Study on the sensitizing effect of SM-1 combined with irradiation on head and neck squamous cell carcinoma.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is globally prevalent with high recurrence, low survival rate, and poor quality of life for patients. Derived from PAC-1, SM-1 can activate procaspase-3 and induce apoptosis in cancer cells to exert anti-tumor effects. However, the inhibitory effect of SM-1 on HNSCC after combination with radiation are unclear. This study aims to investigate the radiosensitizing effect of SM-1 on HNSCC in vitro and in vivo. METHODS: MTT method was used to detect the effect of SM-1 on the viability of HNSCC cell lines (HONE1, HSC-2, and CAL27). The effects of SM-1 combined with radiation on the survival index of HONE1, HSC-2, and CAL27 cell lines were determined by colony formation assay. Flow cytometry was used to investigate the effects of SM-1 and radiation combination on cell apoptosis and cell cycle, and western blot experiments were performed to detect the expression of apoptosis and cell cycle-related proteins. Finally, a xenograft tumor model of CAL27 was established to evaluate the anti-tumor effect of SM-1 combined with radiation in vivo. RESULTS: In vitro, SM-1 effectively inhibited the activity of HNSCC cell lines HONE1, HSC-2, and CAL27 cells, and synergistically showed anti-proliferation activity during combined irradiation. Meanwhile, anti-tumor effect of SM-1 on HNSCC was higher than that of Debio1143, and the radiosensitivity of cells was greatly increased. Flow cytometry and western blot analysis showed that SM-1 induced G2/M phase arrest of head and neck squamous cell carcinoma cells via inhibiting the expression of CyclinB1 and CDC2. Moreover, SM-1 activated caspase-3 activity and up-regulated the cleaved form of PARP1 to induce cell apoptosis. In vivo, SM-1 combined irradiation showed a good anti-tumor effect. CONCLUSION: SM-1 enhances HNSCC cell radiation sensitivity in vitro and in vivo, supporting its potential as a radiosensitizer for clinical trials in combination with radiotherapy.

Freeze-thaw cycles drove chemical weathering and enriched sulfates in the Burns formation at Meridiani, Mars.

Sulfate-rich sedimentary rocks explored by the Opportunity rover during its 14-year surface mission at Meridiani Planum provide an invaluable window into the thousands of sulfate deposits detected on Mars via remote sensing. Existing models explaining the formation of martian sulfates can be generally described as either bottom-up, groundwater-driven playa settings or top-down icy chemical weathering environments. Here, we propose a hybrid model involving both bottom-up and top-down processes driven by freeze-thaw cycles. Freezing leads to cryo-concentration of acidic fluids from precipitations at the surface, facilitating rapid chemical weathering despite low temperatures. Cryosuction causes the upward migration of vadose water and even groundwater with dissolved ions, resulting in the accumulation of ions in near-surface environments. Evaporation precipitates salts, but leaching separates chlorides from sulfates during the thawing period. Freeze-thaw cycles, therefore, can enrich sulfates at the surface. While freeze-thaw is more commonly understood as a mechanism of physical weathering, we suggest that it is a fundamental aspect of chemical weathering on Mars.

[Research progress in prevention and treatment of radiation-induced intestinal injury by traditional Chinese medicine active components].

Radiation-induced intestinal injury(RIII), a common complication of radiotherapy for pelvic malignancies, affects the quality of life and the radiotherapy efficacy for cancer. Currently, the main clinical approaches for the prevention and treatment of RIII include drug therapy, hyperbaric oxygen therapy, and surgical treatment. Among these methods, drug therapy is cost-effective. Traditional Chinese medicine(TCM) containing a variety of active components demonstrates mild side effects and good efficacy in preventing and treating RIII. Studies have proven that TCM active components, such as flavonoids, terpenoids, phenylpropanoids, and alkaloids, can protect the intestine against RIII by inhibiting oxidative stress, regulating the expression of inflammatory cytokines, modulating the mitochondrial apoptosis pathway, adjusting intestinal flora, and suppressing cell apoptosis. These mechanisms can help alleviate the symptoms of RIII. The paper aims to provide a theoretical reference for the discovery of new drugs for the prevention and treatment of RIII by reviewing the literature on TCM active components in the last 10 years.

