The effect of influenza A (H1N1) pdm09 virus infection on cytokine production and gene expression in BV2 microglial cells.

Acute influenza infection has been reported to be associated with neurological symptoms such as influenza-associated encephalopathy (IAE). Although the pathophysiology of this condition remain unclear, neuroinflammation and associated alterations in the central nervous system (CNS) are usually induced. Microglia (MGs), CNS-resident macrophages, are generally the first cells to be activated in response to brain infection or damage. We performed reverse transcriptase droplet digital PCR (RT-ddPCR) and luminex assays to investigate virus proliferation and immune reactions in BV2 MGs infected with influenza A(H1N1)pdm09 virus. Furthermore, isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics methods were used to investigate the dynamic change in the protein expression profile in BV2 MGs to gain insight into the CNS response to influenza A (H1N1) pdm09 infection. Our results showed that the influenza A(H1N1)pdm09 virus was replicative and productive in BV2 MG cells, which produced cytokines such as interleukin (IL)-1ß, IL-6, tumour necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1. The expression of osteopontin (OPN) in the influenza A (H1N1) pdm09-infected BV2 MGs was upregulated at 16 and 32 h post-infection (hpi) compared to that in the control group, resulting in aggravated brain damage and inflammation. Our study indicates that OPN signalling might provide new insights into the treatment of CNS injury and neurodegenerative diseases in IAE.

[Impacts of Riparian Buffer Zone Type on Reduction in Runoff Pollution in the North Canal River Under Different Rainfall Events].

The impact of non-point source pollution on the water quality of the North Canal River is becoming increasingly prominent. In this study, the riparian buffer zones (RBZ) of the Nansha River and Beisha River, the inlet tributaries of the Shahe Reservoir in the North Canal basin, were selected to investigate the purification effect of riparian buffer zones on runoff pollution during the rainfall process. Two RBZ types, Type I RBZ (levee-flood control retaining wall-woodland-grassland) and Type Ⅱ RBZ (levee-woodland-grassland), were classified by the distribution characteristics of RBZ structure and plant communities in the North Canal River basin. The north bank of the Nansha River (NB) and the south bank of the Beisha River (BN) are typical of Type I RBZ, with low total vegetation cover, "short and steep" slopes, and low herbaceous cover but high diversity. The south bank of the Nansha River (NN) is a typical representative of Type Ⅱ RBZ, with "long and slow" slopes and high herbaceous cover (29.16%) but low diversity. In order to investigate the impacts of rainfall characteristics and RBZ types on the runoff pollutant, a 1 km area in each of the three RBZs was selected to carry out the RBZ non-point source pollution prevention and control engineering trials. The results indicated that Type I RBZ required less time and rainfall to produce runoff and had a greater peak runoff. Type Ⅱ RBZ produced runoff only under heavy rainstorm conditions, with greater runoff retention capacity. Energy dissipation ponds with gravel as the main fillers were set up at the runoff inlets of the RBZ, which effectively reduced runoff pollution. ρ(NH4+-N) and ρ(NO3--N) in the runoff were below 1.6 mg·L-1; ρ(TN) was below 5 mg·L-1; and ρ(PO43-P), ρ(DTP), and ρ(TP) were below 1.0 mg·L-1. The grass ditch of the RBZs effectively reduced ρ(NH4+-N) of the runoff. The retention rate of SS and the reduction effect of pollutants in Type Ⅱ RBZ were better than those in Type I except under heavy rainstorm conditions, which is related to the different RBZ structures and vegetation cover. The correlation analysis results showed that slope length, slope gradient, vegetation cover, and rainfall characteristics were significantly correlated with runoff SS, COD, nitrogen, and phosphorus pollution.

Identification of the Largest SCA36 Pedigree in Asia: with Multimodel Neuroimaging Evaluation for the First Time.

