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Modulation of DNA damage repair in lung squamous cell carcinoma (LUSC) can result in the generation of neoantigens and heightened immunogenicity. Therefore, understanding DNA damage repair mechanisms holds significant clinical relevance for identifying targets for immunotherapy and devising therapeutic strategies. Our research has unveiled that the tumor suppressor zinc finger protein 750 (ZNF750) in LUSC binds to the promoter region of tenascin C (TNC), leading to reduced TNC expression. This modulation may impact the malignant behavior of tumor cells and is associated with patient prognosis. Additionally, single-cell RNA sequencing (scRNA-seq) of LUSC tissues has demonstrated an inverse correlation between ZNF750/TNC expression levels and immunogenicity. Manipulation of the ZNF750-TNC axis in vitro within LUSC cells has shown differential sensitivity to CD8+ cells, underscoring its pivotal role in regulating cellular immunogenicity. Further transcriptome sequencing analysis, DNA damage repair assay, and single-strand break analyses have revealed the involvement of the ZNF750-TNC axis in determining the preference for homologous recombination (HR) repair or non-homologous end joining (NHEJ) repair of DNA damage. with involvement of the Hippo/ERK signaling pathway. In summary, this study sheds light on the ZNF750-TNC axis's role in DNA damage repair regulation in LUSC, laying a groundwork for future translational research in immune cell therapy for LUSC. [ABSTRACT FROM AUTHOR]

Recent studies focused on exploring phosphodiesterase type 5 inhibitors (PDE5Is)-related hearing impairment. This study aimed to comprehensively explore real-world hearing impairment associated with PDE5Is based on the US Food and Drug Administration Adverse Event Reporting System (FAERS). The characteristics and correlation of PDE5Is-related hearing impairment reported in the FAERS database from the fourth quarter of 2003 to the second quarter of 2023 were analyzed using disproportionality analysis. The Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) were used to analyze the adverse events (AEs) of hearing impairment. A total of 1,438 reported cases of hearing impairment were associated with four PDE5Is, revealing statistically significant reporting odds ratio (ROR), proportional reporting ratio (PRR), and information component (IC) with the SMQ. The average age of all patients was more than 55 years, over 70% of AEs were reported in men. Most of the reported cases were from the United States. Reports for all the drugs indicated an increase since 2008, except for avanafil. This study showed that the disability rates of PDE5Is were 8.14–40%, the rates of initial or prolonged hospitalization were 6.21–10.24%, and the rates of required intervention were 3.31–9.45%. The pharmacovigilance study identified a potential risk of hearing impairment associated with PDE5Is, indicating the need for continuous monitoring and appropriate management. [ABSTRACT FROM AUTHOR]

Spindle cell sarcoma is a malignant tumor with low incidence. They can occur in the soft tissue, bone, or viscera. The characteristics of morphology, density, and metabolism of spindle cell sarcoma are related to the location of the lesion. A 61-year-old woman presented with vomiting after eating for 2 weeks. Signs of peritoneal irritation were involved, but no response for symptomatic treatment included antiemetic and antispasmodic therapy. Abdominal computed tomography (CT) indicated a mass in the intestinal tract in the pelvic cavity. Then, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/CT was performed, which interestingly detected a jejunal malignancy mass in the left upper abdomen with annular high uptake of 18F-FDG, which was complicated by intussusception and intestinal obstruction. Finally, the jejunal mass was pathologically clarified as an undifferentiated spindle cell sarcoma. [ABSTRACT FROM AUTHOR]

Powdery mildew (PM) is a fungus that causes disease in both the field and the greenhouse. Utilizing resistant cultivars is the most effective approach of disease management. To develop insertion-deletion (InDel) markers associated to this trait, the whole genomes of the PM resistant line M17050 (P1) and the PM-susceptible line 28-1-1 (P2) were sequenced. A total of 1 200 InDels, with an average of 100 markers per chromosome, were arbitrarily chosen from the sequencing data for experimental validation. One hundred InDel markers were ultimately selected due to their informative genetic bands. Further, an F2 segregating population of melons generated from these two parents was inoculated by the PM pathogen. Based on bulk segregant analysis (BSA) using these 100 InDel markers, the powdery mildew resistance was associated with the genomic region LVpm12.1 on the melon chromosome 12. This region overlapped the previously described quantitative trait locus (QTL)-hotspot area carrying multiple PM-resistance QTLs. Moreover, conventional QTL mapping analysis was done, which located LVpm12.1 in the region between 22.72 and 23.34 Mb, where three highly polymorphic InDel markers MInDel89, MInDel92, and MInDel93 were detected. Therefore, these markers could be used to track this resistance locus in melon while the lines carrying this locus could be employed in PM melon resistance breeding programs after validation tests [ABSTRACT FROM AUTHOR]

Background: Chemotherapy resistance is the major cause of recurrence in patients with colorectal cancer (CRC). A previous study found that Fusobacterium (F.) nucleatum promoted CRC chemoresistance. Additionally, metformin rescued F. nucleatum-induced tumorigenicity of CRC. Here, we aimed to investigate whether metformin could revert F. nucleatum-induced chemoresistance and explore the mechanism.Methods: The role of metformin in F. nucleatum-infected CRC cells was confirmed using cell counting kit 8 assays and CRC xenograft mice. Stemness was identified by tumorsphere formation. Bioinformatic analyses were used to explore the regulatory molecules involved in metformin and F. nucleatum-mediated regulation of the sonic hedgehog pathway.Results: We found that metformin abrogated F. nucleatum-promoted CRC resistance to chemotherapy. Furthermore, metformin attenuated F. nucleatum-stimulated stemness by inhibiting sonic hedgehog signaling. Mechanistically, metformin diminished sonic hedgehog signaling proteins by targeting the MYC/miR-361-5p cascade to reverse F. nucleatum-induced stemness, thereby rescuing F. nucleatum-triggered chemoresistance in CRC.Conclusions: Metformin acts on F. nucleatum-infected CRC via the MYC/miR-361-5p/sonic hedgehog pathway cascade, subsequently reversing stemness and abolishing F. nucleatum-triggered chemoresistance. Our results identified metformin intervention as a potential clinical treatment for patients with chemoresistant CRC with high amounts of F. nucleatum. [ABSTRACT FROM AUTHOR]

• Early secretory antigenic target protein 6-culture filtrate protein 10 (EC) skin test is a phase III clinical trial. We validated its accuracy for tuberculosis infection. • We identified that the immune state was associated with the diagnostic accuracy of EC skin test. • This study enriches the clinical evidence in related EC-based skin tests. To verify the diagnostic utility of recombinant fusion protein ESAT6-CPF10 (EC), a novel skin test reagent to detect Mycobacterium tuberculosis infection. A multi-centered, double-blind, randomized controlled trial was conducted from December 17, 2015, to March 2, 2018. Participants involved in this study included those with active tuberculosis (TB), suspected pulmonary TB, or non-TB pulmonary disease. Each participant received three tests simultaneously, TB-specific enzyme-linked immunospot assay (T-SPOT.TB), tuberculin skin test (TST), and EC skin test (ECST), and adverse events were reported. Diagnostic accuracy was analyzed using data from 1085 protocol-compliant participants. The sensitivities of the ECST, TST, and T-SPOT.TB were 91.2% (95% CI, 89.0-93.2%), 91.4% (95% CI, 89.1-93.3%), and 92.1% (95% CI, 89.9-93.9%), respectively. The specificities of the ECST (69.7%, 95% CI, 64.5-74.5%) and T-SPOT.TB (76.1%, 95% CI, 71.2-80.5%) were significantly higher than the TST (54.4%, 95% CI, 48.9-59.7%). The agreements between ECST and TST (kappa = 0.632) and between ECST and T-SPOT.TB (kappa = 0.780) were substantial. No severe adverse event was reported. The diagnostic performance of the ECST was close to the T-SPOT.TB assay in the detection of TB infection and indicated good potential for clinical application in common scenarios. [ABSTRACT FROM AUTHOR]

