after the initial PCN failure. There was 1 major complication of bleeding that required transfusion in 1.9% (1/54) PCNs and there were minor complications of transient gross hematuria through the PCN catheter in 31.5% (17/54) PCNs. Mean duration of the procedure was 15.97 ± 7.81 min and median fluoroscopy time was 4.2 min (range: 1.2-15.3 min). Median dose area product and cumulative dose were 345.37 μGy·m2 (range: 42.57-1659.76 μGy·m2) and 46.9 mGy (range: 7.7-267.8 mGy), respectively. CONCLUSION Ultrasound- and fluoroscopy-guided PCN for nondilated renal collecting system was feasible with acceptable technical success rate, complication rate, procedure time, and radiation exposure.

Excessive phosphate poses a serious ecological and human health risk, and thereby, monitoring its trace concentration is of great significance to environmental protection and human health. In this work, a zirconium-porphyrin framework (PCN-222) with excellent stability and unique luminescence properties was designed to modify the surface of the indium tin oxide electrode, which was first used as a photoelectrochemical (PEC) probe for phosphate detection. The PCN-222-modified PEC probe demonstrated an excellent selectivity and stability and indicated a linear response to phosphate in the range of 0-10

Bacterial infection has been a considerable obstacle for diabetic wound healing. A multifunctional nanoplatform used as nanozyme for bacterial infected diabetic wound is extremely attractive. Therefore, gold nanoclusters modified zirconium-based porphyrin metal-organic frameworks (Au NCs@PCN) were constructed by an

Background No data exist on the actual application of pancreatic cystic neoplasm (PCN) guidelines in clinical practice. Aim Disseminate knowledge on existing PCN guidelines and determine which guidelines are prospectively chosen by iCyst app users for different case scenarios. Methods iCyst is a digital tool providing access to the three main existing guidelines (European, IAP, and AGA). Through a case simulation system, for one year, the app prospectively registered users’ guideline choices. Results During the study period, 276 users downloaded iCyst and entered 1020 completed simulations. Most users were European (88%) and were either surgeons (69%) or gastroenterologists (29%). Six different representative scenarios were identified. Overall, the European guidelines were the most commonly preferred (52%). In 16% of cases, the users did not choose any of the available guidelines. Conclusion Digital apps can be used to disseminate guidelines in clinical practice. Guideline dissemination might serve as the basis for future research lines on specific clinical scenarios that iCyst identifies as critical.

In recent studies, phase junctions constructed as photocatalysts have been found to possess great prospects for organic degradation with visible light. In this study, we designed an elaborate rhombohedral corundum/cubic In

The surface grafting of electro-negative cyano groups on polymer carbon nitrides (PCNs) is an effective way to tail their electronic structure. Despite the significant progress in the synthesis of cyano group-enriched PCN, developing a simple and efficient method remains challenging. Here, a facile strategy was developed for fabricating surface cyano-rich PCN (PCN-DM) with a porous structure via chemical vapor modification using diaminomaleonitrile. The cyano groups of diaminomaleonitrile substituted the amino groups on PCN surface via a deamination. The hydrogen production rate of the PCN-DM was approximately 17 times higher than that of pristine PCN. This significant increase in photocatalytic performance could be assigned to the fusion of cyano groups in the surface of PCN, forming new gap states that broadened the visible-light harvesting and accelerated charge separation for photoredox reactions. This study unveils a promising approach for incorporating functional units in the design of novel photocatalysts for efficient hydrogen production.

To evaluate the impact of the first cement kiln co-processing municipal wastes in northwest China on the surrounding environment, the concentrations of polychlorinated naphthalenes (PCNs), polychlorinated biphenyls (PCBs), and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were determined in 17 soil samples collected around the plant. The concentration ranges of PCNs, PCBs, and PCDD/Fs were 132–1288, 10.8–59.5, and 2.50–5.95 pg/g, and the ranges of toxic equivalents (TEQ) were 1.98–20.8, 2.36–48.0, and 73.2–418 fg/g, respectively. The concentrations of PCNs, PCBs, and PCDD/Fs in this study were generally lower than those in soil around municipal waste incinerators and industrial parks in other areas. An exponential function equation was applied for the relationship between the concentration of the target compounds and the distance from the cement kiln stack, the results showed that PCN and PCB concentrations declined with the increasing of distance from the stack. Furthermore, it was found that the effect of the cement kiln on surrounding soil contaminations with PCNs and PCBs was stronger than that of PCDD/Fs by comparing the PCN, PCB, and PCDD/F homologue profiles in the fly ash sample from the plant and soil samples at different distances. The total carcinogenic risks (CR) of PCNs, PCBs, and PCDD/Fs for children and adults in soil were 1.65 × 10−8–8.93 × 10−8 and 1.70 × 10−8–9.16 × 10−8, respectively, which was less than the risk threshold (CR = 1 × 10−6), and there was no health risk.

Animal derived foods are the primary pathway for human exposure to polychlorinated naphthalenes (PCNs), and various foodstuffs have been reported to contain PCNs. However, information on how PCN emission sources affect surrounding animal farms is scarce. The present study determined PCN levels in cow's milk, excrement, feed, plant and soil samples collected from four dairy farms situated within 10 km of an iron smelting plant in China. PCN concentrations in the milk samples from all four farms were in the range from 470 to 797 pg/g lipid weight while the PCN concentrations in the other specimens decreased in the order: plant soil excrement feed. Higher PCN concentrations appeared in silage than in other feedstuffs, and the relationships between PCNs in milk, excrement and feed were closer than those in plant and soil. Human exposure risk to PCNs by consuming milk from this region was relatively higher than in less polluted areas.