Spinocerebellar ataxias (SCAs) are a large group of hereditary neurodegenerative diseases characterized by ataxia and dysarthria. Due to high clinical and genetic heterogeneity, many SCA families are undiagnosed. Herein, using linkage analysis, WES, and RP-PCR, we identified the largest SCA36 pedigree in Asia. This pedigree showed some distinct clinical characteristics. Cognitive impairment and gaze palsy are common and severe in SCA36 patients, especially long-course patients. Although no patients complained of hearing loss, most of them presented with hearing impairment in objective auxiliary examination. Voxel-based morphometry (VBM) demonstrated a reduction of volumes in cerebellum, brainstem, and thalamus (corrected P < 0.05). Reduced volumes in cerebellum were also found in presymptomatic carriers. Resting-state functional MRI (R-fMRI) found reduced ReHo values in left cerebellar posterior lobule (corrected P < 0.05). Diffusion tensor imaging (DTI) demonstrated a reduction of FA values in cerebellum, midbrain, superior and inferior cerebellar peduncle (corrected P < 0.05). MRS found reduced NAA/Cr values in cerebellar vermis and hemisphere (corrected P < 0.05). Our findings could provide new insights into management of SCA36 patients. Detailed auxiliary examination are recommended to assess hearing or peripheral nerve impairment, and we should pay more attention to eye movement and cognitive changes in patients. Furthermore, for the first time, our multimodel neuroimaging evaluation generate a full perspective of brain function and structure in SCA36 patients.

Central motor conduction time in spinocerebellar ataxia: a meta-analysis.

The dominantly inherited spinocerebellar ataxias (SCAs) are a large class of neurodegenerative diseases. Transcranial magnetic stimulation has been used to evaluate the function of the pyramidal tract, and central motor conduction time (CMCT) is one index used to detect pyramidal tract dysfunction. We conducted a comprehensive search of PubMed, Embase and Web of Science. Eight eligible studies were included in the meta-analysis. For upper limb CMCT, the mean difference (95% confidence interval (CI)) between the combined SCA group and the control group was 2.24 [1.76-2.72], while the mean differences (95% CIs) between the subtypes and the control group were as follows: 4.43 [3.58-5.28] for SCA1, 0.25 [-0.15,0.65] for SCA2, 1.04 [-0.37,2.46] for SCA3 and 0.49 [-0.29,1.28] for SCA6. Additionally, SCA1 significantly differed from SCA2 and SCA3 in terms of CMCT (P=0.0006 and P=0.010, respectively). We also compared lower limb CMCT between the SCA2 and control groups. The mean difference (95% CI) was 6.58 [4.49-8.67], which was clearly statistically significant. The differences in CMCT values among different subtypes suggests diverse pathological mechanisms. In general, CMCT is a promising objective index to judge the severity of disease deserving further investigation.

[Spatio-temporal Evolution and Relationship of Water Environment Quality and Phytoplankton Community in Wenyu River].

The Wenyu River is an important ecological corridor of Beijing. In this study, the spatio-temporal dynamics of water quality and phytoplankton community in the Wenyu River in 2006, 2011, and 2018, as well as their relationship were thoroughly analyzed by historical data analysis and field surveys. Results show that the water quality in the Wenyu River improved significantly from serious pollution owing to pollution containment. The major water pollutant has shifted from ammonia nitrogen (NH4+-N) to total nitrogen (TN). Compared with 2011, the average multiple of NH4+-N and total nitrogen TN exceeding the national standard were reduced by factors of 0.29-0.33 and 2.77-2.39, respectively, in 2018. The average concentration of NH4+-N and TN decreased from 15.52-19.16 mg·L-1 and 20.21-19.58 mg·L-1 in 2011 to 1.93-2.66 mg·L-1 and 5.66-6.79 mg·L-1 in 2018. Moreover, dissolved oxygen (DO) and NH4+-N concentrations in the Wenyu River and its tributaries, the Qinghe River, almost met requirements of their water function zoning target. Corresponding with the water quality improvement, the phytoplankton and community species increased dramatically. Phytoplankton species increased from 6 to 8 phyla, as well as community species. The dominant species changed from Chlorophyta in 2006 to the Cyanophyta in 2011, then to Bacillariophyta in 2018. The Shannon-Wiener diversity index (H') and evenness Pielou index (J) had improved. However, the major dominant species such as Cyclotella and Melosira persisted, and the Wenyu River was still in the eutrophication state in 2018. Statistical analysis results indicated that Cyanophyta, Bacillariophyta, and other algae abundance were significantly correlated with DO, pH, NH4+-N, TN, and TP.

Prevalence, risk factors and clinical characteristics of osteoporosis in Chinese inpatients with schizophrenia.

