Selective enhanced cytotoxicity of amino acid deprivation for cancer therapy using thermozyme functionalized nanocatalyst.

BACKGROUND: Enzyme therapy based on differential metabolism of cancer cells has demonstrated promising potential as a treatment strategy. Nevertheless, the therapeutic benefit of reported enzyme drugs is compromised by their uncontrollable activity and weak stability. Additionally, thermozymes with high thermal-stability suffer from low catalytic activity at body temperature, preventing them from functioning independently. RESULTS: Herein, we have developed a novel thermo-enzymatic regulation strategy for near-infrared (NIR)-triggered precise-catalyzed photothermal treatment of breast cancer. Our strategy enables efficient loading and delivery of thermozymes (newly screened therapeutic enzymes from thermophilic bacteria) via hyaluronic acid (HA)-coupled gold nanorods (GNRs). These nanocatalysts exhibit enhanced cellular endocytosis and rapid enzyme activity enhancement, while also providing biosafety with minimized toxic effects on untargeted sites due to temperature-isolated thermozyme activity. Locally-focused NIR lasers ensure effective activation of thermozymes to promote on-demand amino acid deprivation and photothermal therapy (PTT) of superficial tumors, triggering apoptosis, G1 phase cell cycle arrest, inhibiting migration and invasion, and potentiating photothermal sensitivity of malignancies. CONCLUSIONS: This work establishes a precise, remotely controlled, non-invasive, efficient, and biosafe nanoplatform for accurate enzyme therapy, providing a rationale for promising personalized therapeutic strategies and offering new prospects for high-precision development of enzyme drugs.

Theoretical Study on the Mechanism of the Hydrogenation of Azo (N═N) Bonds to Amines Catalyzed by Manganese.

The mechanism of the transition metal manganese complex Mn(PhPNN)(CO)2Br (CA-4) that catalyzed the hydrogenation of the azo (N═N) bond to amines has been investigated using the PBE0 function. The results show that the whole reaction involves three basic processes: (1) the addition of H2 to CA gives IN2, which can hydrogenate the azo (N═N) bond at the later stage; (2) hydrogenation of azobenzene by IN2, which gives 1,2-diphenylhydrazine (PhNHNHPh); and (3) hydrogenation of 1,2-diphenylhydrazine by IN2, which affords aniline (PhNH2). The results suggest that the hydrogenation of CA and hydrogenation of azobenzene by IN2 to afford PhNHNHPh are easy to occur due to the low barriers, and the overall rate-determining step is the formation of IN11 and PhNH2 by breaking the N-N bond in the stage of hydrogenation of 1,2-diphenylhydrazine by IN2, with an energy barrier of 39.1 kcal/mol. The computed results are in good agreement with the experimental results. The mechanism of the azobenzene reaction catalyzed by manganese was analyzed by charge and orbital analysis in detail. The theoretical results provide a deeper understanding of the mechanism and fully explain the experimental facts.

Alternarialone A, a new curvularin-type metabolite from the mangrove-derived fungus Alternaria longipes.

Alternarialone A (1), one new curvularin derivative, and two known compounds (2 and 3) were isolated from the crude extract of the mangrove-derived fungus Alternaria longipes. Their structures were elucidated by comprehensive spectroscopic analyses, including MS and NMR spectroscopic data. The absolute configuration of 1 was assigned by 13C NMR calculations and a comparison of electronic circular dichroism (ECD) spectra. All compounds were evaluated for their antibacterial activities against Helicobacter pylori. Compounds 2 and 3 showed antibacterial activities against H. pylori G27 with MIC values of 8 and 16 µg/ml, respectively, while compound 3 also displayed antibacterial activity against H. pylori BHKS159 with the MIC value of 16 µg/ml.

New polyketides from the basidiomycetous fungus Pholiota sp.