The construction of non-viral gene delivery faces two major challenges: cytotoxicity caused by high cationic charge units and easy degradation by lysosomes. Herein, highly water-dispersible polymeric carbon nitride (PCN) nanosheets were utilized as the core to construct a light-controlled non-cationic gene delivery system with sufficient lysosomal escape ability. In this system, these nanosheets exhibited efficient DNA condensation, outstanding biocompatibility, transfection tracking, light responsiveness and high transfection efficiency. Once PCN-DNA was taken up by the tumor cells, the accumulated ROS generated by photosensitizers (PSs) under light irradiation would destroy the structure of lysosomes, promote the escape of PCN-DNA and increase the efficiency of gene transfection. Simultaneously, the gene transfection process could be tracked in real time through fluorescence imaging technology, which was conducive to investigate the transfection mechanism.

With the progress of imaging technology and the popularization of healthy examination, the detection rate of pancreatic cystic neoplasm(PCN) has increased significantly. PCN has complex disease spectrum, strong heterogeneity, and diverse surgical treatment strategies. Surgical timing and methods directly affect patients' prognosis. Therefore, how to identify malignant tumors and formulate reasonable treatment strategies are the keys to treat PCN. Many guidelines for clinical diagnosis and treatment of PCN have been released, but there are still many disputes about its surgical indications. Hence, fully assessing the surgical indications is of great significance to improve the PCN patients' prognosis. This paper deeply discusses on the surgical indications of PCN by reviewing the current clinical diagnosis, treatment and research progress of PCN, in order to standardize the diagnosis and treatment of PCN.随着影像学技术的进步及健康体检的普及，胰腺囊性肿瘤（PCN）的检出率呈显著上升趋势。PCN的疾病谱复杂、异质性强，外科治疗策略差异较大。手术时机与方法的选择直接影响着患者的预后，如何识别潜在恶性的肿瘤并制定合理治疗策略是PCN诊治的关键。虽然国内外已发布多个PCN临床诊治相关指南，但其手术指征仍存在诸多争议，给PCN的规范诊治带来一定挑战。因此，充分衡量手术的风险与获益，谨慎把握手术指征对改善PCN患者预后具有重要意义。本文通过总结当前PCN临床诊治与研究的最新进展，深入探讨了PCN手术指征方面的争议，以期进一步规范PCN的诊治。.

As persistent organic pollutants (POPs) newly banned by the Stockholm Convention, polychlorinated naphthalenes (PCNs) have been widely detected in various environmental matrices. To date, however, the occurrence of PCNs in soils and plants in the Arctic environment has not been reported. In the current study, the concentrations and distribution of PCNs in Arctic soils and plants from Svalbard were analyzed. Total PCN concentrations ranged from 5.3 to 2550 pg/g dry weight (dw) in soils and 77 to 870 pg/g dw in plants. The higher levels of PCNs near the research stations and Longyearbyen town highlighted the significant influence of local anthropogenic emission sources. The composition of PCNs in Arctic soils and plants was dominated by lower chlorinated homologues, especially mono- to trichlorinated naphthalenes, which accounted for over 80 % of total PCNs in the soil and plant samples. The correlation analysis indicated the potential influences of total organic carbon (TOC) content on PCN concentrations in the soil, and octanol-air partition coefficients (K

Phenazines are an important class of secondary metabolites and are primarily named for their heterocyclic phenazine cores, including phenazine-1-carboxylic acid (PCA) and its derivatives, such as phenazine-1-carboxamide (PCN) and pyocyanin (PYO). Although several genes involved in the degradation of PCA and PYO have been reported so far, the genetic foundations of PCN degradation remain unknown. In this study, a PCN-degrading bacterial strain, Sphingomonas histidinilytica DS-9, was isolated. The gene pcnH, encoding a novel amidase responsible for the initial step of PCN degradation, was cloned by genome comparison and subsequent experimental validation. PcnH catalyzed the hydrolysis of the amide bond of PCN to produce PCA, which shared low identity (only 26 to 33%) with reported amidases. The K(m) and k(cat) values of PcnH for PCN were 33.22 ± 5.70 μM and 18.71 ± 0.52 s(−1), respectively. PcnH has an Asp-Lys-Cys motif, which is conserved among amidases of the isochorismate hydrolase-like (IHL) superfamily. The replacement of Asp37, Lys128, and Cys163 with alanine in PcnH led to the complete loss of enzymatic activity. Furthermore, the genes pcaA1A2A3A4 and pcnD were found to encode PCA 1,2-dioxygenase and 1,2-dihydroxyphenazine (2OHPC) dioxygenase, which were responsible for the subsequent degradation steps of PCN. The PCN-degradative genes were highly conserved in some bacteria of the genus Sphingomonas, with slight variations in the sequence identities. IMPORTANCE Phenazines have been widely acknowledged as a natural antibiotic for more than 150 years, but their degradation mechanisms are still not completely elucidated. Compared with the studies on the degradation mechanism of PCA and PYO, little is known regarding PCN degradation by far. Previous studies have speculated that its initial degradation step may be catalyzed by an amidase, but no further studies have been conducted. This study identified a novel amidase, PcnH, that catalyzed the hydrolysis of PCN to PCA. In addition, the PCA 1,2-dioxygenase PcaA1A2A3A4 and 2OHPC dioxygenase PcnD were also found to be involved in the subsequent degradation steps of PCN in S. histidinilytica DS-9. And the genes responsible for PCN catabolism are highly conserved in some strains of Sphingomonas. These results deepen our understanding of the PCN degradation mechanism.

