A Near-Infrared Fluorescent Probe for the Rapid Detection of Nitroxyl in Living Cells.

Nitroxyl (HNO) plays an important role in various physiological activities. It has the potential to be used as a treatment for certain diseases such as alcohol poisoning, acute hypertension, and atherosclerosis. However, traditional methods for detecting HNO are challenging due to its rapid polymerization and elimination into N2O. Therefore, it is crucial to establish direct and effective HNO detection methods to comprehend these physiological processes better. In this study, a new near-infrared fluorescent probe called HXM-P based on the intramolecular charge transfer (ICT) mechanism was designed and synthesized. This probe employs 2-((6-hydroxy-2,3dihydro-1 H-xanthen-4-yl)methylene)malononitrile as a fluorophore and 2-(diphenylphosphine) benzoate as a recognition group. The results showed that probe HXM-P can detect HNO with high sensitivity (1.07 × 10- 8 M). A good linear correlation was observed between the fluorescence intensities at 640 nm and the concentrations of HNO in the range of 0-80 µM (R2 = 0.997). Moreover, probe HXM-P exhibited a rapid response rate (within 15 s) toward HNO, and the fluorescent intensity reached a plateau within 5 min, making it easier to track the highly reactive and short-lived HNO in living systems. Additionally, HXM-P was successfully employed for imaging HNO in HepG2 cells.

Facile synthesis of sulfide Bi13S18I2 as a promising anode material for a lithium-ion battery.

A novel Bi13S18I2 structure was synthesized using a facile one-pot hydrothermal method and further optimized as an anode material using graphene. The graphene/Bi13S18I2 composite achieved a high discharge capacity with an initial value of 1126.5 mA h g-1 and a high and stable discharge capacity of 287.1 mA h g-1 after 500 cycles compared with pure Bi13S18I2, which derives from the inhibited volume expansion and high electrical conductivity obtained from graphene. In situ XRD was performed to analyze the Li storage mechanism in depth. The results support the feasibility of the new ternary sulfide Bi13S18I2 as a promising lithium ion battery.

Efficacy and safety of tai chi exercise on bone health: An umbrella review.

PURPOSE: To critically evaluate systematic reviews (SRs) of the Tai Chi (TC) exercise on bone health and provide more recently available evidence. METHODS: SRs with or without meta-analysis (MA) of TC on bone health were comprehensively searched in eight electronic databases (PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database, and Chinese Scientific Journals Database) and in the international prospective register of systematic reviews of (PROSPERO) from initiation to March 2023. Descriptive analyses of SRs were performed, and reporting and methodological quality of the included SRs were evaluated using the updated version of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2). The certainty of the synthesized evidence was assessed with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Eighteen SRs, 15 with MAs, were included. Forty-nine RCTs and 16 NRSIs with 3956 and 1157 participants, respectively, were included in these SRs. The reporting quality of the included SRs ranged from high to low, but most received critically low AMSTAR-2 scores. Efficacy of TC on nine bone health biomarkers has been explored, covering bone mineral density (BMD) and serum biomarkers. The results showed that compare to non-intervention, perimenopausal and postmenopausal participants who practiced TC may benefit in BMD of the lumbar spine [MD = 0.04, 95% CI (0.02, 0.07)], and femoral neck [MD = 0.04, 95% CI (0.02, 0.06)], but not BMD of the femoral proximal trochanter [MD = 0.02, 95% CI (0.00, 0.03)], ward's triangle [MD = 0.02, 95% CI (-0.01, 0.04)], and femoral shaft [SMD = 0.16, 95% CI (-0.11, 0.44)]. Elders practicing TC may benefit in BMD of the femoral neck [SMD = 0.28, 95% CI (0.10, 0.45)], femoral proximal trochanter [SMD = 0.39, 95% CI (0.05, 0.73)], and ward's triangle [SMD = 0.21, 95% CI (0.05,0.37)], but may not in BMD of lumbar spine [SMD = 0.03, 95% CI (-0.22, 0.27)]. CONCLUSION: We have low certainty that for perimenopausal and postmenopausal women, compare to those with no exercise, TC could improve BMD of the lumbar spine, femoral neck. We also have low certainty that in elder population, TC practitioners may benefit in BMD of femoral neck, and Ward's triangle. REGISTRATION: PROSPERO (CRD42020173543).

Auriculotherapy Modulates Macrophage Polarization to Reduce Inflammatory Response in a Rat Model of Acne.