Two new polyketides, pholiotones B and C (1 and 2), and four known compounds, trichodermatide D (3), vermistatin (4), dehydroaltenuene A (5) and terpestacin (6) were isolated from the crude extract of Pholiota sp. Their structures were identified by NMR and MS spectroscopic data. The absolute configurations of compounds 1 and 2 were elucidated by modified Mosher's method, electronic circular dichroism (ECD) calculations and 13C NMR calculations as well as DP4+ probability analyses. All the compounds were evaluated for their antifungal and cytotoxicity.

Amplified Fluorescence by Hollow-Porous Plasmonic Assembly: A New Observation and Its Application in Multiwavelength Simultaneous Detection.

Surface plasmon coupled emission (SPCE) is a new analytical technique that provides increased and directional radiation based on the near-field interaction between fluorophores and surface plasmons but suffers from the limitation of insufficient sensitivity. The assembly of hollow-porous plasmonic nanoparticles could be the qualified candidate. After the introduction of gold nanocages (AuNCs), fluorescence signal enhancement was realized by factors over 150 and 600 compared with the normal SPCE and free space emission, respectively, with a fluorophore layer thickness of approximately 10 nm; hence, the unique enhancement of SPCE by the AuNCs effectively overcomes the signal quenching induced by resonance energy transfer (in normal SPCE). This enhancement was proven to be triggered by the superior wavelength match, the enhanced electromagnetic field, and new radiation channel and process induced by the AuNC assembly, which provides an opportunity to increase the detection sensitivity and establish an optimal plasmonic enhancement system. The amplified SPCE system was employed for multiwavelength simultaneous enhancement detection through the assembly of mixed hollow nanoparticles (AuNCs and gold nanoshells), which could broaden the application of SPCE in simultaneous sensing and imaging for multianalytes.

Genome-wide analysis of Jatropha curcas MADS-box gene family and functional characterization of the JcMADS40 gene in transgenic rice.

BACKGROUND: Physic nut (Jatropha curcas), an inedible oilseed plant, is among the most promising alternative energy sources because of its high oil content, rapid growth and extensive adaptability. Proteins encoded by MADS-box family genes are important transcription factors participated in regulating plant growth, seed development and responses to abiotic stress. However, there has been no in-depth research on the MADS-box genes and their roles in physic nut. RESULTS: In our study, 63 MADS-box genes (JcMADSs) were identified in the physic nut genome, and classed into five groups (MIKCC, Mα, Mß, Mγ, MIKC*) according to phylogenetic comparison with Arabidopsis homologs. Expression profile analysis based on RNA-seq suggested that many JcMADS genes had the strongest expression in seeds, and seven of them responded in leaves to at least one abiotic stressor (drought and/or salinity) at one or more time points. Transient expression analysis and a transactivation assay indicated that JcMADS40 is a nucleus-localized transcriptional activator. Plants overexpressing JcMADS40 did not show altered plant growth, but the overexpressing plants did exhibit reductions in grain size, grain length, grain width, 1000-seed weight and yield per plant. Further data on the reduced grain size in JcMADS40-overexpressing plants supported the putative role of JcMADS genes in seed development. CONCLUSIONS: This study will be useful in order to further understand the process of MADS-box genes involved in regulating growth and development in addition to their functions in abiotic stress resistance, and will eventually provide a theoretical basis for the functional investigation and the exploitation of candidate genes for the molecular improvement of physic nut.

Microbial diversity analysis of jiaoke from Xilingol, Inner Mongolia.

Jiaoke is a traditional Mongolian fermented dairy product that is nutritious and has a unique taste. It is made from the fat separated from fermented milk. In this study, we collected 24 jiaoke samples from the Xilingol region of Inner Mongolia. The microbiota composition of the collected samples was analyzed using 16S rRNA small-molecule real-time sequencing, and the lactic acid bacteria (LAB) population was enumerated and isolated by laboratory culture techniques. We used an electronic tongue device to assess the taste quality of the products. One hundred fifty LAB isolates (5 genera and 14 species) were recovered and identified by 16S rRNA sequencing across all samples. Lactococcus lactis and Lactobacillus plantarum accounted for 51.33% and 10.67% of the total isolates, respectively. The small-molecule real-time sequencing of full-length 16S rRNAs revealed an overall bacterial microbiota composition of 10 phyla, 121 genera, and 186 species, largely represented by sequences of Lactococcus (68.46%) and Lactococcus lactis (52.92%) at the genus and species levels, respectively. The electronic tongue analysis revealed that the sweetness, bitterness, sourness, and saltiness of jiaoke varied greatly between samples. The presence of Lactococcus lactis correlated positively with bitter aftertaste; the presence of Lactococcus piscium correlated positively with umami and negatively with astringent and bitter aftertastes; and the presence of Lactobacillus helveticus correlated positively with sourness and negatively with other taste qualities. These results suggest that the microbiota composition and product taste are closely related. The novel LAB strains collected in this work represent valuable natural microbial resources.

