Comparison of the clinical outcomes between proximal femoral nail anti-rotation with cement enhancement and hemiarthroplasty among elderly osteoporotic patients with intertrochanteric fracture.

BACKGROUND: The proximal femoral nail anti-rotation (PFNA) with cement enhancement enhances the anchorage ability of internal fixation in elderly with osteoporotic intertrochanteric fracture. However, whether it is superior to hemiarthroplasty is still controversial. The present study aimed to determine which treatment has better clinical outcomes among older patients. METHODS: We retrospectively analyzed 102 elderly patients with osteoporosis who developed intertrochanteric fractures and underwent PFNA combined with cement-enhanced internal fixation (n = 52, CE group), and hemiarthroplasty (n = 50, HA group) from September 2012 to October 2018. All the intertrochanteric fractures were classified according to the AO/OTA classification. Additionally, the operative time, intraoperative blood loss, intraoperative and postoperative blood transfusion rates, postoperative weight-bearing time, hospitalization time, Barthel Index of Activities Daily Living, Harris score of hip function, visual analog (VAS) pain score, and postoperative complications were compared between the two groups. RESULTS: The CE group had significantly shorter operative time, lesser intraoperative blood loss, lower blood transfusion rate, and longer postoperative weight-bearing time than the HA group. The CE group had lower Barthel's Index of Activities of Daily Living, lower Harris' score, and higher VAS scores in the first and third months after surgery than the HA group, but no difference was observed between the two groups from 6 months to 12 months. There was no significant difference in the total post-operative complications between the two groups. CONCLUSION: The use of PFNA combined with a cement-enhanced internal fixation technique led to shorter operative time and lesser intraoperative blood loss and trauma in elderly patients as compared to HA.

Expression of Concern: Conjugation of substituted naphthalimides to polyamines as cytotoxic agents targeting the Akt/mTOR signal pathway.

Expression of Concern for 'Conjugation of substituted naphthalimides to polyamines as cytotoxic agents targeting the Akt/mTOR signal pathway' by Zhi-Yong Tian et al., Org. Biomol. Chem., 2009, 7, 4651-4660, https://doi.org/10.1039/B912685F.

2-Phenylquinoline-polyamine conjugate (QPC): Interaction with bovine serum albumin (BSA).

A novel 2-phenylquinoline-polyamine conjugate (QPC) was synthesized and characterized, its interaction with bovine serum albumin (BSA) was evaluated using UV-Vis, fluorescence and circular dichroism (CD) spectroscopy. The results showed that QPC caused a whole train of spectral variation, including enhancement of UV-vis absorption and reduction of fluorescence (FL), indicating QPC-BSA complex formed. FL results showed that the type of FL quenching waslarge static quenching, which was also accompanied with a process of dynamic quenching. Binding constants, thermodynamic parameters and docking results showed that the interaction between QPC and BSA was basically a Van der Waals, hydrogen bond and hydrophobic interaction. Synchronous and 3D-FL analysis revealed that QPC resulted in unapparent conformational alteration of BSA. The docking study suggested QPC was situated at the binding sites II of BSA, and 2-phenylquinoline moiety contributed to the hydrophobic interaction. The results of molecular dynamics revealed QPC altered the conformation of BSA, which showed that the inconsistency between experimental data and theoretical calculation results may be due to the instability of the compound.

Differences in urban heat island and its driving factors between central and new urban areas of Wuhan, China.

Urban heat island (UHI) is one of the important effects of urbanization on built environment. Land surface temperature data was taken from moderate-resolution imaging spectroradiometer (MODIS) to investigate the long-term spatiotemporal patterns of UHI in Wuhan during 2001~2018 and, the UHI intensity changes of built-up land in 13 administrative regions in Wuhan were analyzed. Furthermore, 34 spatial error models and 34 ordinary least squares models were established and compared. Spatial error models showed good fitting effect, which were used to determine the influence of normalized difference vegetation index (NDVI), normalized difference building index (NDBI), and social-economic factors (population and nighttime light) on UHI intensity in central urban area and new urban area. The explanatory power changes of these four indicators during 2001~2018 were explored as well. The average UHI intensity in 2014~2018 has increased by about 0.45 °C compared to that in 2001~2005. NDBI is the most dominant factor contributing to the increase in temperature. The impact of NDVI on UHI intensity changes from negative to positive, and the impact of NDBI on UHI intensity in central urban area is weakened during 2001-2018. Social-economic factors have a greater impact on new urban area than on central urban area. These findings show the effects and the explanatory power changes of driving factors during 18 years, which can provide a better understanding of the formation and development of UHI and support for the future urban planning of Wuhan.

