The Role of Wild-Type p53 in Cisplatin-Induced Chk2 Phosphorylation and the Inhibition of Platinum Resistance with a Chk2 Inhibitor

The major obstacle in platinum chemotherapy is the repair of platinum-damaged DNA that results in increased resistance, reduced apoptosis, and finally treatment failure. Our research goal is to determine and block the mechanisms of platinum resistance. Our recent studies demonstrate that several kinases in the DNA-repair pathway are activated after cells are exposed to cisplatin. These include ATM, p53, and Chk2. The increased Chk2 phosphorylation is modulated by p53 in a wild-type p53 model. Overexpression of p53 by cDNA transfection in wt-p53 (but not p53 deficient) cells doubled the amount of Chk2 phosphorylation 48 hours after cisplatin treatment. p53 knockdown by specific siRNA greatly reduced Chk2 phosphorylation. We conclude that wild-type p53, in response to cisplatin stimulation, plays a role in the upstream regulation of Chk2 phosphorylation at Thr-68. Cells without normal p53 function survive via an alternative pathway in response to the exogenous influence of cisplatin. We strongly suggest that it is very important to include the p53 mutational status in any p53 involved studies due to the functional differentiation of wt p53 and p53 mutant. Inhibition of Chk2 pathway with a Chk2 inhibitor (C3742) increased cisplatin efficacy, especially those with defective p53. Our findings suggest that inhibition of platinum resistance can be achieved with a small-molecule inhibitor of Chk2, thus improving the therapeutic indices for platinum chemotherapy

Airborne Polarimetric Remote Sensing for Atmospheric Correction

The problem, whose targets can not be effectively identified for airborne remote sensing images, is mainly due to the atmospheric scattering effect. This problem is necessary to be overcome. According to the statistical evaluations method and the different characteristics of polarization between the objects radiance and atmospheric path radiation, a new atmospheric correction method for airborne remote sensing images was proposed. Using this new method on the airborne remote sensing images which acquired on the north coast areas of China during the haze weather, we achieved a high quality corrected atmosphere-free image. The results demonstrate the power of the method on the harbor area. The results show that the algorithm, improving image contrast and image information entropy, can effectively identify the targets after atmospheric correction. The image information entropy was enhanced from 5.59 to 6.62. The research provides a new and effective atmospheric correction technical approach for the airborne remote sensing images

Synergic mitigation of saline-alkaline stress in wheat plant by silicon and Enterobacter sp. FN0603

Although microorganisms and silicon are well documented as factors that mitigate salt stress, their effect mitigating saline-alkaline stress in plants remains unknown. In this study, wheat plant seeds were treated with silicon, Enterobacter sp. FN0603 alone and in combination of both. Wheat seeds were soaked in silicon and bacterial solutions and sown in pots containing artificial saline-alkaline soils to compare the effects among all treatments. The results showed that the treatments with silicon and FN0603 alone significantly changed plant morphology, enhanced the rhizosphere soil nutrient content and enzyme activities, improved some important antioxidant enzyme activities (e.g., superoxide dismutase) and the contents of small molecules (e.g., proline) that affected osmotic conditions in the top second leaves. However, treatment with silicon and FN0603 in combination significantly further increased these stress tolerance indexes and eventually promoted the plant growth dramatically compared to the treatments with silicon or FN0603 alone (p < 0.01), indicating a synergic plant growth-promoting effect. High relative abundance of strain FN0603 was detected in the treated plants roots, and silicon further improved the colonization of FN0603 in stressed wheat roots. Strain FN0603 particularly when present in combination with silicon changed the root endophytic bacterial and fungal communities rather than the rhizosphere communities. Bipartite network analysis, variation partitioning analysis and structure equation model further showed that strain FN0603 indirectly shaped root endophytic bacterial and fungal communities and improved plant physiology, rhizosphere soil properties and plant growth through significantly and positively directing FN0603-specific biomarkers (p < 0.05). This synergetic effect of silicon and plant growth-promoting microorganism in the mitigation of saline-alkaline stress in plants via shaping root endophyte community may provide a promising approach for sustainable agriculture in saline-alkaline soils

Thioether-based anchimeric assistance for asymmetric coordination chemistry with ruthenium(II) and osmium(II)