Defective functional-group-endowed polymer semiconductors, which have unique photoelectric properties and rapid carrier separation properties, are an emerging type of high-performance photocatalyst for various energy and environmental applications. However, traditional oxidation etching chemical methods struggle to introduce defects or produce special functional group structures gently and controllably, which limits the implementation and application of the defective functional group modification strategy. Here, with the surface carboxyl modification of graphitic carbon nitride (g-C

Precise shaping of metal-organic frameworks (MOFs) is significant in both fundamental coordination chemistry and practical applications, such as catalysis, separation, and biomedicine. Herein, we demonstrated a linker scissoring strategy for precisely shaping MOFs through surface conformational pairing. In this strategy, the bidentate linkers which were designed according to the original tetratopic ligands and the coordination environment of MOF surfaces, were utilized as the covering agents. The shape of these covering agents and the surface conformation of metals onto MOFs restricted them to coordinate on specific MOF facets thus precisely controlling the shape of the MOFs. Different shapes of PCN-608 from nanoplate (PCN-NP) to nanorod (PCN-NR) have been targeted by adding different bidentate linkers. The universality of this strategy was demonstrated by controlling the shapes of the NU-MOFs from nanoplate to nanorod. This strategy provides a new guiding principle to synthesize MOF nanocrystals with controlled shapes.

As the detection rate of pancreatic cystic neoplasms (PCN) increases,recommendations or guidelines for the diagnosis and treatment of PCN have been released from professional organizations.From the perspective of radiology,we compared seven guidelines in terms of general introduction,preoperative monitoring methods and strategies,stratification of risk factors,surgical indications,and postoperative follow-ups,aiming to provide references for the evaluation of images and the formulation of individualized approach for the treatment of PCN.

In order to develop an attractive generation of bulky oxadithiolate-bridged [FeFe]‑hydrogenase mimics with chelating diphosphines, two new series of asymmetrically diphosphine-substituted diiron model complexes [Fesub2/sub(μ-Rsub2/subodt)(CO)sub4/sub(κsup2/sup-diphosphine)] (3-5) with bulky Phsub2/subodt bridge and their reference counterparts (6-8) with common odt bridge were obtained from the Mesub3/subNO-assisted substitutions of diiron hexacarbonyl precursors [Fesub2/sub(μ-Rsub2/subodt)(CO)sub6/sub] (Rsub2/subodt = (SCHR)sub2/subO, R = Ph (1) and H (2)) with different diphosphines such as (Phsub2/subP)sub2/subNBn (labelled PNsupBn/supP, Bn = benzyl), (Phsub2/subPCHsub2/sub)sub2/subNBn (PCNsupBn/supCP), and (Phsub2/subPCHsub2/sub)sub2/subCHsub2/sub(DPPP)), respectively. All the as-prepared complexes have been characterized by elemental analysis, IR plus NMR spectroscopies, and particularly by X-ray crystallography for 3-8. It is interesting to note that complexes 3 and 6 chelating by small bite-angle PNsupBn/supP diphosphine have the favorable dibasal isomer whereas analogues 4, 5 and 7, 8 chelating by flexible backbone PCNsupBn/supCP or DPPP ligands possess the main apical-basal isomer in solution or in the solid state. Further, the electrochemical properties of two pairs of representative complexes 3, 6 and 5, 8 are explored and compared by cyclic voltammetry (CV) in the absence and presence of trifluoroacetic acid (CFsub3/subCOsub2/subH) as proton source, indicating that the complete protonations of 3, 6 and 5, 8 with higher concentration of CFsub3/subCOsub2/subH lead to two new catalytic waves for the electrocatalytic proton reduction to hydrogen (Hsub2/sub).

To develop and validate a coding framework to identify interventions for upper tract obstructive uropathy (UTOU) in men with locally advanced and metastatic prostate cancer (PCa) using administrative hospital data to assess clinical outcomes. There are no population-based studies on the incidence, treatment, and outcomes of this complication.Patients newly diagnosed with PCa between April 2014 and March 2019 were identified in the English cancer registry. A coding framework based on procedure (Office of Population Censuses and Surveys Classification of Surgical Operations and Procedures fourth edition) and diagnostic (International Classification of Diseases, 10th edition) codes was developed and validated. Subsequent clinical outcomes were determined using Hospital Episodes Statistics to determine the utility of the intervention.A total of 77 010 patients newly diagnosed with locally advanced, and 30 083 patients with metastatic PCa were identified. Of these, 1951 (1.8%) patients underwent an intervention for UTOU according to our coding framework: 830 (42.5%) had locally advanced disease and 1121 (57.5%) had metastatic disease. In all, 844 (43.3%) had a percutaneous nephrostomy (PCN), 473 (24.2%) had a PCN with antegrade stent, and 634 (32.5%) had a retrograde stent. The mean follow-up was 43.2 months. The cumulative incidence of the use of these interventions at 1, 3, and 5 years was 2.5%, 3.6% and 4.2% in men with metastases compared to 0.5%, 0.9% and 1.4% in men with locally advanced disease.A new coding framework, developed to identify procedures for UTOU was applied in the largest study to date of UTOU in men with primary locally advanced and metastatic PCa. Results demonstrated that 2% of men with locally advanced PCa and 4% of men with metastatic PCa require an intervention to resolve UTOU within 5 years of their PCa diagnosis.

