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Thioredoxin reductase (TrxR) is a pivotal antioxidant enzyme, but there remains a challenge for its fast imaging. This work describes the combination of a hydroxyl styrylpyridinium scaffold as the push-pull fluorophore with a carbonate-bridged 1,2-dithiolane unit as the reaction site to develop a fast mitochondrial TrxR2 probe, DSMP . It manifested a plethora of excellent properties including a rapid specific response (12 min), large Stokes shift (170 nm), ratiometric two-photon imaging, favorable binding with TrxR ( K m = 12.5 ± 0.2 μM), and the ability to cross the blood-brain barrier. With the aid of DSMP , we visualized the increased mitochondrial TrxR2 activity in cancer cells compared to normal cells. This offers the direct imaging evidence of the connection between the increased TrxR2 activity and the development of cancer. Additionally, the probe allowed the visualization of the loss in TrxR2 activity in a cellular Parkinson's disease model and, more importantly, in mouse brain tissues of a middle cerebral artery occlusion model for ischemic stroke.

Background: To determine risk factors for intestinal necrosis in intussusception cases among children with failed non-surgical reduction for intussusception., Methods: Totally, 540 hospitalized individuals with unsuccessful air-enema reduction in our hospital between November 2010 and November 2020 were assessed in this retrospective study. The 540 intussusception cases were divided into the intestinal necrosis and non-intestinal necrosis groups. Haemostatic parameters, demographic and clinical features were assessed. Predictors of intestinal necrosis were examined by univariable and multivariable logistic regression analyses., Results: Of the 540 patients included, 113 showed intestinal necrosis. This intestinal necrosis group had a longer duration of symptom or length of illness, younger ages, higher platelet counts, fibrinogen amounts and d-dimer levels (all P = 0.000) compared with the non-intestinal necrosis group. Multivariable analysis revealed that duration of symptom (odds ratio (OR) 1.12; 95% confidence interval (CI) 1.16-1.23, P = 0.000), fibrinogen (OR 1.26; 95% CI 1.10-1.31, P = 0.010) and d-dimer (OR 2.07; 95% CI 1.91-2.28, P = 0.000) independently predicted intestinal necrosis in individuals undergoing surgical reduction for intussusception. Receiver operating characteristic curve analysis showed that d-dimer amounts had the largest area under the curve for predicting intestinal necrosis., Conclusion: On admission, long duration of symptom, high fibrinogen and d-dimer levels are critical risk factors for intestinal necrosis development in children with unsuccessful non-surgical reduction. d-Dimer levels have the best predictive value for intestinal necrosis., (© 2021 Royal Australasian College of Surgeons.)

P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a phenomenon in which cells become resistant to structurally and mechanistically unrelated drugs resulting in low intracellular drug concentrations. It is one of the noteworthy problems in malignant tumor clinical therapeutics. So P-gp protein is one of the ideal targets to solve MDR. Based on the lead compound 5m obtained from our previous work, a series of furan derivatives featuring alkyl-substituted phenols and 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline were designed and synthesized as reversal agents against P-gp in this paper. Compound 16 containing isopropoxy possessed good potency against P-gp mediated MDR in MCF-7/ADR (IC 50 (doxorubicin) = 0.73 μM, RF = 69.6 with 5 μM 16 treated). Western blot results and Rh123 accumulation assays showed that 16 effectively inhibited P-gp efflux function but not its expression. The preliminary structure-activity relationship and docking studies demonstrated that compound 16 would be a potential P-gp inhibitor. Most worthy of mention is that compound 16 has achieved satisfactory results in combination with a variety of anti-tumor drugs, such as doxorubicin, paclitaxel, and vincristine. This study forwards a hopeful P-gp inhibitor for withstanding malignant tumor cell with multidrug resistance setting the basis for further studies., 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 © 2021 Elsevier Masson SAS. All rights reserved.)