The optimal systemic treatment of advanced large cell neuroendocrine carcinoma (LCNEC) is still controversial. We intend to explore advanced LCNEC through SEER database, construct nomogram model of advanced LCNEC, and understand the effect of different treatment regimens on LCNEC. We collected 909 patients, divided them into a training set validation set, constructed nomograms using Cox proportional hazards regression models, and evaluated nomogram discrimination and calibration by C-index and calibration curves. Kaplan–Meier will also be used to compare OS in different groups of patients and to explore the impact of different treatment regimens on advanced LCNEC. On the nomogram plotted, the nomogram predicted AUC values over time were always greater than 0.7, the C-index was 0.681 (95% CI 0.656–0.706) and 0.663 (95% CI 0.628–0.698) in the training and validation sets, respectively, and patients were divided into two groups according to risk, and a significant difference in OS was observed between the high-risk and low-risk groups in the training and validation cohorts. Different treatment analyses showed that chemotherapy is still the best treatment for advanced LCNEC. This nomogram provides a convenient and reliable tool for individual assessment and clinical decision-making of patients with advanced LCNEC. [ABSTRACT FROM AUTHOR]

[Display omitted] • S-nZVI/PAA system could effectively degrade CIP in 60 min. • S doping promotes Fe(II)/Fe(III) cycling and improves the degradation efficiency of CIP. • Reactive oxygen species (ROS) and Fe(IV) contributed to CIP elimination. • S-nZVI/PAA system was effective at mitigating the toxicity of CIP. As commonly observed water pollutants, antibiotics can induce antibiotic-resistance genes and pose significant risks to ecosystems and human health. Consequently, eliminating antibiotics from water environments is essential. We used the sulfidated nano zero-valent iron (S-nZVI) to activate peracetic acid (PAA) system to facilitate ciprofloxacin (CIP) degradation. S-nZVI was fabricated using the liquid-phase method, yielding particles with a predominantly spherical morphology and an average size range of 70–110 nm. Under optimized conditions, the S-nZVI/PAA system had a remarkable CIP removal efficiency of 95.61 % in 60 min. The reactive oxygen species (ROS) and Fe species (Fe(IV)) generated in the S-nZVI/PAA system were fundamental in facilitating the degradation of CIP. The reaction products of CIP were identified, and the toxicity was reduced after degradation. Additionally, an investigation was conducted to explore the practical application potential of the S-nZVI/PAA system. The work provides a promising strategy for the removal of antibiotics in water, and gives new insights into the mechanism of S-nZVI activating PAA to remove antibiotics. [ABSTRACT FROM AUTHOR]

Objective. This study aimed to decipher the bioactive compounds and potential mechanism of traditional Chinese medicine (TCM) formula Fuzi Lizhong Decoction (FLD) for nonalcoholic fatty liver disease (NAFLD) treatment via an integrative network pharmacology approach. Methods. The candidate compounds of FLD and its relative targets were obtained from the TCMSP and PharmMapper web server, and the intersection genes for NAFLD were discerned using OMIM, GeneCards, and DisGeNET. Then, the PPI and component-target-pathway networks were constructed. Moreover, GO enrichment and KEGG pathway analysis were performed to investigate the potential signaling pathways associated with FLD's effect on NAFLD. Eventually, molecular docking simulation was carried out to validate the binding affinity between potential core components and key targets. Results. A total of 143 candidate active compounds and 129 relative drug targets were obtained, in which 61 targets were overlapped with NAFLD. The PPI network analysis identified ALB, MAPK1, CASP3, MARK8, and AR as key targets, mainly focusing on cellular response to organic cyclic compound, steroid metabolic process, and response to steroid hormone in the biological processes. The KEGG pathway analysis demonstrated that 16 signaling pathways were closely correlated with FLD's effect on NALFD with cancer pathways, Th17 cell differentiation, and IL-17 signaling pathways as the most significant ones. In addition, the molecular docking analysis revealed that the core active compounds of FLD, such as 3′-methoxyglabridin, chrysanthemaxanthin, and Gancaonin H, had a high binding activity with such key targets as ALB, MAPK1, and CASP3. Conclusions. This study suggested that FLD exerted its effect on NAFLD via modulating multitargets with multicompounds through multipathways. It also demonstrated that the network pharmacology-based approach might provide insights for understanding the interrelationship between complex diseases and interventions of the TCM formula. [ABSTRACT FROM AUTHOR]

Monitoring outcomes of health care providers, such as patient deaths, hospitalizations, and hospital readmissions, helps in assessing the quality of health care. We consider a large database on patients being treated at dialysis facilities in the United States, and the problem of identifying facilities with outcomes that are better than or worse than expected. Analyses of such data have been commonly based on random or fixed facility effects, which have shortcomings that can lead to unfair assessments. A primary issue is that they do not appropriately account for variation between providers that is outside the providers' control due, for example, to unobserved patient characteristics that vary between providers. In this article, we propose a smoothed empirical null approach that accounts for the total variation and adapts to different provider sizes. The linear model provides an illustration that extends easily to other non-linear models for survival or binary outcomes, for example. The empirical null method is generalized to allow for some variation being due to quality of care. These methods are examined with numerical simulations and applied to the monitoring of survival in the dialysis facility data. [ABSTRACT FROM AUTHOR]

To investigate the effects of different dominant species on the microbial functional diversity of vegetation concrete substrates, the rhizosphere and non-rhizosphere soils of three dominant species (Pennisetum alopecuroides (PA), Arthraxon hispidus (AH) and Pueraria lobata (PL)) of vegetation concrete were studied using the Biolog-Eco method at Xiangjiaba Hydropower Station. The results showed that the microbial activity and microbial functional diversity indices in the rhizosphere soil of the three dominant plants were significantly higher than those in the non-rhizosphere soil and that the microbial activity and functional diversity indices in the rhizosphere and non-rhizosphere soil of AH, as well as in the rhizosphere soil of PL, were at a high level. The carbon sources predominantly used by rhizosphere soil microbes were carbohydrates, amino acids and polymers, while the carbon sources predominantly used by non-rhizosphere soil microbes were carboxylic acids, amino acids and polymers. The governing elements of the carbon source metabolic features of the microbial community were the soil moisture content (WC), organic matter (OM), total nitrogen (TN), potential of hydrogen (pH), microbial carbon (MBC), microbial nitrogen (MBN) and microbial phosphorus (MBP). Based on a thorough examination of these aspects, it was concluded that vegetation had altered the microbial community structure and functional diversity of the vegetation concrete substrate, perhaps improving the overall metabolic activity. A. hispidus with high adaptability should be prioritized in the regeneration of vegetation on concrete slopes. [ABSTRACT FROM AUTHOR]

Background: Immunotherapies targeting ligand-receptor interactions (LRIs) are advancing rapidly in the treatment of colorectal cancer (CRC), and LRIs also affect many aspects of CRC development. However, the pattern of LRIs in CRC and their effect on tumor microenvironment and clinical value are still unclear.Methods: We delineated the pattern of LRIs in 55,539 single-cell RNA sequencing (scRNA-seq) samples from 29 patients with CRC and three bulk RNA-seq datasets containing data from 1411 CRC patients. Then the influence of tumor microenvironment, immunotherapy and prognosis of CRC patients were comprehensively investigated.Results: We calculated the strength of 1893 ligand-receptor pairs between 25 cell types to reconstruct the spatial structure of CRC. We identified tumor subtypes based on LRIs, revealed the relationship between the subtypes and immunotherapy efficacy and explored the ligand-receptor pairs and specific targets affecting the abundance of tumor-infiltrating lymphocytes. Finally, a prognostic model based on ligand-receptor pairs was constructed and validated.Conclusion: Overall, through the comprehensive and in-depth investigation of the existing ligand-receptor pairs, this study provides new ideas for CRC subtype classification, a new risk screening tool for CRC patients, and potential ligand-receptor pair targets and pathways for CRC therapy. [ABSTRACT FROM AUTHOR]