National Science Foundation of P. R. China; "National Thousand Plan" Foundation of P. R. China; "985 Program" of the Chemistry and Chemical Engineering disciplines of Xiamen University(R)-4-(Alkylthiomethyl)-5,5-dimethyl-2-(2'-hydroxyphenyl)-2-oxazolines are demonstrated to be highly suitable chiral auxiliaries for the two-step conversion of the half-sandwich complex [Ru(eta(6)-C6H6)(bpy)Cl]Cl, bpy = 2,2'-bipyridine, into Delta-configured ruthenium polypyridyl complexes. The tailored thioether substituent at the oxazoline ring is essential for this conversion and not only promotes the removal of the benzene moiety but also controls the absolute metal-centered configuration. Applied to osmium, this strategy resulted in the first highly asymmetric synthesis of Delta-[Os(bpy)(3)](PF6)(2)

Antarctic sea ice change based on a new sea ice dataset from 1992 to 2008

The sea ice concentration dataset (covering the period 1992-2008) used in this study is a new dataset based on the Sea Ice Climate Change Initiative (SICCI) algorithm. We investigate whether the SICCI dataset is on a par with other datasets for studying sea ice cover changes in the Southern Ocean. We then examine spatiotemporal variations in sea ice derived from the SICCI dataset over the Southern Ocean, and analyse relationships of sea ice with sea surface temperature (SST). The results indicate that there is no significant difference between the SICCI dataset and the NASA Team dataset, and therefore the former can also be used for studying sea ice changes. Both sea ice extent (SIE) and sea ice area (SIA) derived from the SICCI dataset over the Southern Ocean increased slightly from 1992 to 2008, at rates of (17.75 ± 11.50) × 10^3 and (17.37 ± 9.51) × 10^3 km^2 yr^(–1), respectively. Antarctic sea ice has significant seasonal variations; all seasonally averaged SIE and SIA show an increase, with spring showing the largest positive changing rate. The Weddell Sea, Ross Sea, and Indian Ocean have positive yearly changing rates in SIE and SIA, while the Bellingshausen/Amundsen seas and western Pacific Ocean have negative yearly changing rates. However, overall sea ice over the Southern Ocean has a slight positive trend, which is the same as the sea ice change pattern derived from the NASA Team dataset. This indicates that the contributions to the change in sea ice over the whole Southern Ocean due to the Weddell Sea, Ross Sea, and Indian Ocean dominate over those by the Bellingshausen/Amundsen seas and western Pacific Ocean. Further analysis shows that both SIE and SIA are negatively correlated with SST in the Southern Ocean or each of the 5 longitudinal sectors, and sea ice is more sensitive to SST in spring and autumn

Experimental performance analysis of a dual source heat pump integrated with thermal energy storage

To mitigate disturbances to the electric grid resulting from the growing penetration of intermittent and decentralized renewable generation, a dual-source (air source and ground source) heat pump (DSHP) integrated with thermal energy storage (TES) was developed. The DSHP can use either ambient air or the shallow subsurface of the ground to provide space heating or space cooling to the building as the conventional heat pump and produce hot/cold water for charging TES. Using dual sources (air and ground) can reduce the required size of the expensive ground heat exchangers while retaining high energy efficiency. During the off-peak period, the DSHP cools/heats the TES with low-cost electricity or overproduced renewable power. The stored cooling/heating energy in the TES is released during peak hours of the electric grid to meet the thermal demands of the building without consuming electricity to run the DSHP. A 2-ton (7 kW) prototype DSHP was developed and integrated with a 50-gallon (189 L) TES tank filled with a phase change material. Field tests were conducted to characterize the performance of the integrated system operating in various operation modes

A Nanoscale Shape Memory Oxide

Stimulus-responsive shape memory materials have attracted tremendous research interests recently, with much effort focused on improving their mechanical actuation. Driven by the needs of nanoelectromechnical devices, materials with large mechanical strain particularly at nanoscale are therefore desired. Here we report on the discovery of a large shape memory effect in BiFeO3 at the nanoscale. A maximum strain of up to ~14% and a large volumetric work density can be achieved in association with a martensitic-like phase transformation. With a single step, control of the phase transformation by thermal activation or electric field has been reversibly achieved without the assistance of external recovery stress. Although aspects such as hysteresis, micro-cracking etc. have to be taken into consideration for real devices, the large shape memory effect in this oxide surpasses most alloys and therefore demonstrates itself as an extraordinary material for potential use in state-of-art nano-systems.Comment: Accepted by Nature Communication