Background: The inflammatory response is an important part of the pathogenesis of acne vulgaris. Auriculotherapy has been shown to have a good therapeutic effect on this disease. The aim of this study was to explore the mechanism underlying the anti-inflammatory effect of auriculotherapy in the treatment of acne vulgaris. Methods: Propionibacterium acnes was injected subcutaneously into the ears of rats to establish an animal model of acne. The auriculotherapy intervention in rats consisted of auricular bloodletting therapy (ABT), auricular point sticking (APS), or a combination of both (ABPS). The anti-inflammatory effects of auriculotherapy were evaluated by measuring changes in ear thickness, local body surface microcirculation in the ear, and serum inflammatory factors in rats. The polarization of macrophages was analyzed by flow cytometry, and the expression of TLR2/NF-κB signaling pathway in the target tissues was analyzed using western blot. Results: ABT, APS, and ABPS all reduced the erythema of ear acne, decreased microcirculation in localized ear acne, and decreased serum levels of TNF-α and IL-1ß in rats. Meanwhile, the three interventions reduced M1-type macrophages and increased M2-type macrophages; only APS could reduce the expression of TLR2/NF-κB signaling pathway. Conclusion: ABT, APS, and ABPS can improve the inflammatory symptoms of acne and reduce inflammatory cytokines. APS may exert anti-inflammatory effects by altering macrophage polarization and decreasing TLR2/NF-κB expression.

A tetraphenylethene-based Schiff base AIEgen with a large Stokes shift as probe for highly sensitive and selective detection of aqueous Cu2+ ions and its application in cell imaging.

In this work, an AIE-active tetraphenylethene-based Schiff base fluorescent probe 3 with a large Stokes shift (247 nm) was designed and synthesized. It was found that the aggregated probe 3 exhibited very high selectivity and anti-interference ability for Cu2+ in PBS buffer (70% fw) through a fluorescence "turn-off" strategy. Job's plot and NMR analysis indicated the two phenolic hydroxyl groups of the benzene ring and the N atom (-CH=N-) on probe 3 interacted with Cu2+ ions in a 1:1 stoichiometric ratio. A comprehensive analysis of the Stern-Volmer and binding constant indicated a rather strong interaction between probe 3 and Cu2+ ions. Probe 3 illustrated excellent sensitivity toward Cu2+ under ppb level (4.5 nM) and achieved more than 95% recovery in river, lake and tap water toward estimation of Cu2+ ions in the analytical applications. Moreover, probe 3 was able to realize bioimaging of HepG2 cells and be quenched by intracellular Cu2+ ions, making it promising as a sensitive Cu2+ sensor for organisms.

Regulation of wound healing and fibrosis by galectins.

Galectins are a family of proteins with at least one carbohydrate-recognition domain. Galectins are present in various tissues and organs and participate in different physiological and pathological molecular reactions in vivo. Wound healing is the basic process of traumatic disease recovery. Wound healing involves three overlapping stages: inflammation, proliferation, and remodelling. Furthermore, a comparison of wound healing with the tumour microenvironment revealed that galectin plays a key role in the wound healing process. The current review describes the role of galectin in inflammation, angiogenesis, re-epithelialisation, and fibrous scar formation and evaluates its potential as a therapeutic drug for wounds.

Design and Synthesis of Novel Betulin Derivatives Containing Thio-/Semicarbazone Moieties as Apoptotic Inducers through Mitochindria-Related Pathways.

Two new series of betulin derivatives with semicarbazone (7a-g) or thiosemicarbazone (8a-g) groups at the C-28 position were synthesized. All compounds were evaluated for their in vitro cytotoxicities in human hepatocellular carcinoma cells (HepG2), human breast carcinoma cells (MCF-7), human lung carcinoma cells (A549), human colorectal cells (HCT-116) and normal human gastric epithelial cells (GES-1). Among these compounds, 8f displayed the most potent cytotoxicity with an IC50 value of 5.86 ± 0.61 µM against MCF-7 cells. Furthermore, the preliminary mechanism studies in MCF-7 cells showed that compound 8f could trigger the intracellular mitochondrial-mediated apoptosis pathway by losing MMP level, which was related with the upregulation of Bax, P53 and cytochrome c expression; the downregulation of Bcl-2 expression; activation of the expression levels of caspase-3, caspase-9, cleaved caspase-3 and cleaved caspase-9; and an increase in the amounts of intracellular reactive oxygen species. These results indicated that compound 8f may be used as a valuable skeleton structure for developing novel antitumor agents.

Applying molecular networking for targeted isolation of depsipeptides.