Does Dexmedetomidine Reduce the Risk of Atrial Fibrillation and Stroke After Adult Cardiac Surgery? A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Postoperative atrial fibrillation is a common consequence of cardiac sur-gery with increased stroke complications and mortality. Although dexmedetomidine is thought to prevent postoperative atrial fibrillation and stroke because of its sympa-tholytic and anti-inflammatory properties, data from different studies show the effect of dexmedetomidine on postoperative atrial fibrillation and stroke uncertain in adult patients with cardiac surgery. METHODS: A database including EMBASE, PubMed, and Cochrane CENTRAL was searched for randomized controlled trials comparing dexmedetomidine with placebo or other anesthetic drugs in adult cardiac surgery. The primary outcome was the incidence of postoperative atrial fibrillation. The secondary outcomes were the incidence of postop-erative stroke, mechanical ventilation duration, intensive care unit length of stay, hospi-tal length of stay, and mortality. RESULTS: Eighteen trials with a total of 2933 patients were enrolled in the meta-analyses. Compared with controls, dexmedetomidine significantly reduced the incidence of post-operative atrial fibrillation [odds ratio, 0.82; 95% CI, 0.69-0.98; P = .03]. There was no sig-nificant difference between groups in stroke (odds ratio, 1.36; 95% CI, 0.59-3.16; P = .47), mechanical ventilation duration [weighted mean difference, -0.17; 95% CI, -0.35 to 0.14;P=.39], intensive care unit length of stay (weighted mean difference, -0.03; 95% CI,-0.93 to 0.87; P = .95), hospital length of stay (weighted mean difference, -0.04; 95% CI,-0.40 to 0.32; P = .83) and mortality (odds ratio, 0.72; 95% CI, 0.32-1.60; P = .42). CONCLUSION: Perioperative dexmedetomidine reduced the incidence of postoperative atrial fibrillation in adult patients undergoing cardiac surgery. But there was no signifi-cant difference in the incidence of stroke, mechanical ventilation duration, intensive care unit length of stay, hospital length of stay, and mortality.

Laparoscopic repair of complete intrathoracic stomach with iron deficiency anemia: A case report.

BACKGROUND: Giant paraesophageal hiatal hernias (HH) are very infrequent, and their spectrum of clinical manifestations is large. Giant HH mainly occurs in elderly patients, and its relationship with anemia has been reported. For the surgical treatment of large HH, Nissen fundoplication is the most common antireflux procedure, and the reinforcement of HH repair with a patch (either synthetic or biologic) is still debatable. CASE SUMMARY: We report on a case of giant paraesophageal HH in a middle-aged male patient with reflux symptoms and severe anemia. After performing a series of tests and diagnostic approaches, results showed a complete intrathoracic stomach associated with severe iron deficiency anemia. The patient underwent successful laparoscopic hernia repair with mesh reinforcement and Nissen fundoplication. Postoperatively, reflux symptoms were markedly relieved, and the imaging study showed complete reduction of the hernia sac. More importantly, anemia was resolved, and hemoglobin, serum iron and ferritin level were returned to the normal range. The patient kept regular follow-up appointments and remained in a satisfactory condition. CONCLUSION: This case report highlights the relationship between large HH and iron deficiency anemia. For the surgical treatment of large HH, laparoscopic repair of large HH combined with antireflux procedure and mesh reinforcement is recommended.

[Effects of psychological stress on xanthine oxidase expression, activity and related markers in adipose tissue of mice].

