Circ_100549 promotes tumor progression in lung adenocarcinoma through upregulation of BIRC6.

Lung adenocarcinoma (LUAD) is a subtype of lung cancer with high incidence and mortality globally. Emerging evidence suggests that circular RNAs (circRNAs) exert critical functions in human cancers, including LUAD. CircRNA_100549 (circ_100549) has been reported to be significantly upregulated in non-small cell lung cancer (NSCLC) samples, while its role in modulating LUAD progression remains to be explored. The current study aims at investigating the functional roles of circ_100549 in LUAD and its downstream molecular mechanism. First, we found that the expression of circ_100549 was higher in LUAD cell lines. Loss-of-function assays verified that depletion of circ_100549 repressed LUAD cell proliferation but accelerated cell apoptosis. Furthermore, in vivo experiments demonstrated that silencing of circ_100549 suppressed tumor growth. Subsequently, based on database analysis, we carried out a series of experiments to explore the mechanisms and effects of circ_100549 underlying LUAD progression, including RNA-binding protein immunoprecipitation (RIP), RNA/DNA pull-down, luciferase reporter, and chromatin immunoprecipitation (ChIP) assays. The results indicated that circ_100549 serves as a ceRNA by sponging miR-95-5p to upregulate BPTF expression, thus upregulating BIRC6 expression at a transcriptional level in LUAD. In summary, our study demonstrated that circ_100549 facilitates LUAD progression by upregulating BIRC6 expression.

Phosphine-Catalyzed [4 + 3] Annulation of ß'-Acetoxy Allenoates with 1C,3N-Dinucleophiles: Access to Functionalized Azepine Derivatives.

A novel method for the synthesis of functionalized azepine derivatives has been developed through a phosphine-catalyzed [4 + 3] annulation of ß'-acetoxy allenoates with benzimidazole-derived 1C,3N-dinucleophiles. This approach demonstrates high efficiency and yields ranging from moderate to excellent. The reaction exhibits a wide substrate scope under the optimized conditions. Furthermore, an initial exploration of the asymmetric variant of this reaction has been conducted, utilizing phosphine (R)-SITCP as the catalyst.

Resveratrol triggers autophagy-related apoptosis to inhibit the progression of colorectal cancer via inhibition of FOXQ1.

Colorectal cancer (CRC) is a significant health problem with elevated mortality rates, prompting intense exploration of its complex molecular mechanisms and innovative therapeutic avenues. Resveratrol (RSV), recognised for its anticancer effects through SIRT1 activation, is a promising candidate for CRC treatment. This study focuses on elucidating RSV's role in CRC progression, particularly its effect on autophagy-related apoptosis. Using bioinformatics, protein imprinting and immunohistochemistry, we established a direct correlation between FOXQ1 and adverse CRC prognosis. Comprehensive in vitro experiments confirmed RSV's ability to promote autophagy-related apoptosis in CRC cells. Plasmids for SIRT1 modulation were used to investigate underlying mechanisms. Molecular docking, glutathione-S-transferase pull-down experiments and immunoprecipitation highlighted RSV's direct activation of SIRT1, resulting in the inhibition of FOXQ1 expression. Downstream interventions identified ATG16L as a crucial autophagic target. In vivo and in vitro studies validated RSV's potential for CRC therapy through the SIRT1/FOXQ1/ATG16L pathway. This study establishes RSV's capacity to enhance autophagy-related cell apoptosis in CRC, positioning RSV as a prospective therapeutic agent for CRC within the SIRT1/FOXQ1/ATG16L pathway.

Client-Perpetrated Violence Experience Among Female Sex Worker in Guangdong, South China: Results from a Cross-Sectional Study.

Client-perpetrated violence (CPV) can lead to worse health consequences. However, little attention is paid to the CPV experience among Chinese female sex workers. Our study aimed to assess the association between CPV experience and health risk behaviors among FSWs in China. Data used in this study was from the baseline interviewer-administered questionnaire of a cluster randomized controlled trial conducted in June-October 2020. The collected information included sociodemographic characteristics, HIV/STI symptoms, number of clients, quality of the workplace, and past CPV experience. The association between violence experience and potential HIV/STI risk factors was explored using multivariable regression. Among 480 FSWs who participated in this study, 13.5% experienced CPV in the past. Compared to those who had never experienced CPV, FSWs who experienced CPV were more likely to report previous STI-related symptoms (aOR 4.29, 95% CI 1.73-10.64), more than 15 clients in the past month (aOR 2.56, 95% CI 1.18-5.52), a history of HIV testing (aOR 2.99, 95% CI 1.64-5.46), and work at low-tier workplaces (aOR 2.09, 95% CI 1.18-3.70). Overall, CPV prevalence is not low among Chinese FSWs, and there are some associations with HIV/STI risk factors; a future intervention targeting CPV in HIV/STI prevention programs is needed.