Purpose To identify the predictors of nadir serum creatinine (SCr) after drainage of bilaterally obstructed kidneys (BOKs) by different modes: double-J stent (JJ) versus percutaneous nephrostomy (PCN) and unilateral versus bilateral drainage. Methods A prospective non-randomized study was performed on patients with BOKs and raised SCr during December 2019–November 2021. Relevant variables were studied for improvement and non-improvement and for benign and malignant underlying obstructions (BUO and MUO). Results This study included 107 patients with BOKs including 68 (63.6%) males and 39 (36.4%) females. After drainage, 86 (80.4%) patients get improved, while 21 (19.6%) patients failed to reach a nadir SCr. Drainage by PCN was significantly higher in MUO, while JJ was significantly higher in BUO (p p = 0.03). In contrast, mode of drainage had no significant effect on improvement in BUO (p = 0.84), but bilateral drainage was a significant factor of rapid time to nadir (p = 0.02). Univariate analyses revealed no significant effects on the improvement in SCr from the studied variables, except the male gender (p = 0.01), old age (p p = 0.01), unilateral drainage (p p p = 0.01) and MUO (p Conclusions Male gender, old age, MUO, unilateral drainage, and drainage by PCN were significant predictors of non-improvement in SCr after drainage of BOKs. However, unilateral drainage and MUO were the only independent predictors of non-improvement.

Bacteriocins are a large family of peptides synthesized ribosomally by a variety of bacterial species. The genome of one of the thermophilic Gram-positive bacteria, Aeribacillus pallidus PI8, was found to possess an operon comprising five genes possibly involved in the production of a putative bacteriocin that was named pcnABCDE for the production of "pallidocyclicin." This study investigated the function of the pcn operon experimentally. The heterologous expression of the entire pcn operon from the plasmid was toxic to Escherichia coli but not to Bacillus subtilis. However, when the entire pcn operon was expressed constitutively, even the growth of B. subtilis was impaired, and at least pcnA was implied to serve as the precursor of pallidocyclicin. In addition, a strain of B. subtilis expressing the entire pcn operon from the plasmid showed toxicity to another thermophilic species, Geobacillus kaustophilus, at elevated temperatures, whereas another strain lacking pcnE alone from the pcn operon lost the toxicity, suggesting that pcnE might be involved in the biosynthesis of pallidocyclicin when it is produced in B. subtilis.

The design of new aggregation-induced emission luminogens (AIEgens) has aroused continuous attention. The relationship between structure and performance plays an important role in guiding such efforts. In this contribution, two R-D-A- and R-D-π-A-type AIEgens were facilely designed and synthesized, that is

Atmospheric ozone has long been a threat to human health, however, rational design of high-performance O3-decomposition catalysts remains challenging. Herein, we demonstrate the great potential of a series of isomorphous bimetallic MOFs denoted as PCN-250(Fe2M) (M = Co2+, Ni2+, Mn2+) in catalytic O3 decomposition. Particularly, PCN-250(Fe2Co) showed 100% O3 removal efficiency for a continuous air flow containing 1 ppm O3 over a wide humidity range (0 ‒ 80% RH) at room temperature. Mechanism studies suggested that the high catalytic performance originated from the introduction of open Co(II) sites as well as its porous structure. Additionally, at low pressures around 10 Pa, PCN-250(Fe2Co) exhibited high adsorption capacities (89 ‒ 241 mg g−1) for most VOCs, which are not only a class of hazardous air pollutants but also the precursor of O3. This work opens up a new avenue to develop advanced air purification materials for O3 and VOCs removal in one.

Research Highlight: Trzcinski, M., Cockle, K., Norris, A., Edworthy, A., Wiebe, K.,Martin, K. (2022). Woodpeckers maintain the diversity of cavity-nesting vertebrates in a temperate forest. Journal of Animal Ecology, https://doi.org/10.1111/1365-2656.13626. Whether populations of hole-nesting birds are limited by the availability of cavities is a long-standing, fundamental question in avian community ecology. The structure of cavity-nesting communities, known as nest webs, includes links between tree species that provide natural holes and bird species that nest in those holes (secondary cavity nesters, SCNs), tree species that provide substrates for cavity excavation and bird species such as woodpeckers that create cavities using those substrates (primary cavity nesters, PCNs), and between PCNs and SCNs. Trzcinski et al. (2022) focus on the latter links and provide the most compelling empirical evidence to date that cavities created by PCNs specifically, as opposed to natural holes or holes generally, limit populations of SCNs. Using data from a long-term study, the authors employ three analyses to separate effects of availability of cavities from environmental factors such as food, habitat features and host tree abundance, while controlling for annual variation and autocorrelation within sites, to isolate the relationship between excavated cavities and SCN numbers. They show that nest density of SCNs is positively related to PCN nest density the previous year, an indicator of availability of excavated cavities, and that the effect of PCNs is stronger when other variables are accounted for. North American coniferous forests such as that studied by Trzcinski et al. (2022) are exceptional in that excavated cavities comprise the vast majority of nesting holes. Whether their findings apply to other systems in which PCNs are a major source of cavities, or to particular PCN-SCN relationships in systems in which excavated cavities account for a much lower proportion of nesting holes remains to be investigated.