OBJECTIVE: To investigate the effects of psychological stress on xanthine oxidase (XO) expression, activity and related markers in adipose tissue of mice. METHODS: Twenty male Kunming mice were randomly divided into two groups (10 in each group), stress group and control group (10 in each group). Stress group were restrained in self-made restraint device for 2 hours per day for 14 days, then blood samples and white adipose tissues(WAT) were collected. The expression levels of XO and NADPH oxidase-4 (Nox-4) in WAT were detected by immunohistochemistry. The expression of XO, Nox-4, antioxidant proteins (manganese superoxide dismutase (Mn SOD), glutathione peroxidase (GSH-Px), and catalase (CAT)), adipocytokines (adiponectin (ADPN), monocyte chemotactic protein 1 (MCP-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)) in WAT were further detected by quantitative PCR. Relative expressions of glucose metabolism (insulin receptor substrate-1(IRS-1) and glucose transporter type 4(GLUT-4)) and thrombin(tissue factor (TF) and plasminogen activator inhibitor 1 (PAI-1))were measured. XO activity and serum concentrations of (triglyceride (TG), total cholesterol (T-Cho), free fatty acid, (FFA), and uric acid (UA)) were detected by ELISA. RESULTS: XO expressed in stress mice inguinal WAT was deeper and more abundant than that of control group, mainly expressed in adipocytes. RT-PCR and ELISA results showed that the levels of XO mRNA, serum XO concentration and the activities of XO enzyme in WAT of stress group were significantly higher than those of control group(P ＜0.01). Compared with control group the concentrations of free fatty acid (FFA) and uric acid (UA) in stress group were increased significantly than in control group (P＜ 0.01). Nox-4 positive cells mainly expressed in adipocytes. The expression of Nox-4 in WAT of stress group was significantly higher(P ＜0.01); The levels of antioxidant proteins (Mn-SOD, GSH-Px, Catalase) in WAT of stress group were significantly lower (P＜ 0.01). WAT in stress group showed a large number of infiltration reactions and inflammatory changes of monocytes, neutrophils, eosinophils and plasma cells. Stress significantly decreased the expression of adiponectin in WAT, and significantly increased the expressions of MCP-1, IL-6 and TNF-α (P＜0.01). The levels of IRS-1 and GLUT-4 in WAT of stress mice were increased significantly (P＜ 0.01). The expressions of TF and PAI-1 in WAT of stress mice and blood concentrations were significantly higher (P＜0.01). CONCLUSION: Stress can induce excessive expressions of XO in adipose tissue, which eventaully can lead to adipose inflammation, glycometabolism and abnormal prothrombin.

Correlation of metastasis-associated protein expression with prognosis and chemotherapy in nasopharyngeal carcinoma.

The aim of this study was to elaborate the correlation between metastasis-associated protein (MTA) family and the occurrence, progression, prognosis and chemotherapy efficiency in nasopharyngeal carcinoma (NPC).The expression of MTA1, MTA2 and MTA3 protein were detected by immunohistochemistry in a tissue microarray (TMAs) which contains tissue samples of 152 NPC patients embedded by formalin-fixed paraffin. The MTA proteins were mainly expressed in the nuclei of NPC tissues and the correlations between MTAs expression and clinical parameters as well as prognosis of NPC patients showed ethnical differences according to statistically analysis. The results showed that in Han ethnic group, MTA1 expression was positively correlated with N staging, while the expression of MTA2 was negatively correlated with age, and the expression of MTA3 was positively correlated with gender. Patients with high MTA1 expression had poorprognosis. In Zhuang ethnic group, only MTA3 expression was positively correlated with age, recurrence and metastasis of NPC patients; neither MTA1 nor MTA2 expression had any correlation with clinical indexes. Patients with high MTA3 expression had unfavorable prognosis. In addition, our results showed that overall survival among Zhuang NPC patients with low expression of MTA2 increased significantly owing to "carboplatin + fluorouracil" chemotherapy. This therapeutic success, however, did not translate to longer overall survival among Han NPC patients. The biological function of MTA protein family in NPC patients was different among different ethnic groups. In conclusion, we demonstrated that MTAs had a certain tumor promoting function in patients with NPC, and the biological functions of MTAs might be ethnic differences, which suggesting MTAs to be important markers for guiding clinical treatment of NPC.