Introduction: This phase I clinical trial was conducted to evaluate the safety of RP22 as a skin test reagent for tuberculosis (TB) diagnosis and to explore the appropriate dosage. Methods: We used a randomized, double-blind, placebo-controlled identification allergen (IA) skin test. A total of 72 healthy adult volunteers with negative chest X-ray results were randomized into six groups and given a QuantiFERON-TB Gold (QFT) test. Of the 12 participants in each group, eight received RP22 and four received placebo. The doses of RP22 in the six experimental groups ranged from 0.1 to 4.0 μg in a single intradermal injection of 0.1 ml. Skin reactions and adverse events were recorded at intervals. Results: All doses of RP22 except the highest were well tolerated and safe. No serious adverse events associated with the injection were observed in all groups. There were 11 participants who had positive QFT results, eight had a skin reaction with a redness or induration area diameter of greater than 10 mm at 48–72 h, one had no skin reaction. Among the 60 negative-QFT participants, none had a reaction area diameter of greater than 10 mm. Conclusion: The RP22 skin test was well tolerated and safe, it could play a key role in screening for latent tuberculosis infection (LTBI) by providing a much-wanted alternative to the tuberculin skin test (TST) and interferon-γ release assays (IGRAs). [ABSTRACT FROM AUTHOR]

To investigate effective and reasonable methods for the remediation of nitrate nitrogen pollution in groundwater, two groups of laboratory denitrification experiments were conducted: one on the effect of native denitrifying microbes in groundwater and another on the effect of artificially added denitrifying microbes. The water used in the experiment was typical groundwater with a high concentration of nitrate nitrogen. The temperature was controlled at 15°C. Both groups of experiments established four types of culture environments: anaerobic, anaerobic with an added carbon source (glucose), aerobic, and aerobic with an added carbon source (glucose). The results indicated that native denitrifying microbes in the groundwater have almost no ability to remove high concentrations of nitrate nitrogen. However, artificially added denitrifying microbes can effectively promote denitrification. Artificially added denitrifying microbes had the highest activity in an anaerobic environment in which a carbon source had been added, and the rate removal of a high concentration of nitrate nitrogen in groundwater was the highest and reached as high as 89.52%. [ABSTRACT FROM AUTHOR]

Commercialized implementations of anion exchange membrane water electrolysis (AEMWE) require stable operation at high current density. To achieve this, ohmic, electrochemical and concentration polarizations are supposed to be exceedingly suppressed. Among all crucial materials, porous electrodes with catalyst coatings extensively affect the above polarizations, which are highly sensitive to specific mechanical pressure for cell assembly. However, the imposed mechanical pressure and its effects on cell performance are rarely reported in AEMWE cells. Here, quantitative characterizations of mechanical pressure and its effects on i) physical properties of catalyst coated electrodes and ii) corresponding single-cell performance are comprehensively investigated. First, the imposed mechanical pressure on membrane electrode assembly (MEA) is controlled by different total thickness gaps between anode/cathode and poly-tetra-fluoroethylene (PTFE) gaskets (Δd = 0, 100, 200, 300 μm). Second, the above resulted distributions of mechanical pressure are quantitatively studied by a mechanical pressure tracking method. Third, the influence of the mechanical pressure on the physical properties of the electrodes and cell performance are demonstrated. It is proved that the mechanical pressure of ca. 0.5 MPa is comprehensively beneficial for suppressing internal resistance (R Ω) and charge transfer resistance (R ct), with slightly increased mass diffusion resistance (R md) and hydrogen crossover. This study unveils the intrinsic effects of mechanical pressure on cell performance and provides critical insights into baseline benchmarking and single-cell even stack optimization. [Display omitted] • Dependence of cell mechanics, mass transport, wettability over contact pressure. • Electrochemical performance and internal resistance in the pressure range 0–6 MPa. • 0.5 MPa is optimal contact pressure to suppress R Ω /R ct and relieve R md. • Membrane thickness (≥50 μm) favorable to prevent membrane damage. • Pre-assembly and gradually increased mechanical pressure are esential for mounting. [ABSTRACT FROM AUTHOR]

Aims: To identify transcriptome signatures underlying epileptogenesis in temporal lobe epilepsy (TLE). Methods: Robust rank aggregation analysis was used to integrate multiple microarrays in rodent models of TLE and determine differentially expressed genes (DEGs) in acute, latent, and chronic stages. Functional annotation and protein‐protein interaction analysis were performed to explore the potential functions of the DEGs and identify hub genes with the highest intramodular connectivity. The association between hub genes and hippocampal sclerosis/seizure frequency was analyzed using publicly available RNA‐sequencing datasets from TLE patients. We subsequently established a pilocarpine‐induced status epilepticus (SE) model in rats and validated mRNA expression of hub genes by quantitative reverse transcription PCR (qRT‐PCR). Results: The DEGs in the acute, latent, and chronic phases of TLE in animal models were prominently enriched in inflammatory response. Hub genes identified in the acute phase mainly participated in biological processes including inflammation, blood‐brain barrier damage, and cell adhesion. The hub genes in the latent phase were related to microglia/macrophage activation (Emr1 and Aif1) and phagocytosis (Cd68, Tyrobp, and Lyz). In the chronic phase, the hub genes were associated with activation of complements and microglia/macrophages. We further found that some hub genes identified in human TLE, such as Tlr2, Lgals3, and Stat3, were positively correlated with seizure frequency. Other hub genes, including Lgals3 and Serpine1, were associated with hippocampus sclerosis. qRT‐PCR analysis confirmed that the mRNA levels of hub genes in rat hippocampus were significantly up‐regulated after SE induction. Conclusions: Our integrated analysis identified hub genes in different stages of epilepsy. The functional annotations suggest that the activation and phagocytic activities of microglia/macrophages may play critical roles in epileptogenesis of TLE. [ABSTRACT FROM AUTHOR]

Background The course of disease in mild and moderate COVID-19 has many implications for mobile patients, such as the risk of spread of the infection, precautions taken, and investigations targeted at preventing transmission. Methods Three hundred thirty-one adults were hospitalized from January 21 to February 22, 2020, and classified as severe (10%) or critical (4.8%) cases; 1.5% died. Two hundred eighty-two (85.2%) mild or moderate cases were admitted to regular wards. Epidemiological, demographic, clinical, chest computed tomography (CT) scan, laboratory, treatment, and outcome data from patient records were analyzed retrospectively. Results Patients were symptomatic for 9.82±5.75 (1–37) days. Pulmonary involvement was demonstrated on a chest CT scan in 97.9% of cases. It took 16.81±8.54 (3–49) days from the appearance of the first symptom until 274 patients tested virus-negative in naso- and oropharyngeal (NP) swabs, blood, urine, and stool, and 234 (83%) patients were asymptomatic for 9.09±7.82 (1–44) days. Subsequently, 131 patients were discharged. One hundred sixty-nine remained in the hospital; these patients tested virus-free and were clinically asymptomatic because of widespread persisting or increasing pulmonary infiltrates. Hospitalization took 16.24±7.57 (2–47) days; the time interval from the first symptom to discharge was 21.37±7.85 (3–52) days. Conclusions With an asymptomatic phase, disease courses are unexpectedly long until the stage of virus negativity. NP swabs are not reliable in the later stages of COVID-19. Pneumonia outlasts virus-positive tests if sputum is not acquired. Imminent pulmonary fibrosis in high-risk groups demands follow-up examinations. Investigation of promising antiviral agents should heed the specific needs of mild and moderate COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background We aimed to evaluate the antiviral activity and safety of darunavir/cobicistat (DRV/c) in treating COVID-19 patients. Methods In this single-center, randomized, and open-label trial, mild patients with polymerase chain reaction (PCR)–confirmed COVID-19 were enrolled in Shanghai, China. Participants were randomized to receive DRV/c for 5 days on the top of interferon alpha 2b inhaling or interferon alpha 2b inhaling alone. The primary end point was the virological clearance rate of oropharyngeal swabs at day 7 after randomization in the intention-to-treat population (clinicaltrials.gov: NCT04252274). Results From January 30, 2020, to February 6, 2020, a total of 30 patients were enrolled, of whom 18 (60%) were male, aged 47.2 ± 2.8 years; 63.3% (19/30) of the participants had fever, and 46.7% (14/30) had cough at enrollment. The participants were randomized (range) at 4 (2–5) days after onset of symptoms. The proportion of negative PCR results at day 7 was 46.7% (7/15) and 60.0% (9/15) in the DRV/c and control groups (P  = .72), respectively. The viral clearance rate at day 3 was 20% (3/15) in both study groups, while the number increased to 26.7% (4/15) in the DRV/c group and remained 20% (3/15) in the control group at day 5. Fourteen days after randomization, 1 participant in the DRV/c group progressed to critical illness and discontinued DRV/c, while all the patients in the control group were stable (P  = 1.0). The frequencies of adverse events in the 2 groups were comparable. Conclusions Five days of DRV/c did not increase the proportion of negative conversion vs standard of care alone, although it was well tolerated. [ABSTRACT FROM AUTHOR]