Discovery of (S)-N-(3-isopropylphenyl)-2-(5-phenylthiazol-2-yl)pyrrolidine-1-carboxamide as potent and brain-penetrant TRPV1 antagonist.

Transient receptor potential vanilloid 1 (TRPV1) antagonists can inhibit the transmission of nociceptive signals from the peripheral to the central nervous system (CNS), providing a new strategy for pain relief. In this work, in order to develop potent, CNS-penetrant, and orally available TRPV1 antagonists, three series of novel molecules based on the key pharmacophore structures of classic TRPV1 ligands SB-705498 and MDR-652 were designed and synthesized. Through systematic in vitro and in vivo bioassays, (S)-N-(3-isopropylphenyl)-2-(5-phenylthiazol-2-yl)pyrrolidine-1-carboxamide (7q) was finally identified, which had enhanced TRPV1 antagonistic activity (IC50 (capsaicin) = 2.66 nM), excellent CNS penetration (brain/plasma ratio = 1.66), favorable mode-selectivity, good bioavailability, and no side effects of hyperthermia. Molecular docking and dynamics studies indicated that the high binding affinity of compound 7q to TRPV1 was related to multiple interactions, which resulted in significant conformational changes of TRPV1. Overall, our findings have led to a potent, mode-selective, and CNS-penetrant TRPV1 antagonist as a valuable lead for development of novel TRPV1 antagonists.

Study on the interaction of polyamine transport (PAT) and 4-Chloro-naphthalimide-homospermidine conjugate (4-ClNAHSPD) by molecular docking and dynamics.

Polyamine transporter (PAT) is a protein that can deliver "drug-polyamine" conjugates to tumor cells. 4-Chloro-naphthalimide- homospermidine (4-ClNAHSPD) displayed good antitumor activity and excellent cell selectivity via PAT pathway. In this paper, 4-ClNAHSPD and spermidine (SPD) were docked against PAT. The results showed that 4-ClNAHSPD could bind to PAT through hydrogen bond, Van der Waals, salt bridge or attractive charge and hydrophobic interaction. The interaction of SPD and PAT, however, was hydrogen bond and Van der Waals interaction. Moreover, their binding sites were also different. The primary binding sites of 4-ClNAHSPD with PAT are the residues of VAL59, HIS222, ASP61, ASP179 and GLU64, while SPD interacts with PAT in the sites of ASP37, ASP244, APS275 and SER36. The docked ligand-protein complexes were simulated for 5000ps. In simulations, various binding sites further resulted in the diverse root-mean-square deviation (RMSD) and root-mean-square deviation fluctuation (RMSF) values. The RMSD and RMSF values of 4-ClNAHSPD-PAT indicated that 4-ClNAHSPD caused a weak conformational change of PAT in a different style from SPD. More importantly, the interaction force numbers of 4-ClNAHSPD-PAT were also changed after the simulation. These results supported that 4-ClNAHSPD harnesses PAT pathway for cellular entrance.Communicated by Ramaswamy H. Sarma.

Growth, Physiological, and Photosynthetic Responses of Xanthoceras sorbifolium Bunge Seedlings Under Various Degrees of Salinity.