Oxygen-Free Biochemistry: The Putative CHN Foundation for Exotic Life in a Hydrocarbon World?

Since Earth's biochemistry is carbon-based and water-borne, the main strategies for searching for life elsewhere are "follow the carbon" and "follow the water." Recently, however, there is a growing focus on the prospect that putative exotic life on other planets could rely on unearthly biochemistries. Here, we hypothesize a novel oxygen-free organic chemistry for supporting potential exotic biosystems, which is named CHN biochemistry. This oxygen-free CHN biochemistry starts from simple oxygen-free species (including hydrocarbons, hydrogen cyanide, and nitriles) and produces a range of functional macromolecules that may function in similar ways to terran macromolecules, such as sugars (cyanosugars), acids (cyanoacids), amino acids (amino cyanoacids), and nucleobases (cyanonucleobases). These CHN macromolecules could further interact with each other to generate higher "cyanoester" and "cyanoprotein" systems. In addition, theoretical calculations indicate that the energy changes of some reactions are consistent with their counterparts in Earth's biochemistry. The CHN biochemistry-based life would be applicable in habitats with a low bioavailability of oxygen, such as the alkane lakes of Titan and non-aquatic liquids on extrasolar bodies. Key Words: Oxygen-free biochemistry-Titan-Hydrocarbons-Hydrogen cyanide-Nitriles. Astrobiology 17, 1173-1181.

As(III) removal and speciation of Fe (Oxyhydr)oxides during simultaneous oxidation of As(III) and Fe(II).

Abiotic oxidation of Fe(II) is an important pathway in the formation of Fe (oxyhydr)oxides. However, how can As(III) affect the oxidation rate of Fe(II) and the speciation of Fe (oxyhydr)oxides, and what's the extent of the newly formed Fe (oxyhydr)oxides on the removal of aqueous arsenic are still poorly understood. Oxidation of Fe(II) under neutral pH conditions was therefore investigated under different molar ratios of As:Fe. Our results suggest that co-existence of aqueous As(III) significantly slows down the oxidation rate of Fe(II). Speciation of Fe (oxyhydr)oxides is dependent on pH and As:Fe ratios. At pH 6.0, formation of lepidocrocite and goethite is apparently inhibited at low As:Fe ratios, and ferric arsenate is favored at high As:Fe ratios. At pH 7.0, lepidocrocite gradually degenerates with the increasing As:Fe ratios. At pH 8.0, arsenite significantly inhibits the development of magnetite and favors a formation of lepidocrocite. XPS analysis further reveals that more than half of As(III) is oxidized to As(V) at pH 6.0 and 7.0, whereas at pH 8.0, the rapid oxidation of Fe(II) as well as the rapid formation of Fe (oxyhydr)oxides facilitate a rapid removal of dissolved As(III) before its further oxidation to As(V).

Biomimetic synthesis of struvite with biogenic morphology and implication for pathological biomineralization.

Recent studies have found that certain urinary proteins can efficiently inhibit stone formation. These discoveries are significant for developing effective therapies for stone disease, but the inhibition mechanism of crystallization remains elusive. In the present study, polyaspartic acid (PASP) was employed as a model peptide to investigate the effect of urinary proteins on the crystallization and morphological evolution of struvite. The results demonstrate that selective adsorption/binding of PASP onto the {010} and {101} faces of struvite crystals results in arrowhead-shaped morphology, which further evolves into X-shaped and unusual tabular structures with time. Noticeably, these morphologies are reminiscent of biogenic struvite morphology. Concentration-dependent experiments show that PASP can inhibit struvite growth and the inhibitory capacity increases with increasing PASP concentration, whereas aspartic acid monomers do not show a significant effect. Considering that PASP is a structural and functional analogue of the subdomains of aspartic acid-rich proteins, our results reveal that aspartic acid-rich proteins play a key role in regulating biogenic struvite morphology, and aspartic acid residues contribute to the inhibitory capacity of urinary proteins. The potential implications of PASP for developing therapeutic agents for urinary stone disease is also discussed.

