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Photothermal synergy catalysis for cyclohexane oxidation is recognized as an effective and environmentally friendly strategy for producing a mixture of cyclohexanone and cyclohexanol (known as KA oil). However, certain challenges hinder its application for the one-step production of adipic acid (AA), highlighting the need for further advancements. This study presents a successful strategy for preparing a porous coral-shaped tungsten-iron-lanthanum solid solution (L-WFe 5 La 5 O x -450) through a combination of cold gelation and calcination methods. The surface frustrated Lewis pairs (FLPs) of the L-WFe 5 La 5 O x -450 solid solution were tailored by the abundant chemical oxygen defects and hydroxyls formed during the preparation process. The L-WFe 5 La 5 O x -450 solid solution demonstrated exceptional catalytic performance for the one-step production of AA via solvent-free photothermal oxidation of cyclohexane under visible-light conditions. It achieved a remarkable cyclohexane conversion of 12.5 % with a selectivity of 98.0 % to the desired products (40.3 % and 57.7 % selectivities for the liquid product KA oil and solid product AA, respectively). Compared to S-WFeLaO x -450 prepared by conventional solvothermal methods, the L-WFe 5 La 5 O x -450 solid solution exhibited 2.4- and 2.9-folds higher cyclohexane conversion and AA selectivity, respectively, for photothermal catalytic oxidation. Density functional theory computations and in situ experimental findings clarified the mechanism through which the FLPs on the surface of L-WFe 5 La 5 O x -450 enhance photothermal cyclohexane oxidation. Overall, the involved meticulous design provides insights into the fabrication of porous tungsten-based solid solutions and promotes the customization of surface FLP sites for efficient photothermal synergy oxidation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Background: Endoscopic ultrasound-guided pancreatic duct (PD) drainage (EUS-PDD) is being increasingly performed as an alternative method to surgical drainage to achieve PD decompression after failed endoscopic retrograde pancreatography (ERP). However, no directly study has compared EUS-PDD with surgical PD drainage after failed ERP in patients with chronic pancreatitis., Methods: Consecutive patients who underwent EUS-PDD or longitudinal pancreaticojejunostomy after failed ERP were retrospectively identified from our endoscopy and medical information systems. The primary end point was the Izbicki pain score. The secondary end points were pain relief at the end of follow-up, procedure outcomes, adverse events, readmission, and reintervention., Results: A total of 21 patients (11 EUS-PDD, 10 surgical drainages) were analyzed. There were no significant differences in mean Izbicki pain score (EUS-PDD, 13.6 ± 10.1 vs. surgical drainage 10.7 ± 7.9, p = 0.483) or complete/partial pain relief (60%/30% vs. 70%/30%, p = 0.752) at the end of follow-up of the two groups. The rates of overall adverse events (27.3% vs. 30.0%, p = 0.893) and readmission (63.6% vs. 40.0%, p = 0.290) were similar in the two treatment groups, while patients in EUS-PDD group required more reinterventions (45.5% vs. 0%, p = 0.039) compared with patients in the surgery group., Conclusion: EUS-PDD showed comparable pain relief and safety to surgical PD drainage after failed ERP, with a higher rate of reintervention. The selection of EUS-PDD or surgical drainage may be appropriate based on an individualized strategy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis. SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer., Aim: To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer., Methods: This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years (median age 65) between July 2006 and April 2007. Patients were followed up until death or the study ended (median follow-up duration of 28.5 mo). The samples were used to generate tissue microarrays (TMAs) for immunohistochemical (IHC) staining. The expressions of TGF-β1, pSMAD3C(S423/425), pSMAD3L(S204), and VEGFR-1 in gastric cancer (GC) tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients. Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015. The relationship between TGF-β1, pSMAD3C(S423/425), pSMAD3L(S204), and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient. The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test. A survival curve was generated using the Kaplan-Meier survival analysis., Results: TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent non-cancerous tissue. The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site [pSMAD3C(S423/425): 51.0% and pSMAD3L(S204): 31.6%]. High expression of pSMAD3L(S204) was significantly correlated with larger tumors ( P = 0.038) and later N stages ( P = 0.035). Additionally, high expression of VEGFR-1 was closely correlated with tumor size ( P = 0.015) and pathological grading ( P = 0.013). High expression of both pSMAD3L(S204) and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival (OS). Multivariate analysis indicated that high expression of pSMAD3L(S204) and VEGFR-1 were independent risk factors for prognosis in GC patients. VEGFR-1 protein expression was correlated with TGF-β1 ( r = 0.220, P = 0.029), pSMAD3C(S423/425) ( r = 0.302, P = 0.002), and pSMAD3L(S204) ( r = 0.201, P = 0.047), respectively. Simultaneous overexpression of pSMAD3L(S204) and VEGFR-1 was associated with poor OS in gastric cancer patients., Conclusion: Co-upregulation of pSMAD3L(S204) and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis, and pSMAD3L(204) may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Lung cancer is a highly malignant disease, primarily due to its propensity for metastasis. AMP-activated protein kinase (AMPK), the principal downstream effector of Liver Kinase B1 (LKB1), orchestrates a broad spectrum of molecular targets, thereby constraining tumor invasion and metastasis. In parallel, the RNA-binding protein RBMS3 (RNA-binding motif, single-stranded-interacting protein 3) plays a pivotal role in the epithelial-mesenchymal transition (EMT), a pivotal process in tumorigenesis. Therefore, our research aims to clarify the important role of RBMS3 as a mediator in the LKB1/AMPK inhibition of tumor invasion and metastasis. Methods: We investigated the expression and correlation between RBMS3 and LKB1 in lung cancer tissues utilizing immunohistochemistry and TCGA-LUAD data, respectively. The relationship between RBMS3 and clinical pathological features and prognosis of lung cancer was also analyzed. The functions of RBMS3 in lung cancer cell proliferation, invasion, and migration were investigated in real-time in vitro . Additionally, we investigated the effects of AMPK agonists and inhibitors to explore the mediating role of RBMS3 in AMPK-induced inhibition of lung cancer invasion and migration. Results: The IHC and TCGA data both revealed low expression of RBMS3 in lung cancer. Moreover, we found that low expression of RBMS3 was positively associated with lung cancer's histological grade, clinical stage, and N stage. Additionally, low RBMS3 expression was associated with poor overall survival. Cox regression analysis revealed that RBMS3 was an independent prognostic factor for lung cancer patients. In vitro experiments verified that RBMS3 inhibited lung cancer cell proliferation, invasion, and migration. Furthermore, our findings suggested that RBMS3 played an essential role in mediating AMPK's inhibitory effect on lung cancer invasion and migration. Conclusion: Our study highlights a novel mechanism by which LKB1/AMPK pathway activation inhibits lung cancer invasion and metastasis by promoting RBMS3 expression, offering insights in developing innovative lung cancer therapies., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Animal survival necessitates adaptive behaviors in volatile environmental contexts. Virtual reality (VR) technology is instrumental to study the neural mechanisms underlying behaviors modulated by environmental context by simulating the real world with maximized control of contextual elements. Yet current VR tools for rodents have limited flexibility and performance (e.g., frame rate) for context-dependent cognitive research. Here, we describe a high-performance VR platform with which to study contextual behaviors immersed in editable virtual contexts. This platform was assembled from modular hardware and custom-written software with flexibility and upgradability. Using this platform, we trained mice to perform context-dependent cognitive tasks with rules ranging from discrimination to delayed-sample-to-match while recording from thousands of hippocampal place cells. By precise manipulations of context elements, we found that the context recognition was intact with partial context elements, but impaired by exchanges of context elements. Collectively, our work establishes a configurable VR platform with which to investigate context-dependent cognition with large-scale neural recording., (© 2022. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