Xanthoceras sorbifolium Bunge is priced for its medical and energetic values. The species also plays a key role in stabilizing ecologically fragile areas exposed to excess soil salinity. In this study, the effects of salinity on the growth, physiological, and photosynthetic parameters of X. sorbifolium Bunge were investigated. The X. sorbifolium seedlings were subjected to five salt treatments: 0 (control, CK), 70, 140, 210, and 280 mM of sodium chloride (NaCl) solutions. NaCl caused a decrease in plant height, specific leaf area, biomass, and root parameters. Leaf wilting and shedding and changes in root morphology, such as root length, root surface area, and root tips were observed. This study found that X. sorbifolium is tolerant to high salinity. Compared with the CK group, even if the concentration of NaCl was higher than 210 mM, the increase of the relative conductivity was also slow, while intercellular CO2 concentration had a similar trend. Moreover, NaCl stress caused an increase in the malondialdehyde (MDA), soluble proteins, and proline. Among the enzymes in the plant, the catalase (CAT) activity increases first and decreased with the increase in the intensity of NaCl stress, but the salt treatment had no significant effect on superoxide dismutase (SOD) activity. The peroxidase (POD) showed an increasing trend under salt stress. It was found that the photosynthesis of X. sorbifolium was notably impacted by saline stress. NaCl toxicity induced a noticeable influence on leaf net photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci), transpiration rate (E), and water use efficiency (Wue). As salt concentration increased, the content of chlorophyll decreased. It can be found that a low concentration of NaCl induced the increase of photosynthetic capacity but a high-intensity exposure to stress resulted in the reduction of photosynthetic efficiency and SOD activity, which had a positive correlation. In summary, salt-induced ionic stress primarily controlled root morphology, osmotic adjustment, and enzyme activities of salt-treated X. sorbifolium leaves, whereas the low salt load could, in fact, promote the growth of roots.

Pollutant removal from landfill leachate via two-stage anoxic/oxic combined membrane bioreactor: Insight in organic characteristics and predictive function analysis of nitrogen-removal bacteria.

A two-stage anoxic/oxic combined membrane bioreactor (A/O-A/O-MBR) was operated for 81 d to treat landfill leachate under different reflux ratios (R). The best performance was found under R = 150%, where the chemical oxygen demand (COD), ammonium (NH4+-N) and total nitrogen (TN) removal was 85.6%, 99.3%, and 80.7%, respectively. Particularly, the highest pollutant removal was achieved in the second-stage A/O, where the COD and TN removal capacity was 78.88 and 11.74 g/d, respectively. Meantime, DOM removal was 83.9%, where the removal of aromatic protein substances I and II, fulvic acids-like compounds, soluble microbial products and humic acids-like compounds was 93.4%, 86.4%, 72.0%, 86.6% and 59.4%, respectively. The gene functions of microbial community in the process showed that amoA, hao, nirK and nosZ, etc. were the core genes for nitrification and denitrification. The carbon source for denitrification might come from the conversion of refractory organic matters in landfill leachate.

Investigation of the interaction of a polyamine-modified flavonoid with bovine serum albumin (BSA) by spectroscopic methods and molecular simulation.

The interaction between BSA and compound 1 was studied by UV-vis, fluorescence and circular dichroism spectroscopy under physiological conditions (pH = 7.4). Molecular docking and molecular dynamics analyses were also performed. The results showed that compound 1 could bind to BSA. When compound 1 bound to BSA, there were a series of changes in the spectral properties of BSA, which were an enhancement effect of the UV-Vis spectrum of BSA, fluorescence quenching and a weak conformational change in the CD spectrum. The results of the fluorescence experiments at 298, 303 and 310 K showed that fluorescence quenching caused by the addition of compound 1 to BSA was generally static quenching accompanied by a dynamic quenching process, which was shown by the quenching constants of 2.010 × 104 L∙M-1, 1.850 × 104 L∙M-1, and 1.970 × 104 L∙M-1 at the three different temperatures, respectively. From the obtained binding constants and thermodynamic parameters, it was found that hydrophobic forces played an important role in the binding process of 1 to BSA. The results of synchronous fluorescence and three-dimensional fluorescence showed that compound 1 caused a weak conformational change in BSA. Docking results showed that compound 1 was located at binding site II of bovine serum albumin protease. In addition, the flavonoid moiety of compound 1 contributes to the hydrophobic binding of compound 1 to BSA. The results of molecular dynamics, including the root-mean-square deviation (RMSD) and RMS fluctuation (RMSF) values, showed that the binding of compound 1 to BSA did not cause a significant conformational change in BSA.

A Polyamine-Based Dinitro-Naphthalimide Conjugate as Substrates for Polyamine Transporters Preferentially Accumulates in Cancer Cells and Minimizes Side Effects in vitro and in vivo.