Purpose: China harbors 56 ethnic groups and Han accounts for >92% of the total Chinese population. We investigated the frequencies of 15 autosomal short tandem repeat (STR) loci in the Han population of the Ili Kazakh Autonomous Prefecture with the aim of expanding the available population information in human genetics databases and for forensic DNA analysis. Subjects and Methods: We explored the genetic characteristics of 15 autosomal STR loci in 552 unrelated Chinese Han individuals from Ili Kazakh Autonomous Prefecture, Northwestern China using the AmpFISTR Identifiler PCR Amplification Kit. Moreover, phylogenetic analysis was performed between the Han population and other relevant populations based on the autosomal STR genotyping. The neighbor‐joining tree and principle component analysis were generated based on the Nei's standard genetic distance and allelic frequencies, respectively. Results: A total of 171 alleles were observed among 552 unrelated individuals and allelic frequencies ranged from 0.5145 to 0.0009. The combined power of discrimination and combined power of exclusion of the 15 autosomal STR loci were 0.9999999999999999964 and 0.999998243616671, respectively. Conclusions: Population comparison revealed that the Ili Han population were lining up together with other Han populations in China while showing significant differences from other Chinese and worldwide populations. [ABSTRACT FROM AUTHOR]

Tomato yellow leaf curl virus (TYLCV) responsible for tomato yellow leaf curl disease (TYLCD) causes a substantial decrease in tomato (Solanum lycopersicum L.) yield worldwide. The use of resistant variety as a sustainable management strategy has been advocated. Tremendous progress has been made in genetically characterizing the resistance genes (R gene) in tomato. Breeding tomato for TYLCV resistance has been based mostly on Ty-3 as a race-specific resistance gene by introgression originating from wild tomato species relatives. Improvement or development of a cultivar is achievable through the use of marker-assisted selection (MAS). Therefore, precise and easy use of gene-targeted markers would be of significant importance for selection in breeding programs. The present study was undertaken to develop a new marker based on Ty-3 gene sequence that can be used for MAS in TYLCV resistant tomato breeding program. The new developed marker was named ACY. The reliability and accuracy of ACY were evaluated against those of Ty-3 linked marker P6-25 through screening of commercial resistant and susceptible tomato hybrids, and genetic segregation using F2 population derived from a commercial resistant hybrid AG208. With the use of bioinformatics and DNA sequencing analysis tools, deletion of 10 nucleotides was observed in Ty-3 gene sequence for susceptible tomato variety. ACY is a co-dominant indel-based marker that produced clear and strong polymorphic band patterns for resistant plant distinguishing it from its susceptible counterpart. The obtained result correlates with 3:1 segregation ratio of single resistant dominant gene inheritance, which depicted ACY as gene-tag functional marker. This marker is currently in use for screening 968 hybrids varieties and one thousand breeding lines of tomato varieties stocked in Jiangsu Green Port Modern Agriculture Development Company (Green Port). So far, ACY has been used to identify 56 hybrids and 51 breeding lines. These newly detected breeding lines were regarded as potential source of resistance for tomato breeding. This work exploited the sequence of Ty-3 and subsequently contributed to the development of molecular marker ACY to aid phenotypic selection. We thus recommend this marker to breeders, which is suitable for marker-assisted selection in tomato. [ABSTRACT FROM AUTHOR]

Background: Community health workers (CHWs) have been placed in many rural areas in India to increase villagers’ connections to basic preventive health care. In this study, we describe how pregnant women and mothers of young children react when CHWs inform them that they, or their child, are at high risk of pregnancy-related complications or early childhood developmental delays, and further screening and health care from a physician is recommended. Methods: In this longitudinal study in rural villages in West Bengal, India, pregnant mothers, as well as mothers of children aged 12–24 months, were screened for high risk complications. They were re-contacted and asked questions regarding how and to what extent did visits by the CHWs improve their household’s overall health behavior, along with details about what additional care, if any, they sought. These responses are presented by different demographic and medical characteristics. Results: Of the 231 pregnant women, all said they had sought additional care in response to the CHW visit, and all stated that feedback from the CHW resulted in improvement to their health behaviors. Most (90%) pregnant women gave birth at an institution. Among the 213 mothers of young children who were followed up, all sought additional care in response to the CHW’s visit. Most (67%) mentioned that they had a significant improvement in their health behaviors following feedback from the CHW, and the rest stated that they had some improvement. Conclusions: With the proper training, CHWs can be partners in health care to improve the health of vulnerable populations, not only in rural areas of India, but also in other developing countries. CHWs can promote positive health outcomes in their villages of residence. [ABSTRACT FROM AUTHOR]

Alleviating bacterial-induced clogging is of great importance to improve the efficiency of managed aquifer recharge (MAR). Enzymes (lysozyme and alkaline protease) and sodium hypochlorite (NaClO) are common biological and chemical reagents for inhibiting bacterial growth and activity. To investigate the applicability of these reagents to reduce bioclogging, percolation experiments were performed to simulate a weak alkaline recharge water infiltration through laboratory-scale sand columns, with adding 10 mg/L lysozyme, alkaline protease, and NaClO, respectively. The results showed that, with the addition of lysozyme, alkaline protease, and NaClO, the average clogging rates (the reduced percentages of relative saturated hydraulic conductivity of the sand columns per hour during the percolation experiments) were 0.53%/h, 0.32%/h and 0.06%/h, respectively, which were much lower than that in the control group (0.99%/h). This implied that bioclogging could be alleviated to some extent following the treatments. For further analyzing the mechanisms of the regents on alleviating bioclogging, the bacterial cell amount and extracellular polymeric substances (EPS) concentration were also measured to study the effects of lysozyme, alkaline protease, and NaClO on bacterial growth and EPS secretion. Lysozyme and alkaline protease could disintegrate bacterial EPS by hydrolyzing polysaccharides and proteins, respectively, while they had little effect on the bacterial cell amount. The addition of NaClO significantly decreased the bacterial cell amount (P < 0.05) and thus greatly alleviated bioclogging. Although the lowest average clogging rate was achieved in the NaClO group, it can generate disinfection by-products that are potentially harmful to the environment and human health. Therefore, the biological-based method, i.e., enzyme treatment, could be a promising option for bioclogging control. Our results provide insights for understanding the mechanisms of lysozyme, alkaline protease, and NaClO to alleviate bioclogging, which is of great importance for addressing the clogging problem during MAR activities and achieving groundwater resources sustainable utilization. • Lysozyme, alkaline protease, and sodium hypochlorite could reduce bioclogging. • Sodium hypochlorite alleviated bioclogging by removing bacteria and dissolving EPS. • Lysozyme and alkaline protease hydrolyzed PSs and PNs, respectively. • Enzymes are promising options to reduce bioclogging in managed aquifer recharge. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the role of signal transducer and activator of transcription 3 (STAT3) and mucin 1(MUC1) in non-small cell lung carcinoma (NSCLC) and the use of their inhibitors to reduce chemoresistance. Methods: Cisplatin or vinblastine was provided either with or without STAT3 inhibitor and evaluated for chemoresistance in NSCLC cells and a xenograft mice tumor model. Immunohistochemistry and Kaplan-Meier method of survival analysis were used to determine chemoresistance trends in patients. STAT3 inhibitor treatment, RNAi or ectopic overexpression of STAT3 or MUC1 in NSCLC cells were used to determine their inter-molecular relation and for modulating stemness-related genes. Results: A major subset of chemoresistance patients exhibited a combined aberration of both STAT3 and MUC1 and exhibited a significantly reduced median overall survival (p = 0.008). Subsequent in vitro experiments in NSCLC cells showed that STAT3 levels modulate MUC1 expression (p < 0.01) and increase stemness gene expressions such as AKT (3-fold), OCT4 (4-fold), SOX2 (2-fold) and CXCR4 levels (2-fold). In addition, co-treatment of STAT3 inhibitor with cisplatin or vinblastine enhanced drug efficiency in viability and invasion assays (p < 0.01) and in a xenograft mouse model (p < 0.05). Conclusion: STAT3 inhibitor co-treatment with chemotherapy drugs increases drug efficacy and reduced tumor growth, and therefore, may improve outcomes in patients on NSCLC chemotherapies. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is a method of noninvasive brain stimulation that causes neuromodulation by activating neurons or changing excitability in a certain brain area. Considering the known effects of TMS and the pathophysiology of traumatic brain injury (TBI), TMS was proposed to have potential for treating this condition. Moderate TBI was induced in adult male Sprague Dawley rats using Feeney's weight-dropping method. Injured rats were divided into a TMS group and a control group. Repetitive TMS (rTMS) was administered to rats in the TMS group from post-TBI day 2. At post-TBI days 7, 14 and 28, three or four of the rats were sacrificed, and harvested brains were embedded in paraffin and sectioned. Sections were then treated with hematoxylin and eosin and immunohistochemical staining. Three rats from each group underwent fludeoxyglucose F 18 micro-positron emission tomography scanning on post-TBI day 2 and 13. The unexpected mortality rate after injury was lower in the TMS group than in the control group. The modified neurological severity score of the TMS group was lower compared with the control group at post-TBI day 14. According to the results of hematoxylin eosin staining, relative cerebral parenchyma loss was lower at post-TBI day 28 in the TMS group compared with the control group. However, the aforementioned differences were not found to be statistically significant. There was also no significant difference in glucose metabolism between the two groups. According to immunohistochemical staining, the TMS group showed a significantly higher level of proliferation (indicated by bromodeoxyuridine) in the subventricular zone, as compared with the control group (P<0.05). A significantly higher rate of neuron survival at day 28 (P<0.05; indicated by NeuN) and a significantly reduced rate of apoptosis at days 7 and 14 (P<0.05; indicated by caspase-3) were observed in the perilesional zone of the TMS group, as compared with the control group. The current findings suggest that high-frequency rTMS may promote neurogenesis and provide a basis for further studies in this area. [ABSTRACT FROM AUTHOR]