This work highlights the use of push-pull hydroxylphenylpolyenylpyridinium fluorophores coupled with trimethyl lock quinone to engineer the ratiometric two-photon probes for cellular and intravital imaging of mitochondrial NAD(P)H:quinone oxidoreductase 1 (NQO1), a critical antioxidant enzyme responsible for detoxifying quinones. As a typical representative, QBMP showed favorable binding with NQO1 with a Michaelis constant of 12.74 μM and exhibited a suite of superior properties, including rapid response (4 min), large Stokes shift (162 nm), ultralow detection limit (0.9 nM), favorable two-photon cross section for the released fluorophore (70.5 GM), and deep tissue penetration (225 μm) in fixed brain tissues. More importantly, this probe was successfully applied for distinguishing different NQO1-expressing cancer and normal cells, revealing decreased NQO1 activity in a cellular Parkinson's disease model, screening NQO1 inducers as neuroprotective agents, and imaging of NQO1 in live mouse brain.

Gut microbial β -glucuronidase (GUS) is a potential therapeutic target to reduce gastrointestinal toxicity caused by irinotecan. In this study, the inhibitory effects of 17 natural cinnamic acid derivatives on Escherichia coli GUS (EcGUS) were characterised. Seven compounds, including caffeic acid ethyl ester (CAEE), had a stronger inhibitory effect (IC 50 = 3.2-22.2 µM) on EcGUS than the positive control, D-glucaric acid-1,4-lactone. Inhibition kinetic analysis revealed that CAEE acted as a competitive inhibitor. The results of molecular docking analysis suggested that CAEE bound to the active site of EcGUS through interactions with Asp163, Tyr468, and Glu504. In addition, structure-activity relationship analysis revealed that the presence of a hydrogen atom at R 1 and bulky groups at R 9 in cinnamic acid derivatives was essential for EcGUS inhibition. These data are useful to design more potent cinnamic acid-type inhibitors of EcGUS.

Targeting redox vulnerability of cancer cells by pro-oxidants capable of generating reactive oxygen species (ROS) has surfaced as an important anticancer strategy. Due to the intrinsic narrow therapeutic window and other dangerous side effects of ROS generation, it is highly needed and challenging to develop pro-oxidative anticancer agents (PAAs) with high selectivity for generating ROS in cancer cells. Herein we report a hydrogen peroxide (H 2 O 2 )-activated Cu(II) pro-ionophore strategy to develop naphthazarin (Nap) as such type of PAAs based on the H 2 O 2 -mediated conversion of boronate to free phenol. The boronate-protected Nap (PNap) can exploit increased levels of H 2 O 2 in HepG2 cells to in situ release Nap followed by its efflux via conjugation with reduced glutathione (GSH), allowing that the Nap-GSH adduct works as a Cu(II) ionophore to induce continuously GSH depletion via a reduction-dependent releasing of Cu(I) by GSH. This strategy endows PNap with the unprecedented ability to hit multi-redox characteristics (increased levels of H 2 O 2 , GSH and copper) of HepG2 cells, leading to ROS generation preferentially in HepG2 cells along with their selective death., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To investigate the self-reported prevalence, clinical characteristics, complications of allergic rhinitis (AR) and the sensitization of outdoor air pollen allergens in children in the Inner mongolia grassland region. Methods: A multistage, stratified and random clustered sampling with a face-to-face interview survey study in children from 0 to 17 years old was performed together with 10 common allergen skin prick tests (SPT) and measurements of the daily pollen count in 6 regions in the Inner mongolia grassland region from May to August of 2015. SAS 9.4 software was used for data analysis. Results: A total of 2 443 subjects completed the study. The self-reported prevalence of AR was 26.6%. The prevalence of boys was higher than that of girls (28.8% vs 24.3%, χ(2)=6.157, P< 0.05). Subjects from urban areas showed higher prevalence than rural areas (34.7% vs 18.8%, χ(2)=79.107, P< 0.05). There was significant regional difference in the prevalence of AR among the six areas investigated (χ(2)=221.416, P< 0.05). The main clinical symptoms of AR were sneezing (88.2%) and nasal congestion (78.6%). Among combined diseases, asthma accounted for 16.5% (107/650), rhinoconjunctivitis accounted for 47.9% (311/650). The peak season of AR was April and July, with the top SPT positive allergens of Artemisia species and chenopodium in this area. Conclusions: The prevalence AR in children in the Inner mongolia grassland region is extremely high. Sneezing is the main clinical symptom. Rhinoconjunctivitis is the most common combined disease. High summer and autumn pollen exposure is the main cause of AR.

