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Approximately 41% of 109 species will face extinction risks from climate change; the losing habitat areas in future climate condition will cause the varying of coniferous forest composition and the losing of ecosystem service related to the species; the uncertainty of losing distribution areas for species should not be ignored.PURPOSE We postulate that the deoxyguanosine analogue CNDAG [9-(2-C-cyano-2-deoxy-1-β-D-arabino-pentofuranosyl)guanine] likely causes a single-strand break after incorporation into DNA, similar to the action of its cytosine congener CNDAC, and that subsequent DNA replication across the unrepaired nick would generate a double-strand break. Dihydroartemisinin This study aimed at identifying cellular responses and repair mechanisms for CNDAG prodrugs, 2-amino-9-(2-C-cyano-2-deoxy-1-β-D-arabino-pentofuranosyl)-6-methoxy purine (6-OMe) and 9-(2-C-cyano-2-deoxy-1-β-D-arabino-pentofuranosyl)-2,6-diaminopurine (6-NH2). Each compound is a substrate for adenosine deaminase, the action of which generates CNDAG. METHODS Growth inhibition assay, clonogenic survival assay, immunoblotting, and cytogenetic analyses (chromosomal aberrations and sister chromatid exchanges) were used to investigate the impact of CNDAG on cell lines. RESULTS The 6-NH2 derivative was selectively potent in T cell malignant cell lines. Both prodrugs caused increased phosphorylation of ATM and its downstream substrates Chk1, Chk2, SMC1, NBS1, and H2AX, indicating activation of ATM-dependent DNA damage response pathways. In contrast, there was no increase in phosphorylation of DNA-PKcs, which participates in repair of double-strand breaks by non-homologous end-joining. Deficiency in ATM, RAD51D, XRCC3, BRCA2, and XPF, but not DNA-PK or p53, conferred significant clonogenic sensitivity to CNDAG or the prodrugs. Moreover, hamster cells lacking XPF acquired remarkably more chromosomal aberrations after incubation for two cell cycle times with CNDAG 6-NH2, compared to the wild type. Furthermore, CNDAG 6-NH2 induced greater levels of sister chromatid exchanges in wild-type cells exposed for two cycles than those for one cycle, consistent with increased double-strand breaks after a second S phase. CONCLUSION CNDAG-induced double-strand breaks are repaired mainly through homologous recombination.Physical fitness is defined as an individual's ability to be physically active. The main components are cardiorespiratory fitness (CRF), muscle strength, and flexibility. Regardless of physical activity level, physical fitness is an important determinant of morbidity and mortality.The aim of the current study was to describe the physical fitness assessment methodology in the German National Cohort (NAKO) and to present initial descriptive results in a subsample of the cohort.In the NAKO, hand grip strength (GS) and CRF as physical fitness components were assessed at baseline using a hand dynamometer and a submaximal bicycle ergometer test, respectively. link2 Maximum oxygen uptake (VO2max) was estimated as a result of the bicycle ergometer test. The results of a total of 99,068 GS measurements and 3094 CRF measurements are based on a data set at halftime of the NAKO baseline survey (age 20-73 years, 47% men).Males showed higher values of physical fitness compared to women (males GS = 47.8 kg, VO2max = 36.4 ml·min-1 · kg-1; females GS = 29.9 kg, VO2max = 32.3 ml · min-1 · kg-1). GS declined from the age of 50 onwards, whereas VO2max levels decreased continuously between the age groups of 20-29 and ≥60 years. GS and VO2max showed a linear positive association after adjustment for body weight (males β = 0.21; females β = 0.35).These results indicate that the physical fitness measured in the NAKO are comparable to other population-based studies. Future analyses in this study will focus on examining the independent relations of GS and CRF with risk of morbidity and mortality.BACKGROUND Improving periorbital aging is, currently, of great concern. The previous literature has reported some surgical methods for periorbital aging. The purpose of this study was to compare subbrow blepharoplasty (SBB) with subbrow blepharoplasty combined with periorbital muscle manipulation (SBB-pm) with regard to improving periorbital aging. METHODS A prospective, randomized, controlled study was designed to evaluate and compare the effects of two different surgical techniques on upper lid relaxation, brow shape and periorbital wrinkles. Patients were divided into two groups. Group 1 underwent resection of excess skin; group 2 underwent a modified technique that involved resection of an elliptical island of skin, separation of the corrugator supercilii muscle and dissection of the orbicularis oculi muscle, followed by suturing it to the orbital periosteum and cross-fixation with itself. The upper eyelid and eyebrow height, periorbital wrinkle score and patient satisfaction were measured preoperatively ransient forehead numbness. LEVEL OF EVIDENCE II This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.Infectious diseases caused by bacteria still pose major diagnostic challenges in spite of the availability of various molecular approaches. Irrespective of the type of infection, rapid identification of the causative pathogen with a high degree of sensitivity and specificity is essential for initiating appropriate treatment. While existing methods like PCR possess high sensitivity, they are incapable of identifying the viability status of the pathogen and those which can, like culturing, are inherently slow. To overcome these limitations, we