[TCMATCOV--a bioinformatics platform to predict efficacy of TCM against COVID-19].

There is urgent need to discover effective traditional Chinese medicine(TCM) for treating coronavirus disease 2019(COVID-19). The development of a bioinformatic tool is beneficial to predict the efficacy of TCM against COVID-19. Here we deve-loped a prediction platform TCMATCOV to predict the efficacy of the anti-coronavirus pneumonia effect of TCM, based on the interaction network imitating the disease network of COVID-19. This COVID-19 network model was constructed by protein-protein interactions of differentially expressed genes in mouse pneumonia caused by SARS-CoV and cytokines specifically up-regulated by COVID-19. TCMATCOV adopted quantitative evaluation algorithm of disease network disturbance after multi-target drug attack to predict potential drug effects. Based on the TCMATCOV platform, 106 TCM were calculated and predicted. Among them, the TCM with a high disturbance score account for a high proportion of the classic anti-COVID-19 prescriptions used by clinicians, suggesting that TCMATCOV has a good prediction ability to discover the effective TCM. The five flavors of Chinese medicine with a disturbance score greater than 1 are mainly spicy and bitter. The main meridian of these TCM is lung, heart, spleen, liver, and stomach meridian. The TCM related with QI and warm TCM have higher disturbance score. As a prediction tool for anti-COVID-19 TCM prescription, TCMATCOV platform possesses the potential to discovery possible effective TCM against COVID-19.

Lanthanide-Organic Frameworks Constructed from 2,7-Naphthalenedisulfonate and 1H-Imidazo[4,5-f][1,10]-phenanthroline: Synthesis, Structure, and Luminescence with Near-Visible Light Excitation and Magnetic Properties.

New Ln-metal-organic frameworks (Ln-MOFs), {[Ln(2,7-NDS)(IP)(OH)(H2O)2]·mH2O}n [Ln = Sm 1, Eu 2, Gd 3, Tb 4, Dy 5, m = 0.5-0; 2,7-NDS = 2,7-naphthalenedisulfonate, and IP = 1H-imidazo[4,5-f][1,10]-phenanthroline) were obtained by the hydrothermal method. The Ln-MOFs feature one-dimensional double chain structures. The photoluminescent properties of these complexes were investigated. Notably, the Eu-MOF exhibits a broad excitation band from 250 to 400 nm in the UV-vis region, and it presents red emission from the 5D0 → 7FJ transitions (where J = 0-4) of the Eu3+ ion. It is noteworthy that it still shows intense emission under near-visible irradiation at 350 nm < λex < 385 nm. Using the Eu-MOF as a luminescent sensor, the detection of Fe3+/Ag+ and ornidazole (ODZ)/ronidazole (RDZ) in aqueous medium was realized with long excitation wavelengths of 368 nm or even 385 nm in the near-visible region. This work provides a new approach to designing an efficient red emission with broad-band and near-visible light excitation and with luminescent chemosensor capability for biological applications. In addition, the Eu-MOF red light incorporated Gd-MOF blue-green light, and a white-light emission is realized based on a two-component Gd0.99803Eu0.00197 doped complex. Magnetic studies of the Dy-MOF reveal that it has a single-molecule magnet and slow magnetic relaxation behavior with an energy barrier Ueff of 82.39 K.