The purpose of this study is to assess patients' compliance to recommendations after evaluation of pancreatic cystic neoplasm (PCN) with EUS and investigate how the presence of "worrisome" characteristics including cyst's size, main pancreatic duct dilation and presence of mural nodules might affect the adherence rates of management recommendations.We performed a retrospective cohort study of patients at a private tertiary hospital who were referred for evaluation with EUS over a 5-year period (2015-2019), after the diagnosis of pancreatic cystic neoplasm during radiological imaging.We included 111 patients (mean age 64.1 years, SD = 13.9) with PCN. After the EUS examination, 16 patients were referred for surgical resection, 4 patients needed no further follow up and 91 patients were recommended to follow imaging surveillance. In total, 70 (63.1%) subjects adhered to surveillance recommendations. In the group of subjects who adhered to surveillance, cyst size ≥3cm was found in 27 (38.6%) patients, main pancreatic duct diameter ≥5mm in 12 (17.1%) subjects and only 3 (4.3%) pancreatic cysts demonstrated mural nodules. However, none of the aforementioned cystic "worrisome features" was significantly correlated with increased adherence to follow up (p = 0.709, P = 0.642 and P = 0.630, respectively).Although the majority of patients with PCN adhered to given recommendations after EUS examination, the number of noncompliant subjects was noticeable. The presence of cystic "worrisome" features did not correlate with an increased compliance rate to suggested management plan. Further prospective studies are needed to elucidate the factors that may enhance patients' adherence.

A novel chiral stationary phase (CSP) of Zr-based metal-organic framework, l-Cys-PCN-224, was prepared by one-pot method and applied for the enantioseparation by capillary electrochromatography. The CSP was characterized by X-ray diffraction, thermogravimetric analysis, X-ray photoelectron spectroscopy, Fourier-transform infrared spectra, nitrogen adsorption/desorption, circular dichroism spectrum, zeta-potential, and so on. The results revealed that the CSP had good crystallinity, high specific surface area (2580 m

Atherosclerosis (AS) is the main cause of coronary heart disease, cerebral infarction and peripheral vascular disease, which is an important disease threatening human health. Abnormal levels of protein phosphorylation are closely related to the occurrence and development of diseases. Herein, the ratiometric fluorescence nanosensor (PCN/W- B@BSA) was prepared by using metal-organic frameworks (PCN-224) and fluorescent nanocluster wool-balls, which was applied for ratiometric fluorescence imaging of protein phosphorylation level in the AS mice model. Specific recognition of phosphorylation sites was achieved via specific interaction between active center Zr(IV) and phosphate. Using the two-photon property of porphyrin, the background is significantly reduced, and the sensitivity of imaging analysis is improved by combining with ratio imaging. Bovine serum albumin (BSA) was used to modify the surface of the nanosensor to reduce the non-specific adsorption and improve the biocompatibility of the nanosensor. Finally, the fluorescence nanosensor was successfully apply to fluorescence imaging of protein phosphorylation level in AS mice model, and the results showed that the protein phosphorylation level in the AS mice model was lower than that of the normal mice. The present study provides suitable fluorescence tool for further revealing phosphorylation related signaling pathways and disease mechanisms.

Magnetic composites of Fe

A fluorescence and photothermal dual-signal assay was developed for the determination of ascorbic acid (AA). Cerium/polyacrylic acid modified porphyrin metal-organic frameworks (PCN-224@PAA-Ce MOFs) exhibit oxidase-like activity and can effectively oxidize 3,3 ', 5,5 '-tetramethylbenzidine (TMB) from colorless substrates to blue substrates (oxTMB). The absorption spectrum of oxTMB overlaps with the emission spectrum of PCN-224@PAA-Ce, resulting in quenching of fluorescence emission of PCN-224@PAA-Ce. oxTMB, as an excellent photothermal agent, converts the optical signal into the thermal signal (temperature increasing) driven by 808 nm laser. In the presence of AA, the blue oxTMB was reduced to colorless TMB, which led to the fluorescence recovery of PCN-224@PAA-Ce and at the same time, the photothermal signal was changed with the temperature decreasing under the driving of 808 nm laser. The detection limits (LOD) of fluorescence/photothermal dual-mode AA sensor strategies were as low as 0.73 μM and 1.4 μM, respectively. Rapid analysis of ascorbic acid was accomplished with the present procedure, AA in vitamin C tablets and human serum samples were validated.

We focus on the following problem: Given a collection of unlabeled facial images, group them into the individual identities where the number of subjects is not known. To this end, a Portable clustering algorithm based on Compact Neighbors called PCN is proposed. (1) Benefiting from the compact neighbor, the local density of each sample can be determined automatically and only one user-specified parameter, the number of nearest neighbors k, is involved in our model. (2) More importantly, the performance of PCN is not sensitive to the number of nearest neighbors. Therefore this parameter is relatively easy to determine in practical applications. (3) The computational overhead of PCN is O(nk(k

Pancreatic cystic neoplasms (PCN) are frequently detected on abdominal images performed for non-pancreatic indications. Their prevalence in asymptomatic population ranges from 2.7 to 24.8%, and increases with age. There are several types of pancreatic cysts. Some may contain cancer or have malignant potential, such as mucinous cystic neoplasms, including mucinous cystadenoma (MCN) and intraductal papillary mucinous neoplasms (IPMN). In contrast, others are benign, such as serous cystadenoma (SCA). However, even those cysts with malignant potential rarely progress to cancer. Currently, the only treatment for pancreatic cysts is surgery, which is associated with high morbidity and occasional mortality. The Board of the Chilean Pancreas Club of the Chilean Gastroenterology Society developed the first Chilean multidisciplinary consensus for diagnosis, management, and surveillance of PCN. Thirty experts were invited and answered 21 statements with five possible alternatives: 1) fully agree; 2) partially agree; 3) undecided; 4) disagree and 5) strongly disagree. A consensus was adopted when at least 80% of the sum of the answers "fully agree" and "partially agree" was reached. The consensus was approved by the Board of Directors of the Chilean Pancreas Club for publication.