developed a diagnostic platform based on Raman microspectroscopy, capable of detecting biochemical signatures from a single bacterium for identification as well as viability assessment. The study also establishes a decontamination protocol for handling live pathogenic bacteria which does not affect identification and viability testing, showing applicability in the analysis of sputum samples containing pathogenic mycobacterial strains. The minimal sample processing along with multivariate analysis of spectroscopic signatures provides an interface for automatic classification, allowing the prediction of unknown samples by mapping signatures onto available datasets. Also, the novelty of the current work is the demonstration of simultaneous identification and viability assessment at a single bacterial level for pathogenic bacteria. Graphical abstract.The detection of circulating miRNA through isothermal amplification wields many attractive advantages over traditional methods, such as reverse transcription RT-qPCR. However, it is challenging to control the background signal produced in the absence of target, which severely hampers applications of such methods for detecting low abundance targets in complex biological samples. In the present work, we employed both the cobalt oxyhydroxide (CoOOH) nanoflakes and the chemical modification of hexanediol to block non-specific template elongation in exponential amplification reaction (EXPAR). Adsorption by the CoOOH nanoflakes and the hexanediol modification at the 3' end effectively prevented no-target polymerization on the template itself and thus greatly improved the performance of EXPAR, detecting as low as 10 aM of several miRNA targets, including miR-16, miR-21, and miR-122, with the fluorescent DNA staining dye of SYBR Gold™. Little to no cross-reactivity was observed from the interfering strands present in 10-fold excess. Besides contributing to background reduction, the CoOOH nanoflakes strongly adsorbed nucleic acids and isolated them from a complex sample matrix, thus permitting successful detection of the target miRNA in the serum. We expect that simple but sensitive template-blocking EXPAR could be a valuable tool to help with the discovery and validation of miRNA markers in biospecimens. Graphical abstract.A suite of untargeted methods has been applied for the characterization of aerosol from the Tobacco Heating System 2.2 (THS2.2), a heated tobacco product developed by Philip Morris Products S.A. and commercialized under the brand name IQOS®. A total of 529 chemical constituents, excluding water, glycerin, and nicotine, were present in the mainstream aerosol of THS2.2, generated by following the Health Canada intense smoking regimen, at concentrations ≥ 100 ng/item. The majority were present in the particulate phase (n = 402), representing more than 80% of the total mass determined by untargeted screening; a proportion were present in both particulate and gas-vapor phases (39 compounds). The identities for 80% of all chemical constituents (representing > 96% of the total determined mass) were confirmed by the use of authentic analytical reference materials. Despite the uncertainties that are recognized to be associated with aerosol-based untargeted approaches, the reported data remain indicative that the uncharacterized fraction of TPM generated by THS2.2 has been evaluated to the fullest practicable extent. To the best of our knowledge, this work represents the most comprehensive chemical characterization of a heated tobacco aerosol to date. Graphical abstract.Biothiols, including cysteine (Cys), homocysteine (Hcy), and glutathione (GSH), play key roles in biological processes, and detecting such thiols selectively is critical for understanding functions of biothiols. In this work, a pyridazine annelated perylene-based fluorescent probe PAPC is synthesized for highly selective detection of Cys. PAPC exhibits strong blue emission in PBS, while the red emission at 605 nm can be observed in the presence of Cys. The probe PAPC shows ratiometric fluorescence (I605/I460) detection of Cys with wide linear range of 1-120 μM and low detection limit of 0.19 μM. Super large Stokes shift (170 nm) and ratiometric fluorescence endow the probe low background signal. The discrimination of Cys over Hcy and GSH can be achieved through the difference of the ratiometric fluorescence. In addition, the probe has been proven to track Cys in real samples such as urine and HeLa cells. Therefore, PAPC probe is a promising candidate for detecting Cys in practical application. Graphical abstract.Ultrafiltration/diafiltration (UF/DF) plays an important role in the manufacturing of biopharmaceuticals. Monitoring critical process parameters and quality attributes by process analytical technology (PAT) during those steps can facilitate process development and assure consistent quality in production processes. In this study, a lab-scale cross-flow filtration (CFF) device was equipped with a variable pathlength (VP) ultraviolet and visible (UV/Vis) spectrometer, a light scattering photometer, and a liquid density sensor (microLDS). Based on the measured signals, the protein concentration, buffer exchange, apparent molecular weight, and hydrodynamic radius were monitored. The setup was tested in three case studies. link3 First, lysozyme was used in an UF/DF run to show the comparability of on-line and off-line measurements. The corresponding correlation coefficients exceeded 0.97. Next, urea-induced changes in protein size of glucose oxidase (GOx) were monitored during two DF steps. Here, correlation coefficients were ≥ 0.