Two coexisting pseudo-mirror heteromolecular telomeric G-quadruplexes in opposite loop progressions differentially recognized by a low equivalent of Thioflavin T.

The final 3'-terminal residue of the telomeric DNA G-overhang is inherently less precise. Here, we describe how alteration of the last 3'-terminal base affects the mutual recognition between two different G-rich oligomers of human telomeric DNA in the formation of heteromolecular G-quadruplexes (hetero-GQs). Associations between three- and single-repeat fragments of human telomeric DNA, target d(GGGTTAGGGTTAGGG) and probe d(TAGGGT), in Na+ solution yield two coexisting forms of (3 + 1) hybrid hetero-GQs: the kinetically favourable LLP-form (left loop progression) and the thermodynamically controlled RLP-form (right loop progression). However, only the adoption of a single LLP-form has been previously reported between the same probe d(TAGGGT) and a target variant d(GGGTTAGGGTTAGGGT) having one extra 3'-end thymine. Moreover, the flanking base alterations of short G-rich probe variants also significantly affect the loop progressions of hetero-GQs. Although seemingly two pseudo-mirror counter partners, the RLP-form exhibits a preference over the LLP-form to be recognized by a low equivalent of fluorescence dye thioflavin T (ThT). To a greater extent, ThT preferentially binds to RLP hetero-GQ than with the corresponding telomeric DNA duplex context or several other representative unimolecular GQs.

NMR structural study on the self-trimerization of d(GTTAGG) into a dynamic trimolecular G-quadruplex assembly preferentially in Na+ solution with a moderate K+ tolerance.

Vast G-quadruplexes (GQs) are primarily folded by one, two, or four G-rich oligomers, rarely with an exception. Here, we present the first NMR solution structure of a trimolecular GQ (tri-GQ) that is solely assembled by the self-trimerization of d(GTTAGG), preferentially in Na+ solution tolerant to an equal amount of K+ cation. Eight guanines from three asymmetrically folded strands of d(GTTAGG) are organized into a two-tetrad core, which features a broken G-column and two width-irregular grooves. Fast strand exchanges on a timescale of second at 17°C spontaneously occur between folded tri-GQ and unfolded single-strand of d(GTTAGG) that both species coexist in dynamic equilibrium. Thus, this tri-GQ is not just simply a static assembly but rather a dynamic assembly. Moreover, another minor tetra-GQ that has putatively tetrameric (2+2) antiparallel topology becomes noticeable only at an extremely high strand concentration above 18 mM. The major tri-GQ and minor tetra-GQ are considered to be mutually related, and their reversible interconversion pathways are proposed accordingly. The sequence d(GTTAGG) could be regarded as either a reading frame shifted single repeat of human telomeric DNA or a 1.5 repeat of Bombyx mori telomeric DNA. Overall, our findings provide new insight into GQs and expect more functional applications.

Correlation Between ICU Admission Time and Long-Term Mortality in Elderly Critically Ill Patients.