Naphthalimides, such as amonafide and mitonafide in clinical trials, have been developed as antitumor agents for orthotopic tumor. However, the serious side effects in cancer patients limit their applications. Herein, a new class of polyamine-based naphthalimide conjugates 5a-5c, 7a-7b, and 11a-11b with and without the alkylation of the distant nitrogen in the polyamine chain were synthesized and the mechanism was determined. Compared with amonafide, dinitro-naphthalimide conjugate 5c with a 4,3-cyclopropyl motif preferentially accumulates in cancer cells and minimizes side effects in vitro and in vivo. More importantly, 5c at the dosage of as low as 3 mg/kg (57.97%) displays better antitumor effects than the positive control amonafide (53.27%) at 5 mg/kg in vivo. And a remarkably elevated antitumor activity and a reduced toxicity are also observed for 5c at 5 mg/kg (65.90%). The upregulated p53 and the apoptotic cells (73.50%) indicate that the mechanism of 5c to induce apoptosis may result from its enhanced DNA damage. Further investigation indicates that in addition to target DNA, 5c can modulate the polyamine homeostasis by upregulating polyamine oxidase (PAO) in a different way from that of amonafide. And also by targeting PTs overexpressed in most of cancer cells, 5c downregulates the contents of Put, Spd, and Spm, which are in favor of suppressing fast-growing tumor cells. Our study implies a promising strategy for naphthalimide conjugates to treat hepatic carcinoma with notable activities and reduced toxicities at a low dosage.

Enhanced nitrite accumulation under mainstream conditions by a combination of free ammonia-based sludge treatment and low dissolved oxygen: reactor performance and microbiome analysis.

Partial nitritation under mainstream conditions is one of the major bottlenecks for the application of deammonification processes to municipal wastewater treatment plants. This study aimed at evaluating the combination effect of a side-stream free ammonia (FA) treatment and low dissolved oxygen (0.2 ± 0.1 mg L-1) on inhibiting nitrite oxidizing bacteria (NOB) from enhancing nitrite accumulation in long-term lab-scale experiments. Two continuous floccular sludge reactors treating low-strength synthetic wastewater (60 mg N-NH4 + L-1 without COD) with a fixed nitrogen loading rate of 0.22 ± 0.03 g N per L per day were operated in a varied temperature range of 7-31 °C, with one acting as the experimental reactor and the other as the control. Side-stream sludge treatment with a stepwise elevation of FA concentration (65.2-261.1 mg NH3 L-1) was carried out every day in the experimental reactor; the nitrite accumulation ratio (NAR, (NO2-N/(NO2 --N + NO3 --N) × 100%)) in the experimental reactor was always about twice that in the control one. Quantitative PCR (q-PCR) and high-throughput sequencing analyses showed the dominant NOB was mostly Nitrobacter, while there was an alternating trend between Nitrobacter and Nitrospira. Even though the whole microbial communities of each experimental stage between the two reactors were relatively clustered due to an incomplete NOB washout, three abundant metabolisms (amino acid metabolism, pyruvate metabolism and nitrogen metabolism) and key functional genes of nitrification predicted by PICRUSt in the experimental reactor were enriched, providing a better understanding of nitrite accumulation. These results have demonstrated that the positive hybrid effects of FA side-stream sludge treatment and a low DO could enhance nitrite accumulation. It is expected that a complete washout of NOB would be achieved after further process optimization.

Synthesis and biological evaluation of genistein-O-alkylamine derivatives as potential multifunctional anti-Alzheimer agents.

A series of genistein derivatives were synthesized and evaluated as multifunctional anti-Alzheimer agents. The results showed that these derivatives had significant acetylcholinesterase (AChE) inhibitory activity; compound 5a exhibited the strongest inhibition to AChE with an IC50 value (0.034 µM) much lower than that of rivastigmine (6.53 µM). A Lineweaver-Burk plot and molecular modeling study showed that compound 5a targeted both the catalytic active site and the peripheral anionic site of AChE. These compounds also showed potent peroxy scavenging activity and metal-chelating ability. The compounds did not show obvious effect on HepG2 and PC12 cell viability at the concentration of 100 µM. Therefore, these genistein derivatives can be utilized as multifunctional agents for the treatment of AD.

Influence of reflux ratio on two-stage anoxic/oxic with MBR for leachate treatment: Performance and microbial community structure.