Background: The success of elective colorectal surgery is mainly influenced by the surgical procedure and postoperative complications. The most serious complications include anastomotic leakages and surgical site infections (SSI)s, which can lead to prolonged recovery with impaired long-term health.  Compared with other abdominal procedures, colorectal resections have an increased risk of adverse events due to the physiological bacterial colonisation of the large bowel. Preoperative bowel preparation is used to remove faeces from the bowel lumen and reduce bacterial colonisation. This bowel preparation can be performed mechanically and/or with oral antibiotics. While mechanical bowel preparation alone is not beneficial, the benefits and harms of combined mechanical and oral antibiotic bowel preparation is still unclear., Objectives: To assess the evidence for the use of combined mechanical and oral antibiotic bowel preparation for preventing complications in elective colorectal surgery., Search Methods: We searched MEDLINE, Embase, CENTRAL and trial registries on 15 December 2021. In addition, we searched reference lists and contacted colorectal surgery organisations., Selection Criteria: We included randomised controlled trials (RCTs) of adult participants undergoing elective colorectal surgery comparing combined mechanical and oral antibiotic bowel preparation (MBP+oAB) with either MBP alone, oAB alone, or no bowel preparation (nBP). We excluded studies in which no perioperative intravenous antibiotic prophylaxis was given., Data Collection and Analysis: We used standard methodological procedures as recommended by Cochrane. Pooled results were reported as mean difference (MD) or risk ratio (RR) and 95 % confidence intervals (CIs) using the Mantel-Haenszel method. The certainty of the evidence was assessed with GRADE., Main Results: We included 21 RCTs analysing 5264 participants who underwent elective colorectal surgery. None of the included studies had a high risk of bias, but two-thirds of the included studies raised some concerns. This was mainly due to the lack of a predefined analysis plan or missing information about the randomisation process. Most included studies investigated both colon and rectal resections due to malignant and benign surgical indications. For MBP as well as oAB, the included studies used different regimens in terms of agent(s), dosage and timing.  Data for all predefined outcomes could be extracted from the included studies. However, only four studies reported on side effects of bowel preparation, and none recorded the occurrence of adverse effects such as dehydration, electrolyte imbalances or the need to discontinue the intervention due to side effects. Seventeen trials compared MBP+oAB with sole MBP. The incidence of SSI could be reduced through MBP+oAB by 44% (RR 0.56, 95% CI 0.42 to 0.74; 3917 participants from 16 studies; moderate-certainty evidence) and the risk of anastomotic leakage could be reduced by 40% (RR 0.60, 95% CI 0.36 to 0.99; 2356 participants from 10 studies; moderate-certainty evidence). No difference between the two comparison groups was found with regard to mortality (RR 0.87, 95% CI 0.27 to 2.82; 639 participants from 3 studies; moderate-certainty evidence), the incidence of postoperative ileus (RR 0.89, 95% CI 0.59 to 1.32; 2013 participants from 6 studies, low-certainty of evidence) and length of hospital stay (MD -0.19, 95% CI -1.81 to 1.44; 621 participants from 3 studies; moderate-certainty evidence). Three trials compared MBP+oAB with sole oAB. No difference was demonstrated between the two treatment alternatives in terms of SSI (RR 0.87, 95% CI 0.34 to 2.21; 960 participants from 3 studies; very low-certainty evidence), anastomotic leakage (RR 0.84, 95% CI 0.21 to 3.45; 960 participants from 3 studies; low-certainty evidence), mortality (RR 1.02, 95% CI 0.30 to 3.50; 709 participants from 2 studies; low-certainty evidence), incidence of postoperative ileus (RR 1.25, 95% CI 0.68 to 2.33; 709 participants from 2 studies; low-certainty evidence) or length of hospital stay (MD 0.1 respectively 0.2, 95% CI -0.68 to 1.08; data from 2 studies; moderate-certainty evidence). One trial (396 participants) compared MBP+oAB versus nBP. The evidence is uncertain about the effect of MBP+oAB on the incidence of SSI as well as mortality (RR 0.63, 95% CI 0.33 to 1.23 respectively RR 0.20, 95% CI 0.01 to 4.22; low-certainty evidence), while no effect on the risk of anastomotic leakages (RR 0.89, 95% CI 0.33 to 2.42; low-certainty evidence), the incidence of postoperative ileus (RR 1.18, 95% CI 0.77 to 1.81; low-certainty evidence) or the length of hospital stay (MD 0.1, 95% CI -0.8 to 1; low-certainty evidence) could be demonstrated., Authors' Conclusions: Based on moderate-certainty evidence, our results suggest that MBP+oAB is probably more effective than MBP alone in preventing postoperative complications. In particular, with respect to our primary outcomes, SSI and anastomotic leakage, a lower incidence was demonstrated using MBP+oAB. Whether oAB alone is actually equivalent to MBP+oAB, or leads to a reduction or increase in the risk of postoperative complications, cannot be clarified in light of the low- to very low-certainty evidence. Similarly, it remains unclear whether omitting preoperative bowel preparation leads to an increase in the risk of postoperative complications due to limited evidence. Additional RCTs, particularly on the comparisons of MBP+oAB versus oAB alone or nBP, are needed to assess the impact of oAB alone or nBP compared with MBP+oAB on postoperative complications and to improve confidence in the estimated effect. In addition, RCTs focusing on subgroups (e.g. in relation to type and location of colon resections) or reporting side effects of the intervention are needed to determine the most effective approach of preoperative bowel preparation., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