Objective: The the intensive care unit (ICU), also known as intensive care medicine department and intensive intensive care unit, is a medical place for centralized treatment of critical diseases and continuous monitoring and treatment. To investigate the relationship between the length of intensive care unit (ICU) admission and long-term mortality in elderly critically ill patients. Methods: A total of 2694 critically ill ICU patients admitted to Xianning First People's Hospital from April 2017 to April 2021 were selected. Inclusion criteria including: age ≥ 60 years; meet the diagnostic criteria for critical illness; admission to ICU ≥ 24h. According to admission time, patients were divided into 1684 patients admitted during working hours and 1010 patients admitted during non-working hours. The relationship between the admission time of ICU patients and long-term mortality was taken as the dependent variable. The evaluation was performed using the Acute Physiology and Chronic Health Status Assessment Scale (APACHE II score). Epidemiological questionnaire was used to investigate the status of time to hospital and mortality, and the independent risk factors affecting time to hospital and mortality were analyzed by univariate and multivariate analysis. SPSS 26.0 statistical software was used for analysis and processing. Results: Among 2694 critically ill patients in ICU, 1010 patients were hospitalized during non-working hours, with an admission rate of 37.49%. The acute physiology and chronic health evaluation (APACHE) II score of non-working hours was 19.91±6.62, which is significantly higher than that of working hours (18.21±6.42) (P < .05). The mortality rates of ICU patients hospitalized during non-working hours and during working hours accounted for 30.10 % and 19.71% of all patients, respectively, with statistical significance (P < .05). Comparing the mortality rates of the two groups at different time periods, there was a significant difference between the two groups (P < .05). In order to influence the independent variables of ICU mortality (non-occurrence = 0, occurrence = 1), the significant factors of univariate analysis were included in the logistic regression equation. Time of admission, combined cardiopulmonary disease, APACHE II score, nurse workload and other factors were independent risk factors for ICU mortality. Conclusion: Out-of-hours admission is associated with an increased risk of death and is associated with changes in ICU organizational structure. Therefore, sending patients to ICU in time migh help improve their life.

A Bayesian network-GIS probabilistic model for addressing human disturbance risk to ecological conservation redline areas.

Population growth and associated ecological space occupation are posing great risks to regional ecological security and social stability. In China, "Ecological Conservation Redline" (ECR) that prohibited urbanization and industrial construction has been proposed as a national policy to resolve spatial mismatches and management contradictions. However, unfriendly human disturbance activities (e.g., cultivation, mining, and infrastructure construction) still exist within the ECR, posing a great threat to ecological stability and safety. In this article, a Bayesian network (BN)-GIS probabilistic model is proposed to spatially and quantitatively address the human disturbance risk to the ECR at the regional scale. The Bayesian models integrate multiple human activities, ecological receptors of the ECR, and their exposure relationships for calculating the human disturbance risk. The case learning method geographic information systems (GIS) is then introduced to train BN models based on the spatial attribute of variables to evaluate the spatial distribution and correlation of risks. This approach was applied to the human disturbance risk assessment for the ECR that was delineated in 2018 in Jiangsu Province, China. The results indicated that most of the ECRs were at a low or medium human disturbance risk level, while some drinking water sources and forest parks in Lianyungang City possessed the highest risk. The sensitivity analysis result showed the ECR vulnerability, especially for cropland, that contributed most to the human disturbance risk. This spatially probabilistic method can not only enhance model's prediction precision, but also help decision-makers to determine how to establish priorities for policy design and conservation interventions. Overall, it presents a foundation for later ECR adjustments as well as for human disturbance risk supervision and management at the regional scale.

A facile approach to C-functionalized ß-ketoimine compounds via terminal alkylation of a tetralithiated intermediate.

A series of C-functionalized ß-ketoimine compounds at the terminal methyl groups of the ß-ketoimine precursor LphH2 (Lph = C6H4[NC(Me)CHC(Me)O]2) were prepared. This convenient transformation was realized via straightforward double alkylation on the terminal Cα of a novel bis-dianionic ß-ketoiminate lithium complex [Lph'Li4(THF)4]2 (Lph' = C6H4[NC(Me)CHC(O)CH2]2) followed by hydrolysis.

Significant reduction in atmospheric organic and elemental carbon in PM2.5 in 2+26 cities in northern China.