This paper presents a block identification method for jointed rock masses that is based on exact arithmetic. Block structures are constructed accurately without introducing rounding errors, and therefore the robustness of the block identification algorithm is guaranteed. A rational number type is defined and the basic arithmetic operations of the rational numbers are implemented exactly. Thus, the degenerated geometries can be handled without special measures and accurate modeling results can be obtained even if the fractures are densely packed. In order to ensure the efficiency of the proposed method, floating-point filters and lazy evaluation strategy are used in this study to avoid unnecessary exact computations. The fractures can be either planer or curved and the only limitation to the shape and size of the resulting blocks is the available memory of the host system. Several examples are given to demonstrate the capability and performance of this method. [ABSTRACT FROM AUTHOR]

We present the results of solid state nuclear magnetic resonance (NMR) experiments on HIV-1 capsid protein (CA) assemblies with three different morphologies, namely wild-type CA (WT-CA) tubes with 35-60nmdiameters, planar sheets formed by the Arg18-Leu mutant (R18L-CA), and R18L-CA spheres with 20-100 nm diameters. The experiments are intended to elucidate molecular structural variations that underlie these variations in CA assembly morphology. We find that multidimensional solid stateNMRspectra of 15N,13C-labeledCAassemblies are remarkably similar for the three morphologies, with only small differences in 15N and 13C chemical shifts, no significant differences inNMRline widths, and few differences in the number of detectable NMR cross-peaks. Thus, the pronounced differences in morphology do not involve major differences in the conformations and identities of structurally ordered protein segments. Instead, morphological variations are attributable to variations in conformational distributions within disordered segments, which do not contribute to the solid state NMR spectra. Variations in solid state NMR signals from certain amino acid side chains are also observed, suggesting differences in the intermolecular dimerization interface between curved and planar CA lattices, as well as possible differences in intramolecular helix-helix packing. [ABSTRACT FROM AUTHOR]

Key points Decreased mechanical loading results in skeletal muscle atrophy. The transient receptor potential canonical type 1 (TRPC1) protein is implicated in this process. Investigation of the regulation of TRPC1 in vivo has rarely been reported. In the present study, we employ the mouse hindlimb unloading and reloading model to examine the involvement of TRPC1 in the regulation of muscle atrophy and regrowth, respectively., We establish the physiological relevance of the concept that manipulation of TRPC1 could interfere with muscle regrowth processes following an atrophy-inducing event. Specifically, we show that suppressing TRPC1 expression during reloading impairs the recovery of the muscle mass and slow myosin heavy chain profile. Calcineurin appears to be part of the signalling pathway involved in the regulation of TRPC1 expression during muscle regrowth., These results provide new insights concerning the function of TRPC1. Interventions targeting TRPC1 or its downstream or upstream pathways could be useful for promoting muscle regeneration., Abstract Decreased mechanical loading, such as bed rest, results in skeletal muscle atrophy. The functional consequences of decreased mechanical loading include a loss of muscle mass and decreased muscle strength, particularly in anti-gravity muscles. The purpose of this investigation was to clarify the regulatory role of the transient receptor potential canonical type 1 (TRPC1) protein during muscle atrophy and regrowth. Mice were subjected to 14 days of hindlimb unloading followed by 3, 7, 14 and 28 days of reloading. Weight-bearing mice were used as controls. TRPC1 expression in the soleus muscle decreased significantly and persisted at 7 days of reloading. Small interfering RNA (siRNA)-mediated downregulation of TRPC1 in weight-bearing soleus muscles resulted in a reduced muscle mass and a reduced myofibre cross-sectional area (CSA). Microinjecting siRNA into soleus muscles in vivo after 7 days of reloading provided further evidence for the role of TRPC1 in regulating muscle regrowth. Myofibre CSA, as well as the percentage of slow myosin heavy chain-positive myofibres, was significantly lower in TRPC1-siRNA-expressing muscles than in control muscles after 14 days of reloading. Additionally, inhibition of calcineurin (CaN) activity downregulated TRPC1 expression in both weight-bearing and reloaded muscles, suggesting a possible association between CaN and TRPC1 during skeletal muscle regrowth. [ABSTRACT FROM AUTHOR]

The representative elementary volume (REV) is the premise of the continuous-media method of analysis, and the investigation of the REVs of fractured rock masses is a fundamental area of rock mechanics research. The existence of an REV can be determined based on a variety of physical parameters. This paper presents an analysis of the REV from the view of blockiness, which is defined as the percentage of the volume of isolated blocks formed by fractures in the total rock volume. Seventy-seven types of fractured rock mass models were developed based on 7 classes of fracture persistence and 11 classes of spacing that are suggested by the International Society for Rock Mechanics (ISRM) fracture classification. Rock blocks in each of the 77 types of fractured rock mass models were identified using GeneralBlock to determine the variation in blockiness with model domain sizes, which were changed from 2 to 20 times the fracture spacing. For each model domain size 9 random realizations were carried out to reduce the effects of randomness. The coefficient of variation (C v ) was then used to quantify the variability of the 9 random realizations. The fluctuation in blockiness with the variation in the scale of the model region was also investigated. In this way, the size of the REV in these models can be calculated using the average and the variance of the blockiness as indicators of the convergence. The blockiness of these fractured rock masses can be determined at the REV volume. The results indicate that of the 77 models, 76 REV sizes are between 2 and 20 times the fracture spacing. The fractured rock mass with a wide fracture spacing and very high persistence (WS2–VHP) has a REV size that exceeds 20 times the fracture spacing. Thus, the WS2–VHP model should be investigated further to validate this concept. [ABSTRACT FROM AUTHOR]

In traditional block theory, the removability and stability of rock blocks are analyzed independently; that is, the stability of a removable block is analyzed in detail, and nonremovable blocks are regarded as stable. However, in practical situations, nonremovable blocks may pose more danger than removable blocks. This paper presents a unified method for analyzing the removability and stability of rock blocks. In this method, the cracking of rock bridges is considered and nonremovable blocks are not assumed to be stable. First, possible cracking rock bridges are identified by extending finite-sized fractures and comparing the boundary surfaces of the resulting blocks with those of the original blocks. Then, the sliding direction associated with each possible moving block is determined by solving an optimization problem. The normal force acting on each sliding surface is determined, and the resisting force on each rock bridge is calculated and integrated into the total resisting force when calculating the safety factor of a possible moving block. Procedures to determine all possible moving blocks are introduced, and the possible moving block with the minimum safety factor is regarded as the actual moving block. The corresponding minimum safety factor is defined as the actual safety factor of the block. The proposed method is verified by considering a few examples. The results show that nonremovable blocks may be unstable if the cracking of rock bridges is considered. [ABSTRACT FROM AUTHOR]