The Nod-like receptor (NLR) family CARD domain containing 5 (NLRC5) has been reported as an activator of human leukocyte antigen (HLA) class I that is responsible for immune activity in cancer treatment. This work focuses on the role of BMI1 proto-oncogene (BMI1) in the NLRC5-HLA class I axis and in immune escape in non-small cell lung cancer (NSCLC). First, immunoblot analysis and/or reverse transcription-quantitative polymerase chain reaction were performed, which identified decreased NLRC5 and HLA class I levels in NSCLC tissues and cell lines. NSCLCs were co-cultured with activated CD8 + T cells. Overexpression of NLRC5 in NSCLC cells elevated the expression of HLA class I and increased the activity of T cells and IL-2 production, and it reduced the PD-1/PD-L1 levels. The ubiquitination and immunoprecipitation assays confirmed that BMI1 bound to NLRC5 to induce is ubiquitination and protein degradation. Downregulation of BMI1 in NSCLC cells elevated NLRC5 and HLA class I levels, and consequently promoted T cell activation and decreased PD-1/PD-L1 levels in the co-culture system. However, overexpression of BMI1 in cells led to inverse trends. In summary, this study demonstrates that BMI1 induces ubiquitination and protein degradation of NLRC5 and suppresses HLA class I expression, which potentially helps immune escape in NSCLC., (© 2022 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Spodoptera frugiperda (J. E. Smith), is commonly known as fall armyworm, native to tropical and subtropical regions of America, is an important migratory agricultural pest. It is important to understand the resistance and internal mechanism of action of S. frugiperda against lufenuron in China. Lufenuron is one of the main insecticides recommended for field use in China and has a broad prospect in the future. We conducted a bioassay using the diet-overlay method and found that the current S. frugiperda in China are still at a low level of resistance to lufenuron. Secondly, we examined whether the mutation I1040M (I1042M in Plutella xylostella), associated with lufenuron resistance, was produced in the field. And then we tested the expression of chitin synthase SfCHSA and SfCHSB in different tissues, and the changes of these two genes after lufenuron induction. The results showed that there is still no mutation generation in China and there is a significant change in the expression of SfCHSA under the effect of lufenuron. In conclusion, our study suggests that field S. frugiperda populations in 2019 and 2020 were less resistant to lufenuron. In fall armyworm, chitin synthases included SfCHSA and SfCHSB genes, and after induction treatment with lufenuron, the expression of the SfCHSA gene was significantly increased. In SfCHSA, no mutation has been detected in the site associated with lufenuron resistance. Secondly, in S. frugiperda larvae, the SfCHSA gene was the highest in the head of the larvae, followed by the integument; while the SfCHSB gene was mainly concentrated in the midgut. Therefore, we believe that the SfCHSA gene plays a greater role in the resistance of S. frugiperda to lufenuron than the SfCHSB gene. It is worth noting that understanding the level of resistance to lufenuron in China, the main mechanism of action of lufenuron on larvae, and the mechanism of resistance to lufenuron in S. frugiperda will help in crop protection as well as in extending the life span of this insecticide.

Single-molecule recognition and detection with the highest resolution measurement has been one of the ultimate goals in science and engineering. Break junction techniques, originally developed to measure single-molecule conductance, recently have also been proven to have the capacity for the label-free exploration of single-molecule physics and chemistry, which paves a new way for single-molecule detection with high temporal resolution. In this review, we outline the primary advances and potential of the STM break junction technique for qualitative identification and quantitative detection at a single-molecule level. The principles of operation of these single-molecule electrical sensing mainly in three regimes, ion, environmental pH and genetic material detection, are summarized. It clearly proves that the single-molecule electrical measurements with break junction techniques show a promising perspective for designing a simple, label-free and nondestructive electrical sensor with ultrahigh sensitivity and excellent selectivity.