Polychlorinated naphthalenes (PCNs) are highly toxic and persistent organic pollutants that can cause adverse effects in the environment and on human health. PCNs have been detected in remote areas because of their long-range transportation. Bees and bee products are commonly used as biomonitors for various pollutants in the environment. However, information on PCNs in apiaries is scarce. The aim of this study was to evaluate the occurrences of PCNs in bees and bee products from apiaries located in different geographical regions of China, and to identify potential pollution sources and assess exposure risks to humans. Our results showed that the average Σ

To examine the effect of a clinic workflow intervention on follow-up for routine ercutaneous nephrostomy tube (PCN) exchanges.An intervention consisting of automated electronic tracking for all PCN placements and exchanges followed by phone call reminders to schedule a follow-up exchange 60 days post-procedure was introduced on March 19, 2019. All PCN exchanges performed from March 19, 2018 to September 18, 2019 were identified through a local electronic database search to assess the impact of intervention as a quality improvement project. Basic demographic information and procedure details were collected. Routine follow-up at our institution is recommended every 90 days. The exchange rates within 90 days were compared between groups using a Chi-squared test.A total of 160 PCN placements or exchanges were performed pre-intervention and 69 PCN exchanges were performed post-intervention. Pre-intervention, 75/160 (46.3%) were exchanged within 90 days compared to 47/69 (68.1%) exchanged within 90 days post-intervention. The remainder had delayed follow-up due to loss to follow-up or scheduling delays. Post-intervention, there was a significantly improved rate of compliance for PCN exchanges within the recommended 90 days at our institution (p-value = 0.002).Automated tracking and phone call follow-up at 60 days post-procedure is a simple and effective intervention that can improve compliance for routine PCN exchanges and reduce the number of patients that are lost to follow-up.

The number of death due to cancer-related diseases each year is at the alarming level and is constantly growing. Tools that can effectively and conveniently detect cancer cell apoptosis can play a significant role in cancer research, cancer therapy, and other related industries. Herein, we fabricated, for the first time, an ultrasensitive, disposable, self-enhanced off-on electrochemiluminescence (ECL) biosensor based on ternary Ru-PEI@PCN-333(Al) system to determine caspase-3 activity, the biomarker of apoptosis. The biosensor had a low detection limit of 0.017 pg/mL and was able to enhance the ECL emission and stability. A solid-state (SS) ECL strategy was adopted to overcome the relatively weak ECL emission due to the long distance between electrochemiluminophore and electrode surface. The analysis requires only one incubation step, which can significantly reduce the operational complexity and time. The biosensor had higher sensitivity, and the off-on ECL mode was achieved using caspase-3 as a switch. The on-site and rapid detection capability of the biosensor was achieved by the introduction of disposable screen-printed electrodes (SPEs). This study lays a foundation for the development of more advanced, ingenious, portable and reliable ECL devices for biosensing not only caspase-3, but also other bioanalytes.

Recent evidence suggests that Nod-like receptor protein-3 (NLRP3) inflammasome is a key mediator of inflammatory response and can induce the activation of apoptosis signaling pathways in ischemic stroke. In this research, we assessed the effects of anfibatide (ANF) on inflammatory and apoptosis in cerebral ischemic injury and the potential mechanisms. Middle cerebral artery occlusion (MCAO) model was established on male Sprague-Dawley rats to induce cerebral ischemia/reperfusion (I/R) injury in vivo. Primary cortical neurons (PCN) cells were exposed to oxygen-glucose deprivation and reintroduction (OGD/R) to mimic cerebral I/R injury in vitro. The results showed that ANF markedly alleviated infarct volume, neurological deficit and neurobehavioral impairment in MCAO/R rats, enhanced cell viability and decreased LDH release in PCN after OGD/R. The number of TUNEL-positive cells, Bax, cleaved-caspase-3, p-IκBα, p-p65, NLRP3, ASC, cleaved caspase-1, IL-β and IL-18 proteins expression were significantly upregulated in the cortex of MCAO/R rats and PCN exposed to OGD/R, NLRP3 and caspase-1 mRNA levels were also evidently elevated. Bcl-2 protein expression significantly decreased in the cortex of MCAO/R rats. Treatment with ANF obviously inhibited the expression of p-IκBα, p-p65, NLRP3, ASC, cleaved caspase-1, Bax and cleaved-caspase-3, promoted the expression of Bcl-2, then decreased the TUNEL-positive cell number and the level of inflammatory cytokines (IL-β and IL-18) in cerebral ischemia reperfusion in vito and in vitro. Our findings suggest that ANF exerts effects of alleviating inflammation and apoptosis through inhibiting NF-kappaB/NLRP3 axis. ANF is a potential candidate for treating cerebral I/R injury.