To better understand the change characteristics and reduction in organic carbon (OC) and elemental carbon (EC) in particulate matter (PM) with a diameter of ≤2.5 µm (PM2.5) driven by the most stringent clean air policies and pandemic-related lockdown measures in China, a comprehensive field campaign was performed to measure the carbonaceous components in PM2.5 on an hourly basis via harmonized analytical methods in the Beijing-Tianjin-Hebei and its surrounding region (including 2 + 26 cities) from January 1 to December 31, 2020. The results indicated that the annual average concentrations of OC and EC reached as low as 6.6 ± 5.7 and 1.8 ± 1.9 µg/m3, respectively, lower than those obtained in previous studies, which could be attributed to the effectiveness of the Clean Air Action Plan and the impact of the COVID-19-related lockdown measures implemented in China. Marked seasonal and diurnal variations in OC and EC were observed in the 2 + 26 cities. Significant correlations (p < 0.001) between OC and EC were found. The annual average secondary OC levels level ranged from 1.8-5.4 µg/m3, accounting for 37.7-73.0% of the OC concentration in the 2 + 26 cities estimated with the minimum R squared method. Based on Interagency Monitoring of Protected Visual Environments (IMPROVE) algorithms, the light extinction contribution of carbonaceous PM to the total amount reached 21.1% and 26.0% on average, suggesting that carbonaceous PM played a less important role in visibility impairment than did the other chemical components in PM2.5. This study is expected to provide an important real-time dataset and in-depth analysis of the significant reduction in OC and EC in PM2.5 driven by both the Clean Air Action Plan and COVID-19-related lockdown policies over the past few years, which could represent an insightful comparative case study for other developing countries/regions facing similar carbonaceous PM pollution.

Generation of markerless and multiple-gene knockout in Glaesserella parasuis based on natural transformation and Flp recombinase.

Glaesserella parasuis is an important bacterial pathogen that affects the swine industry worldwide. Research on the pathogenic mechanism and genetically engineered vaccine remains undeveloped because an effective markerless and multiple-gene knockout system is unavailable for G. parasuis yet. To establish a markerless knockout, deleted allelic genes with kanamycin resistance (KanR) cassettes were introduced into the genome of G. parasuis by using natural transformation with suicide plasmids. Then, the KanR cassette was excised with a thermosensitive plasmid pGF conferring a constitutive Flp expression. To realize the markerless and multiple-gene knockout, plasmid pGAF was constructed by placing the Flp gene under the control of an arabinose-inducible promoter. Firstly, pGAF was introduced into G. parasuis by electroporation, and the marked mutants were produced following natural transformation. Finally, the KanR cassette was excised from the genome by the inducible expression of Flp upon arabinose action. Based on the natural transformation and the inducible expression of Flp, the markerless single-gene knockout mutants of ΔhsdR, ΔneuA2, ΔespP2, Δapd, and ΔnanH were constructed. In addition, a five-gene knockout mutant of ΔhsdRΔneuA2ΔespP2ΔapdΔnanH was generated by successive natural transformation with five suicide plasmids. Taken together, a markerless and multiple-gene deletion system was established for G. parasuis in the present study for the first time. This system is simple, efficient, and easy to manipulate for G. parasuis; thus, our technique will substantially aid the understanding of the etiology, pathogenesis, and genetic engineering of G. parasuis and other bacteria that can be naturally transformed in laboratory conditions. KEY POINTS: • Flp recombinase excised the KanR gene flanked by FRT sites in Glaesserella parasuis. • The regulatory expression of Flp enabled a multiple-gene knockout forG. parasuis. • The technique will promote the understanding of Glässer's disease pathogens.

The environmental benefit of Beijing-Tianjin-Hebei coal banning area for North China.

In order to achieve the targets specified in the Action Plan for Air Pollution Prevention and Control (APAPPC), a limited coal banning area (10,000 km2) was designated in the heavily polluted Beijing-Tianjin-Hebei region (BTH) for the first time in 2017. PM2.5 and elements were sampled by the network of BTH to evaluate the effectiveness of this policy. This study found that the fine days with PM2.5 < 75 µg m-3 accounted for 74.3% in the autumn and winter of 2017, which was significantly higher than that in 2016 (43%). The heavily polluted days (PM2.5 > 150 µg m-3) also decreased from 32.2% in 2016 to 4.9% in 2017. Arsenic (As) is an important tracer in coal consumption, which can be used to reflect the influence of the establishment of coal banning areas on north China. The cluster analysis of air mass forward trajectory identified that the number of polluted trajectories with PM2.5 and As in 2017 decreased by 47.6% and 49.7%, respectively. Under the implementation of the coal banning policy, the weighted concentration of PM2.5 and As decreased by 94.2 µg m-3 and 5.1 ng m-3 in the coal banning area, 60.9 µg m-3 and 3.4 ng m-3 in the no coal banning area in BTH, respectively. The influence of weighted concentration of PM2.5 and As in coal banning area on North China were 1.6-49.2 µg m-3 and 0.15-2.8 ng m-3, respectively, which was 38.8% and 29.7% lower than 2016. In coal banning area, BTH and other parts of North China, the reduction of the weight concentration of PM2.5 in 2017 accounted for 41.4%, 26.8% and 31.8% of the total reduction, respectively, so was the As in 39%, 26.3% and 34.6%, indicating that setting up a coal banning area scientifically in limited areas can produce remarkable regional benefit.