Owing to serious influences on well performance, bacteria-induced clogging has become a dilemma for managed aquifer recharge (MAR). During MAR, surface river water is inoculated into aquifer and mixed with groundwater. Therefore, the clogging-functional bacteria may originate from the river water or the groundwater. However, the origin of the clogging-functional bacteria in the aquifer has not yet been well understood. This study conducted a series of laboratory-scale column experiments involving different recharge modes (using river water, groundwater) to simulate the processes of bacteria-induced clogging and used the high-throughput sequencing technology, aiming to elucidate the community characteristics and the origin of the clogging-functional bacteria involved in MAR bioclogging. Analyses of the bacterial-community characteristics showed significant differences between the river water and groundwater. The bacterial-community characteristics of the clogging aquifer in the different recharge modes were similar to each other and have common genera, namely, Acinetobacter , Brevundimonas , Exiguobacterium , Porphyrobacter , Cloacibacterium , and Sphingobium , which suggests that MAR activity could promote bacterial communities to become identical during surface water infiltration into aquifers, despite differences in the bacterial communities present in the subsurface- and surface systems. This knowledge will assist greatly in targeted treatment and prophylaxis of clogging-functional bacteria during managed aquifer recharge. • Clogging occurred in all column experiments involving groundwater and river water. • Bacterial-community features in groundwater were different from those in river water. • Bacterial-community features of biofilms under different recharge modes were similar. • MAR activity might alter the bacterial community to become identical. [ABSTRACT FROM AUTHOR]

Background: Studies have been rarely conducted to provide a comprehensive perspective of pregnant women with the intention to investigate the relationships between periodontal conditions and oral health-related quality of life (OHRQoL). As such, this study aimed to describe the OHRQoL of pregnant women in Shanghai, China and to investigate the relationships between periodontal conditions and OHRQoL of pregnant women. Methods: A cross-sectional study was conducted amongst pregnant women in all stages of pregnancy in Shanghai, China. Clinical examinations were performed to assess periodontal conditions, including tooth loss, visible plaque index, bleeding on probing, probing pocket depth and clinical attachment level. The OHRQoL of pregnant women was determined using the Oral Health Impact Profile (OHIP-14, Chinese version). Information regarding maternal characteristics, socio-demographic background and health-related behaviours was also obtained from the participants through the structured questionnaires. Results: A total of 512 pregnant women (mean age = 27.3 ± 4.0 years)participated in the survey, giving a response rate of 91.4 %. The mean gestational age was 19 weeks (SD = 8.2). The mean and the median OHIP-14 scores were 7.92 (SD = 6.84) and 6, respectively. The mean number of negative impact items (extent) was 0.20 (SD = 0.82). Approximately 10 % of pregnant women reported at least one item with 'fairly often' or 'very often' (prevalence). Results of multivariable analyses showed that periodontal conditions was not significantly associated with three scoring formats of OHRQoL (severity, extent and prevalence of impact) after adjustment for pregnancy-related variables and possible confounders (all p > 0.05). However, frequency of nausea-vomiting was found to be significantly associated with severity of impacts (p = 0.012). Utilization of dental services, age and tooth loss were the significant variables to the extent of negative impacts (all p < 0.05). While no significant variable was related with prevalence of negative impacts (p > 0.05). Conclusion: Pregnant women with different trimesters showed similar impact of oral disease on their OHRQoL in Shanghai, China. Periodontal health status have no impact on their OHRQoL in the fully adjusted models. Their OHRQoL was associated with early pregnancy reaction, utilisation of dental services, age and tooth loss. [ABSTRACT FROM AUTHOR]

Identifying blocks formed by various fractures is important in rock engineering. Most studies focus mainly on blocks formed by planar fractures whereas curved fractures are rarely considered. However, large fractures observed in the field are often curved. This paper presents a new method for identifying rock blocks formed by both curved and planar fractures based on the element-block-assembling approach, in which the study domain is divided into numerous tetrahedral subdomains under the constraint of curved fractures and the subdomains are further decomposed into element blocks by extended planar fractures. When the fractures are restored to finite dimensions, the element blocks are combined and the subdomains are assembled to form complex blocks. The combination of the two subdomains is skipped if and only if their common facet lies on a curved fracture. A computer program was implemented based on the method introduced in this study and the verification examples indicated that this method could effectively handle both convex and concave blocks. [ABSTRACT FROM AUTHOR]

Abstract: Recent advances in NIR triggering upconversion-based photodynamic therapy have led to substantial improvements in upconversion-based nanophotosensitizers. How to obtain the high efficiency of singlet oxygen generation under low 980 nm radiation dosage still remains a challenge. A highly efficient nanophotosensitizer, denoted as UCNPs-ZnPc, was constructed for photodynamic therapy, which is based on near infrared (NIR) light upconversion nanoparticle (UCNP) and Zn(II)-phthalocyanine (ZnPc) photosensitizer (PS). The high 1O2 production efficiency came from the enhancement of the 660 nm upconversion emission of NaYF4:Yb3+, Er3+ UCNP with 25% Yb3+ doping, covalent assemblage of UCNP and ZnPc which significantly shortened the distance and enhanced the energy transfer between the two. The high 1O2 production led to a secure and efficient PDT treatment, as evidenced by the in vivo test where UCNPs-ZnPc of 50 mg per kg body weight was locally injected into the liver tumor in mice, a low 980 nm radiation dose of 351 J/cm2 (0.39 W/cm2) and short irradiation duration of 15 min were sufficient to perform image-guided PDT and caused the liver tumor inhibitory ratio of approximately 80.1%. Histological analysis revealed no pathological changes and inflammatory response in heart, lung, kidney, liver or spleen. [Copyright &y& Elsevier]

Background: Recent studies have reported contrasting results regarding the association of polymorphisms in two integrin genes, ITGA2 and 1TGB3, with ischemic stroke. Aims: The present study aimed to investigate the correlation between the ITGA2 C807T and ITGB3 T176C polymorphic loci with ischemic stroke, as well as plasma lipid and lipoprotein levels. Study Design: Case control study. Methods: Human venous blood samples were collected from patients admitted for ischemic stroke (n=350, 'patients') and healthy individuals (n=300, 'controls'). Blood was genotyped at these loci by polymerase chain reaction-restriction fragment length polymorphism. Plasma lipid and lipoprotein levels were measured by routine enzymatic, masking, and turbidimetry methods. Results: As expected, total cholesterol, triglycerides, and low-density lipoprotein were all significantly higher in patients than in controls (p<0.05). Genotype and allele frequencies of ITGA2 C807T were significantly different between patients and controls (p<0.05), but no difference was detected in genotype or allele frequencies for ITGA3 T176C. For ITGA-2, the T allele conferred a 1.226 times higher relative risk of ischemic stroke than the C allele (odds ratio= 1.226, 95% confidence interval=l.053-1.428). Similarly, total cholesterol was higher in T allele carriers than in non-carriers (p<0.05). Conclusion: ITGA2 C807T polymorphism is associated with ischemic stroke, with the T allele acting as a susceptibility allele that appears to confer increased cholesterol levels.