A lab-scale two-stage Anoxic/Oxic with MBR (AO/AO-MBR) system was operated for 81 days for leachate treatment with different reflux ratio (R). The best system performances were observed with a R value of 150%, and the average removal efficiencies of chemical oxygen demand, ammonia and total nitrogen were 85.6%, 99.1%, and 77.6%, respectively. The microbial community were monitored and evaluated using high-throughput sequencing. Proteobacteria were dominant in all process. Phylogenetic trees were described at species level, genus Thiopseudomonas, Amaricoccus, Nitrosomonas and Nitrobacter played significant roles in nitrogen removal. Co-occurrence analyzing top 20 genera showed that Nitrosomonas-Nitrobacter presented perfect positive relationship, as well as Paracoccus-Brevundimonas and Pusillimonas-Halobacteriovorax.

Synthesis and biological evaluation of naphthalimide-polyamine conjugates modified by alkylation as anticancer agents through p53 pathway.

In this study, a series of novel naphthalimide-polyamine conjugates modified by alkylation at the terminal of the polyamine chain were synthesized. These novel conjugates were evaluated for their anti-cancer activities. The results revealed that the length of the polyamine chain and the terminal alkyl group had influences on anticancer activities. Compound 3g was chosen to further study the anti-cancer mechanism and evaluate the anti-tumor efficacy in vivo. It induced intrinsic apoptosis and suppressed migration of hepatoma cells. The preliminary studies of compound 3gin vivo showed that it might be a promising candidate for cancer therapy.

Denitrification of landfill leachate under different hydraulic retention time in a two-stage anoxic/oxic combined membrane bioreactor process: Performances and bacterial community.

Two-stage anoxic/oxic combined membrane bioreactor (A/O-A/O-MBR) process was used to treat leachate generated from Shenyang Laohuchong landfill, and the effect of hydraulic retention time (HRT) was studied. A long HRT of 9 d and a short HRT of 5 d showed negative effect on the stability of process, resulting in a higher organic concentration of effluent than that with a HRT of 7 d, while the highest removal of chemical oxygen demand (COD), ammonia (NH4+-N) and total nitrogen (TN) were achieved with a HRT of 7 d, which was 82.4%, 99.1% and 75.3% respectively. The analysis of microbial communities by high-throughput sequencing showed that phyla Proteobacteria and Bacteroidetes were the dominant bacteria, which accounted for 36.63-42.39%, 29.21-38.66%, respectively. For genus classification, the most representative of Ferruginibacter, unclassified-Saprospiraceae and Nitrosomonas accounted for 20.76-35.11% totally. The other communities, including Nitrobacter, Planctomyces, Rhodobacteraceae and Nitrospirae, were also developed for organic degradation and denitrification.

Synthesis and biological evaluation of novel alkylated polyamine analogues as potential anticancer agents.

A new class of polyamine analogues modified by alkylation at the terminal of the polyamine chain has been synthesized and their structures were determined by 1H NMR, 13C NMR, ESI-MS and elemental analysis. As the representative compound, 3f displayed a broad spectrum of anti-cancer effects by MTT assays. Tumor xenograft model and pulmonary metastasis model showed that compound 3f significantly suppressed tumor growth and metastasis in vivo, which was more stronger than the reference drug amonafide. Molecular mechanisms indicated that compound 3f exhibited antiproliferative activities and induced the generation of reactive oxygen species (ROS), which resulted in the occurrence of autophagy. The downregulated expression of MMP-9 and ß-catenin by compound 3f accounted for the inhibition of migration. Taken altogether, the in vitro and in vivo biological evaluations corroborated compound 3f to be an effective anticancer agent.

Two-stage anoxic/oxic combined membrane bioreactor system for landfill leachate treatment: Pollutant removal performances and microbial community.

In this study, a laboratory-scale two-stage anoxic/oxic (A/O) combined membrane bioreactor (MBR) was operated for 113d for the treatment of landfill leachate. The average removal of chemical oxygen demand (COD), ammonia (NH4+-N) and total nitrogen (TN) achieved 80.60%, 99.04% and 74.87%, respectively. A mass balance evaluation suggested that the removal of COD, NH4+-N and TN occurred mainly in the second A/O process, and the total removal capacity of COD, NH4+-N and TN were 125.60g/d, 24.35g/d and 22.40g/d, respectively. High-throughput sequencing analysis indicated that the Proteobacteria (44.57-50.36%), Bacteroidetes (22.09-27.25%), Planctomycetes (6.94-8.47%), Firmicutes (3.31-4.53%) and Chloroflexi (3.13-4.80%) were the dominated phyla in the bacterial community during the operation period. At the genus level, Nitrosomonas, Nitrobacter, Planctomyces, Saprospiraceae and Pseudomonas showed relatively high abundance, which played an important role in the removal of pollutants.