Computational Insight into the Mechanism of Ruthenium(II)-Catalyzed α-Alkylation of Arylmethyl Nitriles Using Alcohols.

The ruthenium(II)-catalyzed α-alkylation reaction of arylmethyl nitriles (phenylacetonitrile) using alcohols (ethanol) in toluene has been extensively investigated by means of SMD-M06-2X/6-311G(d,p)-LANL2dz (LAnL2dz for Ru, 6-311G(d,p) for other atoms) calculations. Detailed mechanistic schemes have been proposed and discussed. The catalytically active Ru(II) complex was generated by the base-induced KCl elimination from the catalyst precursor [(PNPPh)RuHCl(CO)]. The overall Ru(II) catalytic cycle consists of three basic processes: (1) ethanol-to-aldehyde transformation catalyzed by the 16-electron unsaturated ruthenium pincer catalyst; (2) a 16-electron unsaturated ruthenium pincer catalyst catalyzed condensation reaction of arylmethyl nitrile with aldehyde, which leads to PhC(CN)=CHCH3; (3) hydrogenation of PhC(CN)=CHCH3, which leads to the formation of the α-alkylated arylmethyl nitrile product (PhCH(CH2CH3)CN). The DFT results revealed that the rate-determining barrier of the overall reaction was 23.9 kcal/mol of the H-transfer step in the third process. The reaction of PhC(CN)=CHCH3 with the dihydride Ru complex, which is generated in the ethanol-to-aldehyde transformation process, is the more preferable hydrogenation mechanism than hydrogenation of vinyl nitrile-Ru complex by H2. Using alcohol as the reactant not only fulfills the requirement of the borrowing-H strategy but also lowers the barriers of the H-migration steps.

Effects of applying Lactobacillus helveticus H9 as adjunct starter culture in yogurt fermentation and storage.

Lactobacillus helveticus H9 is a probiotic bacterium originating from traditional Tibetan kurut. It has high angiotensin-converting enzyme-inhibitory (ACEI) and antihypertensive activities. We aimed to evaluate the effects of L. helveticus H9 supplementation in yogurt fermentation and storage. We monitored changes of multiple parameters over 28 d of storage at 4°C; namely, pH, titratable acidity, free amino groups, ACEI activity, physical properties, volatile flavor compounds, and sensory quality. Supplementation of L. helveticus H9 enhanced fermented milk acidification and proteolysis, resulting in a shorter fermentation time. The H9 treatment significantly increased the ACEI activity of the fermented milks. Fifteen key volatile flavors were detected by solid-phase microextraction-gas chromatography-mass spectrometry across all samples. More alcohols, aldehydes, and nitrogenous compounds, especially acetoin and benzaldehyde, were detected in the H9-supplemented fermented milks. The human sensory scores for flavor and texture, but not appearance, were lower for the H9-supplemented fermented milks, particularly beyond 2 wk of cold storage. Our results will be of interest to the dairy industry for developing novel functional dairy products.

[Value of Procalcitonin, High Sensitivity C-reactive Protein and Pancreatic Stone Protein in Predicting Prognosis of Children with Sepsis].

OBJECTIVES: To determine the value of procalcitonin (PCT), high sensitivity C-reactive protein (hs-CRP) and pancreatic stone protein(PSP) in predicting the prognosis of children with sepsis. METHODS: A total of 106 hospitalized children [(4.4±1.6) year-old] with sepsis were enrolled in this study. The expressions of PTC, hs-CRP and PSP in the serum samples of the children were detected on the first day of admission to hospital. Pearson correlation analyses were performed to test the correlations between pediatric critical illness score (PCIS) and PTC, hs-CRP and PSP. Logistic regression models were established to determine factors predicting death of children. The value of PTC, hs-CRP and PSP in predicting the prognosis of children with sepsis was determined using ROC curves. RESULTS: About 32% children (34 cases) died. Higher expressions of PTC, hs-CRP and PSP were found in those who died (P<0.001). Serum PTC, hs-CRP and PSP were negatively correlated with PCIS (P<0.001). The multivariate logistic regression showed that PTC, hs-CRP and PSP were independent predictors of death in patients with sepsis (P<0.001). PTC, hs-CRP and PSP had an area under the curve (AUC) value of 0.86[ (95% confidence interval (CI), 0.78-0.92], 0.70 (95%CI, 0.61-0.79) and 0.69 (95%CI, 0.60-0.78) , respectively.The AUC value increased (P<0.001) to 0.92 (95%CI, 0.85-0.96) when the three indicators were combined (0.481×PCT+0.392×hs-CRP +0.314*PSP), with a value of less than 122.3 indicating good prognosis in 28 d. CONCLUSIONS: Serum PTC, hs-CRP and PSP can predict prognosis of children with sepsis.