LC-HRMS/MS molecular networking enabled the targeted isolation of three new neoantimycin analogs (1, 3, 5) and two known ones (2, 4) from the culture broth of Streptomyces conglobatus RJ8. After derivatization into C1-hydroxyl form compounds (6-10) respectively, the absolute structures of 1-5 were clearly determined by analyzing the hydrolyzed components from 6-10. Compounds 2 and 3 were confirmed to be a pair of epimers with different stereochemistry at C-2, and so were 4 and 5. This is the first report of the isolation and characterization of epimers of NATs. The most abundant eight compounds we obtained were subjected to a cytotoxicity assay, 1 and 6 exhibited excellent cytotoxicity with the lowest IC50 value in the picomolar range against six human carcinoma cell lines while 7 and 8 showed potent cytotoxicity against PC-9 and PC-9/GR cell lines.

Corrigendum to "Selection of quality markers of Jasminum amplexicaule based on its anti-diarrheal and anti-inflammatory activities: Effect-target affiliation-traceability-pharmacokinetics strategy" [Chinese Herbal Medicines 11 (2019) 379-386].

[This corrects the article DOI: 10.1016/j.chmed.2019.08.002.].

Corrigendum to “Selection of quality markers of Jasminum amplexicaule based on its anti-diarrheal and anti-inflammatory activities: Effect-target affiliation-traceability-pharmacokinetics strategy” Chinese Herbal Medicines 11 (2019) 379–386 (Chinese Herbal Medicines (2019) 11(4) (379–386), (S167463841930070X), (10.1016/j.chmed.2019.08.002)) / 中草药·英文版

When this paper was first published the following ethical statement was omitted in error: All animal experimental protocols were approved by the Animal Ethics Committee of Guangdong Provincial Engineering Technology Institute of Traditional Chinese Medicine (Guangzhou, Guangdong, China, Approval NO: 048483). Further, all methods were performed in accordance with the relevant guidelines and regulations. NIH mice were purchased from the Guangdong Medical Laboratory Animal Center (Guangzhou, Guangdong, China, Certificate NO.44007200031795). The authors would like to apologise for any inconvenience caused.

Flavonoid analogues as urease inhibitors: Synthesis, biological evaluation, molecular docking studies and in-silico ADME evaluation.

A series of novel flavonoid analogues were designed and synthesized. The aimed compounds for urease inhibitory activities were clearly superior to the control drug thiourea (more than 10 times). Among these compounds, L2 (IC50 = 1.343 µM) and L12 (IC50 = 1.207 µM) exhibited the most excellent urease inhibitory activity in vitro. The molecular dockings of L2, L12 and L22 into urease were performed to explore the binding modes and their structure-activity relationship. Furthermore, these aimed compounds showed good druggable properties.

Epidemiological and PK/PD cutoff values determination and PK/PD-based dose assessment of gamithromycin against Haemophilus parasuis in piglets.

BACKGROUND: Gamithromycin is a macrolide approved for the treatment of bovine and swine respiratory diseases. Our study aims to establish the clinical breakpoint and optimum dose regimen for gamithromycin against Haemophilus parasuis in piglets. RESULTS: Gamithromycin was well absorbed and fully bioavailable (87.2-101%) after intramuscular and subcutaneous administrations. The MICs of gamithromycin for 192 clinical H. parasuis isolates ranged from 0.008 to 128 mg/L and the epidemiological cutoff (ECOFF) was calculated as 1.0 mg/L. A large potentiation effect of serum on in vitro susceptibility of gamithromycin was observed for H. parasuis, with broth/serum ratios of 8.93 for MICs and 4.46 for MBCs, respectively. The postantibiotic effects were 1.5 h (1 × MIC) and 2.4 h (4 × MIC), and the postantibiotic sub-MIC effects ranged from 2.7 to 4.3 h. Gamithromycin had rapid and concentration-dependent killing against H. parasuis, and the AUC24h/MIC ratio correlated well with ex vivo efficacy (R2 = 0.97). The AUC24h/MIC targets in serum associated with bacteriostatic, bactericidal and eradication activities were 15.8, 30.3 and 41.2, respectively. The PK/PD-based population dose prediction indicated a probability of target attainment (PTA) for the current marketed dose (6 mg/kg) of 88.9% against H. parasuis. The calculated gamithromycin dose for a PTA ≥ 90% was 6.55 mg/kg. Based on Monte Carlo simulations, the PK/PD cutoff (COPD) was determined to be 0.25 mg/L. CONCLUSION: The determined cutoffs and PK/PD-based dose prediction will be of great importance in gamithromycin resistance surveillance and serve as an important step in the establishment of optimum dose regimen and clinical breakpoints.