Hemorrhagic cystitis (HC) can lead to severe morbidity in treatment-refractory cases. Percutaneous nephrostomy (PCN) drainage was first described in 1993 as a safe, nonoperative procedure to achieve supravesical urinary diversion and treat severe HC. Despite its early success, subsequent studies in the adult population have been limited. This retrospective case series describes long-term outcomes following PCN placement in 24 patients with refractory HC. The overall technical success of the procedure was 100%. Seventeen of 24 (71%) patients experienced resolution of hematuria. The median time for hematuria resolution after the procedure was 12 days (interquartile range, 7-28 days). Postprocedural HC severity grade significantly decreased from a median Grade 3 to Grade 1 (P.01). The complications included catheter obstruction, dislodgement, and associated urinary tract infections occurring at rates of 1.0, 1.6, and 1.7 per 1,000 catheter days, respectively. This study of PCN placement demonstrated and further confirmed the effectiveness of urinary diversion in treating refractory HC.

Acute myocardial infarction (AMI), commonly known as a heart attack, is a life-threatening condition that causes millions of deaths every year. In this study, a transistor-based biosensor is developed for rapid and sensitive detection of cardiac troponin-I (cTnI), a diagnostic biomarker of AMI. A biosensing technique based on a field effect transistor (FET), which uses indium gallium zinc oxide (IGZO) as an excellent semiconducting channel, is integrated with nanosheet materials to detect cTnI. Porous carbon nitride (PCN) decorated with gold nanoparticles (Au NPs) is used as a bridge between the solid-state device and the biorecognition element. We demonstrate that this biosensor is highly sensitive and has an experimental limit of detection of 0.0066 ng/mL and a dynamic range of 0.01 ng/mL–1000 ng/mL. This is the first report of a semiconducting metal oxide FET cardiac biomarker sensor combined with PCN for the detection of cTnI. The reported compact microsystem paves the way for rapid and inexpensive detection of cardiac biomarkers.

This work innovatively integrated the peroxidase-mimicking activity and red emission property of Fe@PCN-222 framework, designed a cascade reaction system for dual-mode glucose sensing. The Fe

In aquatic systems, sediment is both a sink for persistent organic pollutants (POPs) and a potential source of POPs release. Consequently, it is important to understand the pollution characteristics and sources of polychlorinated naphthalenes (PCNs) as POPs of Stockholm Convention in sediment for control of the ecological risk. Atmospheric deposition is a potential source of PCNs in sediment. However, there is no clear report on the contribution of atmospheric deposition to PCNs in sediments. In this study, the Chaobai River in China was selected because it is an important drinking water source that is not affected by wastewater discharge. Surface sediments from the river were analyzed for 75 PCN congeners by using high resolution gas chromatography combined with high resolution mass spectrometry. The total PCNs concentration ranged from 54 to 2266 (mean: 402) pg/g. The toxic equivalent quantity of 19 PCNs in surface sediments was 9.69 × 10

Salmonella enterica serovar Typhimurium (STM) is a major cause of gastroenteritis and transmitted by consumption of contaminated food. STM is associated to food originating from animals (pork, chicken, eggs) or plants (vegetables, fruits, nuts, and herbs). Infection of warm-blooded mammalian hosts by STM and the underlying complex regulatory network of virulence gene expression depend on various environmental conditions encountered in hosts. However, less is known about the proteome and possible regulatory networks for gene expression of STM outside the preferred host. Nutritional limitations and changes in temperature are the most obvious stresses outside the native host. Thus, we analyzed the proteome profile of STM grown in rich medium (LB medium) or minimal medium (PCN medium) at temperatures ranging from 8 °C to 37 °C. LB medium mimics the nutritional rich environment inside the host, whereas minimal PCN medium represents nutritional limitations outside the host, found during growth of fresh produce (field conditions). Further, the range of temperatures analyzed reflects conditions within natural hosts (37 °C), room temperature (20 °C), during growth under agricultural conditions (16 °C and 12 °C), and during food storage (8 °C). Implications of altered nutrient availability and growth temperature on STM proteomes were analyzed by HPLC/MS-MS and label-free quantification. Our study provides first insights into the complex adaptation of STM to various environmental temperatures, which allows STM not only to infect mammalian hosts but also to enter new infection routes that have been poorly studied so far. With the present dataset, global virulence factors, their impact on infection routes, and potential anti-infective strategies can now be investigated in detail. Especially, we were able to demonstrate functional flagella at 12 °C growth temperature for STM with an altered motility behavior.

Knowledge of the transfer features of polychlorinated naphthalenes (PCNs), a class of emerging persistent organic pollutants (POPs), is still lacking concerning the environment-feed-food transfer chain of farm animals. We conducted a controlled feeding experiment with laying hens fed fly ash-contaminated diets to investigate the toxicokinetics and bioaccumulation of PCNs (tri- to octa-CNs) in the hen eggs and tissues. The eggs showed increasing PCNs levels after 14 days of oral exposure, which gradually decreased during the 28-day depuration period but still exceeded the initial levels. The apparent one-compartment half-life of ∑

Herein, corncob waste was used as a scaffold for the fabrication of effective adsorbents. Porphyrinic zirconium metal-organic frameworks (MOFs) PCN-223 and PCN-224 constructed by different numbers of Zr6 cluster nodes were grown on the surface of the corncob. Fe (Ш) ions were implanted in the porphyrin ring by post-synthesis modification. The results showed that the extraction capacity of diuretics on PCN-224@corncob containing suitable pore size was larger than that of PCN-223@corncob. The adsorption of diuretics was further enhanced because of the electrostatic effect caused by implantation of Fe (Ш) ions. PCN-224-Fe@corncob was recyclable and selective for the extraction of furosemide (Fur) and bumetanide (Bum). Coupled in-syringe solid phase extraction (IS-SPE) with ultra-performance liquid chromatography (UPLC), an efficient, sensitive, and stable method was established. With a sensitivity between 0.6 and 1.0 μg/L and a recovery between 83.2% and 119.2%, it is used for the analysis of trace amounts of Fur and Bum in weight loss products and environmental water. The functionalized corncob has potential application for the adsorption of diuretics, and the metal ions implantation in MOFs provides a promising strategy for enhancing extraction capacity.