Significant contribution of secondary particulate matter to recurrent air pollution: Evidence from in situ observation in the most polluted city of Fen-Wei Plain of China.

Particulate matter (PM) pollution in high emission regions will affect air quality, human health and climate change on both local and regional scales, and thus attract worldwide attention. In this study, a comprehensive study on PM2.5 and its chemical composition were performed in Yuncheng (the most polluted city of Fen-Wei Plain of China) from November 28, 2020 to January 24, 2021. The average concentration of PM2.5 was 87.8 ± 52.0 µg/m3, which were apparently lower than those observed during the same periods of past five years, attributable to the clean air action plan implemented in this region. NO3- and organic carbon (OC) were the dominant particulate components, which on average contributed 22.6% and 16.5% to PM2.5, respectively. The fractions of NO3-, NH4+, OC and trace metals increased while those of crustal materials and elemental carbon decreased with the degradation of PM2.5 pollution. Six types of PM2.5 sources were identified by the PMF model, including secondary inorganic aerosol (35.3%), coal combustion (28.7%), vehicular emission (20.7%), electroplating industry (8.6%), smelt industry (3.9%) and dust (2.8%). Locations of each identified source were pinpointed based on conditional probability function, potential source contribution function and concentration weighted trajectory, which showed that the geographical distribution of the sources of PM2.5 roughly agreed with the areas of high emission. Overall, this study provides valuable information on atmospheric pollution and deems beneficial for policymakers to take informed action to sustainably improve air quality in highly polluted region.

Sialidase of Glaesserella parasuis Augments Inflammatory Response via Desialylation and Abrogation of Negative Regulation of Siglec-5.

Siglecs are sialic acid-binding immunoglobulin-like lectins that play an important role in tissue homeostasis, immune response, and pathogen infection. Bacterial sialidases act on natural ligands of Siglecs, interfering with the Siglec-mediated immune response. Glaesserella parasuis is a porcine bacterial pathogen that secretes sialidase. However, little is known about the sialidase of G. parasuis and its impact on immune regulation. Here, we used wild-type G. parasuis, a sialidase-deficient mutant, and complementary strains to investigate the role of sialidase in porcine alveolar macrophage infection. Sialidase induced the release of proinflammatory cytokines, such as interleukin-1α (IL-1α), IL-6, and tumor necrosis factor alpha, from porcine alveolar macrophages. Moreover, sialidase desialylated the surface of porcine alveolar macrophages and altered the expression of Siglecs (the expression of Siglec-5 was reduced). Furthermore, sialidase led to a reduction in endogenous SH2 domain-containing protein tyrosine phosphatase (SHP-2) recruitment to Siglec-5 and simultaneously activated the inflammatory response via the mitogen-activated protein kinase and nuclear factor kappa light chain enhancer of activated B cell signaling pathways. This desialylation occurred before the release of proinflammatory cytokines, suggesting that the sialidase-induced inflammatory response was followed by reduced recruitment of SHP-2 to Siglec-5. Thus, this study is the first to demonstrate the role of sialidase in the inflammatory response of G. parasuis. This role resulted from the abrogation of negative regulation of Siglec-5 on proinflammatory cytokine release. This study helps to understand the molecular mechanism underlying the inflammatory response induced by sialidase secreted by G. parasuis and the acute inflammation caused by G. parasuis.

Calcification of lower extremity arteries is related to the presence of osteoporosis in postmenopausal women with type 2 diabetes mellitus: a cross-sectional observational study.

