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Transcription-blocking lesions (TBLs) stall elongating RNA polymerase II (Pol II), which then initiates transcription-coupled repair (TCR) to remove TBLs and allow transcription recovery. In the absence of TCR, eviction of lesion-stalled Pol II is required for alternative pathways to address the damage, but the mechanism is unclear. Using Protein-Associated DNA Damage Sequencing (PADD-seq), this study reveals that the p97-proteasome pathway can evict lesion-stalled Pol II independently of repair. Both TCR and repair-independent eviction require CSA and ubiquitination. However, p97 is dispensable for TCR and Pol II eviction in TCR-proficient cells, highlighting repairs prioritization over repair-independent eviction. Moreover, ubiquitination of RPB1-K1268 is important for both pathways, with USP7s deubiquitinase activity promoting TCR without abolishing repair-independent Pol II release. In summary, this study elucidates the fate of lesion-stalled Pol II, and may shed light on the molecular basis of genetic diseases caused by the defects of TCR genes.

With aging skeletal muscle fibers undergo repeating cycles of denervation and reinnervation. In approximately the 8th decade of life reinnervation no longer keeps pace, resulting in the accumulation of persistently denervated muscle fibers that in turn cause an acceleration of muscle dysfunction. The significance of denervation in important clinical outcomes with aging is poorly studied. The Study of Muscle, Mobility, and Aging (SOMMA) is a large cohort study with the primary objective to assess how aging muscle biology impacts clinically important traits. Using transcriptomics data from vastus lateralis muscle biopsies in 575 participants we have selected 49 denervation-responsive genes to provide insights to the burden of denervation in SOMMA, to test the hypothesis that greater expression of denervation-responsive genes negatively associates with SOMMA participant traits that included time to walk 400 meters, fitness (VO2peak), maximal mitochondrial respiration, muscle mass and volume, and leg muscle strength and power. Consistent with our hypothesis, increased transcript levels of: a calciumdependent intercellular adhesion glycoprotein (CDH15), acetylcholine receptor subunits (CHRNA1, CHRND, CHRNE), a glycoprotein promoting reinnervation (NCAM1), a transcription factor regulating aspects of muscle organization (RUNX1), and a sodium channel (SCN5A) were each negatively associated with at least 3 of these traits. VO2peak and maximal respiration had the strongest negative associations with 15 and 19 denervation-responsive genes, respectively. In conclusion, the abundance of denervationresponsive gene transcripts is a significant determinant of muscle and mobility outcomes in aging humans, supporting the imperative to identify new treatment strategies to restore innervation in advanced age.

【Objective】 Membrane-regulated subsurface irrigation is a water-saving irrigation technique for water-scarce areas, and this paper is to experimentally determine its technical parameters for irrigation in soils with different textures. 【Method】 The studies were based on laboratory experiment and the HYDRUS-2D model. Infiltration of irrigation water into sandy soil, loam soil, sandy clay loam and silt soil under membrane -regulated irrigation was conducted experimentally with the dripping rate ranging from 0.9 to 3.2 L/h. The measured data were used to calibrate the HDYDRUS-2D model. 【Result】 The HDYDRUS-2D model can accurately simulate water flow in all soils under membrane regulated irrigation, with the relative errors less than 5%, the coefficient of determination and root mean square deviation being 0.97 and 0.007, respectively. The sandy soil was prone to leakage due to its elaborated hydraulic conductivity. In the membrane-regulated irrigation, adjusting the flow rate in the drip irrigation pipe was needed to improve irrigation efficiency in different soils. On average, the membrane-regulated irrigation worked well for all three soil types. At the end of the irrigation, the ratio of the water on the membrane to the total irrigation amount was more than 70% in all soils, indicating a reduction in water leakage loss. As the dripping rate increased, the proportion of water on the film in the loam soil decreased gradually; the dripping rate in irrigation for this soil should be controlled below a critical value. In the sandy soil, it was required to adjust the buried depth of the drip irrigation pipes to reduce leakage loss. The optimal dripping rate for the sandy clay loam soil and the loam soil was 2 L/h. As the flow rate increased, there was no significant change in the proportion of water on the membrane in the silt soil; the optimal dripping rate for the silt soil was 3 L/h. 【Conclusion】 Our experimental and numerical studies showed the optimal dripping rate for the membrane - regulated surface drip irrigation was 2 L/h for the sandy clay loam soil and the loam soil, and 3 L/h for the silt soil.

Objective To investigate whether acupuncture with benefiting the kidney and consolidating the essence could improve the hot flash and the quality of life of breast cancer patients with endocrine therapy. Methods From December 2019 to December 2020, 40 patients with hormone receptor positive breast cancer diagnosed in Jiangsu Provincial Hospital of Chinese Medicine were included, and all the patients had hot flashes after endocrine therapy. The patients were divided into treatment group and control group by random number table method (n=20, each) . The treatment group received acupuncture for benefiting the kidney and consolidating the essence for 10 weeks and self-regulation, while the control group received self-regulation only. The scores of hot flashes, frequency of hot flashes, and quality of life assessment scale (FACT-B) were evaluated before and the 5th and 10th weeks of treatment. Results In the treatment group, the number of hot flashes and the hot flashes fraction at 5 and 10 weeks of acupuncture treatment were significantly lower compared with those before treatment (P＜0.05) . In the control group, the treatment did not change significantly by 5 weeks (P＞0.05) and decreased significantly by 10 weeks (P＜0.05) . The number of hot flashes and the hot flush fraction in the treatment group at 5th and 10th week of treatment were significantly lower than those in the control group (P＜0.05) . The physical, emotional, add-on status, social family and functional status scores in FACT-B were significantly improved in the treatment group at 10th week of acupuncture (P＜0.05) , but did not change in the control group after treatment (P＞0.05) , and the scores improved significantly in the treatment group compared with those in the control group (P＜0.05) . Conclusion Acupuncture with benefiting the kidney and consolidating the essence for 10 weeks can significantly improve the frequency and severity of hot flashes in patients undergoing endocrine therapy for breast cancer, as well as improve the quality of patient survival.