Altered expression of long noncoding RNAs (lncRNAs) by environmental chemicals modulates the expression of xenobiotic biotransformation-related genes and may serve as therapeutic targets and novel biomarkers of exposure. The pregnane X receptor (PXR/NR1I2) is a critical xenobiotic-sensing nuclear receptor that regulates the expression of many drug-processing genes, and it has similar target-gene profiles and DNA-binding motifs with another xenobiotic-sensing nuclear receptor, namely, constitutive andronstrane receptor (CAR/Nr1i3). To test our hypothesis that lncRNAs are regulated by PXR in concert with protein-coding genes (PCGs) and to compare the PXR-targeted lncRNAs with CAR-targeted lncRNAs, RNA-Seq was performed from livers of adult male C57BL/6 mice treated with corn oil, the PXR agonist PCN, or the CAR agonist 1, 4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP). Among 125,680 known lncRNAs, 3843 were expressed in liver, and 193 were differentially regulated by PXR (among which 40% were also regulated by CAR). Most PXR- or CAR-regulated lncRNAs were mapped to the introns and 3′-untranslated regions (UTRs) of PCGs, as well as intergenic regions. Combining the RNA-Seq data with a published PXR chromatin immunoprecipitation coupled with high-throughput sequencing; cytochrome P450 (P450; ChIP-Seq) data set, we identified 774 expressed lncRNAs with direct PXR-DNA binding sites, and 26.8% of differentially expressed lncRNAs had changes in PXR-DNA binding after PCN exposure. De novo motif analysis identified colocalization of PXR with liver receptor homolog (LRH-1), which regulates bile acid synthesis after PCN exposure. There was limited overlap of PXR binding with an epigenetic mark for transcriptional activation (histone-H3K4-di-methylation, H3K4me2) but no overlap with epigenetic marks for transcriptional silencing [H3 lysine 27 tri-methylation (H3K27me3) and DNA methylation]. Among differentially expressed lncRNAs, 264 were in proximity of PCGs, and the lncRNA-PCG pairs displayed a high coregulatory pattern by PXR and CAR activation. This study was among the first to demonstrate that lncRNAs are regulated by PXR and CAR activation and that they may be important regulators of PCGs involved in xenobiotic metabolism.

The gut microbiome regulates important host metabolic pathways including xenobiotic metabolism and intermediary metabolism, such as the conversion of primary bile acids (BAs) into secondary BAs. The nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are well-known regulators for xenobiotic biotransformation in liver. However, little is known regarding the potential effects of PXR and CAR on the composition and function of the gut microbiome. To test our hypothesis that activation of PXR and CAR regulates gut microbiota and secondary BA synthesis, 9-week-old male conventional and germ-free mice were orally gavaged with corn oil, PXR agonist PCN (75 mg/kg), or CAR agonist TCPOBOP (3 mg/kg) once daily for 4 days. PCN and TCPOBOP decreased two taxa in the Bifidobacterium genus, which corresponded with decreased gene abundance of the BA-deconjugating enzyme bile salt hydrolase. In liver and small intestinal content of germ-free mice, there was a TCPOBOP-mediated increase in total, primary, and conjugated BAs corresponding with increased Cyp7a1 mRNA. Bifidobacterium, Dorea, Peptociccaceae, Anaeroplasma, and Ruminococcus positively correlated with T-UDCA in LIC, but negatively correlated with T-CDCA in serum. In conclusion, PXR and CAR activation downregulates BA-metabolizing bacteria in the intestine and modulates BA homeostasis in a gut microbiota-dependent manner.

Pregnane X receptor (PXR) is a xenobiotic-sensing nuclear receptor that regulates drug metabolism in the liver and intestine. In our clinical trials on healthy volunteers to discover novel metabolic functions of PXR activation, we observed that rifampicin, a well-established ligand for human PXR, 600 mg daily for a week, increased the plasma alkaline phosphatase (ALP) significantly compared with the placebo. Further analysis with lectin affinity electrophoresis revealed that especially the bone form of ALP was elevated. To investigate the mechanism(s) of bone ALP induction, we employed osteoblast lineage differentiated from human primary bone marrow-derived mesenchymal stromal cells. Rifampicin treatment increased ALP activity and mRNA level of bone biomarker genes (ALP, MGP, OPN and OPG). PXR expression was detected in the cells, but the expression was very low compared with the human liver. To further investigate the potential role of PXR in the ALP induction, we treated mice and rats with a rodent PXR ligand pregnenolone 16α-carbonitrile (PCN). However, PCN treatment did not increase plasma ALP activity or bone ALP mRNA expression. In conclusion, rifampicin treatment induces the bone form of ALP in the serum of healthy human volunteers. Further studies are required to establish the mechanism of this novel finding.