Patients with schizophrenia have a high prevalence of developing osteoporosis and osteoporosis-related fractures. We examined the prevalence of osteoporosis and its clinical correlates in Chinese patients with schizophrenia, which is not well-studied. A total of 199 inpatients (males/females=132/67; average age: 54.5±11.1years) and 107 healthy controls (males/females=22/85; average age: 41.7±11.9years) were recruited. Bone mineral density (BMD) was measured by ultrasonography of the calcaneus. The prevalence of osteoporosis and low BMD (osteoporosis and osteopenia) was 23.1% and 65.3% for the patient group, versus 7.5% and 39.3% for the control group (both p<0.001). Further, the average BMD T-score in patients was significantly lower than in controls (p<0.05). There was gender difference in the prevalence of low BMD conditions for the patients (males: 56.1% versus females: 76.1%; p<0.01) as well as the BMD T-score (p<0.001). Several risk factors correlated with the osteoporosis classification in the patient group: older age (58.9±11.2years vs. 53.3±11.0years), lower weight (63.7±12.2kg vs. 70.4±15.2kg) and body mass index (BMI) (22.8±4.1kg/m2 vs. 24.2±4.7kg/m2; all p<0.01) than those without osteoporosis. Stepwise multiple logistic regression analysis indicated that age, weight and BMI remained significantly associated with osteoporosis. In addition, correlation analysis showed significant correlations between BMD T-score and the following parameters: gender, age and drug type (clozapine versus non-clozapine) (Bonferroni corrected p's<0.05). Our results suggest a higher prevalence of osteoporosis and osteopenia in Chinese schizophrenic inpatients, with both the expected risk factors of gender and age, as well as drug type.

In Vitro and In Vivo Studies of a New Class of Anticancer Molecules for Targeted Radiotherapy of Cancer.

There is a compelling need to develop anticancer therapies that target cancer cells and tissues. Arising from innovative femtomedicine studies, a new class of non-platinum-based halogenated molecules (called FMD molecules) that selectively kill cancer cells and protect normal cells in treatments of multiple cancers has been discovered. This article reports the first observation of the radiosensitizing effects of such compounds in combination with ionizing radiation for targeted radiotherapy of a variety of cancers. We present in vitro and in vivo studies focused on combination with radiotherapy of cervical, ovarian, head and neck, and lung cancers. Our results demonstrate that treatments of various cancer cells in vitro and in vivo mouse xenograft models with such compounds led to enhanced efficiencies in radiotherapy, while the compounds themselves induced no or little radiotoxicity toward normal cells or tissues. These compounds are therefore effective radiosensitizers that can be translated into clinical trials for targeted radiotherapy of multiple types of cancer. This study also shows the potential of femtomedicine to bring breakthroughs in understanding fundamental biologic processes and to accelerate the discovery of novel drugs for effective treatment or prevention of a variety of cancers. Mol Cancer Ther; 15(4); 640-50. ©2016 AACR.

In Vitro and In Vivo Studies of Non-Platinum-Based Halogenated Compounds as Potent Antitumor Agents for Natural Targeted Chemotherapy of Cancers.

Based on a molecular-mechanism-based anticancer drug discovery program enabled by an innovative femtomedicine approach, we have found a previously unknown class of non-platinum-based halogenated molecules (called FMD compounds) as potent antitumor agents for effective treatment of cancers. Here, we present in vitro and in vivo studies of the compounds for targeted chemotherapy of cervical, breast, ovarian, and lung cancers. Our results show that these FMD agents led to DNA damage, cell cycle arrest in the S phase, and apoptosis in cancer cells. We also observed that such a FMD compound caused an increase of reduced glutathione (GSH, an endogenous antioxidant) levels in human normal cells, while it largely depleted GSH in cancer cells. We correspondingly found that these FMD agents exhibited no or little toxicity toward normal cells/tissues, while causing significant cytotoxicity against cancer cells, as well as suppression and delay in tumor growth in mouse xenograft models of cervical, ovarian, breast and lung cancers. These compounds are therefore a previously undiscovered class of potent antitumor agents that can be translated into clinical trials for natural targeted chemotherapy of multiple cancers.

Hypomethylation of SNCA in blood of patients with sporadic Parkinson's disease.

SNCA is a pathogenic gene identified in rare familial PD, and over-expression of SNCA was suggested in the pathogenesis of familial and sporadic PD. Rep1 polymorphism of SNCA was associated with susceptibility to sporadic PD and SNCA expression in intro and in vivo. Hypomethylation in SNCA intron-1 was associated with increased SNCA expression and was observed in postmortem brains of patients with sporadic PD. We studied the methylation status of SNCA intron-1, SNCA mRNA levels and Rep1 genotypes in PBMCs of 100 sporadic PD patients and 95 controls and explored the relationship between DNA methylation, mRNA expression and Rep1 genotypes. Hypomethylation of SNCA intron-1 was detected in PBMCs of PD patients, and DNA methylation levels were associated with Rep1 polymorphism. The shorter allele was associated with higher level of SNCA intron-1 methylation, and genotypes carrying the shorter allele showed significantly higher methylation level of SNCA intron-1 than genotypes carrying the longer allele. However, SNCA mRNA levels were not associated with disease status, Rep1 polymorphism or DNA methylation of SNCA intron-1 in our study.