Novel Steroidal 5α,8α-Endoperoxide Derivatives with Semicarbazone/Thiosemicarbazone Side-chain as Apoptotic Inducers through an Intrinsic Apoptosis Pathway: Design, Synthesis and Biological Studies.

A series of novel steroidal 5α,8α-endoperoxide derivatives bearing semicarbazone (7a-g) or thiosemicarbazone (7h-k) side chain were designed, synthesized and evaluated for their cytotoxicities in four human cancer cell lines (HepG2, HCT-116, MCF-7, and A549) using the MTT assay in vitro. The results showed that compound 7j exhibited significant cytotoxic activity against HepG2 cells (IC50 = 3.52 µM), being more potent than ergosterol peroxide. Further cellular mechanism studies in HepG2 cells indicated that compound 7j triggered the mitochondrial-mediated apoptosis by decreasing mitochondrial membrane potential (MMP), which was associated with up-regulation of Bax, down-regulation of Bcl-2, activation levels of the caspase cascade, and formation of reactive oxygen species (ROS). The above findings indicated that compound 7j may be used as a promising skeleton for antitumor agents with improved efficacy.

Design, synthesis and biological evaluation of novel 5α, 8α-endoperoxide steroidal derivatives with hybrid side chain as anticancer agents.

A series of novel 5α, 8α-endoperoxide steroidal hybrid derivatives containing isatin or indole substituents on the C-17 side chain were synthesized and characterized. The preliminary anti-proliferative activity of the compounds against HepG2, MCF-7, HT-29 and HeLa cell lines were investigated. Compounds 7g and 7l displayed significant anti-proliferative activity in vitro against HepG2 and Hela cells, with IC50 values lower than 8 µM. Furthermore, the biological functions of 7g were examined by flow cytometry and colony analysis. The results showed that 7g could induce HepG2 cell apoptosis, inhibited cell cycle progression, and colony growth. The studies indicated that structural modification at C-17 position could be a promising launch point for design steroidal anticancer agents.

Nomogram predicting overall survival of rectal squamous cell carcinomas patients based on the SEER database: A population-based STROBE cohort study.

We aimed to evaluate the prognostic value of clinical and pathologic factors in rectal squamous cell carcinomas (SCC) and to construct a nomogram for their outcome prediction.The study cohort was selected from Surveillance, Epidemiology, and End Results (SEER) program between January 2004 and December 2013. Univariate and multivariate analyses were performed using Cox proportional hazards regression model to evaluate the prognostic value of involved variables. All prognostic factors were combined to construct a nomogram to predict the overall survival (OS), followed by discrimination as well as calibration plots and receiver operating characteristic (ROC) curves for assessing the predictive accuracy of the nomogram.We identified 806 patients with a median follow-up time of 35 months. Multivariate analyses revealed that marital status (P < .001), age (P < .001), T stage (P = .008), M stage (P < .001), surgery (P = .004), chemotherapy (P = .003) and radiotherapy (P = .016) were independent prognostic factors of OS. Finally, the 7 variables were combined to construct a 3-year and 5-year OS nomogram. The concordance indexes (C-indexes) of OS were 0.756 (95% CI, 0.726-0.786) for the internal validation and 0.729 (95% CI, 0.678-0.780) for the external validation. Additionally, there was superior discrimination power of the nomogram over the SEER stage or the 8th edition AJCC TNM staging classification (P < .001). Calibration plots further showed good consistency between the nomogram prediction and actual observation. The area under the curve (AUC) of ROC curves for 3-year OS was 0.811 (95% CI: 0.769-0.853) in the training cohort and 0.748 (95% CI: 0.681-0.815) in the validation cohort. The AUC for 5-year OS was 0.770 (95% CI: 0.721-0.819) in the training cohort and 0.797 (95% CI: 0.731-0.863) in the validation cohort. Finally, Kaplan-Meier analysis further validates the predictive potential of the nomogram.Marital status, age, T stage, M stage, surgery, chemotherapy and radiotherapy were significantly associated with OS of patients with rectal SCC. This predictive model has the potential to provide an individualized risk estimate of survival in patients with rectal SCC.

Synthesis of Ergosterol Peroxide Conjugates as Mitochondria Targeting Probes for Enhanced Anticancer Activity.