Developing concise theranostic prodrugs is highly desirable for personalized and precision cancer therapy. Herein we used the glutathione (GSH)-mediated conversion of 2,4-dinitrobenzenesulfonates to phenols to protect a catechol moiety and developed stable pro-catechol-type diphenylpolyenes as small molecule-based prooxidative anticancer theranostic prodrugs. These molecules were synthesized via a modular route allowing creation of various pro-catechol-type diphenylpolyenes. As a typical representative, PDHH demonstrated three unique advantages: (1) capable of exploiting increased levels of GSH in cancer cells to in situ release a catechol moiety followed by its in situ oxidation to o-quinone, leading to preferential redox imbalance (including generation of H 2 O 2 and depletion of GSH) and final selective killing of cancer cells over normal cells, and is also superior to 5-fluorouracil and doxorubicin, the widely used chemotherapy drugs, in terms of its ability to kill preferentially human colon cancer SW620 cells (IC 50  = 4.3 μM) over human normal liver L02 cells (IC 50  = 42.3 μM) with a favourable in vitro selectivity index of 9.8; (2) permitting a turn-on fluorescent monitoring for its release, targeting mitochondria and therapeutic efficacy without the need of introducing additional fluorophores after its activation by GSH in cancer cells; (3) efficiently targeting mitochondria without the need of introducing additional mitochondria-directed groups., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Compared with normal cells, cancer cells harbor increased levels of reactive oxygen species (ROS) including hydrogen peroxide (H 2 O 2 ), and therefore are more vulnerable to further ROS production. This biochemical difference favors the idea of developing new powerful selective prooxidative anticancer agents. However, it still remains a challenge to design them by targeting this difference. Herein, we report the designed dichlorobinaphthoquinone as a prooxidative anticancer agent which is capable of exploiting increased levels of H 2 O 2 of cancer cells to produce in situ lethal hydroxyl radicals (HO•) and thereby kill them selectively, a design strategy inspired from Zhu et al.'s work on the molecular mechanism for metal-independent production of HO•., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Altered redox homeostasis including higher levels of copper, reduced glutathione (GSH) and reactive oxygen species (ROS) in cancer cells than in normal cells illustrates their redox vulnerability, and has opened a window for developing prooxidative anticancer agents (PAAs) to hit this status. However, how to design PAAs with high selectivity in killing cancer cells over normal cells remains a challenge. Herein we designed a 3-hydroxyflavone-inspired copper pro-ionophore (PHF) as a potent PAA based on the GSH-mediated conversion of 2,4-dinitrobenzenesulfonates to enols. Mechanistic investigation reveals that it is capable of exploiting increased levels of GSH in cancer cells to in situ release an active ionophore, 3-hydroxyflavone, inducing redox imbalance (copper accumulation, GSH depletion and ROS generation) and achieving highly selective killing of cancer cells upon specific transport of small amounts of Cu(II). To the best of our knowledge, it is the first example of Cu(II) pro-ionophore type of PAA which hits (changes) the three birds (abnormal copper, GSH and ROS levels in cancer cells) with one stone (PHF) in terms of its ability to induce preferentially redox imbalance of cancer cells by copper accumulation, GSH depletion and ROS generation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to investigate the prevalence of epidemiologic and physician-diagnosed pollen-induced AR (PiAR) in the grasslands of northern China and to study the impact of the intensity and time of pollen exposure on PiAR prevalence., Methods: A multistage, clustered and proportionately stratified random sampling with a field interviewer-administered survey study was performed together with skin prick tests (SPT) and measurements of the daily pollen count., Results: A total of 6043 subjects completed the study, with a proportion of 32.4% epidemiologic AR and 18.5% PiAR. The prevalence was higher in males than females (19.6% vs 17.4%, P = .024), but no difference between the two major residential and ethnic groups (Han and Mongolian) was observed. Subjects from urban areas showed higher prevalence of PiAR than rural areas (23.1% vs 14.0%, P < .001). Most PiAR patients were sensitized to two or more pollens (79.4%) with artemisia, chenopodium, and humulus scandens being the most common pollen types, which were similarly found as the top three sensitizing pollen allergens by SPT. There were significant regional differences in the prevalence of epidemiologic AR (from 18.6% to 52.9%) and PiAR (from 10.5% to 31.4%) among the six areas investigated. PiAR symptoms were positively associated with pollen counts, temperature, and precipitation (P < .05), but negatively with wind speed and pressure P < .05)., Conclusion: Pollen-induced AR (PiAR) prevalence in the investigated region is extremely high due to high seasonal pollen exposure, which was influenced by local environmental and climate conditions., (© 2018 The Authors. Allergy Published by John Wiley and Sons Ltd.)