[Pathogenic spectrum of enteroviruses associated with hand, foot and mouth disease by a GeXP™-based multiplex reverse transcription-PCR assay in Jinan, China, 2009-2012].

We investigated the pathogenic spectrum of enteroviruses associated with hand, foot and mouth disease (HFMD) in Jinan, China. A total of 274 specimens with a clinical diagnosis of HFMD in Jinan from 2009 to June 2012 were used. A GenomeLab™ (GeXP)-based multiplex reverse transcription-polymerase chain reaction (RT-PCR) assay was employed to simultaneously detect 15 serotypes of human enteroviruses: human enterovirus (EV)71; coxsackievirus A (CVA)16, 4, 5, 6, 9, and 10; CVB1, 3 and 5; echovirus (Echo) 6, 7, 11, 13 and 19. Results showed that all samples were enterovirus-positive, with the most common serotypes being EV71 (25.18%) and CVA16 (16.06%), followed by CVA10 (14.23%), CVA6 (7.30%), CVB1 (1.09%), Echo6 (0.73%), CVA9 (0.36%), CVB3 (0.36%) and co-infections (5.11%). CVA10 and CVA6 had the third and fourth highest prevalence of pathogens for HFMD, respec- tively. The most prevalent season for CVA10 was from April to August, with a peak in April; for CVA6 it was from April to August, with a peak in June. This is the first report of the pathogenic spectrum of en- teroviruses associated with HFMD in Jinan using the GeXP-based multiplex RT-PCR assay. These data will provide the scientific evidence for the prevention and control of epidemics, as well as therapy for HFMD patients.

Chimeric antigen receptor-engineered T cells for cancer immunotherapy: progress and challenges.

Recent years have witnessed much progress in both basic research and clinical trials regarding cancer immunotherapy with chimeric antigen receptor (CAR)-engineered T cells. The unique structure of CAR endows T cell tumor specific cytotoxicity and resistance to immunosuppressive microenvironment in cancers, which helps patients to better tackle the issue of immunological tolerance. Adoptive immunotherapy (AIT) using this supernatural T cell have gained momentum after decades of intense debates because of the promising results obtained from preclinical models and clinical trials. However, it is very important for us to evaluate thoroughly the challenges/obstacles before widespread clinical application, which clearly warrants more studies to improve our understanding of the mechanism underlying AIT. In this review, we focus on the critical issues related to the clinical outcomes of CAR-based adoptive immunotherapy and discuss the rationales to refine this new cancer therapeutic modality.

Lithium chloride alleviates neurodegeneration partly by inhibiting activity of GSK3ß in a SCA3 Drosophila model.

Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG trinucelotide repeat that encodes an abnormal polyglutamine (PolyQ) tract in the disease protein, ataxin-3. The formation of neuronal intranuclear inclusions in the specific brain regions is one of the pathological hallmarks of SCA3. Acceleration of the degradation of the mutant protein aggregates is proven to produce beneficial effects in SCA3 and other PolyQ diseases. Lithium is known to be neuroprotective in various models of neurodegenerative disease and can reduce the mutant protein aggregates by inducing autophagy. In this study, we explored the therapeutic potential of lithium in a SCA3 Drosophila model. We showed that chronic treatment with lithium chloride at specific doses notably prevented eye depigmentation, alleviated locomotor disability, and extended the median life spans of SCA3 transgenic Drosophila. By means of genetic approaches, we showed that co-expressing the mutant S9E, which mimicked the phosphorylated S9 state of Shaggy as done by lithium, also partly decreased toxicity of gmr-SCA3tr-Q78. Taken together, our findings suggest that lithium is a promising therapeutic agent for the treatment of SCA3 and other PolyQ diseases.

Modifications of Kyoho grape berry quality under long-term NaCl treatment.