Macrophage-mediated inflammation plays an important role in hypertensive cardiac remodeling, whereas effective pharmacological treatments targeting cardiac inflammation remain unclear. Lipoprotein-associated phospholipase A2 (Lp-PLA2) contributes to vascular inflammation-related diseases by mediating macrophage migration and activation. Darapladib, the most advanced Lp-PLA2 inhibitor, has been evaluated in phase III trials in atherosclerosis patients. However, the role of darapladib in inhibiting hypertensive cardiac fibrosis remains unknown. Using a murine angiotensin II (Ang II) infusion-induced hypertension model, we found that Pla2g7 (the gene of Lp-PLA2) was the only upregulated PLA2 gene detected in hypertensive cardiac tissue, and it was primarily localized in heart-infiltrating macrophages. As expected, darapladib significantly prevented Ang II-induced cardiac fibrosis, ventricular hypertrophy, and cardiac dysfunction, with potent abatement of macrophage infiltration and inflammatory response. RNA sequencing revealed that darapladib strongly downregulated the expression of genes and signaling pathways related to inflammation, extracellular matrix, and proliferation. Moreover, darapladib substantially reduced the Ang II infusion-induced expression of nucleotide-binding oligomerization domain-like receptor with pyrin domain 3 (NLRP3) and interleukin (IL)-1β and markedly attenuated caspase-1 activation in cardiac tissues. Furthermore, darapladib ameliorated Ang II-stimulated macrophage migration and IL-1β secretion in macrophages by blocking NLRP3 inflammasome activation. Darapladib also effectively blocked macrophage-mediated transformation of fibroblasts into myofibroblasts by inhibiting the activation of the NLRP3 inflammasome in macrophages. Overall, our study identifies a novel anti-inflammatory and anti-cardiac fibrosis role of darapladib in Lp-PLA2 inhibition, elucidating the protective effects of suppressing NLRP3 inflammasome activation. Lp-PLA2 inhibition by darapladib represents a novel therapeutic strategy for hypertensive cardiac damage treatment., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Spodoptera frugiperda (Lepidoptera: Noctuidae) is a widely distributed pest of corn. Since it invaded China in 2018, it has caused serious damage to local corn production. Chlorantraniliprole, an anthranilic diamide insecticide, has been widely used to control lepidopteran pests. Tetrachloropyramid is a new allosteric modulator insecticide developed based on chlorantraniliprole, so it has a similar mechanism and insecticidal effect. In this study, we investigated resistance levels to chlorantraniliprole and tetrachloropyramid in S. frugiperda from 13 populations in China. Among the populations tested, the relative highest resistance to chlorantraniliprole occurred in the Guangzhou population, and the most susceptible to chlorantraniliprole was found in the Wuhan population. The lethal dosage LD 50 value of the Guangzhou population against chlorantraniliprole was 27.8-fold higher than that of the Wuhan population. Minimal differences were observed among S. frugiperda populations in terms of sensitivity to tetrachloropyramid. Heterozygous mutations at the I4734 site of the ryanodine receptor (RyR) were found, while no mutations were found in the G4891 site. The mutations were detected in only two of the 786 individuals analyzed, one from the Qinzhou population and other from the Anshun population (frequency below 2% in both cases). There were no significant differences in the expression levels of RyR between Guangzhou and Wuhan populations. In summary, our results indicate that: (i) S. frugiperda has low resistance levels to diamide insecticides in China; and (ii) the differences in relative resistance among the 13 populations analyzed are not caused by the mutations in RyR or the expression of RyR., (© 2020 Institute of Zoology, Chinese Academy of Sciences.)

Spathaspora is an important genus of d-xylose-fermenting yeasts that are poorly studied in China. During recent yeast collections in Yunnan Province in China, 13 isolates of Spathaspora were obtained from rotting wood and all represent undescribed taxa. Based on morphological and phylogenetic analyses (ITS and nuc 28S), five new species are proposed: Spathaspora elongata , Sp. mengyangensis , Sp. jiuxiensis , Sp. parajiuxiensis and Sp. rosae . Our results indicate a high species diversity of Spathaspora waiting to be discovered in rotting wood from tropical and subtropical southwest China. In addition, the two Candida species, C. jeffriesii and C. materiae , which are members of the Spathaspora clade based on phylogeny, are transferred to Spathaspora as new combinations., (Shi-Long Lv, Chun-Yue Chai, Yun Wang, Zhen-Li Yan, Feng-Li Hui.)

As an emerging class of hybrid complexes, donor-acceptor (D-A) hybrid heterostructures with advantages of both photoactive organic and inorganic components have provided an excellent platform for the fabrication of multifunctional photoactive materials. In this context, we have demonstrated three novel host-guest D-A hybrid heterostructures, {[Ln(BCEbpy)(H 2 O) 4 ][Co III (CN) 6 ]·4H 2 O} n (1 (Eu), 2 (Dy), 3 (Sm)), based on the anionic Co(CN) 6 3- and cationic coordination layers assembled from a viologen functionalized tecton and Ln(NO) 3 . Due to the introduction of an electron donor, Co III (CN) 6 3- , the unique hybrid exhibits a highly sensitive and reversible photochromic transformation from light-yellow to brown upon UV-Vis irradiation. More interestingly, accompanied with this photochromic process, hybrid 1 simultaneously possesses a photomodulated fluorescence behaviour. In addition, hybrid 1 shows high sensitivity and selectivity towards Cr 2 O 7 2- anions with a fairly small LOD of ca. 9.6 × 10 -6 M.

Background: The administration of menopausal hormone therapy (MHT) in women with uterine leiomyomas is still debated. The purpose of this article is to study the proliferation and apoptosis of uterine leiomyoma cells under the impact of selective estrogen receptor modulator (SERM) combined with estrogen., Methods: Primary cultured uterine leiomyoma cells in the perimenopausal period were treated with estrogen (17-beta estradiol) + SERM (raloxifene) as the tissue selective estrogen complex (TSEC) group, while both estrogen + medroxyprogesterone acetate (E+P) and estrogen (E) alone as were used as control groups. The expression of proliferating cell nuclear antigen (PCNA) and B-cell lymphoma-2 (Bcl-2) proteins was assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and western-blot analysis, respectively., Results: The proliferation in the TSEC group was weaker than the control groups (P<0.001). There was no statistical difference between the TSEC and blank control group on cell proliferation at 72 h (P=0.13). However, there was a significant difference between the other groups (P<0.001). PCNA expression of TSEC was lower than that of the E + P and E groups (P<0.05). There was no statistical difference in the expression of PCNA between the TSEC and blank control groups (P=0.63). Bcl-2 expression of TSEC was lower than that of the E + P and E groups (P<0.05). There was no statistical difference in the expression of Bcl-2 between the TSEC group and the blank control group (P=0.60)., Conclusions: SERM combined with estrogen may have a better safety for perimenopausal women with uterine leiomyoma in MHT., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr-19-3022a). The authors have no conflicts of interest to declare., (2020 Translational Cancer Research. All rights reserved.)