It is unknown whether there is any relationship between extremity arterial macroangiopathy and osteoporosis in type 2 diabetic mellitus (T2DM) patients. We provide evidence to show the association between lower extremity arterial calcification and the presence of osteoporosis in postmenopausal T2DM women, but not in T2DM men of similar age. PURPOSE: To investigate the relationship between lower extremity arterial calcification and the presence of osteoporosis in type 2 diabetic mellitus (T2DM) patients. METHODS: We performed a retrospective cross-sectional study in patients with T2DM. They were assigned into two groups (patients with or without vascular calcification) in both sexes. Clinical characteristics, presence of osteoporosis, and bone metabolic markers were compared. Arterial calcification was determined by ultrasonography examination. Osteoporosis was defined based on the measurements from dual-energy X-ray absorptiometry. The relationship between the lower extremity arterial calcification and the presence of osteoporosis was analyzed. Statistical analysis was performed in SPSS 26.0. RESULTS: A total of 933 T2DM patients (535 men ≥ 50 years old, and 398 postmenopausal women) were identified and analyzed. A significant association between arterial calcification and osteoporosis was only observed in women, with a higher prevalence of osteoporosis observed in women with calcification (40.8%) than in women without calcification (26.9%) (P = 0.004). Compared to women without calcification, women with calcification had lower bone mineral densities in the hip (P < 0.001) and femoral neck (P < 0.001). Ordinal logistic regression analysis showed that women with calcification had a nearly 2-fold increased risk for osteoporosis, even after adjusting for age, duration of T2DM, body mass index, pulse pressure, clearance of creatinine, glycosylated hemoglobin, and fasting C-peptide. Similar differences were not identified between men with and without calcification. CONCLUSION: Calcification of lower extremity arteries is related with the presence of osteoporosis in postmenopausal T2DM women.

Chromosomal analysis for embryos from balanced chromosomal rearrangement carriers using next generation sequencing.

We aimed to use next generation sequencing (NGS) to investigate chromosomal abnormalities in blastocyst trophectoderm (TE) samples, and reproductive outcomes with the different types of chromosomal rearrangements (CR) and for each sex of CR carrier. A total of 1189 blastocyst TE samples were evaluated using NGS to detect chromosomal unbalanced translocations as well as aneuploidy, including blastocytes from 637 blastocysts from carriers of balanced CR and 552 blastocysts from carriers of normal chromosomes. The optimal embryos had lower chromosomal abnormality rates compared to the poor-quality embryos. The experimental group had significantly reduced rates of normal embryos and euploidy, and higher rates of total abnormalities, aneuploidy and unbalanced chromosomal aberrations. Carriers of reciprocal translocations had a reduced rate of normal embryos and an increased percentage of embryos with total abnormalities and unbalanced chromosomal aberrations compared with carriers of Robertsonian translocations. Couples with female carriers of chromosomal abnormalities had significantly reduced rates of normal embryos and euploidy, and a higher percentage of embryos with total abnormalities, aneuploidy, and unbalanced chromosomal aberrations compared with couples of male carriers. Our preimplantation genetic testing (PGT) study identified higher rates of chromosomal abnormalities, including chromosomal unbalanced translocations and aneuploidy, in blastocysts from CR carriers, especially from the female carriers, in a Chinese population. The PGT cycles successfully improved clinical outcomes by increasing the fertilization rate and reducing the early spontaneous abortion rate compared with the in vitro fertilization and intracytoplasmic sperm injection cycles, especially for CR carriers.

n-Butyllithium as a highly efficient precatalyst for cyanosilylation of aldehydes and ketones.

A highly efficient cyanosilylation protocol mediated by the easily available n-BuLi with a wide range of aldehydes and ketones was developed. This protocol features excellent yields with very low n-BuLi loadings (0.01-0.05 mol%) at room temperature, solvent-free process, good chemo-/regio-selectivity and functional group tolerance and scalability. A possible reaction pathway based upon stoichiometric reactivity was put forward.

Reactive Oxygen Species Mediate 6c-Induced Mitochondrial and Lysosomal Dysfunction, Autophagic Cell Death, and DNA Damage in Hepatocellular Carcinoma.