Different concentrations of a sodium chloride spray were applied to the grapevine cultivar Kyoho to determine the effects of salinity on berry quality. The fruit's fresh weight, relative water content, hardness and titratable acid were gradually enhanced with increased salt concentrations. Anthocyanin and soluble solids increased after treatment with moderate salinity (20 and 60 mM); however, the results were reversed under high salinity (100 and 150 mM). The soluble sugars glucose, fructose and sucrose increased after treatment with moderate salinity, whereas glucose and fructose declined under high salinity. For the six organic acids tested, their total levels were elevated by salinity, which increased the production of tartaric and malic acids. The aroma of the berry was extremely sensitive to salinity and showed a considerable decline in abundance and variety at 20 mM NaCl. In summary, moderate salinity enhanced the overall berry quality, but decreased the aroma quality, whereas high salinity decreased the berry quality.

MdVHA-A encodes an apple subunit A of vacuolar H(+)-ATPase and enhances drought tolerance in transgenic tobacco seedlings.

Vacuole H(+)-ATPases (VHAs) are plant proton pumps, which play a crucial role in plant growth and stress tolerance. In the present study, we demonstrated that the apple vacuolar H(+)-ATPase subunit A (MdVHA-A) is highly conserved with subunit A of VHA (VHA-A) proteins from other plant species. MdVHA-A was expressed in vegetative and reproductive organs. In apple in vitro shoot cultures, expression was induced by polyethylene glycol (PEG)-mediated osmotic stress. We further verified that over-expression of MdVHA-A conferred transgenic tobacco seedlings with enhanced vacuole H+-ATPase (VHA) activity and improved drought tolerance. The enhanced PEG-mimic drought response of transgenic tobacco seedlings was related to an extended lateral root system (dependent on auxin translocation) and more efficient osmotic adjustment. Our results indicate that MdVHA-A is a candidate gene for improving drought tolerance in plants.

[Determination of maleic hydrazide residues and its influence on the quality of Atractylodes macrocephala].

OBJECTIVE: To determine maleic hydrazide (MH) residues and discuss its influence on the quality of Atractylodes macrocephala. METHODS: At the bud stage, A. macrocephala different concentration of MH. Then MH residues,the contents of sugar and lactone were determined by HPLC and UV. The quality of A. macrocephala was comprehensively evaluated by independent sample t test and principal component analysis. RESULTS: The range of MH residues was 0.3-2.2 mg/kg. The results of independent sample t test revealed that the trend of the contents of lactone was low-high-low with the increase of MH, and the effect of MH on the content of sugar was barely obvious. Meanwhile, principal component analysis showed that comprehensive evaluation on the quality of A. macrocephala was the best when MH with 75 or 100 times water was applied. CONCLUSION: Proper concentration MH is applied to ensure low concentration MH residues and improve yield and quality of A. macrocephala.

[Expression of recombinant human IFNa-2b/IgG4 Fc fusion protein in a baculovirus insect cell system].

To investigate a baculovirus insect cell system for expressing an interferon alpha 2b (IFNa2b)/immunoglobulin G-4 (IgG4) Fc fusion protein, which has long-acting antiviral effects. Human IFNa2b and IgG4 Fc cDNAs were generated by molecular cloning and inserted into a baculovirus shuttle vector, which was then transposed into the DH10 Bac strain to form recombinant Bacmid-IFN/Fc. The Bacmid-IFN/Fc was transfected into High five insect cells, and expression of the IFN/Fc fusion protein was detected by Western blotting and its biological activity was assessed by the cytopathic effect inhibition method. The IFNa2b and IgG4 Fc cDNA fragments were successfully amplified by RT-PCR using human peripheral lymphocytes. After cloning into the baculovirus shuttle vector, pFastBac1, and transforming into DH10 Bac competent cells, screening identified positive clones carrying the recombinant Bacmid-IFN/Fc. A Bacmid-IFN/Fc clone was successfully transfected into the High five insect cells and packaged into the baculovirus for expression of the IFN/Fc fusion protein. Western blotting revealed that the fusion protein expression was specific, and yielded a protein of 45 kD in size. The in vitro antiviral activity of the IFN/Fc fusion protein was 580 IU/mL. A novel IFN/Fc fusion protein was successfully generated using a baculovirus insect cell system, which may prove useful for providing future experimental data for development of a new long-acting interferon to treat chronic viral hepatitis.

[Diagnosis of spontaneous isolated superior mesenteric artery dissection using computed tomography angiography].