Three species of Scheffersomyces were identified during a diversity study of yeasts. All three are associated with insects and rotting wood in China. Phylogenetic analyses of a genomic dataset combining ITS and nrLSU revealed that these new collections are distinct from known species, thus three new species are introduced i.e. S. jinghongensis , S. paraergatensis , and S. anoplophorae . In our phylogenetic analyses, Scheffersomyces jinghongensis possesses a strong independent lineage and is closely related to S. titanus . S. paraergatensis is closely related to S. ergatensis , while S. anoplophorae is related to S. stambukii. Several differences in physiological traits and molecular data indicate that S. jinghongensis , S. paraergatensis , and S. anoplophorae are three newly identified species., (Ran-Ran Jia, Shi-Long Lv, Chun-Yue Chai, Feng-Li Hui.)

Ethnopharmacological Relevance: Guilingji (GLJ) is a well-known traditional Chinese medicine (TCM) prescription for the treatment of Kidney-Yang deficiency syndrome (KYDS)., Aim of the Study: This study aimed to address the protective effects of GLJ against KYDS in rats with pharmacodynamic indicators and target tissues (adrenal gland and testis) metabolomics., Materials and Methods: The rats were injected intraperitoneally (i.p) hydrocortisone to simulate KYDS and administered orally of GLJ for 30 days. Traditional pharmacodynamic indicators (body weight, behavioral indicators, biochemical parameters and histological examination) were performed to evaluate the efficacy of GLJ. Furthermore, adrenal gland and testis metabolic profiles obtained by UHPLC-Q Exactive Orbitrap-MS coupled with multivariate analysis were conducted to explore the metabolic regulation mechanism of GLJ., Results: After administration of GLJ, the weight, levels of behavioral indicators and biochemical parameters of rats were increased compared with those of the model group, and the abnormalities of morphology in adrenal and testicular tissues were improved. Furthermore, GLJ had recovering effects via the adjustment of vitamins metabolism, which was accompanied by lipids metabolism, amino acid metabolism and nucleotides metabolism., Conclusions: The study firstly integrated the target tissues metabolic profiles, which were complementary, and GLJ had protective effects on KYDS rats via the regulation of steroid hormone biosynthesis, oxidant-antioxidant balance and energy acquisition., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Astroviruses (AstV) are associated with enteric and systemic disease in mammals and birds. Astroviruses have received increased attention recently as they have been found to be associated with sporadic neurologic disease in mammals including humans. In pigs, porcine astrovirus (PoAstV) can be widely detected and has been grouped in five genotypes (PoAstV1 to PoAstV5). In the present study, we detected multiple PoAstVs in serum samples, nasal swabs, and fecal swabs collected from pigs suffering from respiratory disease or diarrhea but also from asymptomatic pigs, indicating a wide tissue tropism of the identified PoAstV genotypes. Coinfection of different genotypes in the same pig was commonly observed, and within an individual pig a high genetic diversity was observed for viruses belonging to the same PoAstV genotype. Two complete genomes of PoAstV2-WG-R2/2017 and PoAstV4-WG-R2/2017 were successfully obtained and characterized, with genome sizes of 6396 and 6643 nucleotides, respectively. The PoAstV2-WG-R2/2017 genome showed identities of 67.2-77.4% to other known PoAstV2 genomes, and the PoAstV4-WG-R2/2017 genome showed identities of 72.8-80.5% to other known PoAstV4 genomes. The predicted spike domain of open reading frame 2 (ORF2) of these strains showed the highest genetic heterogeneity, with amino acid identities of 13.7-70.9% for PoAstV2-WG-R2/2017 to other known PoAstV2 strains, and identities of 24.4-63.3% for the PoAstV4-WG-R2/2017 to other known PoAstV4 strains. Possible recombination events were identified in each of the two sequences. Two subclades of PoAstV2 and three subclades of PoAstV4 were defined in the present analyses. The obtained data provide further evidence for extraintestinal infectivity of PoAstVs, and confirmed the high genetic diversity of PoAstVs and the coinfection potential of different PoAstV types in a single pig.

Aim: To develop and validate a risk estimation of tumor recurrence following curative resection of operable hepatocellular carcinoma (HCC)., Methods: Data for 128 patients with operable HCC (according to Barcelona Clinic Liver Cancer imaging criteria) who underwent preoperative computed tomography (CT) evaluation at our hospital from May 1, 2013 through May 30, 2014 were included in this study. Follow-up data were obtained from hospital medical records. Follow-up data through May 30, 2016 were used to retrospectively analyze preoperative multiphasic CT findings, surgical histopathology results, and serum α-fetoprotein and thymidine kinase-1 levels. The χ 2 test, independent t -test, and Mann-Whitney U test were used to analyze data. A P -value of < 0.05 was considered statistically significant., Results: During the follow-up period, 38 of 128 patients (29.7%) had a postoperative HCC recurrence. Microvascular invasion (MVI) was associated with HCC recurrence (χ 2 = 13.253, P < 0.001). Despite postoperative antiviral therapy and chemotherapy, 22 of 44 patients with MVI experienced recurrence after surgical resection. The presence of MVI was 57.9% sensitive, 75.6% specific and 70.3% accurate in predicting postoperative recurrence. Of 84 tumors without MVI, univariate analysis confirmed that tumor margins, tumor margin grade, and tumor capsule detection on multiphasic CT were associated with HCC recurrence ( P < 0.05). Univariate analyses showed no difference between groups with respect to hepatic capsular invasion, Ki-67 proliferation marker value, Edmondson-Steiner grade, largest tumor diameter, necrosis, arterial phase enhanced ratio, portovenous phase enhanced ratio, peritumoral enhancement, or serum α-fetoprotein level., Conclusion: Non-smooth tumor margins, incomplete tumor capsules and missing tumor capsules correlated with postoperative HCC recurrence. HCC recurrence following curative resection may be predicted using CT., Competing Interests: Conflict-of-interest statement: The authors declared that there is no conflict of interest related to this study.