14-3-3σ is an independent prognostic biomarker for gastric cancer and is associated with apoptosis and proliferation in gastric cancer.

14-3-3 proteins participate in various cellular processes, including apoptosis, proliferation and malignant transformation. 14-3-3σ, a member of the 14-3-3 protein family, is important in several types of cancer; however, little is known about the clinical significance and biological roles of 14-3-3σ in gastric cancer. The present study analyzed the expression pattern of 14-3-3σ in gastric cancer and investigated its correlation with the prognosis of gastric cancer patients. Furthermore, the association of 14-3-3σ with Ki-67, Bcl-2 and Bax was evaluated. 14-3-3σ was expressed at higher level in gastric cancer tissue compared with healthy gastric tissue, and 14-3-3σ expression was significantly correlated with tumor size and tumor node metastasis stage (P<0.05). To the best of our knowledge, the present study data are the first to suggest that 14-3-3σ expression has been significantly associated with poor prognosis in gastric cancer. Additionally, 14-3-3σ overexpression was positively correlated with Ki-67 and Bcl-2 expression levels. Thus, 14-3-3σ is a potential prognostic marker for gastric cancer patients, and may be involved in regulating the apoptosis and proliferation of gastric cancer cells.

Biomineralization mediated by anaerobic methane-consuming cell consortia.

Anaerobic methanotrophic archaea (ANME) play a significant role in global carbon cycles. These organisms consume more than 90% of ocean-derived methane and influence the landscape of the seafloor by stimulating the formation of carbonates. ANME frequently form cell consortia with sulfate-reducing bacteria (SRB) of the family Deltaproteobacteria. We investigated the mechanistic link between ANME and the natural consortium by examining anaerobic oxidation of methane (AOM) metabolism and the deposition of biogenetic minerals through high-resolution imaging analysis. All of the cell consortia found in a sample of marine sediment were encrusted by a thick siliceous envelope consisting of laminated and cementing substances, whereas carbonate minerals were not found attached to cells. Beside SRB cells, other bacteria (such as Betaproteobacteria) were found to link with the consortia by adhering to the siliceous crusts. Given the properties of siliceous minerals, we hypothesize that ANME cell consortia can interact with other microorganisms and their substrates via their siliceous envelope, and this mechanism of silicon accumulation may serve in clay mineral formation in marine sedimentary environments. A mechanism for biomineralization mediated by AOM consortia was suggested based on the above observations.

Scalable economic extracellular synthesis of CdS nanostructured particles by a non-pathogenic thermophile.

We report microbially facilitated synthesis of cadmium sulfide (CdS) nanostructured particles (NP) using anaerobic, metal-reducing Thermoanaerobacter sp. The extracellular CdS crystallites were <10 nm in size with yields of ~3 g/L of growth medium/month with demonstrated reproducibility and scalability up to 24 L. During synthesis, Thermoanaerobacter cultures reduced thiosulfate and sulfite salts to H2S, which reacted with Cd²âº cations to produce thermodynamically favored NP in a single step at 65 °C with catalytic nucleation on the cell surfaces. Photoluminescence (PL) analysis of dry CdS NP revealed an exciton-dominated PL peak at 440 nm, having a narrow full width at half maximum of 10 nm. A PL spectrum of CdS NP produced by dissimilatory sulfur reducing bacteria was dominated by features associated with radiative exciton relaxation at the surface. High reproducibility of CdS NP PL features important for scale-up conditions was confirmed from test tubes to 24 L batches at a small fraction of the manufacturing cost associated with conventional inorganic NP production processes.

(3R,4S,5R)-Methyl 3,5-bis-[(tert-butyl-dimethyl-sil-yl)-oxy]-4-meth-oxy-cyclo-hex-1-ene-carboxyl-ate.