Wavelet-transform-based active imaging of cavitation bubbles in tissues induced by high intensity focused ultrasound.

Cavitation detection and imaging are essential for monitoring high-intensity focused ultrasound (HIFU) therapies. In this paper, an active cavitation imaging method based on wavelet transform is proposed to enhance the contrast between the cavitation bubbles and surrounding tissues. The Yang-Church model, which is a combination of the Keller-Miksis equation with the Kelvin-Voigt equation for the pulsations of gas bubbles in simple linear viscoelastic solids, is utilized to construct the bubble wavelet. Experiments with porcine muscles demonstrate that image quality is associated with the initial radius of the bubble wavelet and the scale. Moreover, the Yang-Church model achieves a somewhat better performance compared with the Rayleigh-Plesset-Noltingk-Neppiras-Poritsky model. Furthermore, the pulse inversion (PI) technique is combined with bubble wavelet transform to achieve further improvement. The cavitation-to-tissue ratio (CTR) of the best tissue bubble wavelet transform (TBWT) mode image is improved by 5.1 dB compared with that of the B-mode image, while the CTR of the best PI-based TBWT mode image is improved by 7.9 dB compared with that of the PI-based B-mode image. This work will be useful for better monitoring of cavitation in HIFU-induced therapies.

[Analysis of the Puzzle between Acupuncture Community and Acupuncture Clinical Trials].

Recently a number of acupuncture clinical trial projects mainly conducted by conventional scientists have generated many negative results. A large meta-analysis of patient-level acupuncture data for the treatment of chronic pain conditions have demonstrated that the effects of verum acupuncture on pain improvement have statistically significant, but small, differences compared with sham-acupuncture procedures and no difference between acupuncture points and non-points. These conclusions have puzzled the acupuncture community and made confusion for acupuncture research and practices. The purpose of this paper was to compare differences between acupuncture clinical practices and the trial studies, which include "acupuncture technical principles", "acupuncture clinical trial design", and "acupuncture practice based on the theory of traditional Chinese medicine". These factors contribute to the puzzle between the acupuncture community/practice and acupuncture clinical trials, which can be improved in future studies.

Ultrafast active cavitation imaging with enhanced cavitation to tissue ratio based on wavelet transform and pulse inversion.

The quality of ultrafast active cavitation imaging (UACI) using plane wave transmission is hindered by low transmission pressure, which is necessary to prevent bubble destruction. In this study, a UACI method that combined wavelet transform with pulse inversion (PI) was proposed to enhance the contrast between the cavitation bubbles and surrounding tissues. The main challenge in using wavelet transform is the selection of the optimum mother wavelet. A mother wavelet named "cavitation bubble wavelet" and constructed according to Rayleigh-Plesset-Noltingk-Neppiras-Poritsky model was expected to obtain a high correlation between the bubbles and beamformed echoes. The method was validated by in vitro experiments. Results showed that the image quality was associated with the initial radius of bubble and the scale. The signal-to-noise ratio (SNR) of the best optimum cavitation bubble wavelet transform (CBWT) mode image was improved by 3.2 dB compared with that of the B-mode image in free-field experiments. The cavitation-to-tissue ratio of the best optimum PI-based CBWT mode image was improved by 2.3 dB compared with that of the PI-based B-mode image in tissue experiments. Furthermore, the SNR versus initial radius curve had the potential to estimate the size distribution of cavitation bubbles.