Altered redox status including higher levels of copper in cancer cells than in normal cells inspired many researchers to develop copper ionophores targeting this status. We have recently found that flavon-3-ol (3-HF) works as a potent Cu(II) ionophore by virtue of its keto-enol moiety. To further emphasize the significance of this moiety for developing Cu(II) ionophores, we herein designed a β-diketo analog of piperlongumine, PL-I, characterized by the presence of high proportion of the keto-enol form in dimethylsulfoxide and chloroform, and identified its keto-enol structure by NMR and theoretical calculations. Benefiting from deprotonation of its enolic hydroxyl group, this molecule is capable of facilitating the transport of Cu(II) through cellular membranes to disrupt redox homeostasis of human hepatoma HepG2 cells and trigger their death., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Kidney stones are a common urinary system condition that can progress to kidney disease. Previous studies on the association between tea consumption and kidney stones are inconsistent. A cross-sectional study to investigate the association between tea consumption and kidney stones was conducted from 2013 to 2014 and recruited 9,078 northern Chinese adults. A total of 8,807 participants were included in the final analysis. Participants' prevalence of kidney stones was 1.07%, 1.73%, and 2.25% based on their tea consumption frequency of never, occasionally, and often groups, respectively. Compared with the 'never' group, the odds ratios (95% confidence intervals) for the occurrence of kidney stones were 1.57 (1.00-2.46) and 1.65 (1.06-2.57) in the 'occasionally' and 'often' groups, respectively. After adjusting for sex, age, and other potential confounding factors, tea consumption still significantly increased the risk of kidney stones. Tea consumption is independently associated with an increased risk of kidney stones in the investigated population, suggesting that a decrease in the consumption of tea may be a preventive strategy for kidney stones., (Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Meckel diverticulum is the most prevalent congenital abnormality of the gastrointestinal tract in children. The aim of this study was to review and analyze clinical data on the diagnosis and management of Meckel diverticulum in pediatric patients. The records of 102 pediatric patients (<14 years old) who underwent surgery for Meckel diverticulum at our institute between 2001 and 2015 were reviewed. Clinical, imaging, laboratory, surgical, and pathological data were recorded. The series comprised 65 males and 37 females with a median age of 5.6 years. Lower gastrointestinal bleeding was the most frequently identified clinical manifestation of Meckel diverticulum, and this manifestation was observed in 41 patients. Intussusception secondary to Meckel diverticulum was identified in 32 patients. Twelve patients presented clinical features of peritonitis; of these patients, 8 had perforated Meckel diverticulum and 4 had Meckel diverticulitis. In 10 patients, Meckel diverticulum was incidentally diagnosed during other surgeries, including appendectomy and neonatal enterostomy. Seven patients were diagnosed with intestinal obstruction. Technetium-99m pertechnetate imaging offered high diagnostic yield. Open surgery was performed on 59 patients, while a laparoscopic approach was employed in 35 patients. The remaining 8 patients did not undergo resection of the Meckel diverticulum. Histology revealed ectopic gastric mucosa in 42 patients (44.7%), ectopic pancreatic tissue in 35 patients (37.2%), mucosa of the small intestine in 15 patients (16.0%), and both gastric and pancreatic ectopic tissue in 2 patients (2.1%). All patients recovered uneventfully except 2 patients in whom an intestinal adhesion obstruction was identified after discharge. Meckel diverticulum had various clinical manifestations in children. Technetium-99m pertechnetate imaging may be useful for diagnosing Meckel diverticulum. Surgical excision of the Meckel diverticulum may be safe and effective in symptomatic patients, and relatively better outcomes can be achieved using this approach.