This study aims to evaluate the potential of apparent diffusion coefficient (ADC) derived from diffusion-weighted MR imaging for predicting the treatment response to neoadjuvant chemotherapy (NACT) in patients with breast cancer. Magnetic resonance imaging was performed prior to NACT and after two cycles of NACT. The correlation between mean ADC pre values, mean ADC post values, changes in ADC values and changes in tumor diameters after NACT was examined using Spearman rank correlation. A total of 164 breast cancers were enrolled in this study. Mean ADC pre values of responders ([0.85 ± 0.16] × 10 -3 mm 2 /s) and non-responders ([0.84 ± 0.21] × 10 -3 mm 2 /s) had no significant difference ( P = 0.759). While mean ADC post value of responders was significantly higher than that of non-responders ([1.17 ± 0.37] × 10 -3 mm 2 /s vs. [1.01 ± 0.28] × 10 -3 mm 2 /s; P = 0.002). Both mean ADC post values (r = 0.288, P = 0.000) and changes in mean ADC values (r = 0.222, P = 0.004) were positively correlated to changes in tumor diameter after NACT, except for mean ADC pre values (r = 0.031, P = 0.695). Our results indicated that mean ADC post values and changes in ADC values after NACT might be a biological marker for assessing the efficacy of chemotherapy., Competing Interests: CONFLICTS OF INTEREST There is no conflict of interest.

Astroviruses (AstVs) can infect a variety of hosts, including mammalian and avian species, and are commonly associated with enteric infections. Recently, mammalian AstVs have been linked to extra-intestinal manifestations, including neurologic disorders in humans, cattle and minks, demonstrating zoonotic potential. So far, five porcine AstV (PAstV) genotypes have been identified, with PAstV1, PAstV2, PAstV3 and PAstV5 implicated in cross-species transmission. Our knowledge about PAstV epidemiology in China is still limited. In this study, two duplex differential RT-PCR assays were developed to investigate the distribution and prevalence of PAstV1, PAstV2, PAstV4 and PAstV5. Two hundred eighteen samples were collected from 33 farms and pigs with known diarrhea status in nine regions of Hunan province in China. Specifically, 126 small intestines, 51 fecal swabs, 20 lungs, 19 spleens and two kidneys were obtained. PAstVs were detected in all nine regions and in 81.8% (27/33) of the pig farms investigated. The overall prevalence of PAstV was 46.3% (101/218), with PAstV5 as the predominant type, with a positive rate of 24.8% (54/218). The prevalence of PAstV4, PAstV1 and PAstV2 was 16.1% (35/218), 14.7% (32/218) and 10.1% (22/218), respectively. Besides being present in intestines and fecal swabs, PAstV RNA was also detected in lungs, spleens and kidneys. Sequencing revealed a high level of genetic divergence within each genotype, and a higher positive rate of PAstV5 was associated with pigs with diarrhea compared to pigs without diarrhea. This study revealed for the first time that PAstV4 is circulating in China, and that PAstV5 is the dominant genotype in pig herds in Hunan province in China.

Leiomyomas in the female reproductive system are commonly located in the uterus and typically regress following the menopause. Vulval leiomyomas are rare, and to the best of our knowledge, perineal leiomyomas in postmenopausal women have not been previously reported in the literature. The present case describes a 60-year-old Chinese woman who experienced perineal tenderness and lumbosacral radiating pain. The patient, who went through the menopause 12 years previously, had presented with a painful perineal mass for 1 year, which was subsequently diagnosed as a postmenopausal perineal leiomyoma. The mass was locally resected, and histopathological examination of the lesion resulted in a diagnosis of benign epithelioid leiomyoma. Immunohistochemical staining identified that the leiomyoma was positive for estrogen receptor and negative for progesterone receptor expression. The patient was followed up for 1 year and did not experience any pain or recurrence. The symptoms of local and lumbosacral radiating pain are extremely rare and may be induced by peripheral nerve stimulation. The etiology of postmenopausal perineal leiomyoma may be associated with infection, dietary, stress and environmental factors, and the role of estrogen cannot be overemphasized in cases of postmenopausal leiomyoma.

Observational studies have reported controversial results on the association between GSTT1 and GSTM1 genotypes and treatment outcome of breast cancer. The purpose of this study is to evaluate the association between GSTT1 and GSTM1 and treatment outcome in breast cancer patients. Eligible studies were searched in PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure databases. A random-effect model or fixed-effect model was used to calculate the overall combined risk estimates. Twenty-one studies with a total of 4990 patients were included in this meta-analysis. The GSTM1 null genotype (odds ratio (OR) = 1.33, 95 % confidence interval (CI) 1.01-1.75, P = 0.046) and GSTT1/GSTM1 double null genotype (OR = 2.22, 95 % CI 1.02-4.84, P = 0.045) were significantly associated with an increased tumor response. A reduced overall survival (hazard ratio (HR) = 0.84, 95 % CI 0.72-0.98, P = 0.024) was observed in GSTM1 null genotype, especially in mixed descent (HR = 0.77, 95 % CI 0.61-0.96, P = 0.018) and large sample size (HR = 0.85, 95 % CI 0.72-0.99, P = 0.033). Evidence of publication bias was observed in GSTM1 genotype rather than in GSTT1 genotype. This meta-analysis suggests that GSTM1 null and GSTT1/GSTM1 double null polymorphisms might be significantly associated with an increased tumor response. However, the GSTM1 null genotype might be significantly associated with a reduced overall survival. Future studies are warranted to confirm these findings.