[Synthesis, Crystal Structure and Fluorescence Properties of Two Tb(III) Complexes].

Two coordination polymers with formula of [Tb(3-SBA) (IP)OH(H2O)] · H2O(1) and [Tb(dpdc)1.5 (IP) (H2O)]n (2) (3-SBA==3-sulfobenzoate, dpdc=2,2'-diphenyldicarboxylate and IP=1H-imidazo[4,5-f][1,10]-phenanthroline) have been synthesised under hydrothermal condition and characterizated by X-ray single crystal diffraction. The complex 1 possesses a 1D chain structure constructed from Tb(III) ions by 3-SBA ligands and OH groups. Complex 2 shows a 1D chain structure constructed from Tb(III) ions by dpdc ligands. The two complexes display the characteristic (5)D4-->7Fj (J=6-3) transitions at 492, 544,584 and 619 nm of Tb(III) ion, respectively. No emission from the ligand could be observed, which indicates that the ligands absorb and transfer energy efficiently to central Tb( M) ion. The emission decay curves reveal a monoexponential behaviour yielding the lifetime values of 0.287 ms for 1 and 0.439 ms for 2. The quantum yields of luminescence are 9.28% for 1 and 7.07% for 2.

Real-time automatic hospital-wide surveillance of nosocomial infections and outbreaks in a large Chinese tertiary hospital.

BACKGROUND: We aimed to develop a real-time nosocomial infection surveillance system (RT-NISS) to monitor all nosocomial infections (NIs) and outbreaks in a Chinese comprehensive hospital to better prevent and control NIs. METHODS: The screening algorithm used in RT-NISS included microbiological reports, antibiotic usage, serological and molecular testing, imaging reports, and fever history. The system could, in real-time, identify new NIs, record data, and produce time-series reports to align NI cases. RESULTS: Compared with a manual survey of NIs (the gold standard), the sensitivity and specificity of RT-NISS was 98.8% (84/85) and 93.0% (827/889), with time-saving efficiencies of about 200 times. RT-NISS obtained the highest hospital-wide monthly NI rate of 2.62%, while physician and medical record reviews reported rates of 1.52% and 2.35% respectively. It took about two hours for one infection control practitioner (ICP) to deal with 70 new suspicious NI cases; there were 3,500 inpatients each day in the study hospital. The system could also provide various updated data (i.e. the daily NI rate, surgical site infection (SSI) rate) for each ward, or the entire hospital. Within 3 years of implementing RT-NISS, the ICPs monitored and successfully controlled about 30 NI clusters and 4 outbreaks at the study hospital. CONCLUSIONS: Just like the "ICPs' eyes", RT-NISS was an essential and efficient tool for the day-to-day monitoring of all NIs and outbreak within the hospital; a task that would not have been accomplished through manual process.

Enhanced nitrate removal efficiency and microbial response of immobilized mixed aerobic denitrifying bacteria through biochar coupled with inorganic electron donors in oligotrophic water.

The nitrogen removal characteristics and microbial response of biochar-immobilized mixed aerobic denitrifying bacteria (BIADB) were investigated at 25 °C and 10 °C. BIADB removed 53.51 ± 1.72 % (25 °C) and 39.90 ± 4.28 % (10 °C) nitrate in synthetic oligotrophic water. Even with practical oligotrophic water, BIADB still effectively removed 47.66-53.21 % (25 °C), and 39.26-45.63 % (10 °C) nitrate. The addition of inorganic electron donors increased nitrate removal by approximately 20 % for synthetic and practical water. Bacterial and functional communities exhibited significant temperature and stage differences (P < 0.05), with temperature and total dissolved nitrogen being the main environmental factors. The dominant genera and keystone taxa exhibited significant differences at the two temperatures. Structural equation model analysis showed that dissolved organic matter had the highest direct and indirect effects on diversity and function, respectively. This study provides an innovative pathway for utilizing biochar and inorganic electron donors for nitrate removal from oligotrophic waters.