A main biochemical property of cancer cells, compared with normal cells, is altered redox status including increased levels of copper to maintain their malignant phenotypes. Thus, increasing copper accumulation, by using ionophores, to disrupt abnormal redox homeostasis of cancer cells may be an important anticancer strategy. Naturally occurring molecules with extraordinarily diverse chemical scaffolds are an important source of inspiration for developing copper ionophores. Dietary flavonoids are well-characterized copper chelators and show cancer chemopreventive potential, but their ionophoric role for redox-active copper and the related biological implications have remained unknown. This study reports, for the first time, the structural basis, chemical driving forces and biological implications of flavones (a widely distributed subgroup of flavonoids) as Cu(II) ionophores, and also provides new insights into cancer chemopreventive mechanism of flavones bearing 3(or 5)-hydroxy-4-keto group. 3-Hydroxyflavone surfaced as a potent Cu(II) ionophore to induce the mitochondria-dependent apoptosis of cancer cells in a redox intervention fashion via sequential proton-loss Cu(II) chelation, GSH-driving releasing of copper and protonation-dependent efflux of the neutral ligand., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To assess the benefits of use of a tourniquet in one limb in patients undergoing simultaneous bilateral total knee arthroplasty (TKA)., Methods: A prospective randomized trial was designed to evaluate the outcomes of unilateral tourniquet use during simultaneous bilateral TKA. A total of 52 (36 women and 16 men) patients with osteoarthritis who underwent simultaneous bilateral primary TKA between January 2010 and January 2015 were assigned randomly to tourniquet (TG) or non-tourniquet (NG) groups prior to surgery. Operating time, pain score, range of motion, first active straight-leg raise time, swelling, wound healing, deep vein thrombosis, and Knee Society score were observed., Results: Mean operating time in the TG group was shorter than that in the NG group (P < 0.05). Postoperative pain was measured by a visual analog scale (VAS) and straight-leg raise time, which was lower and shorter in limbs operated without the use of a tourniquet (P < 0.05). In addition, this group had less postoperative swelling and lower incidence of wound complications in the early postoperative period (P < 0.05). There was no significant difference in the range of motion (ROM), deep venous thrombosis incidence, and Knee Society scores between the two groups., Conclusions: Tourniquet use in bilateral TKA can reduce intraoperative time but was associated with a higher incidence of wound complications and larger postoperative knee swelling., (© 2017 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Four novel compounds were designed by "tailoring" 3,3'-dihydroxyisorenieratene (a natural carotenoid) based on an isoprene unit retention truncation strategy. Among them, the smallest molecule 1 (2,3,6,2',3',6'-hexamethyl-4,4'-dihydroxy-trans-stilbene) was concisely synthesized in a one-pot Stille-Heck tandem sequence, and surfaced as a promising lead molecule in terms of its selective antiproliferative activity mediated by blocking the NCI-H460 cell cycle in G1 phase. Additionally, theoretical calculations and cell uptake experiments indicate that the unique polymethylation pattern of compound 1 significantly induces a conformational change shift out of planarity and increases its cell uptake and metabolic stability. The observation should be helpful to rationally design resveratrol-inspired antiproliferative agents., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To explore the maternal-fetal transmission patterns and interventional