The title compound, C21H42O5Si2, was synthesized from (3R,4S,5R)-methyl 3,5-bis-[(tert-butyl-dimethyl-sil-yl)-oxy]-4-hy-droxy-cyclo-hex-1-ene-carboxyl-ate by an esterification reaction. The cyclo-hexene ring adopts a half-chair conformation. In the crystal, mol-ecules are linked via C-H⋯O hydrogen bonds, forming helical chains propagating along [010].

Hexagonal platelet-like magnetite as a biosignature of thermophilic iron-reducing bacteria and its applications to the exploration of the modern deep, hot biosphere and the emergence of iron-reducing bacteria in early precambrian oceans.

Dissimilatory iron-reducing bacteria are able to enzymatically reduce ferric iron and couple to the oxidation of organic carbon. This mechanism induces the mineralization of fine magnetite crystals characterized by a wide distribution in size and irregular morphologies that are indistinguishable from authigenic magnetite. Thermoanaerobacter are thermophilic iron-reducing bacteria that predominantly inhabit terrestrial hot springs or deep crusts and have the capacity to transform amorphous ferric iron into magnetite with a size up to 120 nm. In this study, I first characterize the formation of hexagonal platelet-like magnetite of a few hundred nanometers in cultures of Thermoanaerobacter spp. strain TOR39. Biogenic magnetite with such large crystal sizes and unique morphology has never been observed in abiotic or biotic processes and thus can be considered as a potential biosignature for thermophilic iron-reducing bacteria. The unique crystallographic features and strong ferrimagnetic properties of these crystals allow easy and rapid screening for the previous presence of iron-reducing bacteria in deep terrestrial crustal samples that are unsuitable for biological detection methods and, also, the search for biogenic magnetite in banded iron formations that deposited only in the first 2 billion years of Earth with evidence of life.

1-(3-Fluoro-phen-yl)-3-(4-nitro-phen-yl)urea.

In the title compound, C(13)H(10)FN(3)O(3), the dihedral angle between the fluoro-phenyl and nitro-phenyl ring planes is 6.51 (9)°. The crystal structure features N-H⋯O hydrogen bonds.

Abiotic oxidation of Mn(II) and its effect on the oxidation of As(III) in the presence of nano-hematite.

Manganese (hydr)oxides (MnO(x)) is a powerful oxidant in the oxidation of As(III) in natural environment. Under some circumstances, Mn(II) can be oxidized to MnO(x) which in turn accelerates the oxidation of As(III). However, to the best of our knowledge, little is known regarding how Mn(II) affects the oxidation of both the dissolved and the adsorbed As(III) in aquatic environments. In this study, effects of abiotic oxidation of Mn(II) on the oxidation of As(III) were investigated. Kinetic results as well as TEM and XRD analyses confirmed the formation of amorphous MnO(x) after sorption of Mn(II) on hematite nano-particles under oxic conditions. Mn(II) was oxidized to Mn(III) and then to Mn(IV), and this process was dependent upon pH and Mn(II) concentrations. The newly formed MnO(x) played an important role in the further oxidation of the dissolved and the adsorbed As(III) on hematite, and the oxidation rate of As(III) increased with the rising Mn(II) concentrations. As the adsorbed As(III) was oxidized to As(V), a fraction of As(V) was released into the solution, which increased the mobility of As. The present study reveals that abiotic oxidation of Mn(II) affects the oxidation of As(III) in aquatic environment.

Design, synthesis and antitumor activity of 4-aminoquinazoline derivatives targeting VEGFR-2 tyrosine kinase.

We report herein the design and synthesis of novel 4-aminoquinazoline derivatives based on the inhibitors of VEGFR-2 tyrosine kinases. The VEGFR-2 inhibitory activities of these newly synthesized compounds were also evaluated and compared with that of ZD6474. We found that most of target compounds had good inhibitory potency. In particular, compounds 1h, 1n and 1o were found to be 6, 2 and 2-fold more potent than the positive control ZD6474. The leading compound 1h also showed an in vivo activity against HepG2 human tumor xenograft model in BALB/c-nu mice.