Objective: The purpose of this study was to explore the diagnostic performance of apparent diffusion coefficient (ADC) values for breast lesions by different measuring methods and find out the optimum measuring method., Methods: ADCW-mean and ADCW-min were obtained by whole-measurement method, while ADCmean and ADCmin were extracted by spot-measurement method. Four ADCs were analyzed by One-way ANOVA and Independent T-test. The diagnostic performances of these four ADCs were calculated by receiver operating characteristics (ROC) curves and the area under the curves (AUC) were compared through Z-test., Results: For the whole-measurement method, there were significant differences between malignant and benign lesions (ADCW-mean=1.014±0.197 for malignant, ADCW-mean=1.650±0.348 for benign, F=37.511, P<0.001; ADCW-min=0.627±0.144 for malignant, ADCW-min=1.245±0.290 for benign, F=41.446, P<0.001), as well as the spot-measurement method (ADCmean=1.010±0.234 for malignant, ADCmean=1.648±0.392 for benign, F=34.580, P<0.001; ADCmin=0.817±0.203 for malignant, ADCmin=1.411±0.357 for benign, F=40.039, P<0.001). The optimal diagnostic threshold of ADCW-mean, ADCW-min, ADCmean, and ADCmin values were 1.223×10(-3) mm(2)/s, 0.897×10(-3) mm(2)/s, 1.315×10(-3) mm(2)/s, and 1.111×10(-3) mm(2)/s, respectively. ROC curves indicated that the AUC for ADCW-min (0.969) was statistically significant higher than the AUC for ADCW-mean (0.940; Z=2.473, p=0.013), ADCmean (0.919; Z=3.691, P=0.000), and ADCmin (0.928; Z=3.634, P=0.000). The AUC for ADCW-mean was also significantly higher than the AUC for ADCmean (Z=2.863, P=0.004)., Conclusion: The results provided evidence that the most reliable and accurate value in demonstrating the limitation of diffusion may be ADCW-min, and it has the highest diagnostic value in distinguishing breast lesions from malignant to benign.

Objective: The aim of this study is to evaluate the role of current perception threshold (CPT) measurement in peripheral neuropathy in type 1 diabetic patients by using the Neurometer(®), a nerve measuring instrument., Methods: 52 patients with type 1 diabetes mellitus with a disease duration of less than five years and normal neuropathy symptom score (NSS), neuropathy disability score (NDS) and sensory nerve conduction velocity (SCV), and 40 healthy controls were enrolled in this study. Measurement of CPT using the Neurometer(®) at 2000, 250 and 5 Hz assesses function in the bilateral median nerve and sural nerve in all studied cases. We also evaluated the glycated hemoglobin, microalbuminuria, urinary albumin/creatinine ratio and other metabolism indexes of all patients., Results: The CPT of the bilateral median nerve and sural nerve was significantly lower in diabetic patients (P<0.01). Moreover, the number of median nerve injuries in the diabetic group (left side 8/52, right side 8/52) is significantly different from the number of its ipsilateral sural nerve injuries (left side 28/52, right side 22/52) (left side P<0.01, right side P<0.01). By comparing those with DPN and those without DPN in the diabetic group, DPN groups had significantly higher glycated hemoglobin (t=2.518, P<0.05). Using binary logistic regression, high glycated hemoglobin was identified to be an independent risk factor of DPN incidence (OR (95% CI): 1.317 (1.013 -1.712), P<0.05)., Conclusion: These data suggest that CPT is useful in early detection of peripheral neuropathy in patients with type 1 diabetes mellitus. Patients with diabetic peripheral neuropathy, the lower limb nerve is more vulnerable than the upper limb nerve. In addition, patients with DPN had higher glycated hemoglobin which is an independent risk factor of DPN., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Nicotine has been found to induce the proliferation of lung cancer cells through tumor invasion and to confer resistance to apoptosis. Periostin is abnormally highly expressed in lung cancer and is correlated with angiogenesis, invasion and metastasis. Here, we investigated the roles of periostin in the lung cancer cell proliferation, drug resistance, invasion and epithelial-mesenchymal transition (EMT) induced by nicotine. The periostin gene was silenced using small interfering RNA (siRNA) in A549 non-small cell lung cancer (NSCLC) cells. The cells were transfected with control or periostin siRNA plasmids. Periostin mRNA was evaluated by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Cell proliferation was detected using the MTT assay and cell apoptosis was detected by Annexin V-FITC and propidium iodide (PI) double staining. Tumor invasion was detected by the Boyden chamber invasion assay. Western blotting was performed to detect the expression of the EMT marker Snail. Our results revealed that stably periostin-silenced cells were acquired by G418 screening, and the periostin mRNA expression levels of which were decreased by nearly 80%. Periostin-silenced A549 cells exhibited reduced cell proliferation, elevated sensitivity to chemotherapy with cisplatin, decreased cell invasion and Snail expression (P<0.05). Nicotine upregulated the periostin protein levels in the A549 cells and this upregulation was not blocked by the generalized nicotinic acetylcholine receptor (nAChR) antagonist, hexamethonium. In conclusion, periostin is one of the targets regulated by nicotine in lung cancer cells and is involved in the cancer cell growth, drug resistance, invasion and EMT induced by nicotine.

Objective: To establish a nested real-time quantitative polymerase chain reaction (PCR) assay for detection of hepatitis B virus covalently closed circular DNA in PBMC( peripheral blood monocyte) and MMNC (marrow monocyte)., Methods: Based on the structural differences between HBVcccDNA and HBV rcDNA, two pairs of specific primers spanned the gap of the positive and negative chains and a specific TaqMan probe situated downstream were designed. To remove rcDNA, cccDNA was processed by Mung Bean Nuclease,and then amplified by nested real-time quantitative PCR using a pair of outer primers and a pair of inner primers. According to the standard preparation, cccDNA levels of specimen were calculated., Results: We have established a nested real-time fluorescent quantitative PCR method for HBV cccDNA successfully, and the linear range is from 5.0 x 10(2) to 3. 9 x 10(7) copies per milliliter. Of the 25 PBMC samples and 7 MMNC samples of the chronic hepatitis B or liver cirrhosis patients, 3 MMNC samples and 9 PBMC samples were HBV cccDNA positive, while all of the 21 healthy donator blood PBMC samples were negative., Conclusions: The nested real-time fluorescent quantitative PCR method may be applied to detect HBVcccDNA level in PBMC and MMNC. HBVcccDNA can be detected in PBMC and MMNC.