Increasing the level of reactive oxygen species (ROS) in cancer cells has been suggested as a viable approach to cancer therapy. Our previous study has demonstrated that mitochondria-targeted flavone-naphthalimide-polyamine conjugate 6c elevates the level of ROS in cancer cells. However, the detailed role of ROS in 6c-treated cancer cells is not clearly stated. The biological effects and in-depth mechanisms of 6c in cancer cells need to be further investigated. In this study, we confirmed that mitochondria are the main source of 6c-induced ROS, as demonstrated by an increase in 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and MitoSox fluorescence. Compound 6c-induced mitochondrial ROS caused mitochondrial dysfunction and lysosomal destabilization confirmed by absolute quantitation (iTRAQ)-based comparative proteomics. Compound 6c-induced metabolic pathway dysfunction and lysosomal destabilization was attenuated by N-acetyl-L-cysteine (NAC). iTRAQ-based comparative proteomics showed that ROS regulated the expression of 6c-mediated proteins, and treatment with 6c promoted the formation of autophagosomes depending on ROS. Compound 6c-induced DNA damage was characterized by comet assay, p53 phosphorylation, and γH2A.X, which was diminished by pretreatment with NAC. Compound 6c-induced cell death was partially reversed by 3-methyladenine (3-MA), bafilomycin (BAF) A1, and NAC, respectively. Taken together, the data obtained in our study highlighted the involvement of mitochondrial ROS in 6c-induced autophagic cell death, mitochondrial and lysosomal dysfunction, and DNA damage.

The Effectiveness of Next-Generation Sequencing-Based Preimplantation Genetic Testing for Balanced Translocation Couples.

The purpose of this study was to evaluate the effectiveness of next-generation sequencing (NGS)-based preimplantation genetic testing (PGT) for balanced translocation carriers to identify normal/balanced blastocysts and to measure pregnancy outcomes following euploid embryo transfer. We enrolled 75 couples with a balanced translocation who underwent 83 PGT cycles (58 cycles for carriers with reciprocal translocations and 25 cycles for carriers with Robertsonian translocations) and 388 blastocysts were diagnosed. Moreover, we transferred single euploid blastocysts through frozen embryo transfer and calculated the biochemical pregnancy, clinical pregnancy, miscarriage, and ongoing pregnancy rates per embryo transfer cycle. Despite a mean maternal age of 29.8 years and mean of 4.34 embryos biopsied, there was a 32.8% chance of recording no chromosomally normal/balanced embryos for reciprocal translocation carriers. The proportion of normal/balanced embryos was significantly higher (44.1 vs. 27.8%) in Robertsonian translocation carriers than in reciprocal translocation carriers. Female carriers had a significantly lower (23.3 vs. 42.4%, 34.7 vs. 54.7%, respectively) percentage of normal/balanced embryos than male carriers, regardless of the translocation. After transfering single blastocysts, we obtained a 64.4% clinical pregnancy rate per transfer, and the clinical miscarriage rate was 5.7%. Amniocentesis results showed that all karyotypes of the fetuses were consistent with PGT results. The clinical outcomes are probably not influenced by the type of translocation, maternal age, and blastocyst morphology following the transfer of euploid blastocysts. Therefore, we conclude that NGS-based PGT is an efficient method for analyzing balanced translocation carriers, and aneuploidy screening had good clinical outcomes.

Recent Advances in Chain Conformation and Bioactivities of Triple-Helix Polysaccharides.

Natural polysaccharides derived from renewable biomass sources are regarded as environmentally friendly and sustainable polymers. As the third most abundant biomacromolecule in nature, after proteins and nucleic acids, polysaccharides are also closely related with many different life activities. In particular, ß-glucans are one of the most widely reported bioactive polysaccharides and are usually considered as biological response modifiers. Among them, ß-glucans with triple-helix conformation have been the hottest and most well-researched polysaccharides at present, especially lentinan and schizophyllan, which are clinically used as cancer therapies in some Asian countries. Thus, creation of these active triple-helix polysaccharides is beneficial to the research and development of sustainable "green" biopolymers in the fields of food and life sciences. Therefore, full fundamental research of triple-helix polysaccharides is essential to discover more applications for polysaccharides. In this Review, the recent research progress of chain conformations, bioactivities, and structure-function relationships of triple-helix ß-glucans is summarized. The main contents include the characterization methods of the macromolecular conformation, proof of triple helices, bioactivities, and structure-function relationships. We believe that the governments, enterprises, universities, and institutes dealing with the survival and health of human beings can expect the development of natural bioproducts in the future. Hence, a deep understanding of ß-glucans with triple-helix chain conformation is necessary for application of natural medicines and biologics for a sustainable world.