OBJECTIVE: To investigate the characteristics of the spontaneous isolated superior mesenteric artery dissection (SISMAD) on computed tomography angiography (CTA). METHODS: Twenty-five patients with unexplained acute abdominal pain received CTA. RESULTS: Four cases with the SISMAD were found and all were male with a mean age of (45.3±6.7) years. Two patients had hypertension history. CT showed enlarged diameter of the superior mesenteric artery with dissection in 4 cases, intimal flap and visible false lumen in 2 cases, ulcer-like laceration in 1 case, and intramural hematoma in 1 case. The proximal lacerations or entries were all at the proximal segment of the superior mesenteric artery. CTA classifications were type Ia (n=2), IIb (n=1), and III (n=1). Two patients underwent repeated CTA when discharged, and progressive changes were discovered. CONCLUSION: CTA can clearly show the characteristics of the superior mesenteric artery dissection, confirm the diagnosis, and provide an important basis for the classification and follow-up observation.

Cadmium adsorption characteristic of alkali modified sewage sludge.

This paper proposed a new biosorbent preparation method by alkali modification of sewage sludge. The cadmium ion (Cd(2+)) adsorption capacity of alkali modified sewage sludge (AMSS) was evaluated by equilibrium sorption experiments. The amount of released calcium ion (Ca(2+)) in sorption equilibrium experiment were measured in order to reveal the adsorption mechanism. In addition, Zeta potential, specific surface area and Fourier transform infrared (FTIR) spectra of AMSS were tested. The results showed that the cadmium adsorption isotherms of AMSS fitted well with both Langmuir and Freundlich models, and the maximum adsorption capacities increased by 0.713 mmol g(-1). The cadmium adsorption capacity of biosorbent increased with NaOH solution concentration (range from 0.25 to 7.5 mol L(-1)) for sewage sludge modification. The strong cadmium adsorption of AMSS was attributed to ion exchange effect, electrostatic attraction and complexation. This alkali modified sewage sludge may have a potential for serving as cadmium removal biosorbent.

Electron transfer-based combination therapy of cisplatin with tetramethyl-p-phenylenediamine for ovarian, cervical, and lung cancers.

The platinum-based chemotherapy is the standard treatment for several types of cancer. However, cancer cells often become refractory with time and most patients with serious cancers die of drug resistance. Recently, we have discovered a unique dissociative electron-transfer mechanism of action of cisplatin, the first and most widely used platinum-based anticancer drug. Here, we show that the combination of cisplatin with an exemplary biological electron donor, N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD), may overcome the resistance of cancer cells to cisplatin. Our steady-state absorption and fluorescence spectroscopic measurements confirm the effective dissociative electron-transfer reaction between TMPD and cisplatin. More significantly, we found that the combination of 100 µM TMPD with cisplatin enhances double-strand breaks of plasmid DNA by a factor of approximately 3.5 and dramatically reduces the viability of cisplatin-sensitive human cervical (HeLa) cancer cells and highly cisplatin-resistant human ovarian (NIH:OVCAR-3) and lung (A549) cancer cells. Furthermore, this combination enhances apoptosis and DNA fragmentation by factors of 2-5 compared with cisplatin alone. These results demonstrate that this combination treatment not only results in a strong synergetic effect, but also makes resistant cancer cells sensitive to cisplatin. Because cisplatin is the cornerstone agent for the treatment of a variety of human cancers (including testicular, ovarian, cervical, bladder, head/neck, and lung cancers), our results show both the potential to improve platinum-based chemotherapy of various human cancers and the promise of femtomedicine as an emerging frontier in advancing cancer therapy.

Molecular mechanism of the DNA sequence selectivity of 5-halo-2'-deoxyuridines as potential radiosensitizers.

The 5-halo-2'-deoxyuridines bromodeoxyuridine (BrdU) and iododeoxyuridine (IdU) are well-known photosensitizers for inducing DNA/RNA-protein cross-linking and potential radiosensitizers for radiotherapy of cancer. The dependence of the photosensitivity of BrdU and IdU on the DNA sequence has been well-observed, but it is unknown whether there is a similar DNA sequence selectivity in their radiosensitivity. Here we show a new ultrafast electron transfer (UET) mechanism for the likely DNA sequence dependence of the radiosensitivity of BrdU and IdU. Our femtosecond time-resolved transient laser absorption spectroscopic measurements provide the first real-time observation of the UET reactions of BrdU/IdU with the anion states of adenine and guanine. It is shown that the UET between BrdU and dA*(-) (dA(-)) is more effective than that between BrdU and dG*(-). This is related to the recent observation that dG*(-) is highly destructive while dA(-) is long-lived. This mechanistic understanding may lead to the improvement of BrdU and IdU to achieve sufficient radiosensitizing efficacy and the development of more effective radiosensitizers for clinical uses.