Purpose: This study investigated the allelic frequency of 4 short terminal repeats (STRs) in Han and She populations from eastern China. Methods: DNA samples from Han (N = 110) and She (N = 110) healthy subjects were amplified using PCR and primers specific for the STRs. D21S11 and D21S1446 (chromosome 21) and D18S865 and D18S535 (chromosome 18). The frequency and homozygocity of different STRs were evaluated. Results: For both populations, D21S11 and D18S535 were more polymorphic than D21S1446 and D18S865, and the D21S1446 1 allele was very common (48.6% and 55.0% for the Han and She groups, respectively).The Han and She groups significantly differed from one another in respect to the distribution of D21S11, D18S865, and D18S535 allelic frequency (all P -values ≤ 0.48) but had a similar allelic distribution for D21S1446 ( P = 0.106). D21S1446 was found to be homozygous about 50% of the time which was significantly greater compared to the other STRs analyzed. Conclusion: This study found that the Han and She differ genetically at 3 autosomal STRs located on chromosome 18 and 21. The STR D21S1146 was often homozygous within these groups, indicating it would be poor marker for analyzing trisomy within these populations. [ABSTRACT FROM AUTHOR]

Faults, such as broken rotor bars, in induction motors may be detected by estimating the spectral signature of the stator currents, particularly the sidebands around the supply line frequency. However, the amplitude of the fundamental frequency (50 Hz) is considerably greater than the sideband amplitude. How to demodulate the signature frequency components under the heavy background of fundamental frequency, or how to remove the fundamental frequency, is becoming a key problem in motor current signature analysis. This paper puts forward a novel transform demodulation algorithm to solve the problem. The three-phase currents are transformed to a magnetic-torque (M-T) coordinate using this algorithm. It is found that the signature frequency components are demodulated in the magnetizing and torque-producing currents obtained by the transformation. Thus, the two demodulated M-T currents can be used to extract the enhanced signature frequency components of faults, and the incipient fault detection of induction motors is easy to realize. With both simulated and experimental data of broken rotor bars, it shows that the proposed algorithm can extract more detailed fault signature frequency components and realize the incipient fault detection of induction motors. [ABSTRACT FROM AUTHOR]

The identification of novel age‐related biomarkers represents an area of intense research interest. Despite multiple studies associating DNA damage with aging, there is a glaring paucity of DNA damage‐based biomarkers of age, mainly due to the lack of precise methods for genome‐wide surveys of different types of DNA damage. Recently, we developed two techniques for genome‐wide mapping of the most prevalent types of DNA damage, single‐strand breaks and abasic sites, with nucleotide‐level resolution. Herein, we explored the potential of genomic patterns of DNA damage identified by these methods as a source of novel age‐related biomarkers using mice as a model system. Strikingly, we found that models based on genomic patterns of either DNA lesion could accurately predict age with higher precision than the commonly used transcriptome analysis. Interestingly, the informative patterns were limited to relatively few genes and the DNA damage levels were positively or negatively correlated with age. These findings show that previously unexplored high‐resolution genomic patterns of DNA damage contain useful information that can contribute significantly to both practical applications and basic science. [ABSTRACT FROM AUTHOR]

[Display omitted] • High intelligence was inversely correlated with water, urinary, hair and nail fluoride. • Fluoride interacts with a SNP-set of rs3788319, rs1879417, rs57377675, rs11556505 and rs7187776 on intelligence. • Fluoride interacts with mitochondrial function-related genes CLU and TOMM40 on intelligence. • Multiple neurodevelopmental pathways related to metabolism may be involved in the fluoride-induced neurotoxicity. Excessive fluoride exposure has been associated with intelligence loss, but little is known about gene-fluoride interactions on intelligence at SNP-set, gene and pathway level. Here we conducted a population-based study in Chinese school-aged children to estimate the associations of fluoride from internal and external exposures with intelligence as well as to explore the gene-fluoride interactions on intelligence at SNP-set, gene and neurodevelopmental pathway level. A total of 952 resident children aged 7 to 13 were included in the current study. The fluoride contents in drinking water, urine, hair and nail were measured using the ion-selective electrode method. LASSO Binomial regression was conducted to screen the intelligence-related SNP-set. The gene-fluoride interactions at gene and pathway levels were detected by the Adaptive Rank Truncated Product method. The probability of high intelligence was inversely correlated with fluoride contents in water, urine, hair and nail (all P < 0.001). The SNP-set based on rs3788319, rs1879417, rs57377675, rs11556505 and rs7187776 was related to high intelligence (P = 0.001) alone and by interaction with water, urinary and hair fluoride (P = 0.030, 0.040, 0.010), separately. In gene level, CLU and TOMM40 interacted with hair fluoride (both P = 0.017) on intelligence. In pathway level, Alzheimer disease pathway, metabolic pathway, signal transduction pathway, sphingolipid signaling pathway and PI3K-AKT signaling pathway interacted with fluoride on intelligence in men. Our study suggests that fluoride is inversely associated with intelligence. Moreover, the interactions of fluoride with mitochondrial function-related SNP-set, genes and pathways may also be involved in high intelligence loss. [ABSTRACT FROM AUTHOR]

This paper proposes a fast fuzzy classifier of multicategory support vector machines (FMSVM) based on support vector domain description (SVDD). The main idea is that the proposed FMSVM is obtained by directly considering all data in one optimization formulation, using a fuzzy membership to each input point. The fuzzy membership is determined by support vector domain description (SVDD). For making support vector machine (SVM) more practical, we use an implement of the modified sequential minimal optimization (SMO) that can quickly solve SVM quadratic programming (QP) problems without any extra matrix storage or the use of numerical QP optimization steps at all. Compared with the existing SVMs, the newly proposed FMSVM that uses the L2-norm in the objective function shows improvement with regards to accuracy of classification and reduction of the effects of noises and outliers. The experiment also shows the efficiency of the modified SMO for expediting the training of SVM. [ABSTRACT FROM AUTHOR]

In this paper, we use a circular distribution to quantify certain domain properties and model the hysteresis behavior of piezoceramic materials. The model is constructed by bridging the characteristics of microscopic domain distribution into the macroscopic (or bulk) behavior. Contributions, other than those associated with the polarization of domains, to bulk quantities are also counted. A domain orientation distribution function is first selected and the corresponding distribution function parameters are chosen as the internal state variables. For the two-dimensional model, a von Mises-Fisher circular distribution is used. Instead of micromechanical analysis of domain motions that would involve large computation efforts, the delineation of domain evolution is simplified by considering the evolution of the domain orientation distribution, which is determined by the dynamic variations of the internal state variables. We also develop a procedure to identify the material constants introduced in the constitutive equations. The models are used to quantitatively characterize various hysteresis loops observed in piezoceramic materials. [ABSTRACT FROM AUTHOR]

Self-heating or dissipation of piezoelectric ce- ramic elements is observed to be severe under dynamic operations even in the linear range. In this paper, a nonequilibrium thermodynamic model is developed to delineate the coupled irreversible mechanical, electric, and thermal processes, which jointly contribute to dissipation. Specifically, additional nonequilibrium state variables, also known as thermodynamic fluxes, are brought in to describe each of these processes. The characteristic relaxation of these processes is modeled. The nonnegative rate of entropy pro- duction is found to be in quadratic form of thermodynamics fluxes. The energy balance equation, which governs the transformation between different energy forms, is obtained in the framework of extended irreversible thermodynamics. Using this model, the dissipation of a piezoceramic stack actuator under harmonic electric or mechanical loadings in linear operation range is studied. The harmonic-balance methods are utilized as solution techniques. In contrast to the existing piezoelectric dissipation models, the dissipation by the developed model is verified to nonlinearly depend on operating frequency, with a peak dissipation occurring at some operating frequency that is related to characteristic relaxation of irreversible processes. The measurements of newly introduced parameters are also discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: The current study identified microbial (including bacterial and viral) diagnostic models that could discriminate colorectal tumor patients from healthy controls, expanding the potential biomarkers for colorectal tumors. A combination of five colorectal cancer-associated gut bacteria was identified in this study for the discrimination of colorectal cancer patients from healthy controls, with verifiable performance in multiple cohorts. The gene pathways regulated by aberrant gut bacteria were also identified, providing possible directions for studying bacterial carcinogenesis mechanisms. Furthermore, this study revealed the potential interactions of gut bacteria with viruses and within bacteria in adenoma-carcinoma sequences, which may extend our understanding of dysbiosis in colorectal carcinogenesis. The alterations in gut bacteria are closely related to colorectal cancer. However, studies on adenoma are still scarce. Besides, the associations of gut viruses with colorectal tumor, and the interactions of bacteria with viruses in colorectal tumors are still under exploration. Therefore, a metagenomic sequencing of stool samples from patients with colorectal adenoma (CRA), colorectal cancer (CRC), and healthy controls was performed to identify changes in gut microbiome in patients with colorectal tumors. Five CRC-enriched bacteria (Peptostreptococcus stomatis, Clostridium symbiosum, Hungatella hathewayi, Parvimonas micra, and Gemella morbillorum) were identified as a diagnostic model to identify CRC patients, and the efficacy of the diagnostic model was verifiable in 1523 metagenomic samples from ten cohorts of eight different countries. We identified the positive association of Bacteroides fragilis with PD-L1 expression and PD-1 checkpoint pathway, providing a possible direction for studying bacterial carcinogenesis mechanisms. Furthermore, the increased interactions within the microbiome in patients may play roles in the development of CRC. In conclusion, this study identified novel microbiota combinations with discrimination for colorectal tumor, and revealed the potential interactions of gut bacteria with viruses in the adenoma-carcinoma sequence, which implies that the microbiome, but not only bacteria, should be paid more attention in further studies. [ABSTRACT FROM AUTHOR]