methods of syphilis during pregnancy., Methods: A total of 847 cases of syphilis in pregnancy confirmed by rapid plasma reagin test (RPR) and treponema pallidum hemoagglutination test (TPHA) were treated with procaine benzylpenicillin intramuscular injection, and with erythrocin oral medication if hypersensitive to benzylpenicillin. Eight hundred forty seven cases of syphilis during pregnancy were followed up for pregnancy outcomes. And their newborn babies were tested using the RPR. The newborns with positive results were given intervention and followed up until 24 months after birth., Results: (1) A total of 733 cases among the total 847 have given birth to living-babies, in which 626 cases were tested using RPR, and the positive rate was 55.1% (345/626). (2) The RPR positive rate, neonatal mortality, preterm birth rate and low birth rate in the newborn of mothers with an RPR titer higher than or at 1:8 were higher than those of mothers with an RPR titer lower than 1:8 (P < 0.01). (3) The neonatal RPR positive rate was related to the timing of the treatment of the women. (1) The neonatal RPR positive rate was 22.4% (15/67) for treatment compared with 49.6% (330/666) for non-treatment before pregnancy (P < 0.01). (2) The positive RPR rate of neonates between treatment before pregnancy and treatment during pregnancy was different, being 22.4% (15/67) and 40.3% (240/595) respectively (P < 0.05) (3) In comparison between treatment both in the early pregnancy and in late pregnancy with only treatment in the late pregnancy, the positive RPR rate of neonates was 28.5% (45/158) and 56.9% (95/167) respectively (P < 0.01). In comparison between treatment both in the mid-term pregnancy and in late pregnancy and treatment in only one period in the terminal, the positive RPR rate of neonates was 37.0% (100/270) and 56.9% (95/167) respectively (P < 0.01)., Conclusions: The maternal-fetal transmission rate and perinatal prognosis are related to maternal RPR titer and the timing of maternal treatment. Inborn syphilis can be prevented and cured in fetal time. For neonates with anti-syphilis treatment in protestation, RPR positive rate is significantly lower than that without treatment in protestation. Treatment prior to pregnancy is a powerful measure to prevent the maternal-fetal transmission of syphilis.

Two arsenic-resistant plasmids were constructed and introduced into Thiobacillus ferrooxidans strains by conjugation. The plasmids with the replicon of wide-host-range plasmid RSF1010 were stable in T. ferrooxidans. The arsenic resistance genes originating from the heterotroph were expressed in this obligately autotrophic bacterium, but the promoter derived from T. ferrooxidans showed no special function in its original host.

The broad-host-range IncP plasmids RP4, R68.45, RP1::Tn501, and pUB307 were transferred to acidophilic, obligately chemolithotrophic Thiobacillus ferrooxidans from Escherichia coli by conjugation. A genetic marker of kanamycin resistance was expressed in T. ferrooxidans. Plasmid RP4 was transferred back to E. coli from T. ferrooxidans. The broad-host-range IncQ vector pJRD215 was mobilized to T. ferrooxidans with the aid of plasmid RP4 integrated in the chromosome of E. coli SM10. pJRD215 was stable, and all genetic markers (kanamycin/neomycin and streptomycin resistance) were expressed in T. ferrooxidans. By the use of suicide vector pSUP1011, transposon Tn5 was introduced into T. ferrooxidans. The influence of some factors on plasmid transfer from E. coli to T. ferrooxidans was investigated. Results showed that the physiological state of donor cells might be important to the mobilization of plasmids. The transfer of plasmids from E. coli to T. ferrooxidans occurred in the absence of energy sources for both donor and recipient.