MicroRNAs (miRNAs) play important roles in post-transcriptional gene expression control. To gain new insight into human miRNAs, we performed comprehensive sequence-based homology search for known human miRNAs to study the evolutionary distribution of human miRNAs. Furthermore, we carried out a series of studies to compare various features for different lineage-specific human miRNAs. Our results showed that major expansions of human miRNA genes coincide with the advent of vertebrates, mammals and primates. Further system-level analysis revealed significant differences in human miRNAs that arose from different evolutionary time points for a number of characteristics, implicating genetic and functional diversification for different human miRNAs during evolution. Our finds provide more useful knowledge for further exploring origins and evolution of human miRNA genes., (Copyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Objective: To study the relationship between levels of serum HA, LN, IV-C, PC III of chronic hepatitis and indexes of hepatic fibrosis., Methods: The levels of serum HA, LN, IV-C and PC III of chronic hepatitis of 124 cases and health 18 cases were measured by radio immunoassay, combined with clinical characteristics and 33 cases pathologic slice etc. The diagnostic of the indexes of serum was analyzed with statistics., Results: HA and IV-C are parallel in chronic hepatitis periods. LN and PC III are concert in the same pathologic periods. In G4 period PC III is nearly closed with comparative group. The value of HA, LN, NV-C and PC III in the chronic hepatitis group was significantly higher than that in the normal comparative group. Conclusion The levels of serum HA LN IV-C and PC III are in concert with the degree of hepatic fibrosis, and these indexes are valuable for chronic hepatitis diagnoses combined with the clinic. LN and PC III are coincidence with hepatic fibrosis degree before G4 period.

An H(+)-PPase gene, TsVP from Thellungiella halophila, was transferred into two cotton (Gossypium hirsutum) varieties (Lumianyan19 and Lumianyan 21) and southern and northern blotting analysis showed the foreign gene was integrated into the cotton genome and expressed. The measurement of isolated vacuolar membrane vesicles demonstrated that the transgenic plants had higher V-H(+)-PPase activity compared with wild-type plants (WT). Overexpressing TsVP in cotton improved shoot and root growth, and transgenic plants were much more resistant to osmotic/drought stress than the WT. Under drought stress conditions, transgenic plants had higher chlorophyll content, improved photosynthesis, higher relative water content of leaves and less cell membrane damage than WT. We ascribe these properties to improved root development and the lower solute potential resulting from higher solute content such as soluble sugars and free amino acids in the transgenic plants. In this study, the average seed cotton yields of transgenic plants from Lumianyan 19 and Lumianyan 21 were significantly increased compared with those of WT after exposing to drought stress for 21 days at flowering stage. The average seed cotton yields were 51 and 40% higher than in their WT counterparts, respectively. This study benefits efforts to improve cotton yields in arid and semiarid regions.

Gene expression profiles and single-nucleotide polymorphism (SNP) profiles are modern data for genetic analysis. It is possible to use the two types of information to analyze the relationships among genes by some genetical genomics approaches. In this study, gene expression profiles were used as expression traits. And relationships among the genes, which were co-linked to a common SNP(s), were identified by integrating the two types of information. Further research on the co-expressions among the co-linked genes was carried out after the gene-SNP relationships were established using the Haseman-Elston sib-pair regression. The results showed that the co-expressions among the co-linked genes were significantly higher if the number of connections between the genes and a SNP(s) was more than six. Then, the genes were interconnected via one or more SNP co-linkers to construct a gene-SNP intermixed network. The genes sharing more SNPs tended to have a stronger correlation. Finally, a gene-gene network was constructed with their intensities of relationships (the number of SNP co-linkers shared) as the weights for the edges.

The electrochemiluminescence (ECL) of Tb3+-enoxacin-Na2SO3 system (ENX system) and Tb3+-ofloxacin-Na2SO3 system (OFLX system) in aqueous solution is reported. ECL is generated by the oxidation of Na2SO3, which is enhanced by Tb3+-fluoroquinolone (FQ) complex. The ECL intensity peak versus potential corresponds to oxidation of Na2SO3, and the ECL emission spectra (the peaks are at 490, 545, 585 and 620 nm) match the characteristic emission spectrum of Tb3+, indicating that the emission is from the excited state of Tb3+. The mechanism of ECL is proposed and the difference of ECL intensity between ENX system and OFLX system is explained. Conditions for ECL emission were optimized. The linear range of ECL intensity versus concentrations of pharmaceuticals is 2.0 x 10(-10) -8.0 x 10(-7)mol l(-1) for ENX and 6.0 x 10(-10) -6.0 x 10(-7)mol l(-1) for OFLX, respectively. A theoretical limit of detection is 5.4 x 10(-11)mol l(-1) for ENX and 1.6 x 10(-10)mol l(-1) for OFLX, respectively. The ECL was satisfactorily applied to the determination of the two FQs in dosage form and urine sample.

The potential energy surfaces of isomerization, dissociation, and elimination reactions for CH3CH2COCl in the S0 and S1 states have been mapped with the different ab initio calculations. Mechanistic photodissociation of CH3CH2COCl at 266 nm has been characterized through the computed potential energy surfaces, the optimized surface crossing structure, intrinsic reaction coordinate, and ab initio molecular dynamics calculations. Photoexcitation at 266 nm leads to the CH3CH2COCl molecules in the S1 state. From this state, the C-Cl bond cleavage proceeds in a time scale of picosecond in the gas phase. The barrier to the C-Cl bond cleavage on the S1 surface is significantly increased by effects of the matrix and the internal conversion to the ground state prevails in the condensed phase. The HCl eliminations as a result of internal conversion to the ground state become the dominant channel upon photodissociation of CH3CH2COCl in the argon matrix at 10 K.

A simple electrogenerated chemiluminescence (ECL) analysis method for the determination of norfloxacin (NFLX) is reported. It is based on ECL produced by Na(2)SO(3), which is sensitized by the Tb-NFLX complex. The relative ECL intensity of the Tb(3+)-NFLX-Na(2)SO(3) system is proportional to the amount of NFLX. The optimized experimental conditions were investigated. The linear range and detection limit for NFLX were 1.0 x 10(-10)-8.0 x 10(-7) mol/L and 2.8 x 10(-11) mol/L, respectively. This method was successfully applied to the determination of NFLX in a capsule. NFLX in urine can be directly detected without pretreatment or separation.