Acetaminophen overdose is a leading cause of acute liver failure (ALF). Despite the pivotal role of the inflammatory microenvironment in the progression of advanced acetaminophen‐induced liver injury (AILI), a comprehensive understanding of the underlying cellular interactions and molecular mechanisms remains elusive. Mas is a G protein‐coupled receptor highly expressed by myeloid cells; however, its role in the AILI microenvironment remains to be elucidated. A multidimensional approach, including single‐cell RNA sequencing, spatial transcriptomics, and hour‐long intravital imaging, is employed to characterize the microenvironment in Mas1 deficient mice at the systemic and cell‐specific levels. The characteristic landscape of mouse AILI models involves reciprocal cellular communication among MYC+CD63+ endothelial cells, MMP12+ macrophages, and monocytes, which is maintained by enhanced glycolysis and the NF‐κB/TNF‐α signaling pathway due to myeloid‐Mas deficiency. Importantly, the pathogenic microenvironment is delineated in samples obtained from patients with ALF, demonstrating its clinical relevance. In summary, these findings greatly enhance the understanding of the microenvironment in advanced AILI and offer potential avenues for patient stratification and identification of novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: We recently developed two high-resolution methods for genome-wide mapping of two prominent types of DNA damage, single-strand DNA breaks (SSBs) and abasic (AP) sites and found highly complex and non-random patterns of these lesions in mammalian genomes. One salient feature of SSB and AP sites was the existence of single-nucleotide hotspots for both lesions. Results: In this work, we show that SSB hotspots are enriched in the immediate vicinity of transcriptional start sites (TSSs) in multiple normal mammalian tissues, however the magnitude of enrichment varies significantly with tissue type and appears to be limited to a subset of genes. SSB hotspots around TSSs are enriched on the template strand and associate with higher expression of the corresponding genes. Interestingly, SSB hotspots appear to be at least in part generated by the base-excision repair (BER) pathway from the AP sites. Conclusions: Our results highlight complex relationship between DNA damage and regulation of gene expression and suggest an exciting possibility that SSBs at TSSs might function as sensors of DNA damage to activate genes important for DNA damage response. [ABSTRACT FROM AUTHOR]

Aluminosilicates, such as montmorillonite, kaolinite, halloysite, and diatomite, have a uniform bidimensional structure, a high surface-to-volume ratio, inherent stiffness, a dual charge distribution, chemical inertness, biocompatibility, abundant active groups on the surface, such as silanol (Si-OH) and/or aluminol (Al-OH) groups. These compounds are on the list of U.S. Food and Drug Administration-approved active compounds and excipients and are used for various medicinal products, such as wound healing agents, antidiarrheals, and cosmetics. This review summarizes the wound healing mechanisms related to the material characteristics and the chemical components. Numerous wound dressings with different active components and multiple forms have been studied. Then, medicinal mineral resources for use in hemostatic materials can be developed. [ABSTRACT FROM AUTHOR]

Accumulating evidence show a potential association between tuberculosis and COVID-19 disease severity. To further clarify the impact of tuberculosis on COVID-19 disease severity and viral shedding duration, a retrospective study was conducted on 223 COVID-19 patients, including 34 with tuberculosis and 189 without tuberculosis. Clinical information and viral load shedding time were collected. A higher percentage of severe/critical COVID-19 diagnosis and deaths was observed in patients with tuberculosis than in those without tuberculosis (8.8% vs. 3.2%, p = 0.142; 2.9% vs. 1.1%, p = 0.393), and COVID-19 patients with tuberculosis had longer viral shedding than those without tuberculosis (median: 15.0 days vs. 11.0 days; p = 0.0001). Having tuberculosis (HR = 2.21, 95% CI 1.37–3.00; p = 0.000), being of elderly age (HR = 1.02, 95% CI 1.01–1.03; p = 0.001) and being diagnosed with severe or critical COVID-19 (HR = 5.63, 95% CI 2.10–15.05; p = 0.001) were independent factors associated with prolonged virus time of SARS-CoV-2. COVID-19 patients with tuberculosis receiving anti-tuberculosis therapy time (ATT) for <2 months had a significantly longer virus shedding duration than those receiving ATT for ≥ 4 months (17.5 vs. 11.5 days, p = 0.012). Our results demonstrated that COVID-19 patients with tuberculosis tend to have more severe disease and a worse prognosis, and tuberculosis prolonged viral shedding, highlighting special attention and/or care required for COVID-19 patients with tuberculosis receiving ATT for <2 months. [ABSTRACT FROM AUTHOR]

The impacts of coastal embankments on nitrogen (N) dynamics are of great importance in salt marshes. However, effects of embankments on seasonal N dynamics in the plant-soil systems of Suaeda salsa salt marshes are still not well understood. Therefore, the edaphic moisture and salinity, biomass, N concentrations and storage in different plant tissues; the extent of organic and inorganic N subpools in soil subsystems; as well as N immobilization and mineralization by microorganisms in embanked and neighboring natural S. salsa salt marshes through all four seasons were investigated in Yancheng, Eastern China. Our results revealed that embankments increased the biomass and N storage of dead tissues (e.g., litter), while they decreased the biomass and N storage of live tissues (e.g., living aboveground tissues and roots) of S. salsa through decreased edaphic moisture and salinity. Furthermore, under the influence of embankments edaphic water-dissolvable N, e.g.,edaphic dissolved organic N (EDON) and nitrate and nitrite N (TNN), significantly increased with higher N inputs from S. salsa litter. This water-dissolvable N was an important source of N for plants, which translated to higher N concentrations in live plant tissues. However, this excess absorbed N appeared not to facilitate the growth of plants, which would ultimately return to the soil from plant residues. Our results suggested that the decreased edaphic soil moisture and salinity due to embankments had negative impacts on the biomass and N storage of S. salsa plant tissues, which were likely due to shifts in the edaphic osmotic potential. Subsequently, a cascading butterfly effect may be initiated due to the impaired growth of S. salsa , to which more attention should be paid. This study represents a step forward by providing valuable insights and an improved elucidation of the seasonal plant-soil N dynamics of S. salsa salt marshes. • The embankment reduced the N storage of living plant tissues by decreasing the edaphic moisture and salinity. • Increased litter N storage due to the decreasing edaphic moisture and salinity by the embankments. • Enhancing N inputs from litter by the embankment lead to the edaphic water-dissolvable N remarkably increased. • The increased N concentrations of microbes and plants caused by lowering edaphic moisture and salinity due to the embankments. [ABSTRACT FROM AUTHOR]

Reactivity controlled compression ignition (RCCI) is a promising combustion concept which uses two fuels to combine high thermal efficiencies and low engine-out NOx and soot emissions. The combustion concept relies on controlled auto-ignition and is sensitive for changing injection pressure, fuel quality, etc. Consequently, modeling and control of this complex combustion concept is not straightforward. In this work, Gaussian process regression is used to arrive at a data-driven model for a gasoline-diesel RCCI engine. This data-driven model is employed in a robust optimization approach that uses a nested particle swarm optimization. The designed (feedforward) control inputs maximize the efficiency of the RCCI engine while satisfying safety and emissions constraints under various disturbed conditions. In the simulation study, robust performance is obtained, and the robust efficiency is very similar to the efficiency under nominal condition. [ABSTRACT FROM AUTHOR]