Study on the interaction of anthracenyl-methyl homospermidine conjugate (ANTMHspd) with DNA by spectroscopic methods.

The interaction between anthracenyl-methyl homospermidine conjugate (ANTMHspd) with herring sperm DNA was investigated by UV/vis absorption, fluorescent spectra, circular dichroism (CD) spectroscopy and 1HNMR under physiological conditions (pH=7.4). The observed hypochromism effect and fluorescence quenching of ANTMHspd by DNA, and the displacement of EB from DNA-EB system by ANTMHspd suggested that ANTMHspd might interact with DNA by the combined mode of intercalation and groove binding. Further fluorescent tests at different temperatures revealed that the quenching mechanism was a static type. The quenching constant, binding constant and thermodynamic parameter obtained from fluorescence showed that the type of interaction force included mainly hydrogen bonding and van der Waals, which promoted the binding process. The CD test revealed that ANTMHspd could cause the B to A-like conformational change while ANTMHspd is not a typical DNA intercalator. The 1H NMR tests showed that ANTMHspd partially intercalated DNA. The effect of NaCl and KI on ANTMHspd-DNA interaction provided additional evidences of intercalation. Molecular docking simulation was carried out and the docking model in silico suggested that the binding modes of ANTMHspd and DNA were groove binding and intercalation, with the anthracene moiety inserted in DNA base pairs and the polyamine chain embedded in the DNA groove.

Study on the interaction between the 1,4,5,8-naphthalene diimide-spermine conjugate (NDIS) and DNA using a spectroscopic approach and molecular docking.

The interaction of herring sperm DNA with the 1,4,5,8-naphthalene diimide-spermine conjugate (NDIS) was studied by UV/vis absorption, fluorescence and CD spectroscopic methods. Compared with the 1,8-naphthalimide-spermidine conjugate (NIS), the values of KSV (quenching constant) and Kb (binding constant) of NDIS were larger, and the hypochromic effect in the UV/vis spectra and the quenching effect in the fluorescence of NDIS were more significant. The interaction mode between NDIS and DNA was mainly groove binding. The fluorescence experiments at varying temperatures showed that the binding process of NDIS and DNA was static, as both hydrogen bonds and hydrophobic forces played a major role in the binding of NDIS and DNA. The CD spectrum indicated that NDIS caused a conformational change, like the B to A-DNA transition, and the tests using KI and NaCl and 1H NMR spectroscopy indicated that NDIS was not a classical DNA inserter. All the results demonstrated that both the polyamine side chain and the aromatic rings affect the process of NDIS binding to DNA, which is thus obviously different from that of NIS. The conclusion was confirmed by the in silico molecular docking experiments.

Spectroscopic and molecular modeling methods to study the interaction between naphthalimide-polyamine conjugates and DNA.

The effect of polyamine side chains on the interaction between naphthalimide-polyamine conjugates (1-7) and herring sperm DNA was studied by UV/vis absorption and fluorescent spectra under physiological conditions (pH=7.4). The diverse spectral data and further molecular docking simulation in silico indicated that the aromatic moiety of these compounds could intercalate into the DNA base pairs while the polyamine motif might simultaneously locate in the minor groove. The triamine compound 7 can interact more potently with DNA than the corresponding diamine compounds (1-6). The presence of the bulky terminal group in the diamine side chain reduced the binding strength of compound 1 with DNA, compared to other diamine compounds (2-6). In addition, the increasing methylene number in the diamine backbone generally results in the elevated binding constant of compounds-DNA complex. The fluorescent tests at different temperature revealed that the quenching mechanism was a static type. The binding constant and thermodynamic parameter showed that the binding strength and the type of interaction force, associated with the side chains, were mainly hydrogen bonding and hydrophobic force. And the calculated free binding energies of molecular docking are generally consistent with the stability of polyamine-DNA complexes. The circular dichroism assay about the impact of compounds 1-7 on DNA conformation testified the B to A-like conformational change.