Inspired by the significant bioactivity of ergosterol peroxide, we designed and synthesized four fluorescent coumarin and ergosterol peroxide conjugates 8a-d through the combination of ergosterol peroxide with 7-N,N-diethylamino coumarins fluorophore. The cytotoxicity of synthesized conjugates against three human cancer cells (HepG2, SK-Hep1, and MCF-7) was evaluated. The results of fluorescent imaging showed that the synthesized conjugates 8a-d localized and enriched mainly in mitochondria, leading to significantly enhanced cytotoxicity over ergosterol peroxide. Furthermore, the results of biological functions of 8d showed that it could suppress cell colony formation, invasion, and migration; induce G2/M phase arrest of HepG2 cells, and increase the intracellular ROS level.

Increased activity of linezolid in combination with rifampicin in a murine pneumonia model due to MRSA.

Objectives: The chloramphenicol/florfenicol resistance gene cfr, which mediates cross-resistance to linezolid and other classes of antimicrobial agents, represents a global therapeutic challenge due to its dissemination among MDR nosocomial pathogens, including MRSA. This study aimed to compare the efficacy of the linezolid/rifampicin combination in a murine pneumonia model caused by cfr-positive and cfr-negative clinical MRSA strains. Methods: Synergistic activity between linezolid and rifampicin was evaluated by chequerboard and time-kill assays. Pharmacokinetic profiles in plasma and epithelial lining fluid (ELF) as well as the therapeutic efficacy of linezolid alone and in combination with rifampicin were investigated in a murine pneumonia model. The Emax Hill equation was used to model the dose-response relationship. Results: Increased susceptibility of the study MRSA strains to linezolid was observed with the rifampicin combination (MIC decreased 2- to 16-fold versus linezolid alone). The combination had synergistic activity (fractional inhibitory concentration index ≤0.5) against all cfr-positive MRSA isolates. Linezolid demonstrated excellent pulmonary penetration with an ELF/fplasma AUC ratio of 2.68 ±âŸ0.17. The addition of rifampicin significantly improved the efficacy of linezolid in the pneumonia model due to cfr-positive and cfr-negative MRSA strains. The fAUC/MIC targets of linezolid associated with stasis, 1 log10 kill and 2 log10 kill were 15.9, 38.8 and 175 in plasma, and 43.5, 108 and 415 in ELF, respectively. Importantly, the linezolid fAUC/MIC targets in both plasma and ELF were 2.4-6.7 times lower in combined linezolid/rifampicin therapy versus linezolid monotherapy (P < 0.005). Conclusions: Combination of linezolid with rifampicin significantly improved the efficacy of linezolid in the murine pneumonia model caused by MRSA strains in the presence and absence of the cfr gene.

A new oxoaporphine from Sabia limoniacea var. ardisioides / 药学学报

The chemical constituents of Sabia limoniacea var. ardisioides were investigated using chroma­tographic methods, such as silica gel, Sephadex LH-20 and preparative HPLC. Eight compounds were isolated and their structures were elucidated by spectral data and physicochemical properties, which were identified as 5-methoxy-1,2-methylenedioxyl oxoaporphine (1), fuseine (2), N-p-feruloyltyramine (3), N-trans-coumaroyl tyramin (4), quercetin (5), rutin (6), mutabiloside (7), and protocatechuic acid (8). Among those, compound 1 is a new compound, compounds 2−8 were isolated from this plant for the first time.

Establishment of UPLC fingerprints of Jasminum elongatum and determination of two constituents / 中成药

AIM To establish the UPLC fingerprints of Jasminum elongatum (Bergium) Wild.and to determine the contents of isochlorogenic acid B and ethylcaffeate.METHODS The analysis of methanol extract of J.elongatum was developed on a 25 ℃ thermostatic Agilent Ecplise XDB-C18 column (2.1 mm × 100 mm,1.7 μm),with the mobile phase comprising of acetonitrile-0.1％ methanoic acid flowing at 0.5 mL/min in a gradient elution manner,and the detection wavelength was set at 260 nm.RESULTS There were eighteen common peaks in the fingerprints of ten batches of samples,with the similarities of more than 0.85.Isochlorogenic acid B and ethylcaffeate showed good linear relationships within the ranges of 7.67-38.35 μg/mL (R2 =0.999 4),9.60-96.0 μg/mL (R2 =0.999 7),whose average recoveries were 98.61％,99.09％ with the RSDs of 0.84％,1.25％,respectively.CONCLUSION This stable and reliable method can be used for the quality control of J.elongatum.