Clinical efficacy of general anesthesia versus local anesthesia for percutaneous transforaminal endoscopic discectomy

ObjectiveLocal anesthesia (LA) is recommended for percutaneous transforaminal endoscopic discectomy(PTED), but satisfactory pain management is not mostly achieved. The goal of this study was to examine the clinical efficacy of PTED for lumbar disc herniation when performed under local anaesthetic vs. general anesthesia (GA).MethodsFrom August 2018 to August 2020, the clinical data of 108 patients treated with PTED were retrospectively evaluated and separated into two groups: LA and GA based on the anesthesia method. General information and clinical outcomes of patients were included. Visual analog scale (VAS) and Oswestry disability index (ODI) were recorded before operation, 1 week after operation, and 1 year after operation. In addition, VAS for back pain and leg pain on the second postoperative day were also recorded.ResultsWe divided the patients into two groups: 72 in LA and 36 in GA. There were no significant differences in gender, age, course of disease, body mass index, surgical segment, duration of operation, intraoperative bleeding, time of fluoroscopy, length of hospital stay, total hospitalization cost reoperation, surgical satisfaction, Macnab satisfaction, complications, preoperative and 1 year postoperatively VAS for back pain and leg pain and ODI, VAS for leg pain on the second day and 1 week postoperatively between the two groups (P > 0.05). VAS for back pain in GA group on the second day postoperatively, as well as the VAS for back pain and ODI at one week postoperatively, were better than those in LA group (P < 0.05). However, the total hospitalization cost in LA group was significantly lower than that in GA group (P < 0.05). Further analysis of different ages in the two groups showed that there were significant differences in the VAS for back pain on the second day postoperatively and ODI at 1 week postoperatively in the middle-aged group (45 ≤ Y ≤ 59), as well as the VAS for back pain on the second day postoperatively in the senior group (Y ≥ 60) (P < 0.05). However, there were no significant difference among other groups (P > 0.05).ConclusionLong-term outcomes were similar for both PTED under LA and GA, while GA group had better short-term outcomes, especially in middle-aged and elderly patients

HPV Infection and EGFR Activation/Alteration in HIV-Infected East African Patients with Conjunctival Carcinoma

Background There has been substantial growth in the numbers of patients with conjunctival squamous cell carcinoma infected with HIV in East Africa. The natural history of the conjunctival squamous cell carcinoma appears to be unique in this region of the world, but the etiologic mechanism unclear and therapeutic options limited. This research was carried out to determine if conjunctival squamous cell carcinoma harbors human papillomavirus DNA and is associated with activation of the EGFR signaling pathway. Positive findings would identify etiologic causes and provide clinical guidance to improve treatment. Methods/Findings Expression of p-MAPK/MAPK, p-Akt/Akt and p-EGFR/EGFR in cell nuclei and cytoplasm of 38 FFPE specimens were assessed by immunohistochemistry; HPV genotype was detected by qPCR assay; EGFR mutation was assessed by DNA sequencing analysis; and EGFR mRNA expression was measured using relative qPCR. Statistical analyses included two-sided Fisher exact test or chi-square test, Spearman correlation coefficient and ANOVA. HPV 18 was found in 61% of samples, with HPV 16 double-genotype in 6 patients (16%). Immunohistochemistry and qPCR data suggest that activation and expression of the EGFR signaling pathway is related to disease progression of conjunctival cancer. The associations between cytoplasmic p-MAPK, cytoplasmic p-Akt and tumor invasiveness were significant (p = 0.05 or 0.028). Nuclear p-EGFR appeared only in invasive tumors. A significant positive association between EGFR expression and disease invasiveness was observed (p = 0.01). A SNP in 10 patients and one missense mutation were found within EGFR tyrosine kinase domain. Statistical analysis indicates that patients with measurable EGFR expression more likely harbor EGFR mutations, compared to those with negative EGFR expression (35.3% vs. 0%). Conclusions/Significance We conclude that HPV types 16/18 infection is frequent in East African patients with AIDS-associated squamous cell carcinoma of the conjunctiva. EGFR activation/alteration may contribute to and sustain the high prevalence of this cancer. Our findings hint that adoption of HPV vaccination strategies may impact the incidence of conjunctival carcinoma. Agents that target the EGFR pathway may have potential therapeutic benefit