In this study, the differences in total phenol content and metabolite profile among arabic gum, karaya gum and peach gum were analyzed. The results showed that there was a significant difference in total phenol content among the three gums. Peach gum had the highest total phenol content (19.93 μmol/g), followed by arabic gum (4.06 μmol/g) and karaya gum (1.36 μmol/g). Metabolomics analysis showed that all these gums were rich in small molecular metabolites, such as amino acids, organic acids, flavonoids, and lipids. However, there were significant differences in the species and abundance of small molecular metabolites among the gums, which may be associated with producer species and flowing method. The contents of flavonoids and total phenols in peach gum were significantly higher than those in arabic Gum and karaya gum. In addition, the contents of amino acids and organic acids in karaya gum and arabic gum were significantly higher than those in peach gum. The content of lipids in karaya gum was significantly higher than that in arabic gum and peach gum. The metabolic pathways of differential metabolites among the different gums mainly included the pathways of flavonoid biosynthesis, isoquinoline alkaloid biosynthesis, amino acid synthesis and metabolism, and linoleic acid metabolism. The results from our present study may provide technical support for gum quality analysis and the discovery of its functional components.

Nucleotide excision repair (NER) is a major pathway to deal with bulky adducts induced by various environmental toxins in all cellular organisms. The two sub-pathways of NER, global genome repair (GGR) and transcription-coupled repair (TCR), differ in the damage recognition modes. In this review, we describe the molecular mechanism of NER in mammalian cells, especially the details of damage recognition steps in both sub-pathways. We also introduce new sequencing methods for genome-wide mapping of NER, as well as recent advances about NER in chromatin by these methods. Finally, the roles of NER factors in repairing oxidative damages and resolving R-loops are discussed.

Uneven regional development has long been a focal issue for both academia and policymakers, with numerous studies over the past decades actively engaging in discussions on measuring regional development disparities. Generally, most existing studies measure the Human Development Index (HDI) using relatively simple indicators, with a focus on national and provincial scales. As a crucial component of regional development, counties can directly reflect the regional characteristics of socio-economic progress. This study employs a multi-dimensional approach to develop an improved Human Development Index (improved HDI) system, using machine learning techniques to establish the relationship between nighttime light (NTL) data and the improved HDI. Subsequently, NTL data are utilized to infer the spatial distribution characteristics of the improved HDI across China's county-level regions. The improved HDI for county-level areas in the Ningxia Hui Autonomous Region was validated using a machine learning model, resulting in a Pearson correlation coefficient of 0.93. The adjusted R-squared value for the linear fit was 0.86, and the residuals were relatively balanced, ensuring the accuracy of the simulations. This study reveals that 1439 county-level units, representing 50% of all county-level units in China, have development levels at or above the medium level. At the provincial and national levels, the improved HDI shows significant clustering, characterized by a multi-center pattern with declining diffusion. The spatial distribution of the improved Human Development Index remains closely associated with the natural geographic background and socio-economic development levels of the county regions. Lower HDI values are predominantly found in the inland areas of central and western China, often in ecologically sensitive areas, inter-provincial border zones, and mountainous regions of mainland China, sometimes forming contiguous distribution patterns. This underscores the need for the government and society to focus more on these specific geographic development areas, promoting continuous improvements in health, education, and living standards to achieve coordinated regional development. [ABSTRACT FROM AUTHOR]

High-k gate dielectrics have attracted a great deal of attention in the investigation of transistors due to their unique properties such as superior gate controllability. However, their integration into graphene field-effect transistors (GFETs) remains problematic and the physical mechanisms governing the performance of these devices are still not fully understood. In this study, the effects of post-annealing on GFETs utilizing the high-k HfLaO ternary oxide as the gate dielectric were comprehensively investigated. The HfLaO film was deposited on top of graphene by magnetron sputtering, and the device performance with various post-annealing temperatures was conducted. It was found that post-annealing temperature can effectively increase the dielectric constant through balancing the oxygen-vacancy defects and moisture absorption. Both the surface morphology of HfLaO and performance of GFETs were investigated, and the fabricated GFETs exhibit notable electrical performance enhancements. Specifically, GFETs with a 200 °C post-annealed HfLaO gate dielectric demonstrate the optimal device performance, featuring a minimal Dirac point voltage (VDirac) of 1.1 V and a minimal hysteresis (ΔVDirac) of 0.5 V. The extracted hole and electron mobilities are 4012 and 1366 cm2/V · s, respectively, nearly one order of magnitude higher than that of GFETs with as-deposited HfLaO. This work outperforms other existing GFETs utilizing high-k gate dielectric and chemical vapor deposition grown graphene in terms of both carrier mobility and on–off ratio. It is also noted that the excessive post-annealing temperature can negatively impact the GFET performance through introducing oxygen vacancies, increasing the surface roughness, lowering the breakdown voltage, and inducing recrystallization. [ABSTRACT FROM AUTHOR]